Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: results of a phase II study.

BACKGROUND: An intensified multidrug chemotherapy regimen (raltitrexed plus oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant treatment of locally advanced rectal cancer patients, was shown feasible in our previous study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy. MATERIAL AND METHODS: A Phase II study was designed and clinical stage T3-T4 and/ or N ≥ 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic response to pre-operative therapy. According to the Gehan's design study, 25 patients were enrolled. Toxicity was assessed according to the RTOG-EORTC and CTCAE v.3.0 criteria. RESULTS: Twenty-five consecutive patients were treated. Twenty-two of the 25 (88%) patients had a partial clinical response at the time of pre-operative magnetic resonance imaging (MRI). Only one patient showed progressive systemic disease at pre-surgical revaluation and was subjected only to biopsy to evaluate pathological response. Twenty-four patients (96%) underwent surgery. Overall, pathologic complete response was observed in eight patients (32%; CI 0.95:12-55%) and only microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18-63%). Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were the most frequent acute side effects experienced. Eighteen patients had grade 1-2 toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year Local control and actuarial Disease Free Survival were 100% and 91%, respectively. CONCLUSION. An intensified regimen of concomitant boost radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely administered in patients with locally advanced rectal cancer. This regimen produces high rates of pathological complete response. Based on available data, this type of treatment could be offered to patients with more advanced tumors (T4 or local recurrence).

Active Breathing Coordinator in adjuvant three-dimensional conformal radiotherapy of early stage breast cancer: a feasibility study.

AIMS: To investigate the technical feasibility of utilizing the Active Breathing Coordinator for planning of postoperative three-dimensional conformal radiation therapy in patients with early stage breast cancer undergoing breast conservation therapy. METHODS: Patients with early stage breast cancer for whom adjuvant radiotherapy after breast-conserving surgery was planned were consecutively enrolled. Five sessions of simulation with the Active Breathing Coordinator were planned for each patient. Computed tomography for simulation was not acquired until a good level of compliance with the procedure was achieved by the patient. Patients who did not show a satisfactory level of compliance after the planned fifth session were defined as noncompliant. Two simulation computed tomography scans were acquired: the first without the Active Breathing Coordinator during free breathing, the second with the Active Breathing Coordinator. Forward intensity-modulated treatment plans were calculated. Mean lung dose (MLDipsilateral) and V30 (V30lung) for the ipsilateral lung and V30 for the heart (V30heart), were evaluated. RESULTS: Twenty consecutive patients were enrolled (6 with left-sided breast cancer and 14 with right-sided breast cancer). Eighteen of the patients completed the simulation computed tomography with the Active Breathing Coordinator after 1-5 sessions (median, 3). In 16 of the 18 patients, a reduction of V301ung was observed with the Active Breathing Coordinator. In 15 of the 18 patients, a reduction of MLDipsiateral was also observed. In 5 of the 6 patients with left-sided breast cancer, a reduction of V30heart was noted. CONCLUSIONS: Routine application of the Active Breathing Coordinator in clinical practice is feasible, even though it requires an increased workload. Dosimetric results are encouraging in terms of a better sparing of the ipsilateral lung and the heart.

A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer.

PURPOSE: The objective of this study was to determine the effect on resection rate and survival of neoadjuvant chemoradiotherapy for primarily unresectable locally advanced pancreatic carcinoma. METHODS: A systematic review of recently published literature was performed. Resection rates and survival data were derived from reports published from 2000 onwards. Only recent studies, based on radiotherapy with standard dose and fractionation, have been analyzed. RESULTS: Thirteen studies with a total of 510 patients met selection criteria. A resection rate of 8.3-64.2% was reported (median, 26.5%). Of the operated patients, 57.1-100% (median, 87.5%) had R0 tumor resection. Most papers reported occasional pathological complete responses (CR, 3.0-8.8%). When outcome in all patients was considered, median survival ranged from 9 to 23 (median, 13.3) months, comparing favorably with literature data based on concurrent chemoradiation alone (range, 8.6-13 months). Surprisingly, in patients with unresectable tumor at presentation, median survival after surgery ranged from 16.4 to 32.3 (median, 23.6) months. CONCLUSIONS: The finding of a high proportion of R0 resection among all resections performed confirms the activity of neoadjuvant radiochemotherapy and should not be neglected. Based on these data, patients with unresectable pancreatic cancer without disease progression after chemoradiotherapy should be considered for radical surgery.