Angiosarcomas are rare, heterogeneous and a retrospective study was conducted to describe their natural history.
We reviewed 161 files of angiosarcoma treated in three institutions of the French ...Sarcoma Group from 1980 to 2004. Survival and prognostic factors for survival were analyzed.
Median age was 52 years. Primary sites were the breast (35%), skin (20%) and soft tissues (13%). At initial diagnosis, 31 (19%) had metastases. Surgery was the first treatment in 121 (75%) patients combined with chemotherapy or radiotherapy in 34 and 32, respectively. Ninety (74%) of these 121 patients relapsed, mostly locally (50). With an average time since initial diagnosis of 8.1 years, 123 (76%) patients progressed and 76 (47%) died. Median survival was 3.4 years 95% confidence interval (CI) 2.4–5.8, and the 5-year overall survival (OS) rate was 43% (95% CI 33–53). In multivariate analysis, liver primary site relative risk (RR) = 12.62, performance status (PS) of two or more (RR = 3.83), presence of metastases at diagnosis (RR = 2.50), soft tissue tumor (RR = 0.31) were correlated to OS. PS, liver and soft tissue tumors were identified as independent prognostic factors for progression-free survival.
Angiosarcomas have an overall poor outcome, but with a clearly distinct prognosis depending on the primary site.
Targeting HER2 in other tumor types SCHOLL, S; BEUZEBOC, P; POUILLART, P
Annals of oncology,
2001, 2001-00-00, 20010101, Letnik:
12
Conference Proceeding, Journal Article
Recenzirano
The human epidermal growth factor receptor-2 (HER2) is overexpressed/amplified in a range of tumor types including breast, ovarian, bladder, salivary gland, endometrial, pancreatic and non-small-cell ...lung cancer (NSCLC). HER2 is implicated in disease initiation and progression, associated with poor prognosis, and may also predict the response to chemotherapy and hormonal therapy. Anti-HER2 monoclonal antibodies (MAbs) have been designed to specifically antagonize the function of the HER2 receptor in HER2-positive tumors. Clinical phase II and III trials have demonstrated the efficacy of the humanized anti-HER2 MAb, trastuzumab (Herceptin), both as a single agent and in combination with chemotherapy in HER2-positive, metastatic breast cancer patients. However, the prevalence of HER2 overexpression/amplification in various tumor types raises the possibility of using anti-HER2 MAbs to antagonize the abnormal function of overexpressed HER2 receptors in HER2-positive tumors other than breast. Preliminary in vitro studies indicate that anti-HER2 MAbs suppress the proliferation of ovarian, gastric and NSCLC cell lines that overexpress the HER2 receptor. These results indicate that anti-HER2 MAbs may have important therapeutic significance in patients presenting with these or other human carcinomas. Clinical trials are either planned or underway to assess the therapeutic role of trastuzumab in NSCLC, bladder and ovarian cancer.
► We applied the MIQE guidelines to clinical and pre-clinical trials. ► We proposed a solution to handle many samples, keeping the MIQE compliance close to 100%. ► The bench side quality measurement ...in these trials was also part of this work.
The “Minimum Information for the Publication of qPCR Experiments” (MIQE 3) guidelines are very much targeted at basic research experiments and have to our knowledge not been applied to qPCR assays carried out in the context of clinical trials. This report details the use of the MIQE qPCR app for iPhone (App Store, Apple) to assess the MIQE compliance of one clinical and five pre-clinical trials. This resulted in the need to include 14 modifications that make the guidelines more relevant for the assessment of this special type of application. We also discuss the need for flexibility, since while some parameters increase experimental quality, they also require more reagents and more time, which is not always feasible in a clinical setting.
To determine the incidence and the prognostic value of ipsilateral breast tumor recurrence (IBTR) in patients treated with primary chemotherapy and breast-conserving surgery.
Between January 1985 and ...December 1994, 257 patients with invasive T1 to T3 breast carcinoma were treated with primary chemotherapy, lumpectomy, and radiation therapy. The median follow-up time was 93 months. To evaluate the role of IBTR in metastase-free survival, a Cox regression multivariate analysis was performed using IBTR as a time-dependent covariate.
The IBTR rates were 16% (+/- 2.4%) at 5 years and 21.5% (+/- 3.2%) at 10 years. Multivariate analysis showed that the probability of local control was decreased by the following independent factors: age < or = 40 years, excision margin < or = 2 mm, S-phase fraction more than 4%, and clinical tumor size more than 2 cm at the time of surgery. In patients with excision margins of more than 2 mm, the IBTR rates were 12.7% at 5 years and 17% at 10 years. Nodal status, age < or = 40 years, and negative estrogen receptor status were predictors of distant disease in the Cox multivariate model with fixed covariates. The contribution of IBTR was highly significant (relative risk = 5.34) when added to the model, whereas age < or = 40 years was no longer significant. After IBTR, 31.4% (+/- 7.0%) of patients developed metastases at 2 years and 59.7% (+/- 8.1%) at 5 years. Skin involvement, size at initial surgery, and estrogen receptor status were predictors of metastases after IBTR.
