ABSTRACT
Recently modified diagnostic criteria for chronic myelomonocytic leukaemia (CMML) have lowered the cut-off for absolute monocytosis. In the largest series to date, we have analysed 313 CMML patients, including 104 with oligomonocytic (OM)-CMML. Five-year survival was longer for OM-CMML than for other patients (p < 0.001). Multivariate analysis identified OM-CMML as a favourable prognostic factor (HR 0.58; p = 0.002). The 5-year cumulative incidence of progression to classical CMML was 47%. Older age and transfusion dependence were adverse prognostic factors for OM-CMML. Our results support the inclusion of OM-CMML in the CMML category as a subtype with superior outcomes.
Subject(s)
Leukemia, Myelomonocytic, Chronic , Humans , Leukemia, Myelomonocytic, Chronic/diagnosis , Leukocytosis , PrognosisABSTRACT
Primary mediastinal large B-cell lymphoma (PMBCL) is a rare aggressive B-cell lymphoma characterized by the frequent presence of amplification and translocation events at 9p24.1, resulting in the expression of the programmed cell death-1 (PD-1) ligands PD-L1 and PD-L2. Pembrolizumab, a humanized anti-PD-1 monoclonal antibody, binds PD-1 and blocks this interaction, enhancing the activity of the immune system against tumor cells, and has shown activity in PMBCL and in some cases of primary and secondary central nervous system (CNS) lymphoma. We report the case of a 40-year-old woman diagnosed with relapsed PMBCL and secondary CNS involvement who responded to pembrolizumab monotherapy, allowing for a later allogeneic stem cell transplant.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Central Nervous System Neoplasms/therapy , Lymphoma, B-Cell/therapy , Mediastinal Neoplasms/therapy , Stem Cell Transplantation , Adult , Allografts , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Central Nervous System Neoplasms/genetics , Central Nervous System Neoplasms/metabolism , Central Nervous System Neoplasms/pathology , Chromosomes, Human, Pair 9/genetics , Chromosomes, Human, Pair 9/metabolism , Female , Humans , Lymphoma, B-Cell/genetics , Lymphoma, B-Cell/metabolism , Lymphoma, B-Cell/pathology , Mediastinal Neoplasms/genetics , Mediastinal Neoplasms/metabolism , Mediastinal Neoplasms/pathology , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/genetics , Membrane Proteins/metabolism , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Translocation, Genetic , Tumor Suppressor Proteins/antagonists & inhibitors , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolismABSTRACT
Vulvar cancer is a relatively rare neoplasm. The essential treatment is surgery for the primary tumour. However, postoperative recurrence rates are high, even in early-stage disease when tumour-free surgical margins are achieved or in the absence of associated risk factors (lymph node metastases, deep stromal invasion or invasion of the lymphatic vascular space). Radiotherapy plays an important role in the treatment of vulvar cancer. Adjuvant treatment after surgery as well as primary treatment of locally advanced vulvar cancer (LAVC) is composed of two key radiotherapy treatment scenarios, external beam radiation therapy (EBRT) either combined or not combined with brachytherapy (BT). In a recurrence setting, where surgery is not an option, BT alone or in combination with EBRT can be used. Compared to EBRT, BT has the radiobiological potential to improve dose to the target volume, minimise the dose to organs at risk, and facilitate hypofractionated-accelerated treatment. This narrative review presents recent data on the role of BT in the treatment of primary and/or recurrent vulvar cancer, including radiobiological, clinical, and therapeutic aspects.
ABSTRACT
BACKGROUND: The presence of >94% classical monocytes (MO1, CD14++/CD16-) in peripheral blood (PB) has an excellent performance for the diagnosis of chronic myelomonocytic leukemia (CMML). However, the monocyte gating strategy is not well defined. The objective of the study was to compare monocyte gating strategies and propose an optimal one. METHODS: This is a prospective, single center study assessing monocyte subsets in PB. First, we compared monocyte subsets using 13 monocyte gating strategies in 10 samples. Then we developed our own 10 color tube and tested it on 124 patients (normal white blood cell counts, reactive monocytosis, CMML and a spectrum of other myeloid malignancies). Both conventional and computational (FlowSOM) analyses were used. RESULTS: Comparing different monocyte gating strategies, small but significant differences in %MO1 and percentually large differences in %MO3 (nonclassical monocytes) were found, suggesting that the monocyte gating strategy can impact monocyte subset quantification. Then, we designed a 10-color tube for this purpose (CD45/CD33/CD14/CD16/CD64/CD86/CD300/CD2/CD66c/CD56) and applied it to 124 patients. This tube allowed proper monocyte gating even in highly abnormal PB. Computational analysis found a higher %MO1 and lower %MO3 compared to conventional analysis. However, differences between conventional and computational analysis in both MO1 and MO3 were globally consistent and only minimal differences were observed when comparing the ranking of patients according to %MO1 or %MO3 obtained with the conventional versus the computational approach. CONCLUSIONS: The choice of monocyte gating strategy appears relevant for the monocyte subset distribution test. Our 10-color proposal allowed satisfactory monocyte gating even in highly abnormal PB. Computational analysis seems promising to increase reproducibility in monocyte subset quantification.
