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Biomedical subjects

Charles R Thomas

Publications and source records attributed to Charles R Thomas.

At least 37 records · Page 2Linked to original sources
PubMed2005

Metastatic breast cancer presenting as linitis plastica of the stomach.

Early detection and treatment of breast cancer, leading to longer survival, has revealed the natural history of this disease process. Linitis plastica of the stomach is a potential long-term sequela of metastatic breast cancer. Here we present a case of metastatic breast cancer presenting as linitis plastica, as well as the treatment algorithm for this rare clinical entity. The world literature describes a clear pattern of linitis plastica for metastatic infiltrating lobular breast cancer and a discrete nodular pattern for infiltrating ductal cancer, in regard to metastasis to the stomach. To our knowledge, this is the first case of infiltrating ductal cancer presenting as linitis plastica of the stomach.

Breast Neoplasms↗
PubMed2005

The efficacy of conventional external beam, three-dimensional conformal, intensity-modulated, particle beam radiation, and brachytherapy for localized prostate cancer.

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.

Antineoplastic Agents, Hormonal↗
PubMed2005

Radiation therapy in the management of thymic tumors.

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.

Brachytherapy↗
PubMed2005

State of the art: gastrointestinal malignancies in the human immunodeficiency virus (HIV) population.

The gastrointestinal tract is one of the most common sites for the development of primary neoplasms arising in patients with pre-existing infection with the human immunodeficiency virus (HIV). Over the past decade, new information on the clinical manifestation, natural history, treatment options, and related toxicity have been reported, mostly notably the integration of highly active antiretroviral therapy (HAART). The following is a concise review summarizing the current state-of-the-art for GI tract malignancies in the HIV-positive patient and is designed to assist the clinical oncology team in developing a rationale plan when caring for these patients.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Current chemotherapy options for thymic epithelial neoplasms.

Thymomas and thymic carcinoma are rare neoplasms. Surgical resection is the cornerstone of effective therapy. Stage I disease is effectively treated by complete surgical resection. The role of radiation therapy in completely resected stage II disease remains controversial. Adjuvant radiation therapy is useful for local control and may improve survival in patients with incompletely resected tumours. Cisplatin-based chemotherapy regimens play an important role in the treatment of advanced stage III/IV or recurrent disease thymomas, but have proven less effective for thymic carcinoma. Phase II trials of multimodality therapy incorporating neoadjuvant chemotherapy, surgery and postoperative radiation therapy show promise for unresectable disease. This review discusses recent clinical data and the potential role for agents targeting the epidermal growth factor receptor, angiogenesis and apoptotic pathways.

Antineoplastic Agents↗
PubMed2005

Management of anal cancer in the HIV-positive population.

Squamous cell anal cancer remains an uncommon entity; however, the incidence appears to be increasing in at-risk populations, especially those infected with human papillomavirus (HPV) and human immunodeficiency virus (HIV). Given the ability to cure this cancer using synchronous chemoradiotherapy, management practices of this disease are critical. This article considers treatment strategies for HIV-positive patients with anal cancer, including the impact on chemoradiation-induced toxicities and the role of highly active antiretroviral therapy in the treatment of this patient population. The standard treatment has been fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents plus radiation. Consideration to modifying the standard treatment regime is based on the fact that patients with HIV tend to experience greater toxicity, especially when CD4 counts are below 200; these patients also require longer treatment breaks. Additional changes to the chemotherapy dosing, such as giving 5-FU continuously and decreasing mitomycin dose, are evaluated and considered in relation to radiation field sizes in an effort to reduce toxicity, maintain local tumor control, and limit need for colostomy. The opportunity for decreasing the radiation field size and using intensity-modulated radiation therapy (IMRT) is also considered, particularly in light of the fact that IMRT provides dose-sparing while maximizing target volume dose to involved areas. The impact of the immune system in patients with HIV and squamous cell carcinoma of the anus and the associated response to therapy remains unknown. Continued studies and phase III trials will be needed to test new treatment strategies in HIV-infected patients with squamous cell cancer of the anus to determine which treatment protocols provide the greatest benefits.

