A Systematic Review of Adaptive Seamless Clinical Trials for Late-Phase Oncology Development.

INTRODUCTION: Although oncology has seen large scientific and clinical advances over the last decade, it also has one of the lowest success rates for novel agents across therapeutic areas. Adaptive clinical trial design has been a popular option for increasing clinical trial efficiency and the chances of trial success. Seamless clinical trial design are studies in which two or more clinical trial phases are combined into a single study with a pre-specified transition between stages. This integration of phases may enhance efficiency. METHODS: To understand the precedent for the use of seamless designs, this working group was formed to conduct a comprehensive literature search on seamless clinical trials conducted with confirmatory intent in oncology. Trial design features were extracted into a database and analyzed with descriptive statistics. RESULTS: A literature search identified 68 clinical trials meeting inclusion and exclusion criteria. The most common design feature was a gate on treatment efficacy, where the trial would only proceed to the second stage if sufficient efficacy was observed in the first. The next most common feature was a selection of a dose or treatment regimen. Inferentially and operationally seamless designs were approximately equally represented. DISCUSSION: Key statistical considerations for seamless phase II/III designs include optimizing design choices by evaluating and comparing operating characteristics across design alternatives as well as showing control of overall Type I error rates. Executing the transition between phases should be evaluated for issues related to accrual, drug production, and procedures to maintain trial integrity. CONCLUSIONS: While there are unique statistical, regulatory, and operational considerations for seamless designs they are also uniquely suited to many development settings. These include, for example, addressing dose selection under FDA's Project Optimus and addressing the growing use of biomarkers and personalized medicine approaches in cancer treatment.

[An initial exploration of the application of transanal endoscopic microsurgery in rectal cancer patients with clinical complete response after neoadjuvant chemoradiotherapy].

Objective: To preliminarily explore the value of transanal endoscopic microsurgery (TEM) in rectal cancer patients with clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods: Using descriptive case series method, Clinical data of 13 patients who met the criteria of nCRT and were considered to be cCR after MRI or CT scanning, digital rectal examination and colonoscopic biopsy, as well as no lymph node or distant metastasis were found, then underwent TEM from 2013 to 2016 at the Department of General Surgery of Peking Union Medical College Hospital were collected retrospectively. A 3-course combination of capecitabine and oxaliplatin (XELOX) was used for chemotherapy. Besides, a 6MV-X ray radiation was used as radiotherapy simultaneously. Six to eight weeks after completion of radiotherapy, a preoperative assessment was carried out with intrarectal ultrasound, MRI, or pelvic abdominal CT examination. TEM was performed afterwards with informed consent. Postoperative pathological findings and follow-up results were used to evaluate the value of diagnosis and treatment of TEM on those patients. Results: There were 8 males and 5 females with a median age of 63 (27-80) years. Preoperative examination showed that the lesions were located in the anterior wall in 3 cases, the posterior wall in 3 cases, the left side wall in 4 cases, and the right side wall in 3 cases. Before nCRT, the distance between tumor and anal margin was (4.8±1.1) (2.0-7.5) cm; after nCRT, this distance was (5.2±1.3) (3.0-7.5) cm. All the 13 patients underwent extended local resection of rectal cancer via TEM with the placement of urethral catheter. The average operative time was (52.2±3.7) (42-70) minutes, and the average intraoperative blood loss was (19.2±2.8) (5-30) ml. All the patients could engage in daily activities on postoperative day 1, and could cater themselves orally on postoperative day 2. The main discomfort was postoperative anal pain and foreign body sensation (n=5), which could be alleviated by non-steroidal anti-inflammatory drugs. One case had postoperative lung infection and was cured by antibiotic treatment. One case had urinary retention after removing urine catheter, and then a urine catheter was re-inserted. Average postoperative hospital stay was (2.8±2.4) (2-12) days. All specimens were completely resected via TEM. Histopathological examination confirmed that 7 specimens had achieved pathologic complete response (pCR) and the other 6 specimens had obtained partial tumor response of CAP grade 2. Seven patients with pCR received a median follow-up of 24 (8-48) months and no local recurrence or distant metastasis was reported during follow-up period. Among these 7 cases, one developed defecation dysfunction after discharge, mainly for defecation pain and even dare to defecate, who returned to normal defecation within 2 months after surgery; One developed severe anal pain within six months after surgery and the pain disappeared after symptomatic pain relief. The other 6 patients with CAP grade 2 refused to undergo further radical operation because of their strong desire in preserving anus, and received remedial adjuvant chemotherapy instead. Conclusion: For rectal cancer patients with cCR after nCRT, TEM does have certain application values if the patient has a strong desire to preserve anus.

[Studies of localization of black streak body gene in Drosophila melanogaster].

Mutation type of body color shows frequently yellow (y), black (b) and ebony (e) in Drosophila melanogaster and locates on X, second and third chromosom respectively. A mutant of black streak (bsr) is a spontaneous mutation strain building in the laboratory in 1991. Whether this mutation strain is rediscovered on the primary style or not. We have discussed this problem with general cross breeding and complementation test. The result of complementation test indicated that it is a mutant in first filial generation with trans heterozygote and that it is few wild in second filial generation with cis teterozygote due to crossing over in crossing bsr and e. But, we believe that bsr and e is located same loci (93D2) but not the same sites. This report discussed for correlation inter-gene body color and ruleless of heredity passing down for black streak body.

Karyotypes of 33 patients with clonal aberrations in chronic lymphocytic leukaemia. Review of 216 abnormal karyotypes in chronic lymphocytic leukaemia.

We report on 33 unpublished patients with clonal anomalies in chronic lymphocytic leukaemia. The literature was thoroughly reviewed in order 1) to quantify the frequency of anomalies found in chronic lymphocytic leukaemia and to give new status to the rarest, 2) to determine whether a given anomaly was an additional anomaly and/or a primary anomaly, and 3) to find out whether strong associations between different anomalies exist in this disease.