Pamiparib as consolidation treatment after concurrent chemoradiotherapy of limited-stage small cell lung cancer: a single-arm, open-label phase 2 trial.

BACKGROUND: Small cell lung cancer (SCLC) is highly invasive with poor prognosis, and its treatment has historically been hindered due to the absence of targetable driver genomic alterations. However, the high genomic instability and replication stress in SCLC have made poly(ADP-ribose) polymerases (PARPs) inhibitors a focus of research. Pamiparib is an orally available PARP1/2 inhibitor with high selectivity, strong PARP trapping activity, and excellent brain penetration. Utilizing pamiparib as consolidation maintenance therapy in limited-stage SCLC holds promise for improving survival outcomes and offering a viable therapeutic approach. METHODS: This single-arm, open-label phase II trial will enroll patients aged 18-75 years with histologically/cytologically confirmed, limited-stage SCLC who have not progressed following definitive platinum-based cCRT and have an ECOG PS of 0 or 1. Patients will be excluded if they have histologically confirmed mixed SCLC or NSCLC, or have undergone previous tumor resection, or can be treated with surgery or stereotactic body radiation therapy/stereotactic ablative radiation therapy. Participants will receive pamiparib 40 mg twice daily every 3 weeks within 2 to 6 weeks after cCRT for up to 1 year or until disease progression according to RECIST v1.1. The primary endpoint is the 1-year progression-free survival (PFS) rate assessed by investigators per RECIST v1.1. Secondary endpoints include PFS, objective response rate, and duration of response assessed by investigators per RECIST 1.1, overall survival, time to distant metastasis, and safety. DISCUSSION: The study will provide valuable data on the feasibility, safety, and effectiveness of pamiparib as a consolidation therapy after cCRT in patients with LS-SCLC. The correlation between molecular typing or gene expression profile of the disease and curative response will be further explored. TRIAL REGISTRATION: NCT05483543 at clinicaltrials.gov.

New Perspectives for the Consolidation of Mural Paintings in Hypogea with an Innovative Aqueous Nanolime Dispersion, Characterized by Compatible, Sustainable, and Eco-Friendly Features.

Consolidation of mural paintings in hypogea is challenging because of their severe microclimatic conditions, characterized by high humidity levels, low air circulation, the presence of salts efflorescence, and the detrimental growth of biodeteriogen agents. Traditional consolidant products show significant drawbacks when used in hypogeum. Organic compounds, such as acrylic emulsions, are bio-receptive and some inorganic consolidants, such as silica-based products, show a lack of compatibility with the original substrate, which could lead to a reduction in permeability and an increase in the mechanical resistance of the external layer. The presence of solvents in their formulations, particularly short-chain alcohols that can activate germination of fungal spores, leads to the release of great amounts of volatile organic compounds, which are particularly harmful in the hypogeic environment. To solve these problems, restorers of the Istituto Centrale per il Restauro (ICR) decided to use a new aqueous nanolime dispersion, NANOLAQ, consisting of pure and crystalline Ca(OH)2 nanoparticles dispersed in water, produced by an innovative and sustainable patented procedure. After laboratory testing, the product has been applied on site, on a medieval mural painting in the Ss. Peter and Paul hypogeum in the UNESCO site of Matera (Italy), monitoring the performance in terms of cohesion of the paint layer and preservation of aesthetic features.

