Prone breast intensity modulated radiation therapy: 5-year results.

PURPOSE: To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. METHODS AND MATERIALS: Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. RESULTS: Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm(3), mean 19.65 cm(3). In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm(3), mean 1.59 cm(3). There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. CONCLUSIONS: Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and fractionation approach to standard 6-week radiation therapy with a sequential boost.

Anti-Mullerian hormone: determination of ovarian reserve in early breast cancer patients.

Breast cancer is the most common invasive cancer in women of reproductive age. In young women, chemotherapy may induce amenorrhea: it is still uncertain how to assess menopausal status in these patients despite the importance of its definition for choosing appropriate endocrine treatment. In the development of sensitive biomarkers for fertility and ovarian reserve, anti-Müllerian hormone (AMH) is considered a promising marker of ovarian reserve. The clearest data regarding a clinical use of AMH are related to the measurement of the ovarian pool in women who undergo IVF: the available data, also in breast cancer patients, seem to suggest that AMH measurement, before gonadotropin administration, can be a useful marker for the prediction of women at risk for poor-response or no response to ovarian stimulation. The utility of AMH as a potential marker of chemotherapy-induced ovarian follicular depletion and an early plasma marker of chemotherapy-induced gonadal damage has been evaluated both in young women after treatment for cancer in childhood and in young survivors of hematological malignancies and solid tumors. Several studies have demonstrated a potential utility of AMH, inhibin, or follicle-stimulating factor as biomarkers predicting infertility risk in breast cancer patients, but the studies conducted so far are not conclusive. Further studies are needed in order to define the regimen-specific action of chemotherapy on AMH levels, the percentage of post-treatment recovery of plasma levels of the hormone, and the relationship between menopausal status and AMH.

Primary therapy in breast cancer: what have we learned from landmark trials?

Primary anticancer therapy is currently accepted as a therapeutic option for patients with early-stage breast cancer. Its objectives are to increase the chance of achieving a conservative surgery and, similar to adjuvant chemotherapy, to reduce the risk of distant recurrence. The prognostic significance of obtaining a pathological complete response has been evaluated in several randomized clinical trials and meta-analyses. Growing evidence suggests that pathological complete response may act as a valid predictor of overall survival. Of note, a significant association between pathological complete response and outcome has especially been observed in patients with HER2-positive and triple-negative (hormonal receptors negative and HER2-negative) breast cancer. This review focuses on recent trials of neoadjuvant treatment with specific attention to HER2-negative disease.

Making capecitabine targeted therapy for breast cancer: which is the role of thymidine phosphorylase?

Thymidine phosphorylase (TP) expression has been found to be elevated in various solid tumors where it is likely involved in mechanisms that regulate cell proliferation, apoptosis, and angiogenesis. Based on these properties, it is tempting to hypothesize a potential prognostic role of TP, suggesting that a high TP expression could predict a poor outcome. On the other hand, TP expression has been studied for its role in predicting benefit from treatment with fluoropyrimidine-containing chemotherapy. Several studies have been conducted on breast cancer. The current evidence on the value of TP is not mature enough to allow its translation into clinical practice. However, several findings support the potentially predictive role of TP. In this light, TP appears to be a promising marker that can give helpful information to predict the benefit from capecitabine-based chemotherapy in patients with breast cancer.

Dose to craniofacial region through portal imaging of pediatric brain tumors.

The purpose of this study was to determine dose to the planning target volume (PTV) and organs at risk (OARs) from portal imaging (PI) of the craniofacial region in pediatric brain tumor patients treated with intensity-modulated radiation therapy (IMRT). Twenty pediatric brain tumor patients were retrospectively studied. Each received portal imaging of treatment fields and orthogonal setup fields in the craniofacial region. The number of PI and monitor units used for PI were documented for each patient. Dose distributions and dose-volume histograms were generated to quantify the maximum, minimum, and mean dose to the PTV, and the mean dose to OARs through PI acquisition. The doses resulting from PI are reported as percentage of prescribed dose. The average maximum, minimum, and mean doses to PTV from PI were 2.9 ± 0.7%, 2.2 ± 1.0%, and 2.5 ± 0.7%, respectively. The mean dose to the OARs from PI were brainstem 2.8 ± 1.1%, optic nerves/chiasm 2.6 ± 0.9%, cochlea 2.6 ± 0.9%, hypothalamus/pituitary 2.4 ± 0.6%, temporal lobes 2.3 ± 0.6%, thyroid 1.6 ± 0.8%, and eyes 2.6 ± 0.9%. The mean number of portal images and the mean number of PI monitor units per patient were 58.8 and 173.3, respectively. The dose from PI while treating pediatric brain tumors using IMRT is significant (2%-3% of the prescribed dose). This may result in exceeding the tolerance limit of many critical structures and lead to unwanted late complications and secondary malignancies. Dose contributions from PI should be considered in the final documented dose. Attempts must be made in PI practices to lower the imaging dose when feasible.

Diminished visibility of cerebral venous vasculature in multiple sclerosis by susceptibility-weighted imaging at 3.0 Tesla.

Multiple sclerosis (MS) is a disease of the central nervous system characterized by widespread demyelination, axonal loss and gliosis, and neurodegeneration; susceptibility-weighted imaging (SWI), through the use of phase information to enhance local susceptibility or T2* contrast, is a relatively new and simple MRI application that can directly image cerebral veins by exploiting venous blood oxygenation. Here, we use high-field SWI at 3.0 Tesla to image 15 patients with clinically definite relapsing-remitting MS and to assess cerebral venous oxygen level changes. We demonstrate significantly reduced visibility of periventricular white matter venous vasculature in patients as compared to control subjects, supporting the concept of a widespread hypometabolic MS disease process. SWI may afford a noninvasive and relatively simple method to assess venous oxygen saturation so as to closely monitor disease severity, progression, and response to therapy.

Selective side-chain modification of cysteine and arginine residues blocks pathogenic activity of HIV-1-Tat functional peptides.

Extracellular Tat protein of HIV-1 activates virus replication in HIV-infected cells and induces a variety of host factors in the uninfected cells, some of which play a critical role in the progression of HIV infection. The cysteine-rich and arginine-rich basic domains represent key components of the HIV-Tat protein for pathogenic effects of the full-length Tat protein and, therefore, could be ideal candidates for the development of a therapeutic AIDS vaccine. The present study describes selective modifications of the side-chain functional groups of cysteine and arginine amino acids of these HIV-Tat peptides to minimize the pathogenic effects of these peptides while maintaining natural peptide linkages. Modification of cysteine by introducing either a methyl or t-butyl group in the free sulfhydryl group and replacing the guanidine group with a urea linkage in the side chain of arginine in the cysteine-rich and arginine-rich Tat peptide sequences completely blocked the ability of these peptides to induce HIV replication, chemokine receptor CCR-5 expression, and NF-kappaB activity in monocytes. Such modifications also inhibited angiogenesis and migration of Kaposi's sarcoma cells normally induced by Tat peptides. Such chemical modifications of the cysteine-rich and arginine-rich peptides did not affect their reactivity with antibodies against the full-length Tat protein. With an estimated 40 million HIV-positive individuals worldwide and approximately 4 million new infections emerging every year, a synthetic subunit HIV-Tat vaccine comprised of functionally inactive Tat domains could provide a safe, effective, and economical therapeutic vaccine to reduce the progression of HIV disease.