Multiparametric evaluation of preoperative MRI in early stage breast cancer: prognostic impact of peri-tumoral fat

Purpose. Obesity is associated with adverse outcomes in breast cancer patients. Fat-specific cytokines (adipokines) have been proposed as key drivers of breast cancer progression, invasion, and metastasis. We aimed at assessing correlations between peri-tumoral fat, quantified on magnetic resonance imaging (MRI) and pathologic factors potentially impacting therapy recommendations. Methods. We retrospectively reviewed records of 63 patients with early stage breast cancer who underwent preoperative MRI imaging using appropriately weighted series for breast and tumor contouring. Fat volumes were generated through voxel intensity filtering. The peri-tumoral region was defined as the intersection of a 1-cm spherical extension around the tumor and the breast contour. Peri-tumoral fat was defined as the fraction of a fat content in this volume. Surgical pathology records were used to extract clinical data. Statistical analyses were conducted using Pearson and Spearman correlation coefficients. Results. Among reviewed patients, 45 had T1 tumors (1.22 ± 0.85 cm diameter) and 18 had T2 tumors (2.08 ± 1.06 cm). Axillary lymph nodes were dissected in 31 and positive in 17 patients analyzed. Peri-tumoral fat ratio ranged between 25 and 99 %. Peri-tumoral fat ratio significantly correlated with the nodal-positive ratio of positive axillary lymph nodes (r = 0.532). Peri-tumoral fat ratio demonstrated optimally prominent correlation among obese patients upon body mass index categorical stratification. Conclusions. In women with early stage breast cancer, peri-tumoral fat correlates positively with the ratio of pathologically involved axillary nodes. This work highlights a novel method for quantitating peri-tumoral fat content. Preoperative breast MRI may be utilized to predict extent of axillary disease (AU)

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Multiparametric evaluation of preoperative MRI in early stage breast cancer: prognostic impact of peri-tumoral fat.

PURPOSE: Obesity is associated with adverse outcomes in breast cancer patients. Fat-specific cytokines (adipokines) have been proposed as key drivers of breast cancer progression, invasion, and metastasis. We aimed at assessing correlations between peri-tumoral fat, quantified on magnetic resonance imaging (MRI) and pathologic factors potentially impacting therapy recommendations. METHODS: We retrospectively reviewed records of 63 patients with early stage breast cancer who underwent preoperative MRI imaging using appropriately weighted series for breast and tumor contouring. Fat volumes were generated through voxel intensity filtering. The peri-tumoral region was defined as the intersection of a 1-cm spherical extension around the tumor and the breast contour. Peri-tumoral fat was defined as the fraction of a fat content in this volume. Surgical pathology records were used to extract clinical data. Statistical analyses were conducted using Pearson and Spearman correlation coefficients. RESULTS: Among reviewed patients, 45 had T1 tumors (1.22 ± 0.85 cm diameter) and 18 had T2 tumors (2.08 ± 1.06 cm). Axillary lymph nodes were dissected in 31 and positive in 17 patients analyzed. Peri-tumoral fat ratio ranged between 25 and 99 %. Peri-tumoral fat ratio significantly correlated with the nodal-positive ratio of positive axillary lymph nodes (r = 0.532). Peri-tumoral fat ratio demonstrated optimally prominent correlation among obese patients upon body mass index categorical stratification. CONCLUSIONS: In women with early stage breast cancer, peri-tumoral fat correlates positively with the ratio of pathologically involved axillary nodes. This work highlights a novel method for quantitating peri-tumoral fat content. Preoperative breast MRI may be utilized to predict extent of axillary disease.

Racial disparity in estrogen receptor positive breast cancer patients receiving trimodality therapy.

