Computed tomography (CT) scan evaluation of late toxicity following hypofractionated/accelerated radiotherapy with cytoprotection (HypoARC) in breast cancer patients treated with conservative surgery.

BACKGROUND: In the present study we evaluated the long-term radiation toxicity of an hypofractionated accelerated radiotherapy scheme supported with amifostine cytoprotection (hypoARC). PATIENTS AND METHODS: A cohort of 32 breast cancer patients, pretreated with conservative surgery and adjuvant doxorubicin or taxane based chemotherapy, were treated with hypoARC. In contrast to the 45 days required for the delivery of standard breast (+/-supraclavicular) radiotherapy, the proposed scheme delivers the whole radiation dose in 16 days (10 fractions of 3.5Gy plus 2 additional 4Gy fractions to the tumor bed), which is convenient for elderly patients or patients residing away from radiotherapy departments. RESULTS: After a minimum follow up of 24 months (range, 24-36), none of the patients showed any clinical signs of lung or arm toxicity. Increased palpable breast density was evident 16 out of 32 cases. Computed tomography (CT) scan evaluation of the lung and breast densities (calculated in Haunsfield units) showed no signs of lung fibrosis, while increased density of the irradiated breast (1.1-1.3-fold) was confirmed in 8 out of 17 patients examined. None of the patients has relapsed locally. CONCLUSIONS: Although longer follow-up is required to confirm safety of the described radiotherapy regimen, these data are encouraging as the toxicity reported within 2 to 3 years of follow-up is even lower than the one expected from standard radiotherapy.

Hypofractionated accelerated radiotherapy with cytoprotection combined with trastuzumab, liposomal doxorubicine, and docetaxel in c-erbB-2-positive breast cancer.

OBJECTIVES: Trastuzumab, an antic-erbB-2 monoclonal antibody, has become a standard component of chemotherapy for c-erbB-2-positive advanced breast carcinoma. Despite the experimental evidence of its radiosensitizing properties, trastuzumab has never been used in combination with radiotherapy for the treatment of patients with locally advanced disease. PATIENTS AND METHODS: Twenty-two patients with c-erbB-2-positive locally advanced chemoresistant (7 patients) or with high-risk breast cancer (15 patients) were recruited in a treatment protocol combining hypofractionated/accelerated radiotherapy (hypoARC) supported with high-dose amifostine (1000 mg subcutaneous), concurrently with trastuzumab (4 mg/kg every 2 weeks). Thirteen of these patients (including all 7 inoperable cases) received concurrently chemotherapy with liposomal doxorubicin and docetaxel (25 mg/m2 and 40 mg/m2 every 2 weeks, respectively). RESULTS: Administration of trastuzumab together with highly accelerated amifostine-supported radiotherapy was feasible without an increase in early and late radiation toxicity. This was obtained despite the concurrent administration of aggressive chemotherapy. Complete responses were noted in 5 of 7 patients with locally, often far advanced, chemoresistant disease. None of the complete responders or the 15 high-risk breast cancer patients relapsed within the 3- to 26-month follow-up period. CONCLUSION: Inclusion of trastuzumab in the radiochemotherapy protocols for breast cancer does not increase radiation or systemic toxicity. The concurrent administration of aggressive radiotherapy with docetaxel and liposomal doxorubicin is feasible when supported with amifostine. The value of such regimens in the treatment of locally advanced or high risk c-erbB-2 positive breast cancer patients deserves further evaluation.

Nasopharyngeal carcinoma: the impact of CT-scan and of MRI on staging, radiotherapy treatment planning, and outcome of the disease.