Adult↗
PubMed2004

Bubble dynamics near the onset of single-bubble sonoluminescence.

A number of groups have reported measurements of the location in the parameter space of bubble size versus acoustic pressure amplitude of shape- and size-stable bubbles. For air/water systems, a general trend emerges: stable bubbles are found on one of two line paths in this space defined by their range of acoustic pressure. Bubbles on the higher-pressure path emit light. There have been few studies of the transition between these two paths. In this work we describe our observations of this transition regime. In this regime, a slow time scale oscillation (period 2-7 s) in the bubble size, position, and phase of flash timing can be observed. At lower dissolved gas concentrations, a hysteresis in the bubble size as a function of acoustic pressure is observed, complementing previous light intensity measurements reported in the literature.

Journal Article↗
PubMed2004

Daily ultrasound-based image-guided targeting for radiotherapy of upper abdominal malignancies.

PURPOSE: Development and implementation of a strategy to use a stereotactic ultrasound (US)-based image-guided targeting device (BAT) to align intensity-modulated radiotherapy (IMRT) target volumes accurately in the upper abdomen. Because the outlines of such targets may be poorly visualized by US, we present a method that uses adjacent vascular guidance structures as surrogates for the target position. We assessed the potential for improvement of daily repositioning and the feasibility of daily application. METHODS AND MATERIALS: A total of 62 patients were treated by sequential tomotherapeutic IMRT between October 2000 and June 2003 for cholangiocarcinoma and gallbladder carcinoma (n = 10), hepatocellular carcinoma (n = 10), liver metastases (n = 11), pancreatic carcinoma (n = 20), neuroblastoma (n = 3), and other abdominal and retroperitoneal tumors (n = 8). The target volumes (TVs) and organs at risk were delineated in contrast-enhanced CT data sets. Additionally, vascular guidance structures in close anatomic relation to the TV, or within the TV, were delineated. Throughout the course of IMRT, US BAT images were acquired during daily treatment positioning. In addition to the anatomic structures typically used for US targeting (e.g., the TV and dose-limiting organs at risk), CT contours of guidance structures were superimposed onto the real-time acquired axial and sagittal US images, and target position adjustments, as indicated by the system, were performed accordingly. We report the BAT-derived distribution of shifts in the three principal room axes compared with a skin-mark-based setup, as well as the time required to perform BAT alignment. The capability of the presented method to improve target alignment was assessed in 15 patients by comparing the organ and fiducial position between the respective treatment simulation CT with a control CT study after US targeting in the CT suite. RESULTS: A total of 1,337 BAT alignments were attempted. US images were not useful in 56 setups (4.2%), mainly because of limited visibility due to daily variations in colonic and gastric air. US imaging was facilitated in intrahepatic tumors and asthenic patients. The mean +/- SD shift from the skin mark position was 4.9 +/- 4.35, 6.0 +/- 5.31, and 6.0 +/- 6.7 mm in the x, y, and z direction, respectively. The mean magnitude vector of three-dimensional alignment correction was 11.4 +/- 7.6 mm. The proportion of daily alignments corrected by a magnitude of >10, >15, and >20 mm was 48.9%, 25.1%, and 12.7%, respectively. The magnitude of shifts in the principal directions, as well as the three-dimensional vector of displacement, was statistically significant (test against the zero hypothesis) at p <0.0001. The guidance structures that were the most valuable for identification of the TV position were the branches of the portal vein, hepatic artery, and dilated bile ducts in intrahepatic lesions and the aorta, celiac trunk, superior mesenteric artery, and extrahepatic aspects of the portal vein system in retroperitoneal and extrahepatic lesions. The mean total setup time was 4.6 min. The correlation of BAT targeting with target setup error assessment in the control CT scans in 15 patients revealed setup error reduction in 14 of 15 alignments. The average setup error reduction, assessed as a reduction in the length of setup error three-dimensional magnitude vector, was 54.4% +/- 26.9%, with an observed mean magnitude of residual setup error of 4.6 +/- 3.4 mm. The sole worsening of an initial setup was by a magnitude of <2 mm. US targeting resulted in statistically significant improvements in patient setup (p = 0.03). CONCLUSION: Daily US-guided BAT targeting for patients with upper abdominal tumors was feasible in the vast majority of attempted setups. This method of US-based image-guided tumor targeting has been successfully implemented in clinical routine. The observed improved daily repositioning accuracy might allow for individualized reduction of safety margins and optional dose escalation. Compared with the established application of the BAT device for prostate radiotherapy, in which the target can be directly visualized, the TV in the present study was predominantly positioned relative to guidance vascular structures in close anatomic relation. We perceived an enormous potential in improved and individualized patient positioning for fractionated radiotherapy and also for stereotactic extracranial radiotherapy and radiosurgery, especially for tumors of the liver and pancreas.

