Biologically effective dose and breast cancer conservative treatment: is duration of radiation therapy really important?

To evaluate if biologically effective dose (BED), and in particular the duration of radiation treatment, has an effect on local relapse risk. Between January 2000 and December 2008 a total of 762 patients with T1-2 N0/+ breast cancer was treated with breast-conserving surgery and radiotherapy, with and without hormone therapy and chemotherapy. Adjuvant radiation therapy was administered to a total dose of 60-66 Gy in 30-33 fractions. The computed BEDs were divided in four groups: <43.1, 43.1-44.9, 45.0-46.1, and >46.1 Gy (A-D, respectively). Kaplan-Meier method was used to calculate local relapse rates. Cox regression method was used to identify prognostic factors of local relapse. Evaluated variables were age, tumor histology, tumor size, surgical margin status, axillary nodal status, tumor grading, adjuvant therapies, adjuvant chemotherapy alone, adjuvant hormone therapy alone, adjuvant anthracyclines, and BEDs values. 8-year local relapse rates were 18.0% for group A, 8.5% for group B, 4.6% for group C, and 2.7% for group D (P=0.008). Multivariate Cox regression analysis showed that BEDs values were associated with higher local relapse risk (P=0.001). In our study, a prolongation of radiotherapy treatment, intended as a lower BED value, after breast-conserving surgery is associated with an increased risk of local relapse. Considering the wide range of results published in other studies, hypofractionation for breast cancer should be considered, at the moment, feasible in selected patients.

Prognostic impact of triple negative phenotype in conservatively treated breast cancer.

To evaluate overall survival (OS), disease-free survival (DFS), and local-recurrence free survival (LRFS) rates in a subgroup of patients affected by breast cancer expressing a particular phenotype (estrogen receptor negative, progesterone receptor negative, and Human Epidermal Growth Factor receptor 2 negative) known as "triple negative" (TN). Data of 387 women affected by early breast cancer who underwent whole-breast radiotherapy after conservative surgery with or without chemotherapy and/or hormone therapy between January 2002 and December 2008, in the Department of Radiotherapy at Regional Cancer Center, were retrospectively evaluated. Chi-squared test was used to compare prognostic factors (age, histology, tumor size, nodal status, grading, and adjuvant therapy) between TN patients and non-TN patients. OS, DFS, and LRFS rates were analyzed using Kaplan--Meier proportional log-rank test; impact of prognostic factors on poor outcome was evaluated using Cox regression stepwise method on univariate and multivariate analysis. Mean follow-up time was 57.6 months (range13.7-109.7). TN patients were more likely to have ≥T2 tumors (p = 0.0003), grade 3 tumors (p = 0.0001) and to receive chemotherapy as adjuvant therapy (p =< 0.0001). TN patients had lower 5-years-OS (p = 0.039) and lower 5-years-DFS (p = 0.003) compared with non-TN patients. No difference in 5-years LRFS was found (p = 0.49). After multivariate analysis, TN status was found to be a predictive factor for OS (p = 0.004) and for DFS (p = 0.01), but not for LRFS (p = 0.8). TN patients have lower survival when compared with non-TN patients, but similar LRFS rates. These patients can be treated in a conservative surgical protocol, but should receive more aggressive and tailored adjuvant therapies.

Brain Morphology of Cannabis Users With or Without Psychosis: A Pilot MRI Study.

Cannabis is the illicit drug most commonly used worldwide, and its consumption can both induce psychiatric symptoms in otherwise healthy subjects and unmask a florid psychotic picture in patients with a prior psychotic risk. Previous studies suggest that chronic and long-term cannabis exposure may exert significant negative effects in brain areas enriched with cannabinoid receptors. However, whether brain alterations determined by cannabis dependency will lead to a clinically significant phenotype or to a psychotic outbreak at some point of an abuser's life remains unclear. The aim of this study was to investigate morphological brain differences between chronic cannabis users with cannabis-induced psychosis (CIP) and non-psychotic cannabis users (NPCU) without any psychiatric conditions and correlate brain deficits with selective socio-demographic, clinical and psychosocial variables. 3T magnetic resonance imaging (MRI) scans of 10 CIP patients and 12 NPCU were acquired. The type of drug, the frequency, and the duration, as well socio-demographic, clinical and psychosocial parameters of dependency were measured. CIP patients had extensive grey matter (GM) decreases in right superior frontal gyrus, right precentral, right superior temporal gyrus, insula bilaterally, right precuneus, right medial occipital gyrus, right fusiform gyrus, and left hippocampus in comparison to chronic cannabis users without psychosis. Finally, in CIP patients, the results showed a negative correlation between a domain of the Brief Psychiatric Rating Scale (BPRS), BPRS-Activity, and selective GM volumes. Overall, the results suggest that cannabis-induced psychosis is characterized by selective brain reductions that are not present in NPCU. Therefore, neuroimaging studies may provide a potential ground for identifying putative biomarkers associated with the risk of developing psychosis in cannabis users.

Her-2 prognostic value in very early-stage breast cancer: a single-institution retrospective analysis.

