Biomedical subjects
Publications and source records attributed to Tony Y Eng.
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BACKGROUND: Treatment of choroidal melanoma with radiation often involves placement of customized brachytherapy eye-plaques. However, the dosimetric properties inherent in source-based radiotherapy preclude facile dose optimization to critical ocular structures. Consequently, we have constructed a novel system for utilizing small beam low-energy radiation delivery, the Beamlet Low-kVp X-ray, or "BLOKX" system. This technique relies on an isocentric rotational approach to deliver dose to target volumes within the eye, while potentially sparing normal structures. METHODS: Monte Carlo N-Particle (MCNP) transport code version 5.0(14) was used to simulate photon interaction with normal and tumor tissues within modeled right eye phantoms. Five modeled dome-shaped tumors with a diameter and apical height of 8 mm and 6 mm, respectively, were simulated distinct positions with respect to the macula iteratively. A single fixed 9 x 9 mm2 beamlet, and a comparison COMS protocol plaque containing eight I-125 seeds (apparent activity of 8 mCi) placed on the scleral surface of the eye adjacent to the tumor, were utilized to determine dosimetric parameters at tumor and adjacent tissues. After MCNP simulation, comparison of dose distribution at each of the 5 tumor positions for each modality (BLOKX vs. eye-plaque) was performed. RESULTS: Tumor-base doses ranged from 87.1-102.8 Gy for the BLOKX procedure, and from 335.3-338.6 Gy for the eye-plaque procedure. A reduction of dose of at least 69% to tumor base was noted when using the BLOKX. The BLOKX technique showed a significant reduction of dose, 89.8%, to the macula compared to the episcleral plaque. A minimum 71.0 % decrease in dose to the optic nerve occurred when the BLOKX was used. CONCLUSION: The BLOKX technique allows more favorable dose distribution in comparison to standard COMS brachytherapy, as simulated using a Monte Carlo iterative mathematical modeling. Future series to determine clinical utility of such an approach are warranted.
Although adequate prospective data are lacking, radiation therapy seems to be effective for many benign diseases and remains one of the treatment modalities in the armamentarium of medical professionals. Just as medication has potential adverse effects, and surgery has attendant morbidity, irradiation sometimes can be associated with acute and chronic sequelae. In selecting the mode of treatment, most radiation oncologists consider the particular problem to be addressed and the goal of therapy in the individual patient. It is the careful and judicial use of any therapy that identifies the professional. With an understanding of the current clinical data, treatment techniques, cost, and potential detriment, the goal is to provide long-term control of the disease while minimizing unnecessary treatment and potential risks of side effects. The art lies in balancing benefits against risks.
Recent studies have documented changes in adhesion molecule expression and function after exposure to ionizing radiation. Adhesion molecules mediate cell-cell and cell-matrix interactions and are essential for a variety of physiological and pathological processes including maintenance of normal tissue integrity as well as tumor development and progression. Consequently, modulation of adhesion molecules by radiation may have a role in radiation-induced tumor control and normal tissue damage by interfering with cell signaling, radioresistance, metastasis, angiogenesis, carcinogenesis, immune response, inflammation and fibrosis. In addition, the interactions of radiation with adhesion molecules could have a major impact in developing new strategies to increase the efficacy of radiation therapy. Remarkable progress has been made in recent years to design targeted drug delivery to radiation-up-regulated adhesion molecules. Furthermore, the inhibition of adhesion, migration, invasion and angiogenesis by blocking adhesion receptors may represent a new therapeutic approach to improve tumor control and decrease radiation toxicity. This review is focused on current data concerning the mechanistic interactions of radiation with adhesion molecules and the possible clinical-pathological implications in radiotherapy.
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Technologic advances in radiation treatment planning and delivery have generated popular interest in the different radiation therapy techniques used in treating patients with localized prostate cancer. Throughout the past decade, high-energy (> 4 MV) linear accelerators have largely replaced Cobalt machines in external beam radiation therapy (EBRT) delivery. Conventional EBRT has been used to treat prostate cancer successfully since the 1950s. By switching to computed tomography-based planning, three-dimensional conformal radiation therapy provides better relative conformality of dose than does conventional EBRT. Intensity-modulated radiation therapy (IMRT) has further refined dose conformality by spreading the low-dose region to a larger volume. However, the potential long-term risks of larger volumes of normal tissues receiving low doses of radiation in IMRT are unknown. Particle-beam radiation therapy offers unique dose distributions and characteristics with higher relative biologic effect and linear energy transfer. Transperineal prostate brachytherapy offers the shortest treatment time with equivalent efficacy without significant risk of radiation exposure. The addition of hormonal therapy to radiation therapy has been shown to improve the outcome of radiation therapy.
