Objective: To evaluate and compare patient and physician preferences for the benefits and risks of currently available adjuvant melanoma treatments. Methods: Patients with stage II/III melanoma and oncologists in the ...Objective: To evaluate and compare patient and physician preferences for the benefits and risks of currently available adjuvant melanoma treatments. Methods: Patients with stage II/III melanoma and oncologists in the USA were recruited from 6 clinical sites and an online panel to complete a survey. Preferences were assessed using a paired comparison discrete choice experiment that allowed for opt-out (i.e. no treatment). The treatments comprised 7 attributes, each with 3 levels associated with pegylated interferon, high-dose interferon, and ipilimumab. Attributes included efficacy outcomes, dosing regimen, and risks of moderate to severe toxicities. In addition, open-ended maximum acceptable risk (MAR) questions assessed tradeoffs between toxicity risk and efficacy. Results: 142 patients (45 stage II;97 stage III) chose a treatment in 78% of the choice tasks, while physicians (N = 127) chose treatment 79% of the time. The rankings of relative attribute importance were concordant between the patients and physicians for the top 4: 10-year survival in metastatic melanoma, fatigue risk, 3-year recurrence-free survival (RFS), and depression risk. Patients and physicians valued the difference in 21% survival versus no survival benefit about 3 and 4 times as much, respectively, as reducing diarrhea risk from 41% to 1% or reducing depression risk from 40% to 1%. The MAR of severe diarrhea and of a life-threatening event increased as the chance of 3-year RFS increased, with patients reporting higher risks than physicians. Conclusion: Patients and physicians were concordant in their preferences in adjuvant melanoma, preferring treatment versus none and judging potential efficacy to outweigh risks of toxicities.展开更多
Cutaneous melanoma is a common cancer and cases have steadily increased since the mid 70s.For some patients,early diagnosis and surgical removal of melanomas is lifesaving,while other patients typically turn to molecu...Cutaneous melanoma is a common cancer and cases have steadily increased since the mid 70s.For some patients,early diagnosis and surgical removal of melanomas is lifesaving,while other patients typically turn to molecular targeted therapies and immunotherapies as treatment options.Easy sampling of melanomas allows the scientific community to identify the most prevalent mutations that initiate melanoma such as the BRAF,NRAS,and TERT genes,some of which can be therapeutically targeted.Though initially effective,many tumors acquire resistance to the targeted therapies demonstrating the need to investigate compensatory pathways.Immunotherapies represent an alternative to molecular targeted therapies.However,inter-tumoral immune cell populations dictate initial therapeutic response and even tumors that responded to treatment develop resistance in the long term.As the protocol for combination therapies develop,so will our scientific understanding of the many pathways at play in the progression of melanoma.The future direction of the field may be to find a molecule that connects all of the pathways.Meanwhile,noncoding RNAs have been shown to play important roles in melanoma development and progression.Studying noncoding RNAs may help us to understand how resistance e both primary and acquired e develops;ultimately allow us to harness the true potential of current therapies.This review will cover the basic structure of the skin,the mutations and pathways responsible for transforming melanocytes into melanomas,the process by which melanomas metastasize,targeted therapeutics,and the potential that noncoding RNAs have as a prognostic and treatment tool.展开更多
MIT method was applied to assay the cytotoxicityof three reversors, verapamil (VER), dipyridamole (DPM)and cyclosporin (CSA) in K562, K562/ADM and KB celllines. S-P immunocytochemical technique was applied todetect cx...MIT method was applied to assay the cytotoxicityof three reversors, verapamil (VER), dipyridamole (DPM)and cyclosporin (CSA) in K562, K562/ADM and KB celllines. S-P immunocytochemical technique was applied todetect cxpressions of oncoproteins or tumor suppressoroncoproteins in these tumor cell lines before or aftertreatment with these reversors. Results showed that threereversors were capable of inhibiting to a certain extentgrowth of K562 or KB cell lines and reversing greatlyadriamycin (ADM)-resistance in K562/ADM cell line.DPM and CsA were observed to inhibit, partly or wholly,expressions of p53, p16, bcl-2, p21 or cerbB-2oncoproteins. VER showed whole inhibition ofexpressions of P53, p16, p21 and bcl-2 and partlyexpression of p53 oncoprotein in K562 cell line. Theseresults suggest that growth inhibition in K562 or KB celllines by the reversors may be associated with partial orwhole inhibition or expressions of p53, p16, p21 or c-erbB-2 oncoproteins. Inhibitions of expressions p53, p16,p21 oncoproteins by VER but not DPM or CsA, may berespossible for reversing activity of VER for ADM-resistance in K562/ADM cell line.展开更多
