PURPOSE Total neoadjuvant therapy is a new paradigm for rectal cancer treatment. Optimal scheduling of preoperative chemoradiotherapy (CRT) and chemotherapy remains to be established. PATIENTS AND METHODS We conducted a multicenter, randomized, phase II trial using a pick-the-winner design on the basis of the hypothesis of an increased pathologic complete response (pCR) of 25% after total neoadjuvant therapy compared with standard 15% after preoperative CRT. Patients with stage II or III rectal cancer were assigned to group A for induction chemotherapy using three cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy) or to group B for consolidation chemotherapy after CRT. Secondary end points included toxicity, compliance, and surgical morbidity. RESULTS Of the 311 patients enrolled, 306 patients were evaluable (156 in group A and 150 in group B). CRT-related grade 3 or 4 toxicity was lower (37% v 27%) and compliance with CRT higher in group B (91%, 78%, and 76% v 97%, 87%, and 93% received full-dose radiotherapy, concomitant fluorouracil, and concomitant oxaliplatin in groups A and B, respectively); 92% versus 85% completed all induction/consolidation chemotherapy cycles, respectively. The longer interval between completion of CRT and surgery in group B (median 90 v 45 days in group A) did not increase surgical morbidity. A pCR in the intention-to-treat population was achieved in 17% in group A and in 25% in group B. Thus, only group B ( P < .001), but not group A ( P = .210), fulfilled the predefined statistical hypothesis. CONCLUSION Up-front CRT followed by chemotherapy resulted in better compliance with CRT but worse compliance with chemotherapy compared with group A. Long-term follow-up will assess whether improved pCR in group B translates to better oncologic outcome.

A novel procedure is proposed to extract T 1 , T 2 , and relative spin density from the signal time course sampled with a series of TrueFISP images after spin inversion. Generally, the recovery of the magnetization during continuous TrueFISP imaging can be described in good approximation by a three parameter monoexponential function S(t) ‫؍‬ S stst (1-INV exp(-t/T* 1 ). This apparent relaxation time T* 1 ≤ T 1 depends on the flip angle as well as on both T 1 and T 2 . Here, it is shown that the ratio T 1 /T 2 can be directly extracted from the inversion factor INV, which describes the relation of the signal value extrapolated to t ‫؍‬ 0 and the steady-state signal. The balanced SSFP MR imaging technique (1), also named balanced FFE and FIESTA, here referred to as TrueFISP (2), was proposed more than a decade ago and has generated much renewed interest during recent years due to technical advances in gradient and receiver performance. It provides the capability of extremely rapid imaging while preserving a high SNR efficiency. With a fixed flip angle ␣, the steady-state signal is an increasing function of the ratio T 2 /T 1 , so that high signal is generally obtained from fluid compartments with a long T 2 . The resulting image contrast renders the technique beneficial for several different applications, e.g., evaluation of cardiac function (3) or coronary angiography (4,5).In practice, magnetization reaches its steady-state condition after a certain transition period. A smooth signal time course towards steady state can be achieved by preparation with an RF pulse of flip angle -␣/2, preceding the imaging sequence at a time TR/2 before the first ␣ pulse (6). Whereas new elaborate pulse schemes have also been described (7), the ␣/2-based technique is robust and allows the implementation of additional magnetization preparation experiments immediately before a TrueFISP readout. In combination with the ␣/2 prepulse, an inversion recovery TrueFISP sequence has been proposed for magnetization prepared steady-state imaging (6). This approach has recently gained renewed interest as a promising tool for fast T 1 quantification (8). The intensities of a TrueFISP image series acquired after spin inversion and ␣/2 preparation were reported to follow the free longitudinal relaxation curve very closely, even at comparatively high flip angles of 50°.In a subsequent study from our group using numerical simulations and phantom experiments, it was also found that the recovery time course under a train of TrueFISP pulses can be described by monoexponential behavior (9). However, apparent relaxation times T* 1 were measured which strongly depended on the flip angle, T 1 and T 2 . It was demonstrated that this property can be used to quantify both T 1 and T 2 by fitting T* 1 curves measured with different flip angles to theoretical response curves. This numerically described behavior was confirmed by the results of a recent publication wherein an elegant simplifying calculation was presented, yielding a compact mathematical descripti...

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