Abdominal Neoplasms↗
PubMed2004

Phase III study of adjuvant chemotherapy and radiation therapy compared with chemotherapy alone in the surgical adjuvant treatment of colon cancer: results of intergroup protocol 0130.

PURPOSE: Some patients with colon cancer have a high risk of local recurrence postoperatively. This trial was undertaken to determine whether radiation therapy added to an adjuvant chemotherapy regimen improves outcome in high-risk patients. PATIENTS AND METHODS: Patients with resected colon cancer with tumor adherence or invasion of surrounding structures, or with T3N1 or T3N2 tumors of the ascending or descending colon were randomly assigned to receive fluorouracil and levamisole therapy with or without radiation therapy. Patients who received chemotherapy and radiation therapy (chemoRT) received 45 to 50.4 Gy in 25 to 28 fractions beginning 28 days after starting chemotherapy. Patient enrollment was terminated because of slow accrual after 222 patients enrolled (original goal was 700 patients); 187 patients were assessable. RESULTS: Overall 5-year survival was 62% for chemotherapy patients and 58% for chemoRT patients (P >.50); 5-year disease-free survival was 51% for both groups (P >.50). Toxicity (>/= grade 3) occurred in 42% of chemotherapy patients and 54% of chemoRT patients (P =.04). Leukopenia (>/= grade 3) occurred in 10% of chemotherapy patients and 22% of chemoRT patients (P =.02). No significant difference in nonhematologic toxicity (>/= grade 3) was observed between chemoRT and chemotherapy patients (35% v 44%; P =.26). CONCLUSION: Patients who received chemotherapy or chemoRT had similar overall survival and disease-free survival. Toxicity was higher among chemoRT patients. These results must be interpreted with caution because of the high number of ineligible patients and the limited power of the study to detect potentially meaningful differences.

Administration, Oral↗
PubMed2004

Thymic carcinoma: state of the art review.

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.

Humans↗
PubMed2004

Melatonin as a radioprotective agent: a review.

Melatonin (N-acetyl-5-methoxytryptamine), the chief secretory product of the pineal gland in the brain, is well known for its functional versatility. In hundreds of investigations, melatonin has been documented as a direct free radical scavenger and an indirect antioxidant, as well as an important immunomodulatory agent. The radical scavenging ability of melatonin is believed to work via electron donation to detoxify a variety of reactive oxygen and nitrogen species, including the highly toxic hydroxyl radical. It has long been recognized that the damaging effects of ionizing radiation are brought about by both direct and indirect mechanisms. The direct action produces disruption of sensitive molecules in the cells, whereas the indirect effects ( approximately 70%) result from its interaction with water molecules, which results in the production of highly reactive free radicals such as *OH, *H, and e(aq)- and their subsequent action on subcellular structures. The hydroxyl radical scavenging ability of melatonin was used as a rationale to determine its radioprotective efficiency. Indeed, the results from many in vitro and in vivo investigations have confirmed that melatonin protects mammalian cells from the toxic effects of ionizing radiation. Furthermore, several clinical reports indicate that melatonin administration, either alone or in combination with traditional radiotherapy, results in a favorable efficacy:toxicity ratio during the treatment of human cancers. This article reviews the literature from laboratory investigations that document the ability of melatonin to scavenge a variety of free radicals (including the hydroxyl radical induced by ionizing radiation) and summarizes the evidence that should be used to design larger translational research-based clinical trials using melatonin as a radioprotector and also in cancer radiotherapy. The potential use of melatonin for protecting individuals from radiation terrorism is also considered.