文摘Objective: To evaluate and compare patient and physician preferences for the benefits and risks of currently available adjuvant melanoma treatments. Methods: Patients with stage II/III melanoma and oncologists in the USA were recruited from 6 clinical sites and an online panel to complete a survey. Preferences were assessed using a paired comparison discrete choice experiment that allowed for opt-out (i.e. no treatment). The treatments comprised 7 attributes, each with 3 levels associated with pegylated interferon, high-dose interferon, and ipilimumab. Attributes included efficacy outcomes, dosing regimen, and risks of moderate to severe toxicities. In addition, open-ended maximum acceptable risk (MAR) questions assessed tradeoffs between toxicity risk and efficacy. Results: 142 patients (45 stage II;97 stage III) chose a treatment in 78% of the choice tasks, while physicians (N = 127) chose treatment 79% of the time. The rankings of relative attribute importance were concordant between the patients and physicians for the top 4: 10-year survival in metastatic melanoma, fatigue risk, 3-year recurrence-free survival (RFS), and depression risk. Patients and physicians valued the difference in 21% survival versus no survival benefit about 3 and 4 times as much, respectively, as reducing diarrhea risk from 41% to 1% or reducing depression risk from 40% to 1%. The MAR of severe diarrhea and of a life-threatening event increased as the chance of 3-year RFS increased, with patients reporting higher risks than physicians. Conclusion: Patients and physicians were concordant in their preferences in adjuvant melanoma, preferring treatment versus none and judging potential efficacy to outweigh risks of toxicities.
基金The reported work was supported in part by research grant from the National Institutes of Health(CA226303 to TCH,and DE030480 to RRR)WW was supported by the Medical Scientist Training Program of the National Institutes of Health(T32 GM007281)+2 种基金This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430TCH was also supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund.
文摘Cutaneous melanoma is a common cancer and cases have steadily increased since the mid 70s.For some patients,early diagnosis and surgical removal of melanomas is lifesaving,while other patients typically turn to molecular targeted therapies and immunotherapies as treatment options.Easy sampling of melanomas allows the scientific community to identify the most prevalent mutations that initiate melanoma such as the BRAF,NRAS,and TERT genes,some of which can be therapeutically targeted.Though initially effective,many tumors acquire resistance to the targeted therapies demonstrating the need to investigate compensatory pathways.Immunotherapies represent an alternative to molecular targeted therapies.However,inter-tumoral immune cell populations dictate initial therapeutic response and even tumors that responded to treatment develop resistance in the long term.As the protocol for combination therapies develop,so will our scientific understanding of the many pathways at play in the progression of melanoma.The future direction of the field may be to find a molecule that connects all of the pathways.Meanwhile,noncoding RNAs have been shown to play important roles in melanoma development and progression.Studying noncoding RNAs may help us to understand how resistance e both primary and acquired e develops;ultimately allow us to harness the true potential of current therapies.This review will cover the basic structure of the skin,the mutations and pathways responsible for transforming melanocytes into melanomas,the process by which melanomas metastasize,targeted therapeutics,and the potential that noncoding RNAs have as a prognostic and treatment tool.
文摘MIT method was applied to assay the cytotoxicityof three reversors, verapamil (VER), dipyridamole (DPM)and cyclosporin (CSA) in K562, K562/ADM and KB celllines. S-P immunocytochemical technique was applied todetect cxpressions of oncoproteins or tumor suppressoroncoproteins in these tumor cell lines before or aftertreatment with these reversors. Results showed that threereversors were capable of inhibiting to a certain extentgrowth of K562 or KB cell lines and reversing greatlyadriamycin (ADM)-resistance in K562/ADM cell line.DPM and CsA were observed to inhibit, partly or wholly,expressions of p53, p16, bcl-2, p21 or cerbB-2oncoproteins. VER showed whole inhibition ofexpressions of P53, p16, p21 and bcl-2 and partlyexpression of p53 oncoprotein in K562 cell line. Theseresults suggest that growth inhibition in K562 or KB celllines by the reversors may be associated with partial orwhole inhibition or expressions of p53, p16, p21 or c-erbB-2 oncoproteins. Inhibitions of expressions p53, p16,p21 oncoproteins by VER but not DPM or CsA, may berespossible for reversing activity of VER for ADM-resistance in K562/ADM cell line.