Clinical Study of Jiawei Xiaochaihutang Combined with Microwave Ablation in Treatment of Primary Hepatocellular Carcinoma / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Jiawei Xiaochaihutang combined with microwave ablation （MWA） in the treatment of primary hepatocellular carcinoma （HCC） and its influence on tumor microenvironment. MethodA total of 128 patients were randomly divided into control group （64 cases： 2 cases of dropout，2 cases of elimination，and 60 cases of completion） and observation group （64 cases： 3 cases of dropout，2 cases of elimination，and 59 cases of completion）. Both groups were given comprehensive treatment after MWA surgery. Patients in control group took Biejiajian Wan orally （3 g/time，3 times/d）， and those in observation group took Jiawei Xiaochaihutang （1 dose/d）. The treatment lasted for 3 consecutive months. The size of solid tumor before and after treatment was evaluated to record the progression-free survival （PFS）. The alpha-fetoprotein-L13 （AFP-L3），des-γ-carboxy prothrombin （DCP），Golgi protein 73 （GP73），tumor necrosis factor-α （TNF-α），transforming growth factor-β （TGF-β），vascular endothelial growth factor （VEGF） and matrix metalloproteinase-2 （MMP-2） levels，as well as performance status （PS），liver function and syndrome of liver depression and Qi stagnation scores were also detected before and after treatment. In addition， the incidence of side effects of grade Ⅲ and above was compared. ResultThe total effective rate of solid tumor in observation group was 91.53% （54/59），higher than that （76.67%， 46/60） in control group（χ2=4.895，P<0.05）. The PFS in observation group was （7.16±0.95） months， longer than that （6.24±0.89 months） in control group （P<0.01）. The effective rate of traditional Chinese medicine （TCM） syndrome in observation and control groups were 88.14% （52/59）and 70.00% （42/60）， respectively （χ2=5.897，P<0.05）. The observation group （57.63%，34/59） had higher marked effective rate of TCM syndrome than control group （31.67%，19/60） （χ2=8.116，P<0.01）. The AFP-13，DCP，GP73，TNF-α，TGF-β，VEGF and MMP-2 levels and the PS，liver function and syndrome of liver depression and Qi stagnation scores in observation group were lower than those in control group （both P<0.01）. The cumulative incidence of side effects of grade Ⅲ and above in observation and control groups was 16.95% and 33.33%， respectively（χ2=4.261，P<0.05）. ConclusionConsolidation treatment of HCC after MWA surgery with Jiawei Xiaochaihutang relieved symptoms and side effects，improved PS and liver function，regulated tumor microenvironment，inhibited tumor markers and prolonged survival time. The clinical effect was better than that of Biejia decoction pill， and thus it was worthy of clinical use.

Consolidation cetuximab after concurrent triplet radiochemotherapy+cetuximab in patients with advanced head and neck cancer: A randomized phase II study.

BACKGROUND AND PURPOSE: Preclinical data suggest that cetuximab should be continued after end of concurrent radiotherapy+cetuximab due to its efficacy against residual tumor cells in the irradiated tumor bed. Based on this concept the phase II add-on cetuximab (AOC) study was designed. MATERIALS AND METHODS: Altogether 63 patients with advanced head and neck cancer were treated with radiochemotherapy (70 Gy, cisplatin 40 mg/m2 weekly) in combination with concurrent cetuximab (loading dose 400 mg/m2, then 250 mg/m2 weekly). Thereafter patients were randomized to cetuximab consolidation (500 mg/m2 biweekly × 6) or no further treatment. The primary endpoint was the 2-year locoregional control (LRC) rate. As translational research endpoints serum markers were analyzed before and during treatment and CT-based quantitative image analysis (radiomics) was performed. RESULTS: Median follow-up was 24 months. The 2-year LRC rates were 67.9% and 67.7% in the treatment arms with and without consolidation cetuximab, respectively. Higher than median levels of three serum markers were negatively associated with the 2-year LRC rate in the overall patient cohort: Osteopontin, IL8 and FasL2 (p ≤ 0.05). A radiomics model consisting of two radiomics features could be built showing that higher entropy and higher complexity of tumor Hounsfield unit distribution indicates worse LRC (concordance index 0.66). No correlation was found between biological and imaging markers. CONCLUSIONS: There was no evidence that consolidation cetuximab would improve the 2-year LRC rate. Prognostic biological and imaging markers could be identified for the overall patient cohort. Studies with larger patient numbers are needed to correlate biological and imaging markers.

Adjuvant intensity modulated whole-abdominal radiation therapy for high-risk patients with ovarian cancer FIGO stage III: final results of a prospective phase 2 study.

BACKGROUND: To assess late toxicity, quality of life and oncological outcome after consolidative whole abdominal radiotherapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high risk patients with advanced ovarian cancer FIGO stage III using IMRT (Intensity modulated radiation therapy). METHODS: The OVAR-IMRT-02 study is a multi-center single-arm phase-II-trial. Twenty patients with optimally debulked ovarian cancer stage FIGO III with complete remission after chemotherapy were treated with intensity modulated WART. A total dose of 30 Gy in 20 fractions was applied to the entire peritoneal cavity. Primary endpoint was treatment tolerability; secondary objectives were acute and chronic toxicities, quality of life, rates of therapy disruption/abortion, progression-free survival (PFS) and overall survival (OS). RESULTS: All patients completed treatment and 10/20 patients (50%) reached the final study follow-up of 36 months. Late side effects consisted of °1-°2 lower limb edema (44.5%), with one patient (5.6%) showing °3 edema. Three patients (16.7%) showed elevated gamma-Glutamyltransferase. There were no severe late side effects regarding renal or hepatic function or any gastrointestinal toxicity greater than °2. During WART, mean global health status decreased by 18.1 points (95%-CI: 7.1-29.0), but completely normalized after 6 months. The same trend was observed for the function scale scores. Kaplan-Meier-estimated 1-, 2- and 3-year PFS was 74, 51 and 40%, respectively. 1-, 2- and 3-year OS was 89, 83 and 83%, respectively. CONCLUSIONS: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late toxicity and minor impact on long-term quality of life. Together with the promising results for PFS and OS, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov ( NCT01180504 ). Registered 12 August 2010 - retrospectively registered.