To evaluate overall survival, distant metastases-free survival and local relapse-free survival rates in a subgroup of patients affected by breast cancer expressing Her-2/neu. Data of 195 women affected by very early-stage breast cancer (pT1a-b pN0) who underwent whole breast radiotherapy after conservative surgery with or without chemotherapy and/or hormone therapy between January 2000 and December 2006 were evaluated. Chi-square test was used to compare the distribution of variables (age, tumour histology, oestrogens and progesterone receptors, tumour grading and adjuvant chemotherapy) between Her-2-positive and Her-2-negative patients. Survival rates were analysed with Kaplan-Meier curves; impact of variables on poor outcome was evaluated with Cox regression method. Median follow-up time was 63.5 months (range 13.8-113.6). Her-2/neu-positive patients (32/16.4%), compared to Her-2/neu-negative patients (163/83.6%), were younger (P = 0.0001), were affected by ductal infiltrating carcinoma (P = 0.039), had negative oestrogens receptors (P = 0.0001) and were not treated with chemotherapy (P = 0.001). Her-2-positive patients had lower overall survival (P = 0.00001) and lower distant metastases-free survival (P = 0.00001) compared to Her-2-negative patients, but no difference in local relapse-free survival was found between the two groups (P = 0.28). After multivariate analysis, Her-2-positive status was a prognostic factor for overall survival (P = 0.00001) and for distant metastases-free survival (P = 0.0001), but not for local relapse-free survival (P = 0.97). Her-2-positive patients have lower overall survival and distant metastases-free survival when compared to Her-2 negative patients but similar local relapse-free survival rates. These patients could be treated with conservative surgery, if feasible, but should receive more aggressive and tailored systemic adjuvant therapies.

Comparative dosimetric and radiobiological assessment among a nonstandard RapidArc, standard RapidArc, classical intensity-modulated radiotherapy, and 3D brachytherapy for the treatment of the vaginal vault in patients affected by gynecologic cancer.

To evaluate a nonstandard RapidArc (RA) modality as alternative to high-dose-rate brachytherapy (HDR-BRT) or IMRT treatments of the vaginal vault in patients with gynecological cancer (GC). Nonstandard (with vaginal applicator) and standard (without vaginal applicator) RapidArc plans for 27 women with GC were developed to compare with HDR-BRT and IMRT. Dosimetric and radiobiological comparison were performed by means of dose-volume histogram and equivalent uniform dose (EUD) for planning target volume (PTV) and organs at risk (OARs). In addition, the integral dose and the overall treatment times were evaluated. RA, as well as IMRT, results in a high uniform dose on PTV compared with HDR-BRT. However, the average of EUD for HDR-BRT was significantly higher than those with RA and IMRT. With respect to the OARs, standard RA was equivalent of IMRT but inferior to HDR-BRT. Furthermore, nonstandard RA was comparable with IMRT for bladder and sigmoid and better than HDR-BRT for the rectum because of a significant reduction of d(2cc), d(1cc), and d(max) (p < 0.01). Integral doses were always higher than HDR-BRT, although the values were very low. Delivery times were about the same and more than double for HDR-BRT compared with IMRT and RA, respectively. In conclusion, the boost of dose on vaginal vault in patients affected by GC delivered by a nonstandard RA technique was a reasonable alternative to the conventional HDR-BRT because of a reduction of delivery time and rectal dose at substantial comparable doses for the bladder and sigmoid. However HDR-BRT provides better performance in terms of PTV coverage as evidenced by a greater EUD.

Interval between breast-conserving surgery and start of radiation therapy in early-stage breast cancer is not predictive of local recurrence: a single-institution experience.

BACKGROUND: The aim of this study was to evaluate if the interval between breast-conserving surgery and the start of radiotherapy has an effect on local relapse risk. MATERIALS AND METHODS: Between January 2000 and December 2006 a total of 387 patients with T1-2N0+ breast cancer were treated with breast-conserving surgery and radiotherapy, with and without hormone therapy and chemotherapy. Adjuvant radiotherapy was administered to a total dose of 60 to 66 Gy in 30 to 33 fractions. The time intervals between breast-conserving surgery and the start of radiotherapy were < 60, 61 to 120, 121 to 180 and > 180 days. The Kaplan-Meier method was used to calculate local relapse-free survival rates, and the Cox regression method was used to identify predictive factors of local relapse. Evaluated variables were age, tumor location, tumor histologic type, tumor size, surgical margin status, axillary node status, estrogen receptors, tumor grading, adjuvant therapy, adjuvant chemotherapy, radiation therapy, boost dose, and interval between breast-preserving surgery and start of radiation therapy. RESULTS: Five-year local relapse-free survival rates were 97.3% ± 1.5% for patients who did not receive chemotherapy and 94.5% ± 1.9% for patients who received chemotherapy (P = .71). There was no significant difference in local relapse among the 4 interval groups (P = .9). Multivariate Cox regression analysis showed that intervals between breast-conserving surgery and radiotherapy were not associated with higher local relapse risk. CONCLUSION: In our study a delay in administering radiotherapy after breast-conserving surgery was not associated with an increased risk of local relapse. Taking into account contrasting results of many published studies, a larger evaluation of this issue is warranted.