Concurrent use of aromatase inhibitors and hypofractionated radiation therapy

AIM: To retrospectively assess the acute and long-term toxicity using aromatase inhibitors (AI) therapy concurrently with hypofractionated radiotherapy (HFRT) in breast cancer patients. METHODS: From November 1999 to October 2007, 66 patients were treated with breast HFRT and concurrent AI. In 63 patients (95.5%), HFRT delivered a total dose of 32.5 Gy to the whole breast within 5 wk (five fractions, one fraction per week). Other fractionations were chosen in three patients for the patients’ personal convenience. A subsequent boost to the tumor bed was delivered in 35 patients (53.0%). Acute toxicities were scored according to the Common Toxicity Criteria for Adverse Events v3. Late toxicity was defined as any toxicity occurring more than 6 mo after completion of HFRT and was scored according to the Late Effects Normal Tissue Task Force-Subjective, Objective, Management and Analytic scale. RESULTS: At the end of the HFRT course, 19 patients (28.8%) had no irradiation-related toxicity. Acute grade 1-2 epithelitis was observed in 46 patients (69.7%). One grade 3 toxicity (1.5%) was observed. With a median follow-up of 34 mo (range: 12-94 mo), 31 patients (47%) had no toxicity, and 35 patients (53%) presented with grade 1-2 fibrosis. No grade 3 or greater delayed toxicity was observed. CONCLUSION: We found that AI was well tolerated when given concurrently with HFRT. All toxicities were mild to moderate, and no treatment disruption was necessary. Further prospective assessment is warranted.     

Validation and Limitations of Use of a Breast Cancer Nomogram Predicting the Likelihood of Non–Sentinel Node Involvement After Positive Sentinel Node Biopsy

Background Axillary lymph node dissection (ALND) for patients with positive sentinel lymph nodes (SLNs) is currently under discussion in the literature. The breast cancer nomogram (BCN), an online tool developed by the Memorial Sloan-Kettering Cancer Center (MSKCC), aims to predict the risk of positive non-SLN in SLN-positive patients. The purpose of this study was to test the accuracy of the nomogram on patients with macrometastatic and micrometastatic SLN-positive biopsy findings. Methods Patient characteristics, tumor pathology, and positive SLN characteristics were collected on 588 consecutive patients who underwent completion ALND. The MSKCC BCN tool was used to calculate risk of metastases for all 588 cases that included a subgroup of the 213 patients with SLN micrometastases. The BCN was performed for positive SLN biopsy findings regardless of the method of metastasis detection. Evaluation of the BCN was performed by the area under the curve method. Results The BCN applied to all 588 patients achieved an area under the receiver operating characteristic curve (ROC) of .724 (range, .677–.771) compared with .76 in the MSKCC study. When the tool was applied solely to micrometastases found by hematoxylin and eosin staining and metastases found by immunohistochemistry, the area under the ROC was .538 (range, .423–.653). Conclusions The MSKCC nomogram has been validated for all the patients having a metastatic SLN at the Institut Curie. However, this model was not reliably predictive for positive non–SLN in cases with micrometastic positive SLN.     

The 8.1 ancestral MHC haplotype is strongly associated with colorectal cancer risk

Many recent data indicate that some alleles encoded in the central major histocompatibility complex (MHC) region (Class III) of short arm of chromosome 6 may modify the risk of cancer development. Therefore we determined 4 single nucleotide polymorphisms (SNPs) of this region (TNF-alpha -308 G > A, RAGE -429 T > C, HSP70-2 -1267 A > G, LTA 252 A > G) in genomic DNA samples from 183 Hungarian patients with colorectal cancer and 141 age matched control subjects representing the Hungarian population of the same age and gender. No significant differences were found in either SNP tested. When, however, three- or four-locus haplotypes consisting of known constituents of the so-called 8.1 ancestral haplotype (8.1AH) were considered, marked differences were observed. Frequency of TNF-alpha -308A, RAGE -429C, HSP70-2 -1267G, LTA 252G (8.1AH) haplotype was significantly (p = 0.006) more frequent (19.1%) among patients than in the controls (7.7%). Age- and gender-adjusted ratio of the 8.1AH carriers vs. non-carriers to have colorectal cancer was 2.514 (1.130-5.594). This risk was higher in 相似文献   

Ancestral haplotype 8.1 and lung disease severity in European cystic fibrosis patients

BackgroundThe clinical course of cystic fibrosis (CF) lung disease varies between patients bearing identical CFTR mutations. This suggests that additional genetic modifiers may contribute to the pulmonary phenotype. The highly conserved ancestral haplotype 8.1 (8.1AH), carried by up to one quarter of Caucasians, comprises linked gene polymorphisms on chromosome 6 that play a key role in the inflammatory response: LTA + 252A/G; TNF −308G/A, HSP70-2 + 1267A/G and RAGE −429T/C. As inflammation is a key component inducing CF lung damage, we investigated whether the 8.1AH represents a lung function modifier in CF.MethodsWe analyzed the lung function of 404 European CF patients from France (n = 230), Germany (n = 95) and UK (n = 79). FEV₁ differences between 8.1AH carriers and non-carriers were calculated in each country and pooled using a random effects model.ResultsThe frequency of 8.1AH carriers was similar between French (22%), German (29%) and UK (27%) patients. We found that 8.1AH carriers had significantly lower FEV₁, adjusted for age classes and countries (P < 0.04, mean FEV₁ difference − 6.4% CI95% [− 12.4%, − 0.5%]). No difference was observed with respect to BMI Z-scores and chronic colonization with P. aeruginosa.ConclusionsThese findings support the concept that 8.1AH is an important genetic modifier of lung disease in CF. To conclude, multiple linked genes outside the CF locus might explain some of the variability in lung phenotype.