INTRODUCTION: We assessed racial differences in progression-free survival (PFS) and overall survival (OS) in relation to subtype in uniformly treated stage II-III breast cancer patients. METHODS: We reviewed records of 582 patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 and evaluated the effect of demographic, tumor, and treatment characteristics on PFS and OS. RESULTS: Median follow up was 44.7 months. 24% of patients were black and 76% white. All had mastectomy and PMRT; 98% had chemotherapy; Estrogen receptor (ER)+ patients received endocrine therapy. Black patients were more likely to have ER- (56% vs. 38%, p=0.0001), progesterone receptor (PR)- (69% vs. 54%, p = 0.002), and triple negative (TN) (46% vs. 24%, p < 0.0001) tumors. Overall, black patients had worse PFS (60.6% vs. 78.3%, p = 0.001) and OS (72.8% vs. 87.7%, p < 0.0001). There was no racial difference in PFS (p = 0.229 and 0.273 respectively) or OS (p = 0.113 and 0.097 respectively) among ER- or TN. Among ER+, black patients had worse PFS (55% vs. 81%, p < 0.001) and OS (73% vs. 91%, p < 0.0001). The difference in PFS was seen in the ER+/PR+/HER2- subgroup (p = 0.002) but not ER+/PR-/HER2- (p = 0.129), and in the post-menopausal ER+/HER2- subgroup (p = 0.004) but not pre/peri-menopausal ER+/HER2- (p = 0.150). CONCLUSIONS: Black women had worse survival outcomes in this cohort. This disparity was driven by (1) a higher proportion of ER- and TN tumors in black women and (2) worse outcome of similarly treated black women with ER+ breast cancer. The underlying causes of racial disparity within hormone receptor categories must be further examined.

Risk of locoregional recurrence by receptor status in breast cancer patients receiving modern systemic therapy and post-mastectomy radiation.

We assessed differences in locoregional outcome based on receptor status combinations in a cohort of stage II-III breast cancer patients treated with modern trimodality therapy. Medical records of 582 consecutively treated patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 were reviewed. Rate of local regional recurrence (LRR) was estimated by the method of cumulative incidence allowing for competing risks. The effect of prognostic factors was examined by Gray's test and by Fine and Gray's modeling approach. Median follow-up was 44.7 months. Five-year progression-free survival (PFS) was 73.9% and overall survival (OS) was 84%. The cumulative 5-year incidence of LRR as first site of failure was 6.2% (95% CI 4.2-8.7). Five-year cumulative incidence of LRR was 8.6 versus 4.4% for estrogen receptor (ER) negative versus ER positive (P = 0.017), 8.5 versus 3.4% for progesterone receptor (PR) negative versus PR positive (P = 0.011), and 1.7 versus 7.5% for HER2 positive (86% received trastuzamab) versus HER2 negative (P = 0.032). Five-year cumulative incidence of LRR was 11.8% for the triple negative subtype and 3.9% for other receptor combinations (P < 0.001). Among patients whose disease is ER positive, 5-year LRR rate was 7.8 versus 3.4% for PR negative versus PR positive (P = 0.130). The prognostic value of the triple negative and HER2 negative subtypes was maintained on multivariate analysis. In the era of HER-2 targeted therapy, tumors that are HER-2 over expressing and are treated with trastuzumab have a very low rate of LRR. ER negative, PR negative, and triple negative status are associated with increased risk of LRR.

A novel applicator for low-dose-rate brachytherapy of gynecological cancers.

The standard low-dose-rate (LDR) delivery system utilized in the definitive management of patients with cervical carcinoma involves an intrauterine tandem and a pair of vaginal colpostats (ovoids). This well-known application system may deliver inadequate dosage if the tumor extends to the lower vaginal mucosa. During the gauze packing of the ovoids, either operator error or narrowing of the vaginal apex can result in mal-alignment of the colpostats and subsequent inadequate dosing to the ecto-cervix. A novel vaginal cylinder has been designed to address these concerns. Beginning January 1, 2001, patients with cancer of the cervix, endometrium, or vagina requiring LDR brachytherapy have been enrolled into an institutionally sanctioned clinical trial. As of May 31, 2001, a total of 11 patients have been entered but only 10 were successfully implanted with the test device. Patient follow-up has ranged from 0.81 years to 1.2 years (median: 0.96 years). Using our study applicator, all patients received within 10% of the preimplant prescribed dose to tumor. Also, no one had cumulative dosage that exceeded 10% of the maximum allowed dose to the critical normal tissues. Thus far, all study patients have had no clinical evidence of persistence/recurrence of disease or complications from treatment. The preliminary results presented herein clearly demonstrate the feasibility of this novel LDR vaginal cylinder in the treatment of a variety of clinical situations involving gynecological cancers. Our institutional trial is continuing.