Animals↗
PubMed2004

Recursive partitioning analysis of pretreatment variables of 416 patients with locoregional esophageal cancer treated with definitive concomitant chemoradiotherapy on Intergroup and Radiation Therapy Oncology Group trials.

PURPOSE: To analyze the relative contributions of uniformly collected pretreatment patient- and tumor-related variables to survival and to identify the terminal nodes via recursive partitioning analysis (RPA) that could be used as a stratification variable for future Phase III trials. METHODS AND MATERIALS: From two Intergroup trials (85-01, n = 130; and 94-05, n = 218) and one Radiation Therapy Oncology Group trial (92-07, n = 68), we identified 416 patients who were treated with definitive concomitant cisplatin and 5-FU-based chemoradiotherapy and analyzed their data for survival by RPA to define prognostic classes. The following pretreatment factors were evaluated: histologic type, age, weight loss, Karnofsky performance status, gender, race, T stage, tumor location, tumor size, N stage, and degree of dysphagia. The entire data set was considered as the initial node. The criterion for split points was the smallest p value less than unadjusted 0.05. RESULTS: Of the 416 patients, 336 (81%) were dead at the time of the analysis. The RPA identified only one significant split: pretreatment weight loss in the prior 6 months of <10% vs. > or =10%. After adjusting for multiple comparisons, no other split approached statistical significance. CONCLUSION: Unlike our experience with malignant glioma, brain metastases, and locally advanced non-small-cell lung cancer, RPA failed to identify novel prognostic information that could be incorporated into the stratification scheme of future chemoradiotherapy trials for esophageal cancer. Furthermore, our analysis validated the percentage of weight loss as a stratification variable for esophageal cancer.

Adenocarcinoma↗
PubMed2004

Recent clinical trials summary.

The current standard of care for the treatment of anal cancer as demonstrated by all of the completed phase 3 clinical trials remains 5-FU and mitomycin C in combination with radiation therapy. The basic elements of the approach outlined by Nigro have not changed in the last 30 years. Future phase 3 trials will serve to further perfect this approach and outline the role of HPV and dysplasia in the development and progression of this disease.

Antibiotics, Antineoplastic↗
PubMed2004

Uncommon anal neoplasms.

The neoplasms of the anus discussed in this article are uncommon, and therefore lack a consistent diagnostic and treatment algorithm derived from prospective clinical trial datasets. There may be an opportunity to design prospective Phase II clinical trials, with established uniform surgical pathology, surgical technique guidelines, and endpoints. The American College of Surgeons Oncology Group may have an opportunity to design and carry out controlled clinical trials for select rare anal neoplasms. Such an effort may yield modern benchmarks with which to base subsequent patient care algorithms.

Adenocarcinoma↗
PubMed2004

Candida glabrata is an emerging cause of oropharyngeal candidiasis in patients receiving radiation for head and neck cancer.

Oropharyngeal candidiasis (OPC) is relatively common in patients receiving radiation for head and neck cancer occurring in approximately 25% of patients. Candida albicans has been described as the primary infecting organism. Recently, other organisms, particularly Candida glabrata, have emerged as causative agents of OPC among immunocompromised patients. This study describes the characteristics of 6 patients with head and neck cancer treated with radiotherapy at our institution, who were found to have Candida glabrata-associated OPC and their responses to oral fluconazole. All 6 patients were successfully treated with oral fluconazole. However, most did not respond to the usual dose of 100 mg/day necessitating doses ranging from 200 to 800 mg/day to achieve clinical cure. All 3 patients receiving radiation only were successfully treated with up to 200 mg/day; 2 of 3 patients receiving concomitant chemoradiation required doses ranging from 400 to 800 mg/day. As with systemic infection, previous fluconazole use appears to be a risk factor for this infection, but not with all patients.

Adult↗