e21568 Background: One year ofadjuvant anti-programmed cell death protein-1 (anti-PD1) or dabrafenib-trametinib are standards of care for patients (pts) with resected stage III-IV melanoma. There is limited data regarding the incidence, spectrum and resolution or persistence of toxicities from the pt’s perspective. We describe this in a real-world population up to 2 years post initiation of adjuvant therapy. Methods: A prospective, longitudinal study of pts with resected stage IIB-IV melanoma receiving adjuvant anti-PD1 or dabrafenib-trametinib at an Australian comprehensive cancer center. Fourteen items from the Patient-Reported Outcome version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) reflecting potential toxicities were collected pre-treatment and at 1, 3, 6, 12, and 24 months post treatment initiation using Research Electronic Data Capture (REDCap). PRO-CTCAE responses were converted to CTCAE-equivalent grades using a published algorithm. Chronic toxicities were defined as those persisting >3 months after treatment cessation. Results: From September 2021-December 2024 , 70 pts were eligible and 52 (74%) consented: 17 (33%) female, median age 64 years (IQR 60-71), 46 (89%) had resected stage III, 32 (62%) adjuvant anti-PD1. 41 pts had completed treatment and 11 were still receiving treatment at data cut off (17 December 2024). The table shows the most common toxicities by PRO-CTCAE composite grade up to 2 years post initiation of adjuvant therapy. Most toxicities reported at 12 months persisted at 24 months (71/103 reported toxicities, 71%). Fatigue was the most commonly reported toxicity at 12 and 24 months. Of the 18 pts with data at both 12 and 24 months, 15 pts had fatigue at 12 months, persisting at 24 months in 14 pts (93%). In terms of chronic toxicities, 19 pts completed at least one survey >3 months post treatment cessation and 18 (95%) reported ongoing toxicities. 16 (84%) had chronic fatigue, including 9 (82%) on adjuvant anti-PD1 and 7 (88%) on adjuvant targeted therapy. Conclusions: Both acute and chronic toxicities from adjuvant therapy are common. This data can inform shared decision-making regarding risks, benefits and expectations from adjuvant therapy and identify priorities for supportive care interventions. PRO-CTCAE term (n, %) Pre-treatment (n=51) 12 months (n=31) 24 months (n=18) No. of pts who completed item Any grade G1 > G2 No. of pts who completed item Any grade G1 > G2 No. of pts who completed item Any grade G1 > G2 Fatigue 50 30 (60%) 23 (46%) 7 (14%) 31 24 (77%) 10 (32%) 14 (45%) 18 14 (78%) 5 (28%) 9 (50%) Skin dryness 51 13 (26%) 10 (20%) 3 (6%) 31 20 (65%) 14 (45%) 6 (20%) 18 12 (67%) 7 (39%) 5 (28%) Itching 51 12 (24%) 10 (20%) 2 (4%) 31 18 (58%) 14 (45%) 4 (13%) 18 10 (56%) 5 (28%) 5 (28%) Muscle pain 50 17 (34%) 11 (22%) 6 (12%) 30 17 (57%) 10 (33%) 7 (24%) 18 10 (56%) 4 (22%) 6 (34%) Joint pain 51 21 (41%) 13 (25%) 8 (16%) 31 17 (55%) 9 (29%) 8 (26%) 18 8 (44%) 2 (11%) 6 (33%)
<p>Antitumor activity following treatment with FAP-IL2v of CPI-experienced patients in the extension part with at least one postbaseline tumor assessment (<i>n</i> = 62). Best percentage change in the sum of diameters of target lesion from baseline (column color indicates confirmed best overall response) in CPI-experienced patients in the Q3W extension part (<i>n</i> = 41; <b>A</b>) and in the QW/Q3W extension part (<i>n</i> = 21; <b>B</b>). <b>C,</b> Kaplan–Meier estimate of progression-free survival in patients in the Q3W (blue) and QW/Q3W (red) extension part. Tick marks on the Kaplan–Meier plot show censoring of the data at the last time the patient was known to be alive. NE, not evaluable; PD, progressive disease; SD, stable disease; SLD, sum of longest diameters.</p>
Histone deacetylase inhibitors (HDACIs) are a class of antineoplastic agent targeting the epigenome, specifically chromatin remodelling, resulting in modulation of genes responsible for apoptosis and cell cycle regulation, and also hyperacetylation of many non-histone proteins. Panobinostat is a potent pan-histone inhibitor of HDAC enzymes implicated in cancer development and progression. Activity has been demonstrated in hematological diseases, such as cutaneous T-cell lymphoma (CTCL), Hodgkin lymphoma (HL), myeloma and myeloid malignancies.We discuss basic pharmacology, followed by early phase trial results and analyse recent large Phase II trials in HL, CTCL, myeloid malignancies and Waldenstrom's macroglobulinemia (WM). Future directions for drug development including potential predictive biomarkers are considered.The results of Phase II trials prove that oral panobinostat is deliverable with dosing regimens of three times per week, either weekly or biweekly. The major hematologic side-effect of myelosuppression, in particular thrombocytopenia, is transient and manageable, as are the non-hematologic side-effects. Encouraging responses are observed in HL, CTCL, myelofibrosis and WM. The safety and efficacy results from studies of combination therapy with azacitidine in acute myeloid leukemia and myelodysplastic syndromes suggest that this agent may find a place in the management of a range of hematologic cancers.
Due to complexities from the interaction between steel tube and concrete filling of concrete-filled steel tubular (CFST) columns, their strengths are very complicated, which is a highly nonlinear relation with material strengths and geometry. Categorical gradient Boosting (CatBoost), which is advanced boosting machine, is presented to solve the problems. A total of 3103 tests, which is divided in four datasets, is trained and tested the learners to determine the ultimate axial strength as the output variable while the strength of materials (concrete and steel) and geometry (e.g., diameters/width/heights, thickness, effective length, eccentricities) are the input ones. The comparison of the present results from 10-fold cross validation and those from the code predictions (AISC 360-16, Eurocode 4 and AS/NZS 2327) and previous study shows very high prediction accuracy in terms of coefficient of determination (R2), which is the lowest value (R2 = 0.964) for Dataset 2 and the highest one (R2 = 0.996) for Dataset 1. While the predictions from three codes beyond material limit and slenderness are less conservative than those within it, CatBoost provides nearly similar experiment results with the mean values as unity without any limits. This algorithm can be used to predict an accurate strength of CFST columns.
