Biomedical subjects

Kevin Hughes

Publications and source records attributed to Kevin Hughes.

9 recordsLinked to original sources

PubMed2006

Accelerated partial-breast irradiation using proton beams: initial clinical experience.

PURPOSE: We present our initial clinical experience with proton, three-dimensional, conformal, external beam, partial-breast irradiation (3D-CPBI). METHODS AND MATERIALS: Twenty patients with Stage I breast cancer were treated with proton 3D-CPBI in a Phase I/II clinical trial. Patients were followed at 3 to 4 weeks, 6 to 8 weeks, 6 months, and every 6 months thereafter for recurrent disease, cosmetic outcome, toxicity, and patient satisfaction. RESULTS: With a median follow-up of 12 months (range, 8-22 months), no recurrent disease has been detected. Global breast cosmesis was judged by physicians to be good or excellent in 89% and 100% of cases at 6 months and 12 months, respectively. Patients rated global breast cosmesis as good or excellent in 100% of cases at both 6 and 12 months. Proton 3D-CPBI produced significant acute skin toxicity with moderate to severe skin color changes in 79% of patients at 3 to 4 weeks and moderate to severe moist desquamation in 22% of patients at 6 to 8 weeks. Telangiectasia was noted in 3 patients. Three patients reported rib tenderness in the treated area, and one rib fracture was documented. At last follow-up, 95% of patients reported total satisfaction with proton 3D-CPBI. CONCLUSIONS: Based on our study results, proton 3D-CPBI offers good-to-excellent cosmetic outcomes in 89% to 100% of patients at 6-month and 12-month follow-up and nearly universal patient satisfaction. However, proton 3D-CPBI, as used in this study, does result in significant acute skin toxicity and may potentially be associated with late skin (telangiectasia) and rib toxicity. Because of the dosimetric advantages of proton 3D-CPBI, technique modifications are being explored to improve acute skin tolerance.

Aged↗

PubMed2006

Effects of Trichinella spiralis infection on intestinal pathology in mice lacking interleukin-4 (IL-4) or intestinal trefoil factor (ITF/TFF3).

The nematode Trichinella spiralis induces pathological changes in the small intestine of the host, which are known to be controlled by immune and inflammatory mediators. The detail of this control has still to be completely understood. Mice deficient in interleukin 4 (IL-4) or in intestinal trefoil factor/trefoil family factor 3 (ITF/TFF3) were infected with T. spiralis and the resultant changes in the intestinal mucosa followed by quantifying numbers of mucosal mast cells, goblet cells, Paneth cells and by monitoring structural changes in villus length and crypt depth. Mice lacking IL-4 were unable to mount a normal protective response to infection, such that worm survival was increased. These mice failed to mount a mucosal mast cell response, but did make goblet cell and Paneth cell responses comparable to normal controls. Mice lacking ITF/TFF3 similarly made normal levels of goblet cell and Paneth cell responses. They also underwent profound changes in mucosal architecture, with marked villus atrophy and crypt hyperplasia. These results are discussed in relation to known patterns of T cell and cytokine control of protective immunity to T. spiralis. They suggest that increased numbers of goblet cell and Paneth cell are not, by themselves, required for protective immunity. ITF/TFF3 appears not to influence cellular responses and does not alter parasite-induced pathological changes in the small intestine.

Animals↗

PubMed2006

Initial dosimetric experience using simple three-dimensional conformal external-beam accelerated partial-breast irradiation.

PURPOSE: Several accelerated partial-breast irradiation (APBI) techniques are being investigated in patients with early-stage breast cancer. We present our initial experience using three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: Sixty-one patients with tumors of 2 cm or less and negative axillary nodes were treated with 3D-CRT accelerated partial-breast irradiation (APBI) between August 2003 and March 2005. The prescribed radiation dose was 32 Gy in 4-Gy fractions given twice daily. Efforts were made to minimize the number of beams required to achieve adequate planning target volume (PTV) coverage. RESULTS: A combination of photons and electrons was used in 85% of patients. A three-field technique that consisted of opposed, conformal tangential photons and enface electrons was employed in 43 patients (70%). Nine patients (15%) were treated with a four-field arrangement, which consisted of three photon fields and enface electrons. Mean PTV volumes that received 100%, 95%, and 90% of the prescribed dose were 93% +/- 7%, 97% +/- 4%, and 98% +/- 2%, respectively. Dose inhomogeneity exceeded 10% in only 7 patients (11%). Mean doses to the ipsilateral lung and heart were 1.8 Gy and 0.8 Gy, respectively. CONCLUSIONS: Simple 3D-CRT techniques of APBI can achieve appropriate PTV coverage while offering significant normal-tissue sparing. Therefore, this noninvasive approach may increase the availability of APBI to patients with early-stage breast cancer.

Adult↗

PubMed2005

Radiological reasoning: male breast mass with calcifications.

