RÉSUMÉ
BACKGROUND: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. METHODS: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. RESULTS: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of -48% and -90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was -79% and -94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. CONCLUSIONS: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.
RÉSUMÉ
BACKGROUND: Dose-dense administration of chemotherapy and the addition of taxanes to anthracycline-based adjuvant chemotherapy have improved breast cancer survival substantially. However, clinical trials directly comparing the additive value of taxanes with dose-dense anthracycline-based chemotherapy are lacking. PATIENTS AND METHODS: In the multicentre, randomised, biomarker discovery Microarray Analysis in breast cancer to Tailor Adjuvant Drugs Or Regimens (MATADOR) trial, patients with pT1-3, pN0-3 breast cancer were randomised (1:1) between six adjuvant cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 weeks (ddAC) and six cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks (TAC). The primary objective was to discover a predictive gene expression profile for ddAC and TAC benefit. Here we report the preplanned secondary end-point recurrence-free survival (RFS) and overall survival (OS). RESULTS: Between 2004 and 2012, 664 patients were randomised. At 5 years, RFS was 87% (95% confidence interval [CI] 83%-91%) in the ddAC-treated patients and 88% (84-92%) in the TAC-treated subgroup (hazard ratio [HR] 0.89, 95% CI 0.62-1.28, P = 0.53). OS at 5 years was 93% (90%-96%) in the ddAC-treated and 94% (91%-97%) in the TAC-treated patients (HR 0.89, 95% CI 0.57-1.39, P = 0.61). Anaemia was more frequent in ddAC-treated patients (62/327 patients [18.9%] versus 15/319 patients [4.7%], P < 0.001) and diarrhoea (21 [6.4%] versus 53 [16.6%], P<0.001) and peripheral neuropathy (15 [4.6%] versus 46 [14.4%], P < 0.001) were observed more often in TAC-treated patients. CONCLUSIONS: With a median follow-up of 7 years, no significant differences in RFS and OS were observed between six adjuvant cycles of ddAC and TAC in high-risk breast cancer patients. TRIAL REGISTRATION NUMBERS: ISRCTN61893718 and BOOG 2004-04.
Sujet(s)
Adénocarcinome/traitement médicamenteux , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Tumeurs du sein/traitement médicamenteux , Cyclophosphamide/administration et posologie , Doxorubicine/administration et posologie , Adénocarcinome/mortalité , Adénocarcinome/secondaire , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Tumeurs du sein/mortalité , Tumeurs du sein/anatomopathologie , Traitement médicamenteux adjuvant , Cyclophosphamide/effets indésirables , Évolution de la maladie , Doxorubicine/effets indésirables , Femelle , Humains , Adulte d'âge moyen , Récidive tumorale locale , Stadification tumorale , Pays-Bas , Survie sans progression , Appréciation des risques , Facteurs de risque , Facteurs tempsRÉSUMÉ
BACKGROUND: Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma. METHODS: In this side study of the BELOB trial, 141 patients with recurrent glioblastoma were randomised to receive single-agent bevacizumab or lomustine, or bevacizumab plus lomustine. Before treatment, after 4 weeks and after 6 weeks of treatment, CECs were enumerated. RESULTS: The number of CECs increased during treatment with bevacizumab plus lomustine, but not during treatment in the single-agent arms. In patients treated with lomustine single agent, higher absolute CEC numbers after 4 weeks (log10CEC hazard ratio (HR) 0.41, 95% CI 0.18-0.91) and 6 weeks (log10CEC HR 0.16, 95% CI 0.05-0.56) of treatment were associated with improved overall survival (OS). Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated with OS. CONCLUSION: CEC numbers increased during treatment with bevacizumab plus lomustine but not during treatment with either agent alone, suggesting that this combination induced the greatest vascular damage. Although the absolute number of CECs was not associated with OS in patients treated with bevacizumab either alone or in combination, they could serve as a marker in glioblastoma patients receiving lomustine single agent.
