Women with estrogen-positive breast cancers receive endocrine treatment such as tamoxifen and aromatase inhibitors (AI) for 5–10 years. An important side effect of these drugs is vaginal dryness for ...which local hormonal therapy (LHT) represents the most effective treatment but is theoretically contraindicated. This study aimed to assess whether the use of LHT increases the risk of breast cancer recurrence among women receiving endocrine treatment. We conducted a cohort study with nested case–control analysis using the United Kingdom General Practice Research Database (GPRD). The cohort included female patients at least 18 years of age, newly diagnosed with breast cancer who received at least one AI or tamoxifen prescription between January 1, 1998 and June 30, 2008. Cases, who were patients experiencing a breast cancer recurrence during follow-up, were each matched with up to 10 controls based on age, date of cohort entry, type of endocrine treatment received, and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RR), and 95 % confidence intervals. A total of 13,479 women were included in the study, of which 2,673 received AIs, 10,806 received tamoxifen, and 271 received LHT. Mean (SD) age at cohort entry was 63.7 (14.1) years, and mean follow-up was 3.5 (2.6) years. The crude recurrence rate 25.9 per 1,000 per year. Overall, the use of LHT was not associated with an increased risk of recurrence (RR: 0.78, 95 % CI 0.48–1.25) compared with non-use. In stratified analyses, LHT did not increase the risk of recurrence among tamoxifen-treated patients (RR: 0.83, 95 % CI 0.51–1.34), while the risk was not estimable among AI-treated patients since no patients receiving LHT experienced a recurrence. The use of LHT is not associated with an increase in breast cancer recurrence among women receiving a hormone therapy.
Background
The optimal treatment for advanced leiomyosarcoma is still debated. Given histotype‐specific prospective controlled data lacking, this study retrospectively evaluated doxorubicin plus ...dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone as first‐line treatments for advanced/metastatic leiomyosarcoma treated at European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC‐STBSG) sites.
Methods
The inclusion criteria were a confirmed histological diagnosis, treatment between January 2010 and December 2015, measurable disease (Response Evaluation Criteria in Solid Tumors 1.1), an Eastern Cooperative Oncology Group performance status ≤2, and an age ≥ 18 years. The endpoints were progression‐free survival (PFS), overall survival (OS), and overall response rate (ORR). PFS was analyzed with methods for interval‐censored data. Patients were matched according to their propensity scores, which were estimated with a logistic regression model accounting for histology, grade, age, sex, performance status, tumor site, and tumor extent.
Results
Three hundred three patients from 18 EORTC‐STBSG sites were identified. One hundred seventeen (39%) received doxorubicin plus dacarbazine, 71 (23%) received doxorubicin plus ifosfamide, and 115 (38%) received doxorubicin. In the 2:1:2 propensity score–matched population (205 patients), the estimated median PFS was 9.2 months (95% confidence interval CI, 5.2‐9.7 months), 8.2 months (95% CI, 5.2‐10.1 months), and 4.8 months (95% CI, 2.3‐6.0 months) with ORRs of 30.9%, 19.5%, and 25.6% for doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone, respectively. PFS was significantly longer with doxorubicin plus dacarbazine versus doxorubicin (hazard ratio HR, 0.72; 95% CI, 0.52‐0.99). Doxorubicin plus dacarbazine was associated with longer OS (median, 36.8 months; 95% CI, 27.9‐47.2 months) in comparison with both doxorubicin plus ifosfamide (median, 21.9 months; 95% CI, 16.7‐33.4 months; HR, 0.65; 95% CI, 0.40‐1.06) and doxorubicin (median, 30.3 months; 95% CI, 21.0‐36.3 months; HR, 0.66; 95% CI, 0.43‐0.99). Adjusted analyses retained an effect for PFS but not for OS. None of the factors selected for multivariate analysis had a significant interaction with the received treatment for both PFS and OS.
Conclusions
This is the largest retrospective study of first‐line treatment for advanced leiomyosarcoma. In the propensity score–matched population, doxorubicin and dacarbazine showed favorable activity in terms of both ORR and PFS and warrants further evaluation in prospective trials.
In this propensity score‐adjusted, multi‐institutional series, doxorubicin and dacarbazine show better outcomes for the first‐line treatment of advanced leiomyosarcoma and warrant further studies. This series represents a benchmark for the future development of trials for leiomyosarcoma.
The aim of this randomized, phase II trial was to explore the activity and safety of adding bevacizumab to paclitaxel once per week in treatment of angiosarcomas (AS).
