60. Factors detremining local control in patients (Pts) with locally advanced breast cancer (Labc) managed with radiotherapy (RT) as the primary locoregional treatment

IntroductionRT plays an important role in the management of LABC, yet clinical outcomes still remain far from satisfactory. The aim of this study was to evaluate retrospectively factors determining local control in a large series of consecutive LABC pts managed with RT as the primary locoregional treatment.Material and methodsThe records of 261 primarily inoperable LABC pts treated between 1991 and 1997 at two institutions: Medical University of Gdansk, Poland and Velindre NHS Trust, Cardiff, UK were analysed. All pts received megavoltage RT to the breast with two tangential fields, and the adjacent lymph node areas were irradiated using customised fields. Due to a large scale of RT doses and fractionation schedules, normalised total dose (NTD) was calculated for all patients using a linear quadratic model. In 241 pts RT constituted the only local treatment and the remaining 20 pts were subsequently subjected to mastectomy. Most pts received chemotherapy and/or endocrine therapy prior or after RT.ResultsWithin the median follow-up of 37 months, locoregional recurrence occurred in 95 of 251 evaluable pts (38%). Three-year and five-year locoregional-free survival rates were 59% and 48%, respectively. At multivariate analysis of variables predicting the risk of locoregional relapse, inflammatory carcinoma (

37. Multicenter, randomized study assessing the impact of amifostine on normal tissue radiation tolerance during head and neck cancer radiotherapy

A prospective, randomized multicenter study was conducted to assess the value of amifostine (Ethyol®) as a radioprotectant in head and neck cancer radiotherapy. The aim of the study was to evaluate the impact of the addition of daily amifostine (150 mg/m2) on the degree of early (mucositis, dysphagia, xerostomia) and late (mucosal, cutaneous, salivary gland, mandible and spinal cord) radiation reactions. Assessed were also patients’ quality of life, local control and overall survival. Sixty two patients from five Polish institutions were randomly assigned to radiotherapy alone (Arm A – 28 patients) or radiotherapy + amifostine (Arm B – 34 patients). There were 43 men and 19 women. Primary tumor was located in the oral cavity (27 patients), oropharynx (25 patients), nasopharynx (2 patients) and larynx/hypopharynx (8 patients). In 43 patients radiotherapy was used as the sole modality of treatment and 19 patients were irradiated postoperatively. The side effects of amifostine were manageable. In 6 patients amifostine infusion had to be temporarily stopped due to hypotension and in 5 patients its administration was permanently terminated due to hypotension, nausea and vomiting, septicemia or fever and visual disturbances. The early results of the study, focusing on early radiation reactions, will be presented at the conference

STELLAR: Final updated results of a phase II trial of TTFields with chemotherapy for unresectable malignant pleural mesothelioma

Background: Tumor Treating Fields (TTFields), an anti-mitotic, regional treatment approved for glioblastoma utilizes low intensity, alternating electric fields delivered non-invasively to the tumor using a portable medical device. In-vitro, human mesothelioma cells were highly susceptible to TTFields. Methods: The trial accrued 80 patients with unresectable, previously untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields (>18h/day) in combination with pemetrexed and cisplatin or carboplatin. Inclusion criteria included ECOG PS of 0-1 and pathologically proven mesothelioma. The primary endpoint was overall survival (OS). A visual analog scale was used to assess EOCG performance status and cancer-related pain assessed until disease progression. The sample size provided 80% power with two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months compared to historical controls (Vogelzang, JCO 2003). Results: All 80 patients had a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology, similar to the Vogelzang study. Median OS was 18.2 months (95% CI 12.1-25.8) versus 12.1 months in the historical control. Median OS for epithelioid patients was 21.2 months (95% CI 13.2-25.8). ECOG score was stable during the first year of follow up. Median time to deterioration in performance status was 13.1 months. Average score of pain was lower compared to baseline during the first 7 months of the treatment and was higher later on the study, with a median time to a clinical significant 33% increase in pain of 8.4 months. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Four patients (5%) had grade 3 dermatitis. Conclusions: The study met primary endpoint of significant extension of overall survival in previously untreated mesothelioma patients. TTFields was not associated with a decrease in performance status or an increase in pain for the duration of TTFields use. TTFields in combinati

Genetic locus in Rhizobium japonicum (fredii) affecting soybean root nodule differentiation.

A genetic locus in fast-growing Rhizobium japonicum (fredii) USDA 191 (Fix+ on several contemporary soybean cultivars) was identified by random Tn5 mutagenesis as affecting the development and differentiation of root nodules. This mutant (MU042) is prototrophic and shows no apparent alterations in its surface properties. It induces aberrant nodules, arrested at the same early level of differentiation, on all its host plants. An 8.1-kilobase EcoRI fragment containing Tn5 was cloned from MU042. In USDA 191 as well as another fast-growing strain, USDA 201, the affected locus was found to be unlinked to the large symbiotic plasmid and appears to be chromosomal. An analogous sequence has been shown to be present in Bradyrhizobium japonicum (J. Stanley, G.G. Brown, and D.P.S. Verma, J. Bacteriol. 163:148-154, 1985) as well as in R. trifolii and R. meliloti. MU042 was complemented for effective nodulation of soybean by a cosmid clone from USDA 201, and the complementing locus was delimited to a 6-kilobase EcoRI subfragment. An R. trifolii strain (MU225), whose indigenous symbiotic plasmid was replaced by that of strain USDA 191, induced more highly differentiated nodules on soybean than did MU042. This suggests that the mutation in MU042 can be functionally substituted by similar loci of other fast-growing rhizobia. Leghemoglobin and nodulin-35 (uricase II) were present in the differentiated Fix- nodules induced by MU225, whereas both were absent in MU042-induced pseudonodule structures

60. Factors detremining local control in patients (Pts) with locally advanced breast cancer (Labc) managed with radiotherapy (RT) as the primary locoregional treatment

IntroductionRT plays an important role in the management of LABC, yet clinical outcomes still remain far from satisfactory. The aim of this study was to evaluate retrospectively factors determining local control in a large series of consecutive LABC pts managed with RT as the primary locoregional treatment.Material and methodsThe records of 261 primarily inoperable LABC pts treated between 1991 and 1997 at two institutions: Medical University of Gdansk, Poland and Velindre NHS Trust, Cardiff, UK were analysed. All pts received megavoltage RT to the breast with two tangential fields, and the adjacent lymph node areas were irradiated using customised fields. Due to a large scale of RT doses and fractionation schedules, normalised total dose (NTD) was calculated for all patients using a linear quadratic model. In 241 pts RT constituted the only local treatment and the remaining 20 pts were subsequently subjected to mastectomy. Most pts received chemotherapy and/or endocrine therapy prior or after RT.ResultsWithin the median follow-up of 37 months, locoregional recurrence occurred in 95 of 251 evaluable pts (38%). Three-year and five-year locoregional-free survival rates were 59% and 48%, respectively. At multivariate analysis of variables predicting the risk of locoregional relapse, inflammatory carcinoma (p<0.01; RR 2.1), T4 disease (p<0.01; RR 2.9) and involvement of supraclavicular lymph nodes (p<0.01; RR 2.4) were the most significant clinical factors, whereas response to RT (p<0.01; RR 1.2) and NTD (p<0.01; RR 0.7) were the most important therapeutic factors. Increasing the total dose to the tumour by 10 Gy was associated with 30% reduction of local relapse.ConclusionsDue to large heterogeneity of LABC pts, judicious tailoring of RT, particularly in terms of dose prescribing, is essential to increase the chance of locoregional cure