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Anticorps monoclonaux humanisés/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Tumeurs du cerveau/traitement médicamenteux , Cellules endothéliales/physiologie , Glioblastome/traitement médicamenteux , Lomustine/usage thérapeutique , Récidive tumorale locale/traitement médicamenteux , Adulte , Sujet âgé , Anticorps monoclonaux humanisés/administration et posologie , Antigènes CD/analyse , Bévacizumab , Tumeurs du cerveau/mortalité , Tumeurs du cerveau/anatomopathologie , Mouvement cellulaire , Cellules endothéliales/cytologie , Femelle , Protéines liées au GPI/analyse , Glioblastome/mortalité , Glioblastome/anatomopathologie , Humains , Cinétique , Lomustine/administration et posologie , Mâle , Adulte d'âge moyen , Protéines tumorales/analyse , Récidive tumorale locale/mortalité , Récidive tumorale locale/anatomopathologie , Pronostic , Modèles des risques proportionnels , Études prospectivesRÉSUMÉ
A 68-year-old woman had had a TNM stage-III rectal carcinoma at the age of 54 for which she had undergone a low anterior resection followed by postoperative radiotherapy and adjuvant chemotherapy with fluorouracil and levamisol. More than 10 years later she presented with a swelling in the right groin, which turned out to be a metastasis; this was a poorly differentiated carcinoma with some of the characteristics of a transitional epithelial carcinoma, for which no primary tumour was found. The lymph node was excised. One year later, a swelling was detected on the labium majus, caused by a poorly differentiated transitional epithelial carcinoma of the glandula vestibularis major (Bartholin's gland). The patient was treated by means ofhemivulvectomy and postoperative radiotherapy.
Sujet(s)
Glandes vestibulaires majeures/anatomopathologie , Carcinome transitionnel/diagnostic , Carcinome transitionnel/secondaire , Tumeurs de la vulve/diagnostic , Sujet âgé , Carcinome transitionnel/radiothérapie , Carcinome transitionnel/chirurgie , Diagnostic différentiel , Femelle , Humains , Métastase lymphatique , Radiothérapie adjuvante , Tumeurs de la vulve/anatomopathologie , Tumeurs de la vulve/radiothérapie , Tumeurs de la vulve/chirurgieRÉSUMÉ
BACKGROUND: Familial cylindromatosis is a rare genetic disorder, giving rise to neoplasms of the skin appendages. We have recently shown that loss of the cylindromatosis tumour suppressor gene leads to activation of NF-kappaB, a transcription factor having antiapoptotic activity. This provides a possible explanation for the deregulated growth of cylindromas. In cell-based assays, salicylate can prevent NF-kappaB activation caused by loss of the cylindromatosis gene, suggesting that salicylic acid application might be a potential treatment for cylindromatosis. OBJECTIVES: To assess the effectiveness of topical application of salicylic acid on familial cylindromas. METHODS: Cylindromas in five patients from four different cylindromatosis families were treated with twice daily and then once daily topical salicylic acid. Clinical response was determined by serial tumour measurements. RESULTS: In total 17 cylindromas in five patients were studied: 12 target lesions and five control lesions. The median size of the cylindromas was 1.0 cm (range, 0.6-2.8 cm). Two of the 12 cylindromas showed a complete remission. Another eight lesions showed some response, but not sufficient to qualify as partial remission. The control lesions remained stable or increased in size. CONCLUSIONS: Salicylic acid is a well-tolerated and potential new treatment for cylindromatosis.
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Carcinome adénoïde kystique/traitement médicamenteux , Carcinome des annexes cutanées/traitement médicamenteux , Kératolytiques/administration et posologie , Syndromes néoplasiques héréditaires/traitement médicamenteux , Acide salicylique/administration et posologie , Administration par voie topique , Carcinome adénoïde kystique/génétique , Carcinome adénoïde kystique/métabolisme , Carcinome des annexes cutanées/génétique , Carcinome des annexes cutanées/métabolisme , Femelle , Études de suivi , Gènes suppresseurs de tumeur , Humains , I-kappa B Kinase/métabolisme , Kératolytiques/usage thérapeutique , Facteur de transcription NF-kappa B/métabolisme , Syndromes néoplasiques héréditaires/génétique , Syndromes néoplasiques héréditaires/métabolisme , Projets pilotes , Induction de rémission , Acide salicylique/usage thérapeutiqueRÉSUMÉ
The relationship between aplastic anaemia (AA) and pregnancy remains uncertain. To assess whether an association between pregnancy and severe aplastic anaemia (SAA) exists, we compared the frequency of pregnancy in 35 young women with newly diagnosed SAA with the expected frequency in the general population. The observed pregnancy rate in the SAA group was 3-6%. This percentage approximates the expected pregnancy rate of 4.4% in the general population and is not compatible with a strong association between pregnancy and SAA.