Aperture modulated arc therapy.

We show that it is possible to translate an intensity modulated radiation therapy (IMRT) treatment plan and deliver it as a single arc. This technique is referred to in this paper as aperture modulation arc therapy (AMAT). During this arc, the MLC leaves do not conform to the projection of the target PTV and the machine output of the accelerator has a constant value. Dose was calculated using the CORVUS 4.0 IMRT system, which uses a pencil beam dose algorithm, and treatments were delivered using a Varian 2100C/D Clinac. Results are presented for a head and neck and a prostate case, showing the equivalence of the IMRT and the translated AMAT delivery. For a prostate AMAT delivery, coronal plane film dose for the IMRT and AMAT deliveries agreed within 7.19 +/- 6.62%. For a meningioma the coronal plane dose distributions were similar to a value of 4.6 +/- 6.62%. Dose to the isocentre was measured as being within 2% of the planned value in both cases.

MR appearance of paraganglioma of the cauda equina. Case reports.

PURPOSE: To investigate the value of MR imaging for preoperative diagnosis of paraganglioma of the cauda equina. MATERIAL AND METHODS: A retrospective review of 2 cases of paraganglioma of the cauda equina examined with MR imaging was undertaken. Features assessed included the homogeneity of the lesions, presence or absence of serpiginous flow void and thin hypointense margins. RESULTS: In case 1, the tumor was hyperintense on the postcontrast examination and serpiginous flow void suggested vessels in the upper pole of the tumor. In case 2, the tumor was encapsulated by a thin hypointense margin on both T1- and T2-weighted images, which suggested hemosiderin. CONCLUSION: The MR appearance may be of great value in the preoperative diagnosis of paraganglioma of the cauda equina.

The quantitative and qualitative defect of CD4+ CD45RO+ memory-type T cells are involved in the abnormality of TH1 immunity in atopic dermatitis patients.

Peripheral blood mononuclear cells (PBMCs) obtained from atopic dermatitis (AD) patients produced low levels of IFN-gamma in response to Dermatophagoides farinae antigen (Der f Ag) plus IL-2 or OKT3 MoAb in contrast with PBMCs obtained from healthy donors. The reduced IFN-gamma production in AD patients' T cells appeared to be derived from the defect of CD4+ T cells but not CD8+ T cells. Indeed, from the cytoplasmic staining analysis of cytokines, it was demonstrated that the frequency of IFN-gamma producing CD4+ T cells (TH1 cells) in AD patients was markedly lower than that of healthy donors. From the phenotypic analysis using flow cytometry, it was also found that the number of CD4+ CD45RO+ memory type T cells was significantly reduced in AD patients compared with that of healthy donors. In addition to quantitative defect of memory type CD4+ T cells, functional defect of CD4+ CD45RO+ memory type T cells was also demonstrated in AD patients. Enriched CD4+ CD45RO+ T cells obtained from AD patients, who exhibited greatly reduced delayed-type hypersensitivity (DTH) response in tuberculin test, showed no significant TH1 immunity in terms of IFN-gamma production by stimulation with OKT3 MoAb or purified protein derivative (PPD). Thus, the immunological abnormality of TH1 immunity in AD patients appeared to be induced in concomitant with both the quantitative and qualitative defect of memory type CD4+ T cells.