Aesthetic compatibility assessment of consolidants for wall paintings by means of multivariate analysis of colorimetric data.

BACKGROUND AND METHODS: Wall paintings and architectural surfaces in outdoor environments are exposed to several physical, chemical and biological agents, hence they are often treated with different products to prevent or slow down their deterioration. Among the factors that have to be taken into account in the selection of the most suitable treatment for decorated surfaces, the aesthetic compatibility with the substrate is of great importance in the cultural heritage field; minimizing colour variation after treatment application is a crucial issue in particular for painted surfaces. In the framework of the European Project Nanomatch the color variation induced on wall painting mock-ups by the two innovative consolidants (calcium alkoxides) developed was evaluated using colorimetry in comparison with two traditional products. In this work these innovative consolidants have been also tested in combination with two commercial biocides and the results of colorimetric measurements discussed. Moreover, as the univariate approach didn't allow to draw clear conclusions on the relation between the different sources of data variability, multivariate analysis was performed on colorimetric data. RESULTS: Principal Component Analysis and multi-way Parallel Factor Analysis (PARAFAC) were successfully applied to colorimetric data to investigate the short-term effects of the application of different consolidants on wall painting surfaces, making it possible to study at the same time the different sources of data variability, i.e. treatments, painting techniques, pigments. Finally, a ranking list of the treatments under study in terms of colour variation induced on the surface was established, in function of the painting technique and pigment, taking also in consideration the combination consolidant/biocide. In particular, given the true multi-way nature of the data, PARAFAC model turned out to be extremely useful in the study of the dependence of colour variation on pigments, a critical issue for painted surfaces, that was not clear using univariate approach. CONCLUSIONS: Multivariate approach to colorimetric data and especially 3-way PARAFAC method resulted a powerful technique to evaluate in short-term the color compatibility of consolidants for wall paintings, improving data interpretation and visualization, and thus outperforming the univariate statistical analysis.

Fludarabine, High Dose Cytarabine and Granulocyte Colony-Stimulating Factor (FLAG) as Consolidation Chemotherapy in Older Patients with Acute Myeloid Leukemia: A Retrospective Cohort Study.

The study aimed to investigate the effect of consolidation treatment with fludarabine, high-dose cytarabine and granulocyte colony-stimulating factor or FLAG in older AML patients. The study included 41 eligible patients above 54 years old, who received both induction and consolidation chemotherapy for AML from 2008 to 2013. The study cohort had a minimum 24 months follow-up period. Survival analysis was carried out to assess patients' overall survival and disease free survival based on types of consolidation regimens. The consolidation treatment with FLAG exerted a protective effect to both overall survival and disease free survival in older patients. Patients who were consolidated with FLAG regimen had a significant longer overall survival (log-rank, p = 0.0025) and disease free survival (log-rank, p = 0.0026). The median overall survival was longer (18.70 months) with the use of FLAG when compared to non-FLAG group (8.09 months). The median disease free survival was also longer (13.84 months) with use of FLAG when compared to the non-FLAG group (4.44 months). Regression analysis with Cox model yielded hazard ratio of 0.245 (p = 0.0094) in overall survival and 0.217 (p = 0.0068) in disease free survival. The use of FLAG as consolidation treatment was associated with approximately 60-80% reduction in hazard rates. The result was adjusted for age, race and gender in regression analysis. Older AML patients had longer remission and survival when consolidated with FLAG regimen after the induction chemotherapy.

Medical costs of treatment and survival of patients with acute myeloid leukemia in Belgium.