The present study is a critical review of the role of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis and therapy of nasopharyngeal cancer. It is estimated that following CT-scan/MRI, T,N staging of the disease changes in about half of cases, which results in important adjustments of the radiotherapy treatment planning, both in terms of radiation field dimensions and of dose specifications. The development of novel technology with CT-scan-simulated 3-D conformal or intensity-modulated radiotherapy (IMRT) planning is gradually becoming the standard therapy for nasopharyngeal carcinoma (NPC). CT-scan/MRI is also of value in detecting massive parapharyngeal involvement, low-neck lymphadenopathy or fixation of nodes onto adjacent structures, which are important features indicating the necessity to integrate chemotherapy or surgical neck dissection in the overall treatment policy. CT-positron emission tomography (PET) scan is recently under evaluation for the identification of the most active tumor regions, which will allow a biological radiotherapy planning (RTP) using IMRT techniques.

Duodenal duplication. Is ultrasound appearance enough to confirm the diagnosis?

A case of duodenal duplication is reported. It is a rare anomaly and is commonly discovered during infancy. Symptoms of partial obstruction dominate the clinical picture. Abdominal ultrasound (US) seems to be the best method to confirm the diagnosis especially when the two-layer pattern is present. In our case the radiological evaluation apart from US comprised plain film of the abdomen, upper gastrointestinal series and CT scan. The diagnosis of duodenal duplication made by US examination as well as by gastrointestinal series and CT scan was confirmed surgically. We consider that when at US the sign of two-layer pattern is present there is no need for further radiological evaluation for alimentary tract duplication.

Conformal hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC) for high risk prostatic carcinoma: rationale, technique and early experience.

Recent radiobiological analysis of the radiotherapy results for prostate cancer revealed that prostate carcinoma behaves as a late responding tissue, sharing an alpha/beta ratio lower than 2Gy. These findings suggest that hypofractionation may be more effective. Reduction of the overall treatment time could further increase response by abrogating the effect of rapid tumor repopulation. In the present study we report a conformal technique applied (to pelvis and prostate) for the treatment of high-risk prostate cancer, using hypofractionated and accelerated radiotherapy (3.4Gy x 15 consecutive fractions) supported with high-dose daily amifostine (1000mg subcutaneously) to protect normal tissues against early and late effects. The biological dose delivered to the prostate cancer by this HypoARC (hypofractionated accelerated radiotherapy with cytoprotection) technique is estimated to be 71.4Gy (alpha/beta= 1.5 Gy). The time-adjusted biological dose is estimated to 77-94 Gy. Amifostine tolerance was excellent. All seven patients recruited up to now have accomplished their treatment with grade 0-1 cystitis or diarrhoea (5/7 grade 0). The study is ongoing to assess efficacy and late effects of HypoARC.

Loss of FEV1 in cystic fibrosis: correlation with HRCT features.

The purpose of this study was to determine which high-resolution computed tomography (HRCT) features in patients with cystic fibrosis are most strongly associated with functional impairment as expressed by forced expiratory volume in one second (FEV1). Forty-seven patients with cystic fibrosis underwent chest HRCT and had pulmonary function tests. The HRCT examinations were evaluated for 11 features scored using a modification of Bhalla system and FEV1 was recorded as percentage of the predicted value. Univariate and multivariate correlations between HRCT scores and FEV1 were performed. The most common HRCT feature was bronchiectasis (98%) followed by atelectasis-consolidation (81%), bronchial wall thickening (77%), tree-in-bud sign (74%), mucous plugging (72%) and mosaic perfusion pattern (47%). On univariate analysis the following features correlated strongly with FEV1: bronchial wall thickening ( p<0.0000001), tree-in-bud sign ( p<0.0000001), mucous plugging ( p<0.0000001), atelectasis-consolidation (p<0.0000001), thickening of interlobular septa ( p<0.0002), severity ( p<0.0002) and extent of bronchiectasis ( p<0.0002). On multivariate analysis bronchial wall thickening and atelectasis-consolidation were the strongest independent determinants of the FEV1. We found a regression equation between FEV1 and the two HRCT features: FEV1=constant variable+a multiplied by bronchial wall thickening+b multiplied by atelectasis-consolidation (a and b=regression coefficients, R(2)=0.48). The major morphological determinants of functional abnormality in cystic fibrosis, as expressed by the loss of FEV1, are bronchial wall thickening and atelectasis-consolidation.