Thymic tumors including thymomas, thymic carcinomas, and thymic carcinoid tumors, are relatively infrequent. These tumors with a wide spectrum of histological and biological features may exhibit an indolent clinical course (thymomas) or manifest an aggressive behavior (thymic carcinoma) with a high risk of relapse and metastasis. Successful management of these tumors depends on accurate diagnosis, thorough staging, proper assessment of patient health status, and selection of treatment modality. Surgery remains the mainstay of therapy whereas radiation therapy plays an important role in subtotally resected or unresectable cases. The risk of side effects and late sequelae is generally low when proper radiation technique is employed. This review examines the current role of radiation therapy in the management of these tumors.
Thymic carcinoma is a rare neoplasm with distinct clinical and pathological characteristics. The prognosis is often poor with an aggressive course that belies its numerical rarity. Potentially prognostic factors for survival include histopathologic grade, clinical stage, and resectability of the tumor. Five-year survival rates for all patients are approximately 30-50%, with a significant survival time differential between low-grade and high-grade neoplasms. Owing to the paucity of cases, optimal management of thymic carcinoma has yet to be defined. At present, a multimodality approach involving aggressive surgical resection, platinum-based combination chemotherapeutic interventions, and radiotherapy represent the preferred therapeutic approach. Though our knowledge remains somewhat speculative at present, several scientific, technological and therapeutic innovations may have a potentially significant impact on the future of this disease.
PURPOSE: To ascertain the potential for dose reduction to bladder and rectal points by using intravaginal Foley balloon catheters as a mechanism for structural displacement during tandem and ovoid high-dose-rate intracavitary brachytherapy of the uterine cervix. METHODS AND MATERIALS: In 22 patients, two Foley balloons were placed intravaginally, with one balloon placed anterior to the tandem and one posterior, as close to the flange as patient geometry allowed. A series of 57 consecutive digitized treatment plans was assessed with and without liquid contrast inflation of Foley catheter balloons. Planning X-rays were acquired and digitized. Software calculated dose was then defined for two bladder and two rectal points, both with and without Foley balloon inflation. Results were then assessed using parametric statistical analysis. RESULTS: Collectively and between equivalent points, a statistically significant (p < or = 0.01) diminution in calculated dose was observed with inflation of intracavitary balloon catheters, with a mean reduction in calculated dose of 16% and 17.6% for bladder and rectal points, respectively. CONCLUSION: The potential advantages available from dose reduction using intracavitary balloon catheters include decreased high-dose-rate-induced organ toxicity, case-by-case customizability, and low cost of implementation. As such, further exploration of this technique is warranted.
A patient with base of tongue squamous sell carcinoma, with significant CT artifact-inducing metallic alloy, non-removable dental restorations in both the mandible and maxilla was identified. Simultaneous with IMRT treatment, thermoluminescent dosimeters (TLDs) were placed in the oral cavity. After a series of three treatments, the data from the TLDs and software calculations were analyzed. Analysis of mean in vivo TLD dosimetry reveals differentials from software predicted dose calculation that fall within acceptable dose variation limits. IMRT dose calculation software is a relatively accurate predictor of dose attenuation and augmentation due to dental alloys within the treatment volume, as measured by intra-oral thermoluminescent dosimetry. IMRT represents a safe and effective methodology to treat patients with non-removable metallic dental work who have head and neck cancer.
Sinonasal teratocarcinosarcoma (SNTCS) is a distinctly rare tumor characterized by a variegated histologic architecture of epithelial and mesenchymal components. By reported accounts, SNTCS is a highly malignant tumor displaying rapid, aggressive growth. Prognosis is poor: less than 45% of all patients survive past 5 years. Combination surgery and radiotherapy currently appear to be the most effective treatment. This report presents a 76-year-old African American man with a SNTCS in the right nasal cavity and paranasal sinuses. The patient was treated with combination surgical excision and postoperative radiation therapy. The clinical and pathologic features and clinical course will be discussed.
