FOxTROT2: innovative trial design to evaluate the role of neoadjuvant chemotherapy for treating locally advanced colon cancer in older adults or those with frailty.

Treating older adults with cancer is increasingly important in modern oncology practice. However, we currently lack the high-quality evidence needed to guide optimal management of this heterogeneous group. Principally, historic under-recruitment of older adults to clinical trials limits our understanding of how existing evidence can be applied to this group. Such uncertainty is particularly prevalent in the management of colon cancer (CC). With CC being most common in older adults, many patients also suffer from frailty, which is recognised as being strongly associated with poor clinical outcomes. Conducting clinical trials in older adults presents several major challenges, many of which impact the clinical relevance of results to a real-world population. When considering this heterogeneous group, it may be difficult to define the target population, recruit participants effectively, choose an appropriate trial design, and ensure participants remain engaged with the trial during follow-up. Furthermore, after overcoming these challenges, clinical trials tend to enrol highly selected patient cohorts that comprise only the fittest older patients, which are not representative of the wider population. FOxTROT1 was the first phase III randomised controlled trial to illustrate the benefit of neoadjuvant chemotherapy (NAC) in the treatment of CC. Patients receiving NAC had greater 2-year disease-free survival compared to those proceeding straight to surgery. Outcomes for older adults in FOxTROT1 were similarly impressive when compared to their younger counterparts. Yet, this group inevitably represents a fitter subgroup of the older patient population. FOxTROT2 has been designed to investigate NAC in a full range of older adults with CC, including those with frailty. In this review, we describe the key challenges to conducting a robust clinical trial in this heterogeneous patient group, highlight our strategies for overcoming these challenges in FOxTROT2, and explain how we hope to provide clarity on the optimal treatment of CC in older adults.

Serum estradiol in the differential diagnosis of ectopic pregnancy.

In a prospective study using a cutoff value of 140 pg/mL, serum estradiol 17-beta assay had a sensitivity of 83% and a specificity of 100% in differentiating ectopic pregnancy (6 patients) from normal pregnancy with threatened abortion proceeding to viability (7 patients). In differentiating threatened abortion from spontaneous abortion (9 patients), the estradiol assay had a sensitivity of 88.9% and a specificity of 100%. All but one of the patients with ectopic pregnancy had estradiol levels below the cutoff value of 140 pg/mL, as did all but one of the patients who had spontaneous abortion. All the patients who had threatened abortion that progressed to viability had values well above the cutoff level. The mean estradiol values for the viable pregnancy group were significantly different from those of the other two groups. These data suggest that, at the institution where this study was done, serum estradiol determinations may be of value in the differentiation of both ectopic pregnancy and spontaneous abortion from threatened abortion but appears to be of very limited usefulness in distinguishing ectopic pregnancy from spontaneous abortion. The validity of these conclusions is limited by the small number of subjects. Further studies comprising greater numbers of subjects are needed.