Patients were treated with ...paclitaxel alone (90 mg/m(2) per week for six cycles of 28 days each; arm A) or with paclitaxel combined with bevacizumab (10 mg/kg once every 2 weeks; arm B). In the combination treatment arm, bevacizumab was administered after the six cycles of chemotherapy as maintenance therapy (15 mg/kg once every 3 weeks) until intolerance or progression occurred. Stratification factors were superficial versus visceral AS and de novo versus radiation-induced AS. The primary end point was the 6-month progression-free survival (PFS) rate, which was based on RECIST, version 1.1. Statistical assumptions were P0 = 20%, P1 = 40%, a = 10%, and b = 20%. P0 was the PFS rate at 6 months defining inactive drug, and P1 was the PFS rate at 6 months defining promising drug.
A total of 52 patients were enrolled, and 50 were randomly assigned in 14 centers. The most common primary sites were the breast (49%) and skin (12%). There were 17 (34%) visceral and 24 (49%) radiation-induced AS. The performance status was 0 in 24 patients (49%) and 1 in the remaining 25 patients (51%). The median follow-up time was 14.5 months. Both treatment regimens were considered active, with 6-month PFS rates of 54% (14 of 26) in arm A and 57% (14 of 24) in arm B. The median overall survival rates were 19.5 months in arm A and 15.9 months in arm B. Toxicity was higher with the combination arm and included one fatal drug-related toxicity (intestinal occlusion).
The primary objective was met in both treatment arms. However, the present data do not support additional clinical investigation of combined paclitaxel/bevacizumab for the treatment of advanced AS.
Phase I trials aim to identify the recommended dose for further development. Health-related quality of life (HRQoL) could be a complement to the usual National Cancer Institute Common Terminology ...Criteria for Adverse Events (NCI-CTCAE) scale to detect adverse events and define the doses. The objective of this study is to review the phase I in oncology which used HRQoL as endpoint.
A search in PubMed database identified phase I trials in oncology with HRQoL as endpoint, published between January 2012 to May 2016. Hematological and pediatric phase I were excluded.
A total of 1333 phase I were identified and 15 trials were identified with HRQoL as endpoint (1.1%). The European Organisation for Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was the most frequently used instrument: 5 studies (33.3%). The targeted dimensions of HRQoL and the minimal clinically important difference were prespecified in 1 study (6.7%) and 2 studies (13.3%), respectively. Twelve studies (80%) described the statistical approach to analyze HRQoL data. Eight studies used the mean change from baseline (60%) to analyse longitudinal HRQoL data, two the mean score at certain times (13.3%), one the linear mixed model for repeated measures (6.7%), one the time to HRQoL score deterioration (6.7%), one percentage of patient-reported symptoms (6.7%). None of the studies used HRQoL to determine the recommended doses.
Few phase I studies used HRQoL as endpoint and among studies with HRQoL as endpoint, the methodology of HRQoL measurement and statistical analysis was heterogeneous. HRQoL. endpoint not used for assessing the recommended phase II doses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study examined the types of discordance occurring in the diagnosis of soft tissue and visceral sarcomas, gastrointestinal stromal tumors (GIST), and desmoid tumors, as well as the economic ...impact of diagnostic discrepancies.
We carried out a retrospective, multicenter analysis using prospectively implemented databases performed on a cohort of patients within the French RRePS network in 2010. Diagnoses were deemed to be discordant based on the 2013 World Health Organization (WHO) classification. Predictive factors of discordant diagnoses were explored. A decision tree was used to assess the expected costs of two strategies of disease management: one based on revised diagnoses after centralized histological review (option 1), the other on diagnoses without centralized review (option 2). Both were defined based on the patient and the disease characteristics, according to national or international guidelines. The time horizon was 12 months and the perspective of the French National Health Insurance (NHI) was retained. Costs were expressed in Euros for 2013. Sensitivity analyses were performed using low and high scenarios that included ± 20% estimates for cost.
A total of 2,425 patients were included. Three hundred forty-one patients (14%) had received discordant diagnoses. These discordances were determined to mainly be benign tumors diagnosed as sarcomas (n = 124), or non-sarcoma malignant tumors diagnosed as sarcomas (n = 77). The probability of discordance was higher for a final diagnosis of desmoid tumors when compared to liposarcomas (odds ratio = 5.1; 95%CI 2.6-10.4). The expected costs per patient for the base-case analysis (low- and high-case scenarios) amounted to €8,791 (€7,033 and €10,549, respectively) for option 1 and €8,904 (€7,057 and €10,750, respectively) for option 2.