IBTR is a strong predictor for distant metastases. There are implications for conservative surgery after downstaging of the tumor and therapy at the time of IBTR.
From 1981 to 1995, 1755 patients aged 70 years or over who had nonmetastatic unilateral breast carcinoma received curative local or regional treatment in our institute. Median follow-up was 8 years. ...The median age of these patients was 75 years (range: 70–94), and 86% were under 81 years of age. Tumors were classed as T3–4 in 24% of them; 18% had N1b/N2 tumors, and in 12% grade 3 disease was present. Only 19% were both ER and PR negative. The S phase fraction was <5% in 79% of patients. In 1046 patients (60%) modified radical mastectomy was performed, while 20% underwent lumpectomy and in 20% radiotherapy was the only treatment administered. Adjuvant endocrine therapy was given in 463 (26%) cases, and only 3% of patients received chemotherapy. The median overall survival time was 121 months. The overall cancer-related death rate was 49%. The 10-year disease-free survival (DFS) rate was 64%, and the 10-year local relapse rate was 14%. Prognostic factors determined on univariate analysis were tumor size, clinical nodal status (ER and PR), and grade. No significant difference in outcome was observed between mastectomy and conservative treatment. Parameters for which correlations with DFS were found on multivariate analysis were clinical nodal status (
P<0.0001), tumor size (
P<0.0001), ER (
P<0.0001), and PR (
P=0.04). Breast cancer in elderly women is frequently hormone-dependent (81%) with a low proliferation index. Prognostic factors are the same as in younger postmenopausal patients. More than 50% of these patients died from a cause other than their breast cancer.
Although all studies confirm that BRCA1 tumors are highly proliferative and poorly differentiated, their outcomes remain controversial. We propose to examine, through a cohort study, the pathologic ...characteristics, overall survival, local recurrence, and metastasis-free intervals of 40 patients with BRCA1 breast cancer.
A cohort of 183 patients with invasive breast cancer, treated at the Institut Curie and presenting with a familial history of breast and/or ovarian cancer, were tested for BRCA1 germ-line mutation. Tumor characteristics and clinical events were extracted from our prospectively registered database.
Forty BRCA1 mutations were found among the 183 patients (22%). Median follow-up was 58 months. BRCA1 tumors were larger in size (P =.03), had a higher rate of grade 3 histoprognostic factors (P =.002), and had a higher frequency of negative estrogen (P =.003) and progesterone receptors (P =.002) compared with non-BRCA1 tumors. Overall survival was poorer for carriers than for noncarriers (5-year rate, 80% v 91%, P =.002). Because a long time interval between cancer diagnosis and genetic counseling artificially increases survival time due to unrecorded deaths, the analysis was limited to the 110 patients whose diagnosis-to-counseling interval was less than 36 months (19 BRCA1 patients and 91 non-BRCA1 patients). The differences between the BRCA1 and non-BRCA1 groups regarding overall survival and metastasis-free interval were dramatically increased (49% v 85% and 18% v 84%, respectively). Multivariate analysis showed that BRCA1 mutation was an independent prognostic factor.
Our results strongly support that among patients with familial breast cancer, those who have a BRCA1 mutation have a worse outcome than those who do not.
Whether or not young age at diagnosis is an adverse prognostic factor in breast cancer has long been controversial, in part because much previous work has not taken due account of menopausal status ...and confounding factors. We have analysed the influence of age on prognosis in a consecutive series of 1703 patients with stage I-III breast cancer. All were premenopausal and all were treated in one centre (Institut Curie, Paris) between 1981 and 1985. Mean age was 44 years (range 23-55) and median follow-up was 82 months.
Younger patients had significantly lower survival rates and higher local and distant relapse rates than older patients. The hazard rate of relapse decreased over time in the youngest age group (≤33) to reach that of older patients after 5 years. The relation between the hazard of recurrence and age was a continuous one, best fitted by a log-linear function and indicating a 4% decrease in recurrence for every year of age. Multivariate analysis of both survival and disease-free interval demonstrated that the worse prognosis of young age was independent of other factors such as clinical tumour size, clinical node status, histological grade, hormone receptor status, locoregional treatment procedure, and adjuvant systemic therapy.