PURPOSE: The purpose of this study was to evaluate the treatment of Merkel cell carcinoma. MATERIALS AND METHODS: We reviewed 85 cases of Merkel cell carcinoma. There were 68 males and 17 females. The majority of cases involved head and neck sites (48%), followed by the extremities (38%) and trunk (14%). Sixty-seven percent of the patients had stage I disease that was localized to the skin of origin at presentation. Twenty-five percent and 8% were stage II (nodal metastasis) and stage III (distant metastasis), respectively. Surgical intervention included local or wide local excision +/- nodal dissection (68%), radical resection +/- nodal dissection (22%), and amputation (4%). Five patients (6%) underwent biopsy only because of metastatic disease or unresectability at presentation. Fifty-one percent received adjuvant therapy consisting of external beam radiation therapy and/or combination chemotherapy. RESULTS: With an average follow-up time of 39.5 months, 12% had persistent disease and 40% had recurrent disease. The median time to recurrence was 8 months with a mean of 10.6 months. Although the addition of adjuvant therapy did not affect survival, the recurrence rate was 32.5% for surgery +/- adjuvant radiation therapy +/- chemotherapy as compared with 52.7% for surgery-only patients. Although the 40.7% recurrence rate for patients receiving surgery and adjuvant radiation therapy was approximately the same as for patients receiving surgery and adjuvant chemotherapy (40%), the effect of systemic chemotherapy on recurrence is less clear as a result of the small number of patients who received such therapy. Although tumor size and site of presentation were not observed to be statistically significant in overall survival, significant differences were observed based on sex and tumor stage. For females, the median survival time was 96 months (mean, 94.5 months) compared with 63 months (mean, 76.8 months) for males. This difference was significant (P < 0.01). Patients presenting with low-stage (stage I) disease had a significant (P < 0.01) survival benefit when compared with high-stage individuals (stages II and III). The 5-year actuarial survival rates were 68% and 42%, respectively. CONCLUSION: In this retrospective study, surgery remains the primary modality for Merkel cell carcinoma, and adjuvant radiation therapy +/- systemic chemotherapy reduces local recurrence. Female patients and those who present with early-stage disease appear to have a better prognosis.
The purpose of this article is to assess the long-term fertility and attitudes towards fecundity in men after radical inguinal orchiectomy and radiation therapy (RT) for seminoma, and also to assess how often sperm cryopreservation is being offered to patients with seminoma prior to treatment. A retrospective review was conducted at 3 institutions (Wilford Hall Air Force Medical Center, Brooke Army Medical Center, and Fitzsimmons Army Medical Center) to identify patients who had undergone treatment of stage 1 or 2A seminoma during the period from 1975 to 1997. Seventy-three of 212 (34%) patients meeting the selection criteria of stage 1 or 2A seminoma provided information for this analysis. This was thought to be a good response rate, given that many of the patients had changed duty stations or had separated from the military by the time this study started. We performed a review of RT and tumor board records of 73 patients who were treated for testicular seminoma at selected treatment facilities from 1975 to 1997. Patients completed questionnaires and phone interviews that focused on prior fertility, the desire to father (more) children, other fertility-affecting factors (varicocele, cryptorchidism, infection, and erectile dysfunction), and incidence of physician counseling with regard to cryopreservation. All patients were asked to obtain a current semen analysis (SA). Eleven (15%) patients reported that they had tried to father children since completion of their RT. Seven of 11 (64%) successfully achieved pregnancy within a mean time of 3.5 years since RT (range: 1 month to 5 years). Of the 4 couples that were not successful, 1 had severe female factor infertility problems and a second had organic erectile dysfunction. A third had a past surgical history remarkable for vasectomy with subsequent vasectomy reversal. Nine patients provided SA. Mean sperm count and motility were 24.2 Mil/mL (range: 5-81 Mil/mL) and 63.1% (range: 30-90%), respectively (normal SA values: count = 20-250 Mil/mL, motility >50%, and volume = 1.5-5.0 mL). No patients were azoospermic. Overall mean time interval from radiation therapy was 7.9 years. Radiation dose and time since RT did not correlate with either SA results or conception. Only 16 of 73 (22%) men had been offered pretreatment sperm cryopreservation by their counseling physician. It is concluded that (1) patients who are treated for early stage seminoma by orchiectomy and RT have greater than a 50% chance of regaining normal semen parameters, and all regain at least some spermatogenesis; 2) recovery of spermatogenesis is not related to therapeutic radiation dose with the use of modern shielding and RT portals; (3) the majority of treated patients who desire children can conceive; and (4) sperm cryopreservation remains an underutilized option for seminoma patients.
This report describes the course of recurrent Merkel cell carcinoma and defines possible treatment strategies for recurrent disease as seen in a long-term multisite retrospective analysis. Merkel cell carcinoma is a highly aggressive neuroendocrine skin cancer. Surgery and radiation therapy have been demonstrated ability to control this disease; however, recurrence is common. Systemic chemotherapy has, as yet, no presently defined role in primary treatment, and few conclusions can be reached regarding optimal treatment of disease recurrence. Forty-six patients were identified over the last 15 years in a retrospective analysis of patient records from several hospitals in the San Antonio, TX area. Hospital charts as well as outpatient treatment records were reviewed. Almost all patients developing recurrent disease did so within the first 2 years after primary treatment. Patients presenting distant disease had a median survival of 12 months, faring worse than those who display local or nodal disease. For patients with nodal or local recurrence, the mean survival after combination therapy (chemotherapy, radiation +/- surgery) was 36.5 months as compared with 17.5 months for those treated with a single modality (surgery or radiation or chemotherapy). The overall survival rate for the 46 patients with recurrence was 37%. Multimodality therapy has shown the best results for recurrent Merkel cell carcinoma thus far, and should be used if tolerated by the patient. Aggressive salvage surgery for local or nodal recurrence is encouraged, because this disease has a tendency to become more destructive upon recurrence. Adjuvant radiation therapy should also be used, if the patient has not exceeded their dose limitations. Disseminated disease, whether primary or recurrent, warrants further investigation in terms of optimal treatment.