Subject(s)
Leukemia, Myelomonocytic, Chronic , Monocytes , Humans , Monocytes/pathology , Leukemia, Myelomonocytic, Chronic/diagnosis , Leukemia, Myelomonocytic, Chronic/pathology , Prospective Studies , Reproducibility of Results , Flow Cytometry , Receptors, IgG , Lipopolysaccharide ReceptorsABSTRACT
PURPOSE: To compare, in a randomized trial, 5-fluorouracil (FU) plus leucovorin (LV) (FU+LV) vs. oral uracil and tegafur (UFT) plus LV (UFT+LV) given concomitantly with preoperative irradiation in patients with cT3-4 or N+ rectal cancer. METHODS AND MATERIALS: A total of 155 patients were entered onto the trial. Patients received pelvic radiotherapy (4500-5,040 cGy in 5 to 6 weeks) and chemotherapy consisting of two 5-day courses of 20 mg/m(2)/d LV and 350 mg/m(2)/d FU in the first and fifth weeks of radiotherapy (77 patients) or one course of 25 mg/d oral LV and 300 mg/m(2)/d UFT for 4 weeks beginning in the second week of radiotherapy (78 patients). The primary endpoints were pathologic complete response (pCR) and resectability rate. Secondary endpoints included downstaging rate, toxicity, and survival. RESULTS: Grade 3-5 acute hematologic toxicity occurred only with FU+LV (leukopenia 9%; p = 0.02). There were no differences in resectability rates (92.1% vs. 93.4%; p = 0.82). The pCR rate was 13.2% in both arms. Tumor downstaging was more frequent with UFT+LV (59.2% vs. 43.3%; p = 0.04). Three-year overall survival was 87% with FU+LV and 74% with UFT+LV (p = 0.37). The 3-year cumulative incidences of local recurrence were 7.5% and 8.9%, respectively (p = 0.619; relative risk, 1.46; 95% confidence interval 0.32-6.55). CONCLUSION: Although this study lacked statistical power to exclude clinically significant differences between both groups, the outcome of patients treated with UFT+LV did not differ significantly from that of patients treated with FU+LV, and hematologic toxicity was significantly lower in the experimental arm.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Administration, Oral , Adult , Aged , Aged, 80 and over , Combined Modality Therapy/methods , Disease-Free Survival , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Leucovorin/administration & dosage , Male , Middle Aged , Neoplasm Staging , Preoperative Care , Prospective Studies , Radiotherapy Dosage , Rectal Neoplasms/mortality , Rectal Neoplasms/surgery , Survival Analysis , Tegafur/administration & dosage , Uracil/administration & dosage , Vitamin B Complex/administration & dosageABSTRACT
Recently, numerous pretest-posttest study designs have evaluated attention impairments and effectiveness of attention training. However, some of the attention tasks used in these studies show a lack of temporal stability analysis that reduces confidence in attention training outcomes. We aim to analyze the temporal stability within three attention tasks using different measures of attention (speed measures, accuracy measures, and global attention indexes) and the convergent validity between the measures. A total of 178 university students completed three attention tasks with a time interval of one week. Speed measures of attention showed higher test-retest reliability and higher convergence than accuracy measures. Accuracy measures showed nonnormal distributions and small range of variability to provide sufficient discrimination. Speed measures showed high practice effects. These results are consistent with previous studies of temporal stability and convergent validity of attention tasks. However, further studies of commonly used attention tasks are necessary in healthy and clinical samples. Additionally, attention training studies should include a control group to subtract the practice effect of speed measures.
Subject(s)
Attention/physiology , Neuropsychological Tests , Adolescent , Adult , Female , Humans , Male , Probability , Reproducibility of Results , Students , Universities , Young AdultABSTRACT
PURPOSE: As many as 50% of patients with cancer develop acute skin reactions to some degree with radiotherapy. Proactive skin care is often recommended to minimise these skin reactions and maintain the integrity of the epidermal barrier; nevertheless, no consensual guidelines are systematically used. This multicentre, observational, prospective study evaluated the tolerability and benefit of supportive and barrier protective skin care products in preventing radiotherapy-induced skin reactions in 253 women initiating radiotherapy (exclusive or adjuvant) for breast cancer. METHODS: Patients received a kit of 5 commercially available skin care products before the first radiotherapy treatment. The following variables were assessed: cutaneous adverse events, investigator-assessed skin reactions (oedema, erythema, dryness, desquamation) before and after radiotherapy course, investigator, and patient opinion on products benefit. Results were analysed by frequency of product use (heavy versus low). RESULTS: Average age was 60 years (range: 34-85). Over 92% of patients reported good to excellent tolerance on irradiated skin for each product. During the 6-week radiotherapy period, we observed that heavy product users had less skin reactions than the low users, particularly within 10 days of radiotherapy initiation (8% versus 18%; p = .031). Positive physician's opinion on product use was more frequent for high (66.6%) versus low (32%) users. Patient-assessed patient benefit index was generally >1, indicating relevant treatment benefit, with a tendency for better benefit in high versus low users. CONCLUSIONS: These results support recommendations to use skin care products to minimise the impact of secondary cutaneous reactions with radiotherapy cancer treatment.