Our findings highlight misdiagnoses of sarcomas, which were found to most often be confused with benign tumors. Centralized histological reviews are likely to provide cost-savings for the French NHI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the OS2006 study, patients younger than 18 years were treated with a methotrexate‐based regimen (MTX), patients older than 25 years with a doxorubicin–cisplatin–ifosfamide‐based regimen (API–AI), ...whereas patients aged 18–25 years received either API–AI or MTX. We herein report the prespecified subgroup analysis of the outcome of 106 patients treated with API–AI. Preoperative chemotherapy combined three doxorubicin–ifosfamide–cisplatin (API) and two doxorubicin–ifosfamide (AI) courses. Postoperative chemotherapy was assigned by risk group: localised patients with a good histological response (<10% viable cells) received two AI and two cisplatin–ifosfamide (PI) courses; patients with synchronous metastases, poor histological response or unresectable primary received five cycles of etoposide–ifosfamide (EI). Of the 106 patients, 61 were randomised to receive or not zoledronate. Median age was 30 years (range 18–67), 66 (62%) patients were >25 years. The primary tumours were axial in 28 patients (26%), and 28 (26%) presented with metastases. Ninety‐six patients (91%) had surgery, conservative in 82 (85%); 36 patients (38%, 95% CI 28–48%) were good responders. Toxicity was manageable, with no significant difference in severe acute toxicity between patients aged >25 years and those younger. With a median follow‐up of 4.8 years, the 5‐year event‐free survival and overall survival rates were 46% (95% CI 36–56) and 57% (95% CI 47–67), respectively. The primary tumour size and initial metastases correlated with a higher risk of event. In these 106 osteosarcoma adult patients, API–AI proved feasible with no excess of toxicity, and favourable activity despite poor‐prognosis factors.
What's new?
Osteosarcoma paediatric patients are commonly treated with high‐dose methotrexate combined to other active agents. Methotrexate pharmacokinetics varies considerably with age, however, with few prospective studies dedicated to adult patients and currently no consensus concerning the optimal chemotherapy regimen in these patients. This paper describes the population of 106 adult osteosarcoma patients enrolled in the OS 2006 phase III study, their treatment and their outcomes using a chemotherapy backbone without methotrexate that combines doxorubicin, cisplatin, and ifosfamide. This study confirms prior findings that the API‐AI regimen has acceptable toxicity and yields favourable activity in adult osteosarcoma patients with poor prognosis factors.
The increased risk of venous thromboembolism (VTE) associated with pregnancy is well-known and prophylaxis guidelines consider a number of risk factors. Although non-O blood group and red blood cell ...(RBC) transfusion are known to be associated with VTE risk, their contribution to pregnancy-associated VTE has received little attention. This study was conducted in a population-based cohort of 1,000,997 deliveries to women with no prior history of VTE or thrombophilia. The independent contributions of ABO blood type and RBC transfusion to the risks of antepartum, peripartum and postpartum VTE are reported as odds ratios adjusted for risk factors that are considered in current prophylaxis guidelines and other potential confounders. Compared with type O, A and B blood types have higher risk of antepartum and postpartum VTE, with odds ratios between 1.4 and 1.8. Transfusion around delivery has the largest increased risks and a dose-response effect, with adjusted odds ratios from 2.60 (1.71-3.97) for 1-2 units to 3.55 (1.32-9.55) for more than 5 units. ABO blood type and RBC transfusion were found to be independent risk factors for pregnancy-associated VTE. Further research is required to understand the underlying mechanisms and to conduct a risk-benefit assessment of the small volumes of RBCs transfused around delivery.
Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. Within-country studies have reported racial differences in the presentation and outcome, but little is ...known about differences between countries.
To compare preeclampsia prevalence, risk factors, and pregnancy outcomes between the Swedish and Chinese populations.
This cross-sectional study compared deliveries from the Swedish national Medical Birth Register (2007-2012) and the China Labor and Delivery Survey (2015-2016). The Swedish Medical Birth Register records maternal, pregnancy, and neonatal information for nearly all deliveries in Sweden. The China Labor and Delivery Survey was conducted throughout China, and these data were reweighted to enable national comparisons. Participants included 555 446 deliveries from Sweden and 79 243 deliveries from China. Data management and analysis was conducted from November 2018 to August 2020 and revised in February to March 2021.
Maternal characteristics, parity, multiple gestation, chronic and gestational diabetes, cesarean delivery.
Preeclampsia prevalence and risk factors, overall and for mild and severe forms and rates of adverse neonatal outcomes compared with pregnancies with no gestational hypertension.