OBJECTIVE: We encountered a mammographically calcified breast mass in a 30-year-old man. It was initially thought to be comedo-type ductal carcinoma in situ because of the dense calcifications, but sonography and MRI suggested a highly vascular lesion. The final pathologic diagnosis was hemangioma. CONCLUSION: Vascular tumors of the breast occur infrequently and are even more rare in males. The clinical and radiologic diagnosis of breast hemangioma is often difficult, but different imaging techniques, when used together, can provide important information for differential diagnosis and management. A biopsy is required.

Adult↗

PubMed2004

The age at which women begin mammographic screening.

BACKGROUND: The American Cancer Society recommends yearly mammographic screening for women starting at the age of 40 years. The authors examined the age at which women began screening at a large tertiary care center. METHODS: Utilization of mammography was assessed in a population of 72,417 women who received 254,818 screening mammograms at the Massachusetts General Hospital Avon Comprehensive Breast Center from January 1, 1985 to February 19, 2002, of which 940 received their first mammogram between January 16, 2000 and February 19, 2002. RESULTS: The median age at first mammogram for women in the population as a whole was 40.4 years. Sixty percent of women had their first mammogram by the end of their 40th year, and almost 90% had begun screening by age 50 years. However, these reassuring findings were not seen in several specific subpopulations of women. Black women began screening at a median age of 41.0 years, 0.7 years later than white women. Hispanic women began screening at a median age of 41.4 years, 1.1 years later than non-Hispanic women. Obese women began screening at a median age of 41.2 years, 1.6 years later than thin women. Women without a primary care physician began screening at a median age of 42.1 years, 1.8 years later than women with a primary care physician. Women without private health insurance began screening at a median age of 46.6 years, 6.3 years later than women with private health coverage. Women who did not speak English began screening at a median age of 49.3 years, 9.0 years later than women for whom English was the primary language. Women who both lacked private health insurance and spoke a language other than English began screening at a median age of 55.3 years, 15.2 years later than women without these characteristics. CONCLUSIONS: The analysis presented in the current study provided one of the most detailed descriptions of the age at screening initiation to be performed to date. Most women in the study population began screening by the end of their 40th year. This contrasted with the widespread failure of women to return promptly for subsequent annual examinations. However, specific subpopulations of women were at risk for not beginning screening on time, including women without private insurance, women without a primary care physician, and women who did not speak English. These findings suggest that there is little to be gained from populationwide efforts to encourage entry into the screening process, and that public health efforts should be focused on those subpopulations of women at highest risk for not using screening. These results also indicate that public health efforts to encourage women to start screening may be less critical than interventions to improve prompt return once they have entered the screening system.

Adult↗

PubMed2003

The effect of tumor size and lymph node status on breast carcinoma lethality.

BACKGROUND: It has long been known that both tumor size and the presence of malignant disease in the regional lymph nodes are indicators of outcome for patients with invasive breast carcinoma; however, the way in which these two characteristics could be integrated into an overall assessment of prognosis has not been obvious. METHODS: Kaplan-Meier survival estimates (15 years) according to tumor size and lymph node status were obtained for women with invasive breast carcinoma who were observed at the University of Southern California/Van Nuys Breast Center (Van Nuys, California) or at Massachusetts General Hospital (Boston, Massachusetts). RESULTS: To isolate the individual contributions to death made by tumor size and lymph node status, data were sorted according to both of these variables. For women with tumors of equivalent size, lethality increased with increasing number of positive lymph nodes, such that there was an extra approximately 6% chance of death associated with each positive lymph node. For women with equivalent lymph node status, tumor size was associated with increased lethality, such that each millimeter of tumor diameter was associated with an additional approximately 1% chance of death. The overall lethality was equal to the sum of the contribution from lymph node status and the contribution from tumor size, and this finding led to the creation of a new technique (the Size+Nodes method) for predicting outcome. CONCLUSIONS: The Size+Nodes method was shown to be capable of accurately estimating the risk of death due to invasive breast carcinoma from information on the size of the primary tumor and the number of positive lymph nodes. In addition, this method was used to stratify women into groups according to breast carcinoma lethality. In contrast, classification of women according to lymph node positivity, T status, or disease stage created groups with wide and overlapping levels of lethality.

Adult↗

PubMed2003

Gauging the impact of breast carcinoma screening in terms of tumor size and death rate.

BACKGROUND: While the question of whether the trials of breast cancer screening have resulted in a reduction in breast cancer death has been the subject of much scrutiny, there has been less attention to the reduction in tumor size achieved by screening. METHODS: Size data for invasive breast tumors were assembled from a variety of sources. The health consequences that can be expected from finding tumors of various sizes were determined using a recently developed mathematical method for relating tumor size to death rate. RESULTS: First, in both the Swedish two-country trial and at the MGH Breast Imaging Division, the sizes of the invasive breast cancers in the screening population (those masses seen at screening together with those found as palpable masses after screening examinations) were sufficiently smaller than the cancers found among women who had not used screening to have lead to considerable reductions in death. Second, the lack of reduction in death rates detected in both Canadian National Breast Screening Studies could be ascribed to the small reductions in tumor size achieved in these studies. Third, radiographic density had a small effect, whereas age had a negligible effect, on the capacity of mammographic screening to find breast carcinomas at smaller, and thus less lethal, sizes. CONCLUSIONS: Prompt attendance at annual mammographic screening offers the potential to reduce tumor size and, presumably, breast carcinoma death, in women of all ages and density groups.

