Clinical conditions of long-term cure in childhood-onset epilepsy: a 45-year follow-up study.

Clinical conditions of long-term cure in childhood-onset epilepsy, defined as sustained remission off antiepileptic drug (AED) treatment, are not well known. To address that clinically important question, we determined clinical factors predictive of long-term seizure cure in a population-based cohort of 133 patients followed up since their first seizure before the age of 16 years. At the end of the 45-year follow-up (mean=39.8, median=44, range=11-47), 81 (61%) of the 133 patients had entered at least 5-year remission off AEDs, meeting our definition of cure. The 81 patients were seizure-free off AEDs for a mean of 34.4 (median=38, range=6-46) years and 59 (73%) of the 81 patients following the first standard medication until the end of follow-up (mean=36.5, median=39, range=14-46 years). Four independent factors were found to be associated with cure compared with having seizures while on AEDs: seizure frequency less than weekly during the first 12 months of AED treatment (p=0.002), pretreatment seizure frequency less than weekly (p=0.002), higher IQ (>70; p=0.021), and idiopathic or cryptogenic vs. symptomatic etiology (p=0.042). Patients with seizure frequency of less than once a week during early treatment and idiopathic etiology had a ninefold chance to of being cured since the onset of the first adequate antiepileptic therapy until the end of follow-up compared with patients who a symptomatic etiology had at least weekly seizures while on AEDs (RR=8.7, 95% CI=2.0-37.0; p<0.001). In conclusion, IQ, etiology, and seizure frequencies both in the first year of AED treatment and prior to medication appear to be clinical predictors of cure in childhood-onset epilepsy.

Sequential Treatment of Arsenic Trioxide Followed by All Trans Retinoic Acid with Anthracyclines has Excellent Long-Term Cure in Acute Promyelocytic Leukemia.

Acute promyelocytic leukemia (APL) remains the most curable myeloid leukemia made feasible through effective use of two differentiating agents, all trans retinoic acid (ATRA) and arsenic trioxide (ATO) with or without chemotherapy (CT). However, early morbidity and mortality remains a problem. With the objective of reducing early death a strategy of sequential induction ATO followed by consolidation ATRA in combination with CT was adopted by our group. The long-term outcomes of patient of APL treated on this sequential approach at our center was analyzed. In this retrospective analysis of prospectively maintained database consecutive adult patients with APL irrespective of their Sanz risk group were treated using a protocol of ATO (10 mg IV infusion over 3 h daily for 45 days) in the first phase followed by ATRA (45 mg/m2 for 60 days) in combination with Daunorubicin (60 mg/m2 for 3 days × 3 cycles) in second phase. All patients received maintenance ATRA (45 m/m2 for 15 days every 3 months) for a period of 18 months in phase 3. Patients were monitored for cytogenetic and molecular responses after phase 1 and 2. All patients were followed up for toxicity, event free and overall survival. 131 consecutive patients were treated in this study. At a median follow up of 60 months, 84.81% patients are alive with an overall event free survival (EFS) of 77.82%. Sanz low risk patients fared better (85%) versus intermediate and high-risk patients who had a 76% EFS. Proportion of patients alive at last follow up were 100% in Sanz low risk group and 82% in intermediate and high-risk group. The sequential schedule showed excellent tolerance and toxicity profile when treating newly diagnosed APL. The long-term follow-up data shows comparable if not better survival compared with the published real-world data and this has been consistent across all risk group.

Statistical adaptation to oncology drug development evolution.

Cancer treatment started with surgery at least three thousand years ago. Radiation therapy was added in 1896 with chemotherapy started 50 years later. These "cut, burn, and poison" techniques try to kill cancer cells directly and have been the main approaches in treating cancer until recently. In the past few years, immunotherapies have revolutionized cancer treatment. Instead of treating the disease, immunotherapies treat the patient with the disease; more precisely, correct the patient's immune system so that it can fight cancer in a long term, which makes the cure of metastatic cancers a real possibility. To adapt to the evolution of oncology treatment, clinical trial designs and statistical analysis methodologies are required to change accordingly in order to efficiently bring novel oncology medicines to cancer patients. For example, one of the major differences between immunotherapies and chemotherapies is that immunotherapies may take longer to have an effect but generally last longer with some patients cured. Trial design assumptions and adaptation rules (if adaptive design is used) need to take account of this delayed effect and long-term cure effect phenomenon. At the same time, more efficient statistical tests such as Fleming-Harrington test and Zmax test can be used to improve statistical power over the conventional logrank test for the analyses of time-to-event data that often exhibit non-proportional hazards. This article intends to describe how oncology drug development evolves over time and how statistical methods change accordingly.