Squamous-cell carcinoma of the head and neck includes a heterogeneous group of tumours of the upper air and food passages for which prognosis is difficult to assess. In fact, patients in comparable stages may have diverse clinical courses and responses to similar treatments. In order to better define the prognosis of each patient there is therefore a need to identify novel biological markers which reflect more accurately growth rate, progression and metastatic potential of each tumour. We assessed whether metastases correlate with microvessel counts (i.e. intratumoral vascularity) using the CD-31 monoclonal antibody (MAb) and p53 mutant protein expression, determined in the primary by immunocytochemical methods in 70 patients with locally advanced head and neck cancer. Patients were treated with concurrent chemo-radiotherapy; 50 of these presented loco-regional node metastasis at diagnosis whereas 3 cases, initially node-negative, developed distant metastasis during the period of observation. No feature was predictive for objective response to treatment. The overall mean and median blood vessel density at "hot spots" was 37.42 and 36, respectively, and 57% of the tumours expressed p53 mutant proteins. These 2 biological markers were significantly associated. Patients with metastases (loco-regional and distant) had a significantly higher mean blood-vessel density than those without tumour spread. Also, patients with p53-positive (+/++) tumours had a significantly higher incidence of metastasis than those with negative ones. Multivariate analysis showed that both vascularity and stage, but not p53 expression, are significant and independent predictors of metastasis in this series.

This study shows that VNB is an effective and well-tolerated agent in pretreated patients with advanced breast cancer. This drug does not seem to present cross-resistance with previous CMF or anthracycline regimens. Future clinical trials should be designed to prove whether the inclusion of VNB in combination chemotherapy regimens, or whether an enhancement of its dose-intensity using bone marrow growth factors, is able to improve further the efficacy of this drug in breast carcinoma.

This study suggests that overexpression of the c-erbB-2 oncoprotein appears to be an important indicator of relapse in stage I-II breast cancer when singly evaluated. Multivariate analysis shows that the determination both of nodal status and DNA ploidy improves our ability to identify subsets of patients with different prognoses, and allows for a better selection of patients for systemic adjuvant treatments.

Objective: To evaluate dose to organs at risk, target coverage and treatment compliance in left-sided breast cancer patients (LSBCP) treated with deep inspiration breath-hold (DIBH) and intensity modulated radiation therapy (IMRT) technique in a contest of daily clinical practice. Methods: A total of 280 consecutive LSBCP referred for adjuvant radiotherapy were systematically screened for suitability of DIBH technique. 239 were able to comply with the requirement for DIBH. Whole breast or chest wall were irradiated in DIBH, monitored by Varian RPM™ Respiratory Gating System, and two tangential inverse-planned beams with dynamic dose delivery. Dose prescription was 42.4 Gy/16 fractions in 205 patients and 50 Gy/25 fractions in 34. 23 patients received local and nodal treatment. Boost to tumor bed, of 10 Gy/5 fractions was used in 135 patients. Relevant dose metrics for heart, left anterior descending (LAD) coronary artery, lungs, contralateral breast and planning target volume were retrospectively analyzed. Results: The average mean heart dose (MHD) for all patients was 0.94 Gy and mean maximum LAD dose was 13.82 Gy. MHD and LAD maximum dose were significantly higher in patients treated with conventional fractionation whether expressed in absolute dose (1.44 vs 0.85 Gy, p < 0.0005 and 20.78 vs 12.45 Gy, p < 0.0005 respectively) or in equivalent doses of 2 Gy fractionation (0.88 vs 0.52 Gy, p =< 0.0005 and 17.68 vs 10.63 Gy, p = 0.0002 respectively). In 57 patients (23.8%) the maximum LAD dose was >20 Gy. Mean V20 ipsilateral lung dose was 8.5%. Mean doses of contralateral breast and lung were 0.13 Gy and 0.09 Gy respectively. Mean planning target volume V95% coverage was 96.1%. Compliance rate of DIBH technique was 84.5% (239/280). Conclusion: DIBH and IMRT in daily clinical practice are feasible in high percentage of unselected patients and allows low levels of irradiation of organs at risk without compromising target coverage. However, despite low MHD a significant proportion of patients receives a maximum LAD dose superior to 20 Gy. Advances in knowledge: The value of MHD used exclusively is not able to describe entirely the risk of late heart toxicity, which can be better evaluated with the joint analysis of the maximum dose to LAD region. The vast majority of LSBCP referred to adjuvant radiotherapy in the setting of routine practice are able to comply with the requirement of DIBH.

VNB, in this series of heavily pre-treated patients with head & neck cancer, did not reveal an antitumor activity of interest.