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Traditionally process planning, scheduling and due date assignment are treated separately. Some works are done on integrated process planning and scheduling and on scheduling with due-date assignment. However integrating all of these functions is not treated. Since scheduling problems alone belong to NP-hard class problems, integrated problems are even harder to solve. In this study process planning and scheduling and SLK due date assignment are integrated using genetic algorithms and Random search techniques. Earliness, Tardiness and length of due-dates are punished. While earliness and tardiness are punished quadratically, due-date is punished linearly. Three results were compared. One is ordinary solution, another one is random search solution and the third one is genetic algorithm solution. Genetic algorithm solution outperforms the other solutions and Random search solution is the second best and ordinary solution is the worst solution. 1

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Introduction: Ado-trastuzumab emtansine (T-DM1) is an antibody–drug conjugate and its survival advantage has been shown in advanced human epidermal growth factor receptor 2 (HER2)–positive breast cancer. However, clinical trials underrepresent patients ⩾65 years of age, leading to a lack of information in this population. We analyzed the real-world outcomes of older women who were treated with T-DM1 therapy. Methods: We performed a multicenter, observational, retrospective analysis of patients aged ⩾65 years treated with T-DM1. A total of 93 patients from 10 cancer centers were involved in the study. Our goal was to determine the survival, response rates, and toxicity profile in T-DM1–treated patients, as well as the factors that influence survival. Results: Median follow-up was 12.2 months. Objective response rate was 29%. Median progression-free survival (PFS) and overall survival (OS) were 8.47 and 15.0 months, respectively. In multivariate analysis, Eastern Cooperative Oncology Group Performance Score 2 was found to be an independent prognostic factor for worse PFS (hazard ratio [HR] 1.81, p = 0.032) and OS (HR 2.33, p = 0.006). Any adverse event (AE) was seen in 92.5% of patients; grade 3 or 4 AEs were seen in 30.1%. Dose reduction or treatment discontinuation rates were 11.8% and 6.5%, respectively. Conclusion: The efficacy of T-DM1 was acceptable and it was generally well-tolerated among older patients with advanced HER2-positive breast cancer.