This difference in outlook has yet to be explained biologically but it does suggest the need for a closer look at the natural history of breast cancer in young women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBJE, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
We have prospectively analyzed blood samples of 122 patients with breast
disease for the presence of circulating expressing MUC1
cells before and after treatment. Among them, 28 patients had
...histologically confirmed benign breast disease (group 1), 34 patients
had operable breast cancer (group 2), and 60 patients had advanced
breast cancer (group 3). Circulating epithelial cells were isolated
with BerEP4-coated immunomagnetic beads. Total RNA was extracted and
reverse transcribed before analysis by real-time PCR of a
MUC1- specific cDNA sequence.
The sensitivity of the reverse transcription-PCR tested with blood
spiked with MCF7 cells was one cell in 5 ml of blood. The
immunomagnetic separation step was mandatory to obtain the maximum
specificity. Control samples from healthy donors never displayed cycle
threshold (Ct) values for MUC1 lower than 38.
Circulating cells (Ct, <38) were detected in 3 of 28 (11%) cases in
group 1, in 8 of 34 (24%) cases in group 2, and in 27 of 60 cases
(45%) in group 3. A semiquantitative estimate of blood-borne cells
could be derived from the Ct value when below 32 (the lowest was 28) or
by the number of positive aliquots of the same blood sample. Thus,
immunomagnetic separation, followed by MUC1- specific
RT-PCR, allows the semiquantitative detection of circulating mammary
cells. A significant correlation between the presence of
MUC1- positive cells and the group of breast tumors was
observed. The clinical significance of blood-borne cells in breast
cancer, especially at the operable stage, may be investigated by
following these patients.
This multicentre phase II open-label study evaluated safety and antitumour activity of oxaliplatin in cisplatin or carboplatin (cis/carboplatin) +/- taxane-pretreated advanced ovarian cancer (AOC) ...patients.
Forty-eight patients received oxaliplatin 130 mg/M2 intravenously every 3 weeks, 94% having a performance status (PS) 0-1. All were pretreated with cis/carboplatin and 21 (44%) with paclitaxel. The median number of involved organs was two, 18 (38%) had liver metastasis, 23 (48%) were platinum-resistant and 14 (29%) were taxane-resistant. Forty-two patients were evaluable for a response, 18 (43%) were platinum-resistant and 11 (26%) were taxane-resistant.
A total of 253 cycles was administered (median: 5.5/patient). Median cumulative oxaliplatin dose was 666 mg/m2. National Cancer Institute-Common Toxicity Criteria toxicity analysis showed that seven patients (15%) had grade 3/4 thrombocytopenia, two patients (4%) had grade 3 neutropenia, and one patient had grade 3 anaemia. Eleven patients (23%) experienced grade 3 neurosensory toxicity. Of the 29 patients with peripheral neuropathy at the end of treatment, 55% had recovered or improved 1 month later. Eleven objective responses (two complete) were obtained in the 42 evaluable patients ORR 26%, 95% confidence interval (CI) 14% to 42%, with 10/24 (42%, 95% CI 22% to 63%) in platinum-sensitive, and 1 of 18 (5.6%, 95% CI 0% to 27%) in platinum-resistant patients. Median response duration was 9.2 months (95% CI 6.6% to 11.8%), and median progression-free and overall survival in all treated patients were 4.3 months (95% CI 3.0% to 5.7%) and 15.0 months (95% CI 11.1% to 18.8%), respectively.
Oxaliplatin has a good safety profile and is active in cis/carboplatin +/- paclitaxel-pretreated AOC patients.
The aim of this retrospective study was to assess predictive factors for clinical response to preoperative chemotherapy and prognostic factors for survival. From 1981 to 1992, 936 patients with ...T2-T3, N0-N1 breast cancer who received 2–6 months (median 4) of preoperative chemotherapy were selected from the Institute Curie database. Preoperative treatment was followed by surgery and/or radiotherapy. Median follow-up was 8.5 years (range 7–211 months). The objective response rate before surgery and/or radiotherapy was 58.3%. In stepwise multivariate analysis (Cox model), favourable prognostic factors for survival were the absence of pathological axillary lymph node involvement (Relative Risk (RR) 1.54; P=0.0004), low histological tumour grade (RR=1.54; P=0.0017), clinical response to preoperative chemotherapy (RR=1.45, P=0.0013), positive progesterone receptor (PR) status (RR=1.56; P=0.0001), smaller tumour size (RR=1.37; P=0.005) and lack of clinical lymph node involvement (RR=1.42; P=0.007). The association of clinical tumour response with survival is independent of the baseline characteristics of the tumour. Clinical response could be used as a surrogate marker for evaluation of the efficacy of neoadjuvant chemotherapy before assessment of the pathological response.
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