Does routine clinical practice reproduce the outcome of large prospective trials? The analysis of institutional database on patients with limited-disease small-cell lung cancer.

We performed the analysis of database on 409 patients with LD-SCLC to evaluate as to what extent the clinical outcome of large prospective trials was reproduced in routine practice. The analysis has shown that the hazard rate of death in the absence of prophylactic cranial irradiation (PCI) adjusted for the effects of confounding factors, appeared larger than that reported in the trials on PCI in LD-SCLC, and was comparable to that estimated for extensive disease. Less intense routine staging procedures, compared to the trial settings, contributed for such outcome. Hyperfractionated thoracic radiotherapy provided survival advantage similar to that reported in the literature.

Moderately low alpha/beta ratio for rectal cancer may best explain the outcome of three fractionation schedules of preoperative radiotherapy.

PURPOSE: To estimate the alpha/beta ratio for rectal cancer according to the outcome of three fractionation schedules of preoperative radiotherapy. METHODS AND MATERIALS: Between 1996 and 2002, 168 patients with locally advanced rectal cancer were treated as follows: 53 patients received 25 Gy in 5 Gy per fraction, 45 received 30 Gy in 3.0 Gy per fraction, and 70 were treated with accelerated hyperfractionation (42 Gy, 1.5 Gy per fraction, given twice daily). No patients received concurrent chemotherapy. The clinical characteristics of the groups were comparable. Surgery was performed shortly after radiotherapy. Crude data on locoregional tumor control were fitted directly using a linear-quadratic model, and the actuarial data were analyzed using Cox model. RESULTS: A linear-quadratic model provided an alpha estimate of 0.339 (SE 0.115) and beta estimate of 0.067 (SE 0.027), which resulted in an alpha/beta ratio of 5.06 Gy (95% confidence interval -0.1 to 10.3). In all three schemes the overall radiation treatment time was short, which limits the rationales for incorporating time effect into the model. If, however, time was incorporated the alpha/beta ratio was 11.1 Gy and the dose increment required to compensate for repopulation was 0.15 Gy/day. The actuarial analysis provided similar alpha/beta estimates. CONCLUSION: Although because of the retrospective character of the study, nonrandomized selection of fractionation schedule, and uncontrolled quality of surgery the present results can be regarded as hypothesis generating only, the control rates obtained in the pelvis are consistent with a moderately low alpha/beta ratio for rectal cancer.

Pre-operative hyperfractionated concurrent radiochemotherapy for locally advanced rectal cancers: a phase II clinical study.

OBJECTIVE: The study was prospectively designed as a single-arm, single-institution prospective trial of pre-operative concomitant hyperfractionated radiotherapy (HART) with co-administration of chemotherapy based on 5-fluorouracil (5FU) in patients with T2/N+ or T3/any N resectable mid-low primary rectal cancer. The aim of the study was to assess the safety and efficacy of accelerated HART with concurrent 5FU-based chemotherapy in patients with locally advanced rectal cancer. METHODS: Patients with resectable locally advanced (≥T3 or N+) rectal cancer were eligible. The patients received total dose 42 Gy in 28 fractions of 1.5 Gy, two times daily, with at least 8 h of interval, with concurrent chemotherapy: 325 mg m-2 of 5FU (bolus) on Days 1-3 and Days 16-18 (except for cN0 patients for whom only one cycle on Days 1-3 was prescribed). The primary end point included tolerance, post-operative complication rate and pathological response rate. The secondary end points included locoregional relapse-free survival, metastasis-free survival and overall survival. RESULTS: Out of 53 enrolled patients; 2 did not undergo surgery. Of the 51 patients evaluable for pathological response, there were 8 (15.6%), 20 (39.3%), 18 (35.3%) and 5 (9.8%) patients with tumour regression grade 0, 1, 2 and 3, respectively. Downstaging of the primary tumour and lymph nodes was observed in 22 (43%) and 25 (49%) patients, respectively. The primary tumour ypCR (ypT0) rate was 15% (8/51). The nodal ypCR rate for cN+ patients was 60% (21/35). The total ypCR (ypT0N0M0) rate was 11% (6/51). Toxicity included: Grade 3 diarrhoea (4/51, 7.8%), Grade 2 diarrhoea (22/51, 43.1%), Grade 2 leukopenia (7/51, 13.7%), Grade 2 neutropenia (6/51, 11.7%) and Grade 1 thrombocytopenia (3/51, 5.9%). No Grade 4 toxicity was reported. Nine patients (18%) presented with post-operative complications (during the 3 months after surgery). There were 6 locoregional relapses (11.8%) and distant metastasis occurred in 11 patients (21.6%). The 2-year cumulative locoregional relapse-free survival, metastasis-free survival and overall survival was 87%, 79% and 89%, respectively. CONCLUSION: The proposed pre-operative HART with co-administration of 5FU had acceptable toxicity profile and provided satisfactory rate of ypCR. This created rationale to initiate a Phase III randomized study that was registered under ClinicalTrials.gov Identifier: NCT01814969. Advances in knowledge: The results of this research show that responders to pre-operative radiochemotherapy have favourable outcome. Tumour regression grade as prognostic clinical feature holds the promise of better classifying patients at high risk of local and systemic recurrence and this issue may be an interesting objective for future research.