PURPOSE: To characterize non-albicans Candida oral infections in patients with head-and-neck cancer receiving external beam radiotherapy (EBRT) with or without concurrent chemotherapy. METHODS AND MATERIALS: Thirty-seven patients with head-and-neck cancer received EBRT in 2.0-Gy daily fractions to a median dose of 60.4 Gy (range 38-82.8, mean 64.6). They were followed for oropharyngeal candidiasis (OPC) confirmed by positive examination, positive KOH smear, and/or positive swab or swish culture. Samples were identified and plated on chromogenic media to identify non-albicans yeasts. Colonies were plated on Sabouraud dextrose slants for microdilution antifungal susceptibility testing to fluconazole. DNA typing, including karyotyping, restriction fragment length polymorphism analysis, and Southern blot hybridization with the moderately repetitive Ca3 probe, was performed on selected isolates to confirm individual species. RESULTS: Of the 37 patients, 10 (27%) developed OPC, and 26 (70.3%) displayed Candida carriage state. The median EBRT dose at time of positive culture was 22.5 Gy and at time of OPC was 28.6 Gy. Of the 6 patients receiving chemotherapy and EBRT, 4 (66%) developed OPC at median dose of 27.6 Gy. Three (8%) of 37 patients were infected with non-albicans Candida, and 3 (30%) of all 10 infections were caused by these organisms. CONCLUSION: Non-albicans Candida is emerging as a relatively common cause of OPC in head-and-neck cancer patients. Chromogenic media are helpful to screen these infections. Our data also suggest a greater likelihood of developing OPC in patients receiving concomitant chemotherapy and EBRT.
Urethral cancer is rare, encompassing less than 1% of all malignancies. Optimal management, at present, often relies on the limited experience gained from the study of retrospective cases. Therefore, it is imperative to share all available information regarding urethral cancer treatment via reportage of pertinent cases, thus enabling more complete comprehension and decision-making options by both clinicians and researchers. A retrospective review of 18 consecutive patients with primary urethral cancer was performed. An analysis was performed of clinical stage, treatment modality, and outcome. Overall patient survival rate for this retrospective was 44%, with a mean follow-up of 63.5 months. Seven of 10 patients with low-stage diagnosis remained disease free. Comparatively, only one of eight patients with high-stage cancer had no apparent disease. Patients with advanced cancer treated with surgery alone had a shorter disease-free survival (23.3 months) versus those treated with combination chemo/radiation therapy (45.2 months). The major characteristic with prognostic impact was statistically found to be low (T1-2, N0, M0) versus high (T3-4, N1, M1) stage, as assessed by Mann-Whitney U test (z = 2.83, p = 0.0023). Clinical staging afforded the strongest prognostic indication of survival. Patients with low-stage disease exhibited increased survival with single-modality therapy. However, patients with advanced cancer benefited from combined treatment using chemotherapy and radiation therapy.
Secondary to the paucity of pheochromocytoma, very limited data exist regarding the optimal treatments of metastatic disease. Malignant pheochromocytomas are often considered unresponsive to radiotherapy, but this decision is based on the few case reports performed before 1970. There have been a handful of reports about metastatic resolution and palliation from radiation therapy. Nevertheless, radiotherapy is not considered a mainstay of pheochromocytoma treatment. In this case report, we describe a patient with a malignant extraadrenal pheochromocytoma, metastatic to the right humerus, and her treatment course of surgery and radiotherapy.
Malignant fibrous histiocytoma (MFH) of the spermatic cord represents an uncommon location for the most common soft-tissue tumor in adults. MFH of the spermatic cord is such a rare entity that only 28 case reports have been described in the literature to date. The rarity of MFH of the spermatic cord has made diagnosis, staging, and treatment difficult. Solutions to such questions will only be answered as our database continues to expand. Therefore, this case report is presented in hopes of lending statistical power to future analysis of the correct treatment planning, mortality rates, and prognostic indications of a relatively unknown subset of a common disease.