The advent of new cell-based immunotherapies for leukemia offers treatment possibilities for certain leukemia subgroups. The wider acceptability of these new technologies in clinical practice will depend on its impact on survival and costs. Due to the small patient groups who have received it, these aspects have remained understudied. This non-randomized single-center study evaluated medical costs and survival for acute myeloid leukemia between 2005 and 2010 in 50 patients: patients treated with induction and consolidation chemotherapy (ICT) alone; patients treated with ICT plus allogeneic hematopoietic stem cell transplantation (HCT), which is the current preferred post-remission therapy in patients with intermediate- and poor-risk AML with few co-morbidities, and patients treated with ICT plus immunotherapy using autologous dendritic cells (DC) engineered to express the Wilms' tumor protein (WT1). Total costs including post- consolidation costs on medical care at the hematology ward and outpatient clinic, pharmaceutical prescriptions, intensive care ward, laboratory tests and medical imaging were analyzed. Survival was markedly better in HCT and DC. HCT and DC were more costly than ICT. The median total costs for HCT and DC were similar. These results need to be confirmed to enable more thorough cost-effectiveness analyses, based on observations from multicenter, randomized clinical trials and preferably using quality-adjusted life-years as an outcome measure.

90Y-Ibritumomab-Tiuxetan Consolidation Therapy for Advanced-Stage Mantle Cell Lymphoma After First-Line Autologous Stem Cell Transplantation: Is It Time for a Step Forward?

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive lymphoma with a dismal prognosis because of numerous relapses. Because the most promising results have been obtained with immunochemotherapy followed by autologous cell stem transplantation (ASCT), we evaluated the efficacy of yttrium-90 ibritumomab ((90)Y-IT) consolidation after such an intensive treatment. PATIENTS AND METHODS: We retrospectively assessed 57 patients affected by intermediate or high-risk MCL in complete remission (CR) or partial remission (PR) after 3 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], prednisolone) plus 3 cycles of R-DHAP (dexamethasone, cytarabine [Ara-C], cisplatin [platinum]) followed by ASCT and additional consolidation treatment with (90)Y-IT in 28 cases. All patients underwent 2 years of rituximab maintenance. RESULTS: After ASCT, 94% achieved CR and 4% achieved PR. The median follow-up was 6.2 years (range, 1.8-9.7 years). Treatment intensification was well tolerated and led to a significantly longer response duration in comparison to standard treatment. In contrast to the historical cohort, the addition of (90)Y-IT seems to overcome important risk factors such as Mantle Cell Lymphoma International Prognostic Index (MIPI) score and bone marrow infiltration. CONCLUSION: In the present retrospective analysis, immunochemotherapy followed by ASCT resulted in a very high response rate, and subsequent (90)Y-IT consolidation significantly reduced the number of relapses and increased survival, suggesting that (90)Y-IT consolidation might be a valid option in first-line treatment. However, a prospective confirmatory trial is warranted.

Advances in the Treatment of Multiple myeloma / 昆明医科大学学报

Multiple myeloma is a monoclonal plasma cell malignant proliferative disease,accounting for about 10％ of malignaut tumors of blood system.In recent years,due to the application of hematopoietic stem cell transplantation and the application of MDT by combining new drug such as thalidomide,lenalidomide and bortezomib,the average survival of MM patients was significantly longer than before.The treatment strategy should be individualized before treatment according to the patient's age,physical condition and complications.In this paper,the treatment strategy of multiple myeloma patients were reviewed.

Role of consolidation with yttrium-90 ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma.

Non-Hodgkin's lymphoma (NHL) accounts for 4% of all cancers diagnosed in the United States. Follicular lymphoma (FL) is the most common type of indolent NHL with a survival from 5 to 15 years. Although it is very sensitive to chemotherapy and radiotherapy, relapses are the main cause of therapeutic failure, and currently there is no consensus on the first-line treatment and optimal therapeutic strategies for patients with FL. Immediate treatment offers any survival benefit for asymptomatic and more indolent disease. In order to improve outcomes in FL, extend the remission, postpone the need for chemotherapy and improve OS, maintenance therapies with rituximab and consolidation treatments represent very attractive strategies. (90)Y-ibritumomab tiuxetan ((90)Y-IT, Zevalin®) is approval as consolidation therapy in previously untreated FL patients who achieve response to first-line chemotherapy. Consolidation therapy with (90)Y-IT after initial induction treatment has shown improved activity compared with induction chemotherapy alone, even in patients previously treated with rituximab, in one phase III and several phase II trials, improving progression-free survival (PFS) and rate of conversion from partial response (PR) to complete response (CR). The phase III international FIT trial shows an improvement in PFS that is maintained after a median follow up of 7.3 years. Several phase II trials show high rate of conversion from PR to CR and a significant improvement in PFS. Treatment is feasible and well tolerated although myelodysplastic syndrome cases has been observed in some trials. (90)Y-IT should be considered for the initial treatment of FL in patients who are unable to tolerate standard chemotherapy, e.g., elderly or frail patients and otherwise in high-risk patients who achieve a PR or CR due to improvements in CR rate and PFS.