Adult↗

PubMed2003

A simple model of breast carcinoma growth may provide explanations for observations of apparently complex phenomena.

BACKGROUND: There has been great debate regarding the importance of ductal carcinoma in situ (DCIS) in the breast. Autopsy results that demonstrate a much greater number of these lesions compared with the number of invasive carcinomas, and the numbers of deaths from breast carcinoma each year have been cited as evidence that DCIS rarely leads to invasion and death. These analyses have overlooked the fact that, to sustain a rate of detection each year, there would have to be a reservoir of undetected breast carcinomas growing in the population. The authors developed a simple model that makes this clear. In addition, complex phenomena have been suggested to explain why invasive breast disease may grow more rapidly among very young women and more slowly among the very old. A simple model provides some insight that may simplify the explanation of these observations. METHODS: The simple model of breast carcinoma growth assumes that there are three types of breast carcinoma that begin each year in a cohort of women. It assumes that all breast carcinomas begin as DCIS and take 9 years to go from a single cell to an invasive lesion for the slowest growing lesions, 6 years for intermediate growing DCIS lesions, and 3 years for fast-growing DCIS lesions. Furthermore, once an invasive clone forms, the model assumes that it will double in 60 days for fast-growing lesions, 120 days for intermediate growing lesions, and 180 days for slow-growing lesions. Three new tumors begin to grow in each successive year (one of each type). The model uses simple vectors that are defined by the size of the tumors and the time since tumor initiation, and it assumes that all tumors are detected when they reach 2 cm in greatest dimension. The model can be used to show graphically how many undetected tumors (DCIS as well as invasive carcinomas) there may be in the population to sustain the detection of three invasive tumors each year. RESULTS: Using the assumptions described above, the model showed that, by the time the first slow-growing breast carcinoma reaches 2 cm in greatest dimension, there will be 29 other slow-growing tumors that have not reached that size (9 DCIS and 20 smaller invasive carcinomas), 19 moderately growing tumors (6 DCIS and 13 smaller invasive carcinomas), and 9 fast-growing tumors (3 DCIS and 6 smaller invasive carcinomas). This means that, for every three breast tumors that reach 2 cm, the model predicted that there would be another 57 tumors (39 smaller invasive carcinomas and 18 DCIS) that would be undetected "below the surface". The model showed clearly that faster growing tumors would be expected to predominate among the youngest women, because they are the first to "reach the surface"; and, if the number of newly initiated tumors decreases with age, then there will be more of the slowest growing tumors that are left to reach the surface among the oldest women in the population. CONCLUSIONS: Even if the authors' assumptions are incorrect, their model made it clear that, to diagnose several breast carcinomas per 1000 women each year means that there have to be many more undetected carcinomas in the population to sustain the rate of detection. Although the model did not prove that DCIS may become potentially invasive and lethal, it did demonstrate that, even if all of these in situ lesions become invasive and lethal, many more DCIS lesions would have to be expected in the population than the number of invasive carcinomas detected each year and the number of deaths from breast carcinoma each year. Furthermore, the model provided a simple, purely mechanical illustration that may explain the preponderance of faster growing breast carcinomas among very young women and the preponderance of slower growing tumors among elderly women.

Age Factors↗

PubMed2002

Predicting the survival of patients with breast carcinoma using tumor size.

BACKGROUND: Tumor size has long been recognized as the strongest predictor of the outcome of patients with invasive breast carcinoma, although it has not been settled whether the correlation between tumor size and the chance of death is independent of the method of detection, nor is it clear how tumor size at the time of treatment may be translated into a specific expectation of survival. In this report, the authors provide such a method. METHODS: A Kaplan-Meier survival analysis was carried out for a population of 1352 women with invasive breast carcinoma who were treated at the Van Nuys Breast Center between 1966 and 1990, and the data were analyzed together with survival data published by others. RESULTS: The authors found that the survival of patients with invasive breast carcinoma was a direct function of tumor size, independent of the method of detection. The results showed that the correlation between tumor size and survival was well fit by a simple equation, with which survival predictions could be made from information on tumor size. For example, a comparison of three large populations studied over the last 5 decades revealed a marked improvement (approximately 35% absolute) in the survival of patients with invasive breast carcinoma diagnosed on clinical grounds that could be ascribed to a reduction in tumor size. However, the capacity of screening mammography to find smaller tumors remains the best way reduce breast carcinoma deaths, with the potential for adding an additional approximately 20% absolute reduction in breast carcinoma deaths. The mathematic correlation between tumor size and survival is consistent with a biologic mechanism in which lethal distant metastasis occurs by discrete events of spread such that, for every invasive breast carcinoma cell in the primary tumor at the time of surgery, there is approximately a 1-in-1-billion chance that a lethal distant metastasis has formed. CONCLUSIONS: The correlation between tumor size and lethality is well captured by a simple equation that is consistent with breast carcinoma death as the result of discrete events of cellular spread occurring with small but definable probabilities.

Breast Neoplasms↗