O'Neill B P, Wang C H, O'Fallon J R, Colgan J P, Earle J D, Krigel R L, Brown L D, McGinnis W J
Department of Neurology, Mayo Clinic and Foundation, 200 SW First St., Rochester, MN 55905, USA.
Neuro Oncol. 1999 Jul;1(3):196-203. doi: 10.1093/neuonc/1.3.196.
Per protocol, patients with primary CNS non-Hodgkin's lymphoma in an intergroup phase II trial conducted by the North Central Cancer Treatment Group and the Eastern Cooperative Oncology Group had their cognitive functions measured using the Folstein and Folstein Mini-Mental Status Examination (MMSE) and their physical functions measured using the Eastern Cooperative Oncology Group Performance Score (PS) at study entry, at each treatment evaluation, and at quarterly intervals thereafter until disease progression or death. Of the 53 eligible participants who began therapy, 46 (87%) had baseline MMSE scores recorded, 36 (68%) had at least one follow-up MMSE, and 32 (60%) had both, while 52 (98%) had baseline PS, 49 (92%) had at least one follow-up PS, and 48 (91%) had both. Patterns of MMSE and PS values over time were studied in each individual, in the group as a whole, in the 20 patients who completed the study regimen, in the 23 who survived more than a year, and in patients who were classified as nonprogressors at each key evaluation. For each patient, all recorded values were plotted versus time, with dates of disease progression and death included, to look for signs of decline in cognitive or physical function preceding adverse events. Long-term declines in scores of both cognitive and physical function were observed in many treated patients with primary CNS non-Hodgkin's lymphoma. Nearly all patients who were alive more than 52 weeks after study entry had a demonstrable decline in cognitive and physical functionality. Such declines may occur before disease progression is documented; they may also occur in some patients who have long-term follow-up without evidence of disease progression. Declining MMSE and PS was a poor predictor of disease progression. There was no association of PS and toxicity. The data from this study demonstrated the considerable difficulties we encountered conducting an ancillary study such as this within a multicenter clinical trial. Firstly, the test instruments written into the protocol were unable to tell if the declines seen were due to disease, treatment, co-morbidity, or other factors. Secondly, the missing data created difficulties in interpreting outcome.
根据方案，在由北中部癌症治疗组和东部肿瘤协作组开展的一项组间II期试验中，原发性中枢神经系统非霍奇金淋巴瘤患者在研究入组时、每次治疗评估时以及此后每季度进行一次测量，使用福尔斯坦简易精神状态检查表（MMSE）评估认知功能，使用东部肿瘤协作组体能状态评分（PS）评估身体功能，直至疾病进展或死亡。在开始治疗的53名符合条件的参与者中，46名（87%）记录了基线MMSE评分，36名（68%）至少有一次随访MMSE评分，32名（60%）两者都有；而52名（98%）有基线PS评分，49名（92%）至少有一次随访PS评分，48名（91%）两者都有。研究了每个个体、整个组、完成研究方案的20名患者、存活超过一年的23名患者以及在每次关键评估中被归类为病情无进展的患者中MMSE和PS值随时间的变化模式。对于每位患者，将所有记录的值与时间作图，包括疾病进展和死亡日期，以寻找不良事件之前认知或身体功能下降的迹象。在许多接受治疗的原发性中枢神经系统非霍奇金淋巴瘤患者中观察到认知和身体功能评分的长期下降。几乎所有在研究入组后存活超过52周的患者都有明显的认知和身体功能下降。这种下降可能在记录到疾病进展之前就已发生；也可能发生在一些长期随访但无疾病进展证据的患者中。MMSE和PS下降并不能很好地预测疾病进展。PS与毒性之间没有关联。这项研究的数据表明，我们在多中心临床试验中开展这样一项辅助研究时遇到了相当大的困难。首先，方案中写入的测试工具无法判断所观察到的下降是由于疾病、治疗、合并症还是其他因素。其次，缺失的数据给解释结果带来了困难。