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Anémie aplasique/étiologie , Complications hématologiques de la grossesse/étiologie , Adolescent , Adulte , Femelle , Études de suivi , Humains , Grossesse , Troubles du postpartum/étiologie , Études rétrospectivesRÉSUMÉ
Mucins, including MUC-1, are generally considered to be products of epithelial tissues and of their tumors. To examine the possible expression of MUC-1 in other cell types, a panel of human epithelial and non-epithelial tumor cell lines was studied by reverse transcriptase polymerase chain reaction (RT-PCR), Northern blot analysis, immunocytology and radioimmunoprecipitation. Using the highly sensitive RT-PCR method, products corresponding to the non-repetitive 5' and 3' MUC-1 sequences were detected in all the cell lines examined. Amplified products lacking the tandem repeat region of MUC-1, including a new short form (designated MUC-1/Z) different from the previously reported MUC-1/Y protein, were also detected in most cell lines tested. Northern blot analysis, using a probe to the variable number tandem repeat (VNTR) region, confirmed the presence of MUC-1 mRNA in the astrocytoma, melanoma and neuroblastoma cell lines studied. MUC-1 protein was detected by immunocytology in these cell lines using monoclonal antibody (MAb) 139H2. Immunoprecipitation analysis with [3H]-glucosamine-labeled cell lysates and MAb 139H2 or an antibody to the cytoplasmic domain, CT-1, detected MUC-1 protein in 2 epithelial cell lines, an astrocytoma cell line (SK-MG-4) but not in the melanoma and neuroblastoma cell lines studied. Northern blot analysis using a probe to the 3' end of MUC-1 mRNA, confirmed the presence of MUC-1 mucin and also identified short products corresponding to the size of the short variant forms. Protein products corresponding to the MUC-1/Y and MUC-1/Z variant forms were not observed using either [3H]-glucosamine-labeled OVCAR-3 cells or [3H]-amino acid-labeled MCF-7 cells and either CT-1 antibody or MAb 232A1, detecting an epitope to the C-terminal region. Thus, depending on the sensitivity of the assay used, varying amounts of MUC-1 mRNA and protein could be detected in non-epithelial tumor cell lines. Although the amounts of MUC-1 in these cell lines are much lower than in carcinomas, it is possible that MUC-1 mucin serves a similar function in non-epithelial as in epithelial cells. The possible role of MUC-1/Y and MUC-1/Z variant forms in these cell lines is not understood.
Sujet(s)
Mucine-1/métabolisme , Mucines/métabolisme , Tumeurs/métabolisme , Astrocytome/métabolisme , Séquence nucléotidique , Technique de Northern , Tumeurs du sein/métabolisme , Tumeurs du côlon/métabolisme , Épithélium/métabolisme , Femelle , Humains , Tumeurs du rein/métabolisme , Mélanome/métabolisme , Données de séquences moléculaires , Mucines/génétique , Protéines tumorales/métabolisme , Neuroblastome/métabolisme , Tumeurs de l'ovaire/métabolisme , Réaction de polymérisation en chaîne , ARN messager/analyse , Cellules cancéreuses en cultureSujet(s)
Arthrite/étiologie , Maladie des éleveurs d'oiseaux/complications , Purpura hyperglobulinémique/étiologie , Complexe antigène-anticorps/sang , Maladie des éleveurs d'oiseaux/sang , Humains , Immunoglobuline A/sang , Immunoglobuline G/sang , Mâle , Adulte d'âge moyen , Vascularite leucocytoclasique cutanée/étiologieRÉSUMÉ
Vintriptol, a tryptophan ester of vinblastine, is a new vinca alkaloid derivative. Preclinical studies have demonstrated its antitumour activity in a large variety of animal models. In this phase I study, 47 patients with advanced cancer were exposed to escalating doses of vintriptol, starting at 6 mg/m2 and following a modified Fibonacci schedule. The drug was administered as an intravenous push on a weekly schedule. Myelosuppression was the dose-limiting toxicity and the maximum tolerated dose was 45 mg/m2. Other toxicities consisted of mild nausea and vomiting and the occurrence of fever and dryness of the mouth immediately after drug administration. Neurotoxicity, a major side-effect of other vinca alkaloids, was insignificant. 1 partial remission in a patient suffering from colorectal cancer and 1 minor response in a patient with a metastatic tumour of the cutaneous appendagous glands were documented. Pharmacokinetics of vintriptol were evaluated at the highest dose levels. A dose schedule of 40 mg/m2 vintriptol per week is recommended for phase II studies.