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1.
Cancer Med ; 10(24): 9040-9046, 2021 12.
Article in English | MEDLINE | ID: mdl-34766461

ABSTRACT

BACKGROUND: Systemic therapy prolongs overall survival (OS) in advanced non-small cell lung cancer (NSCLC), but diagnostic tests, staging and molecular profiling take time, and this can delay therapy initiation. OS approximates first-order kinetics. METHODS: We used OS of chemo-naive NSCLC patients on a placebo/best supportive care trial arm to estimate % of patients dying while awaiting therapy. We digitized survival curves from eight studies, calculated OS half-life, then estimated the proportion surviving after different times of interest (tn ) using the formula: X=exp-tn∗0.693/t1/2 , where EXP signifies exponential, * indicates multiplication, 0.693 is the natural log of 2, and t1/2 is the survival half-life in weeks. RESULTS: Across trials, the OS half-life for placebo/best supportive care in previously untreated NSCLC was 19.5 weeks. Hence, based on calculations using the formula above, if therapy were delayed by 1, 2, 3, or 4 weeks then 4%, 7%, 10%, and 13% of all patients, respectively, would die while awaiting treatment. Others would become too sick to consider therapy even if still alive. CONCLUSIONS: This quantifies why rapid baseline testing and prompt therapy initiation are important in advanced NSCLC. It also illustrates why screening procedures for clinical trial inclusion must be faster. Otherwise, it is potentially hazardous for a patient to be considered for a trial due to risk of death or deterioration while awaiting eligibility assessment. It is also important to not delay initiation of systemic therapy for procedures that add relatively little value, such as radiotherapy for small, asymptomatic brain metastases.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/diagnosis , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Progression-Free Survival
2.
Stat Methods Med Res ; 28(9): 2787-2801, 2019 09.
Article in English | MEDLINE | ID: mdl-29916309

ABSTRACT

Marginal structural models are causal models designed to adjust for time-dependent confounders in observational studies with dynamically adjusted treatments. They are robust tools to assess causality in complex longitudinal data. In this paper, a marginal structural model is proposed with an innovative dose-delay joint-exposure model for Inverse-Probability-of-Treatment Weighted estimation of the causal effect of alterations to the therapy intensity. The model is motivated by a precise clinical question concerning the possibility of reducing dosages in a regimen. It is applied to data from a randomised trial of chemotherapy in osteosarcoma, an aggressive primary bone-tumour. Chemotherapy data are complex because their longitudinal nature encompasses many clinical details like composition and organisation of multi-drug regimens, or dynamical therapy adjustments. This manuscript focuses on the clinical dynamical process of adjusting the therapy according to the patient's toxicity history, and the causal effect on the outcome of interest of such therapy modifications. Depending on patients' toxicity levels, variations to therapy intensity may be achieved by physicians through the allocation of either a reduction or a delay of the next planned dose. Thus, a negative feedback is present between exposure to cytotoxic agents and toxicity levels, which acts as time-dependent confounders. The construction of the model is illustrated highlighting the high complexity and entanglement of chemotherapy data. Built to address dosage reductions, the model also shows that delays in therapy administration should be avoided. The last aspect makes sense from the cytological point of view, but it is seldom addressed in the literature.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bone Neoplasms/drug therapy , Drug Administration Schedule , Models, Statistical , Osteosarcoma/drug therapy , Adolescent , Adult , Child , Child, Preschool , Confounding Factors, Epidemiologic , Female , Humans , Longitudinal Studies , Male , Prognosis , Randomized Controlled Trials as Topic
3.
Ophthalmologe ; 115(12): 1035-1041, 2018 Dec.
Article in German | MEDLINE | ID: mdl-29138977

ABSTRACT

BACKGROUND: Critical prerequisites for successful therapy of neovascular age-related macular degeneration (nvAMD) are an early initiation and continuous monitoring; however, delays in starting therapy and non-medically indicated discontinuation of therapy are frequent, which limits therapy efficacy and, thus, visual outcomes. OBJECTIVE: To identify the reasons for delay in therapy and non-medically indicated termination of therapy. MATERIAL AND METHODS: Patients who had started a new therapy (starters) and those who independently terminated therapy (dropouts) were interviewed by telephone with a specific, standardized questionnaire. Results were summarized descriptively. RESULTS: A total of 100 starters and 55 dropouts were interviewed. The mean therapy delay was 22 (±28 SD) days. This was mainly due to the time until the decision to see an ophthalmologist was made. Main reasons for dropping out were: transportation issues (27%), poor general health (25%) and the assumption that there is no benefit from therapy (11%). Of the patients who dropped out 63% would have liked to continue therapy. CONCLUSION: There is potential for improvement in nvAMD management regarding therapy start as well as therapy maintenance. Sensitizing for initial nvAMD symptoms is important as is reduction of barriers to therapy maintenance, since most therapy dropouts would like to continue the therapy.


Subject(s)
Macular Degeneration , Age Distribution , Angiogenesis Inhibitors , Humans , Intravitreal Injections , Surveys and Questionnaires
4.
Cancer ; 117(11): 2364-70, 2011 Jun 01.
Article in English | MEDLINE | ID: mdl-24048783

ABSTRACT

BACKGROUND: It is unclear whether delays in commencing adjuvant chemotherapy after surgical resection of colon adenocarcinoma adversely impact survival. METHODS: Patients with stage II-III colon adenocarcinoma who received adjuvant chemotherapy at 2 centers were identified through the institutional tumor registry. Time to adjuvant chemotherapy, overall survival (OS), and relapse-free survival (RFS) were calculated from the day of surgery. Patients were dichotomized into early (time to adjuvant chemotherapy ≤ 60 days) and late treatment (time to adjuvant chemotherapy >60 days) groups. OS and RFS were compared using log-rank test and multivariate analysis by the Cox proportional hazards model. RESULTS: Of 186 patients included in the study, 49 (26%) had received adjuvant chemotherapy >60 days after surgical resection. Thirty percent of the delays were system related (eg, late referrals, insurance authorizations). Time to adjuvant chemotherapy >60 days was associated with significantly worse OS in both univariate analysis and a Cox proportional hazards model (hazard ratio, 2.17; 95% confidence interval, 1.08-4.36). Although difference in RFS between the 2 groups favored time to adjuvant chemotherapy <60, this did not reach statistical significance. CONCLUSIONS: Adjuvant chemotherapy delay >60 days after surgical resection of colon cancer is associated with worse OS.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Antineoplastic Agents/therapeutic use , Colonic Neoplasms/drug therapy , Colonic Neoplasms/mortality , Adenocarcinoma/pathology , Adult , Aged , Chemotherapy, Adjuvant , Colonic Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Risk Factors , Time Factors
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