The 555 446 Swedish pregnancies and 79 243 Chinese pregnancies had mean (SD) maternal age of 30.9 (5.3) years and 28.6 (4.6) years, respectively. The overall prevalence of preeclampsia was similar in Sweden and China, 16 068 (2.9%) and 1803 (2.3%), respectively, but with 5222 cases (32.5%) considered severe in Sweden and 1228 cases (68.1%) considered severe in China. Obesity (defined as BMI ≥28 in China and BMI ≥30 in Sweden) was a stronger risk factor in China compared with Sweden (China: odds ratio OR, 5.12; 95% CI, 3.82-6.86; Sweden: OR, 3.49; 95% CI, 3.31-3.67). Nulliparity had a much stronger association with severe preeclampsia in Sweden compared with China (Sweden: OR, 3.91; 95% CI, 3.65-4.18; China: OR, 1.65; 95% CI, 1.20-2.25). The overall stillbirth rate for singleton in China was more than 3-fold higher than in Sweden (846/77 5121.1% vs 1753/547 219 0.3%, P < .001), and 10-fold higher among women with preeclampsia (66/1652 4.6% vs 60/14 4990.4%, P < .001).
In this study, the prevalence rates of preeclampsia in Sweden and China were similar, but women in China had more severe disease and worse pregnancy outcomes than women in Sweden. The associations of obesity and nulliparity with preeclampsia suggest a role for lifestyle and health care factors but may reflect some differences in pathophysiology. These findings have relevance for current efforts to identify high-risk pregnancies and early serum markers because the value of risk prediction models and biomarkers may be population specific.
Well-designed observational studies of individuals with rare tumors are needed to improve patient care, clinical investigations, and the education of healthcare professionals.
The patterns of care, ...outcomes, and prognostic factors of a cohort of 2225 patients with metastatic soft tissue sarcomas who were diagnosed between 1990 and 2013 and documented in the prospectively maintained database of the French Sarcoma Group were analyzed.
The median number of systemic treatments was 3 (range, 1-6); 27% of the patients did not receive any systemic treatment and 1054 (49%) patients underwent locoregional treatment of the metastasis. Half of the patients who underwent chemotherapy (n = 810) received an off-label drug. Leiomyosarcoma was associated with a significantly better outcome than the other histological subtypes. With the exception of leiomyosarcomas, the benefit of a greater than third-line regimen was very limited, with a median time to next treatment (TNT) and overall survival (OS) ranging between 2.3 and 3.7 months and 5.4 and 8.5 months, respectively. The TNT was highly correlated with OS. Female sex, leiomyosarcoma histology, locoregional treatment of metastases, inclusion in a clinical trial, and treatment with first-line polychemotherapy were significantly associated with improved OS in the multivariate analysis.
The combination of doxorubicin with a second drug, such as ifosfamide, represents a valid option, particularly when tumor shrinkage is expected to provide clinical benefits. After failure of the second-line therapy, best supportive care should be considered, particularly in patients with non-leiomyosarcoma histology who are not eligible to participate in a clinical trial. Locoregional treatment of metastasis should always be included in the therapeutic strategy when feasible. TNT may represent a useful surrogate endpoint for OS in clinical studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although the mutational status in gastrointestinal stromal tumors (GIST) can predict the response to treatment with tyrosine kinase inhibitors, the role of tumor genotype as a prognostic factor ...remains controversial. The ConticaGIST study sought to determine the pathologic and molecular factors associated with disease-free survival (DFS) in patients with operable, imatinib-naive GIST.
Clinicopathologic and molecular data from 1,056 patients with localized GIST who underwent surgery with curative intention (R0/R1) and were registered in the European ConticaGIST database were prospectively obtained and reviewed. Risk of tumor recurrence was stratified using the modified NIH criteria. The median follow-up was 52 months.
On testing for potential prognostic parameters, the following were associated with inferior DFS on multivariable Cox model analysis: primary nongastric site, size >10 cm, mitotic index >10 mitoses per 50 high power field, and the KIT exon 9 duplication hazard ratio (HR), 1.47; 95% confidence interval (CI), 0.9-2.5; P = 0.037 and KIT exon 11 deletions involving codons 557 and/or 558 KITdel-inc557/558; HR, 1.45; 95% CI, 1.0-2.2; P = 0.004. Conversely, PDGFRA exon 18 mutations were indicators of better prognosis HR, 0.23; 95% CI, 0.1-0.6; P = 0.002. KITdel-inc557/558 were an adverse indicator only in GIST localized in the stomach (P < 0.001) but not in tumors with nongastric origin. In gastric GIST, all other mutations presented remarkably superior 5-year DFS.
In conclusion, tumor genotype is an independent molecular prognostic variable associated with gastric GIST and should be used for optimizing tailored adjuvant imatinib treatment.
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