Mycobacterium avium complex infections, common in patients with AIDS as either pulmonary or disseminated disease, are infrequent in patients without AIDS. Participants were 45 HIV-negative patients ...with lung disease and positive sputum cultures for M avium; 10 had documented immunocompromise, and 24 had preexisting lung disease. Clarithromycin dosage was 500 to 2,000 mg daily (mean ± SD=1,633 ± 432 mg). The drug was administered either alone (n=14) or in combination with rifampin (n=8), aminoglycoside (n=1), quinolone (n=10), clofazimine (n=18), isoniazid (n=5), ethambutol (n=9), pyrazinamide (n=1), or minocycline (n=6). At 3 months, 36 patients among 39 bacteriologically assessed had negative sputum cultures, 3 had positive culture, 3 were dead, and 3 discontinued treatment. At the end of treatment, 32 patients remained negative, 7 were positive. The success rate was 15 of 22 (64%) in patients previously treated with antimycobacterial drugs for M avium disease and 17 of 23 (74%) in new patients. Adverse effects included mild hearing loss (n=4), increase in liver enzyme levels (n=5), and gastrointestinal pain (n=10, two of whom had to stop treatment). Patients stopped treatment after 300 ± 186 days due to side effects (3), death (4), or the patient's (5) or physician's decision (33). During the follow-up, one patient suffered a relapse with peripheral lymph nodes. A daily dose of 30 mg/kg of clarithromycin in the treatment of M avium infections appears to be effective and safe. Concomitant drug therapy should be assessed for its ability to prevent relapse.
Chronic obstructive pulmonary disease (COPD) is an obstructive lung disorder characterized by progressive airflow limitation that is not reversible or only partially reversible, including chronic ...bronchitis and emphysema.
Confronting COPD in North America and Europe was the first large-scale international survey to attempt to quantify the country-specific burden of the disease, collecting data on clinical outcomes, healthcare resource utilization, and lost productivity, from patients and physicians in France and seven other countries.The economic analysis of the French survey results showed that patients with COPD required considerable utilization of healthcare resources, with annual direct costs estimated at €530 per patient. In addition, COPD-related illness or disability prevented many patients from working, with an estimated annual indirect cost of €1078 per patient.
The survey suggested underdiagnosis and undertreatment of COPD by healthcare professionals, and patients reported poor symptom control. The cost of unscheduled care (€15 I) was almost double the cost of scheduled visits to healthcare professionals (€82). This suggests that improving the long-term management of chronic symptoms by healthcare professionals could reduce the burden of disease. As in other countries, the clinical management of COPD in France may be improved by following guideline recommendations for COPD treatment. These include smoking cessation at all stages of the disease, regular treatment of chronic symptoms with bronchodilators in dyspnoeic patients, and pulmonary rehabilitation. The results of the survey also showed that the societal cost of COPD was considerably greater in patients with severe disease (€2882) compared with mild COPD (€289). This suggests that interventions that could help delay the progression of COPD to the advanced stages of the disease (such as smoking cessation) could be of economic benefit.
Chronic obstructive pulmonary disease (COPD) has become a real public health problem throughout the world. In spite of its association with high rates of morbidity and mortality, it is not accorded ...sufficient attention. In this paper, we present the results of the French part of the international survey "Confronting COPD in North America and Europe" concerning the impact of COPD from the perspective patients'.
Subjects were randomly recruited by means of telephone questionnaires. Patients included in the survey were to be aged > or =45 years with a cumulative cigarette consumption of > or =10 packets-yrs, and having been diagnosed with COPD, emphysema or chronic bronchitis, or whose symptoms fulfilled a definition of chronic bronchitis.
According to this survey, the prevalence of COPD among smokers (mean number of packets per year: 38.2 +/- 26.1) was 3.2%. COPD was undiagnosed in 17% of patients in spite of the presence of characteristic symptoms. Respiratory difficulties had a marked adverse effect on the quality of life although patients tended to play down the severity of their problems.
This survey reveals that COPD appears to be under-diagnosed and under-treated in France, as shown by the results of the same survey in the other 7 countries taking part. Considerable efforts are thus required to improve the speed and precision of diagnosis and to improve management of these patients.
We studied atrial natriuretic factor (ANF), plasma renin activity (PRA), and plasma levels of leukotrienes (LTs) B4 and C4 in 23 patients with COPD undergoing right cardiac catheterization for ...suspected pulmonary hypertension. Hemodynamic measurements together with concomitant ANF levels (both in venous and pulmonary artery blood and right atrial and pulmonary artery plasma levels of LTC4 and LTB4, were determined at rest (TO), after 30 min of breathing oxygen (3 L/min) (Tl), and after 30 min recovering and breathing air (T2). Patients with effective exacerbation or definitive evidence of left ventricular disease, hypertension, arrhythmias, or vasodilator or diuretic therapy were excluded. Increased levels of ANF, both in peripheral venous blood (117 ±65 pg/ml) and the pulmonary artery (153±75 pg/ml), were found in patients with COPD, with or without pulmonary hypertension. Levels of LTC4 were also significantly increased (366±406 pg/ml) when compared with our control values. No correlations among ANF, LTC4 values, functional tests, and hemodynamic measurements were found. Brief increased levels of oxygen did not modify ANF or LTC4 plasma levels, either in patients with or without pulmonary hypertension.
Recent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab and pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB ...efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB.
This prospective pilot study was conducted in patients with nonsmall cell lung cancer, uveal melanoma, or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie. ctDNA levels were assessed at baseline and after 8 weeks (w8) by bidirectional pyrophosphorolysis-activated polymerization, droplet digital PCR or next-generation sequencing depending on the mutation type. Radiological evaluation of efficacy of treatment was carried out by using immune-related response criteria.
ctDNA was detected at baseline in 10 out of 15 patients. At w8, a significant correlation (r = 0.86; P = 0.002) was observed between synchronous changes in ctDNA levels and tumor size. Patients in whom ctDNA levels became undetectable at w8 presented a marked and lasting response to therapy. ctDNA detection at w8 was also a significant prognostic factor in terms of progression-free survival (hazard ratio = 10.2; 95% confidence interval 2.5–41, P < 0.001) and overall survival (hazard ratio = 15; 95% confidence interval 2.5–94.9, P = 0.004).
This proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs.
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.
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