Biomedical subjects
Publications and source records attributed to Charles R Thomas.
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PURPOSE: The Radiation Therapy Oncology Group (RTOG) 9413 trial demonstrated a better progression-free survival (PFS) with whole-pelvis (WP) radiotherapy (RT) compared with prostate-only (PO) RT. This secondary analysis was undertaken to determine whether "mini-pelvis" (MP; defined as > or = 10 x 11 cm but < 11 x 11 cm) RT resulted in progression-free survival (PFS) comparable to that of WP RT. To avoid a timing bias, this analysis was limited to patients receiving neoadjuvant and concurrent hormonal therapy (N&CHT) in Arms 1 and 2 of the study. METHODS AND MATERIALS: Eligible patients had a risk of lymph node (LN) involvement > 15%. Neoadjuvant and concurrent hormonal therapy (N&CHT) was administered 2 months before and during RT for 4 months. From April 1, 1995, to June 1, 1999, a group of 325 patients were randomized to WP RT + N&CHT and another group of 324 patients were randomized to receive PO RT + N&CHT. Patients randomized to PO RT were dichotomized by median field size (10 x 11 cm), with the larger field considered an "MP" field and the smaller a PO field. RESULTS: The median PFS was 5.2, 3.7, and 2.9 years for WP, MP, and PO fields, respectively (p = 0.02). The 7-year PFS was 40%, 35%, and 27% for patients treated to WP, MP, and PO fields, respectively. There was no association between field size and late Grade 3+ genitourinary toxicity but late Grade 3+ gastrointestinal RT complications correlated with increasing field size. CONCLUSIONS: This subset analysis demonstrates that RT field size has a major impact on PFS, and the findings support comprehensive nodal treatment in patients with a risk of LN involvement of > 15%.
Several measurement techniques have been developed to address the capability for target volume reduction via target localization in image-guided radiotherapy; among these have been ultrasound (US) and fiducial marker (FM) software-assisted localization. In order to assess interchangeability between methods, US and FM localization were compared using established techniques for determination of agreement between measurement methods when a 'gold-standard' comparator does not exist, after performing both techniques daily on a sequential series of patients. At least 3 days prior to CT simulation, four gold seeds were placed within the prostate. FM software-assisted localization utilized the ExacTrac X-Ray 6D (BrainLab AG, Germany) kVp x-ray image acquisition system to determine prostate position; US prostate targeting was performed on each patient using the SonArray (Varian, Palo Alto, CA). Patients were aligned daily using laser alignment of skin marks. Directional shifts were then calculated by each respective system in the X, Y and Z dimensions before each daily treatment fraction, previous to any treatment or couch adjustment, as well as a composite vector of displacement. Directional shift agreement in each axis was compared using Altman-Bland limits of agreement, Lin's concordance coefficient with Partik's grading schema, and Deming orthogonal bias-weighted correlation methodology. 1,019 software-assisted shifts were suggested by US and FM in 39 patients. The 95% limits of agreement in X, Y and Z axes were +/-9.4 mm, +/-11.3 mm and +/-13.4, respectively. Three-dimensionally, measurements agreed within 13.4 mm in 95% of all paired measures. In all axes, concordance was graded as 'poor' or 'unacceptable'. Deming regression detected proportional bias in both directional axes and three-dimensional vectors. Our data suggest substantial differences between US and FM image-guided measures and subsequent suggested directional shifts. Analysis reveals that the vast majority of all individual US and FM directional measures may be expected to agree with each other within a range of 1-1.5 cm. Since neither system represents a gold standard, clinical judgment must dictate whether such a difference is of import. As IMRT protocols seek dose escalation and PTV reduction predicated on US- and FM-guided imaging, future studies are needed to address these potential clinically relevant issues regarding the interchangeability and accuracy of novel positional verification techniques. Comparison series with multiple image-guidance systems are needed to refine comparisons between targeting methods. However, we do not advocate interchangeability of US and FM localization methods.
PURPOSE: Clinical and technical parameter analysis of patients treated with ultrasound-based image-guided tomotherapeutic IMRT for gallbladder cancer. METHODS AND MATERIALS: Between 8/2001 and 5/2005, 10 patients with primary tumors of the gallbladder were treated by image-guided IMRT to median doses of 59 Gy. To analyze normal tissue radiation exposure reduction using this novel approach, a virtual plan comparison between actually delivered IMRT plans and re-computed plans with identical inverse planning parameters but more conventional PTV safety margins was conducted. RESULTS: Average CTV was 379 cm(3), with a mean initial PTV of 834 cm(3). In 9/10 patients, a boost was delivered to a mean CTV(boost) of 171 cm(3) and average PTV(boost) of 241 cm(3). One patient reported RTOG grade 3 acute toxicity. All other patients exhibited Grade 2 or lower acute toxicity. Preliminary median overall survival was 16.7 months (range 3.2-34.9 months), with 5/10 patients alive at analysis. Virtual plan comparison revealed significant organ-at-risk sparing by the enabled PTV margin reduction. CONCLUSION: Ultrasound-based image-guided IMRT is a feasible mechanism of delivering conformal radiation doses to tumors of the gallbladder with acceptable toxicity. Early outcome data with this novel radiation planning and delivery technique are encouraging and comparable to previously reported literature.
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.
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BACKGROUND: Keloids are common benign tumors of the dermis, typically arising after insult to the skin. While typically only impinging on cosmesis, large or recurrent keloids may require therapeutic intervention. While no single standardized treatment course has been established, several series report excellent outcomes for keloids with post-surgery radiation therapy. CASE PRESENTATION: We present a patient with a history of recurrent keloids arising in the absence of an ascribed trauma and a maternal familial history of keloid formation, whose physical examination several large perineal keloids of 6-20 cm in the largest dimension. The patient was treated with surgical extirpation and adjuvant radiation therapy. Radiotherapy was delivered to the scar bed to a total dose of 22 Gy over 11 daily fractions. Acute radiotherapy toxicity necessitated a treatment break due to RTOG Grade III acute toxicity (moderate ulceration and skin breakdown) which resolved rapidly during a 3-day treatment break. The patient demonstrated local control and has remained free of local recurrence for more than 2 years. CONCLUSION: Radiotherapy for keloids represents a safe and effective option for post-surgical keloid therapy, especially for patients with bulky or recurrent disease.
PURPOSE: To analyze two methods of image-guided radiotherapy (IGRT) for external beam radiotherapy of prostate cancer. METHODS AND MATERIALS: The prostate was localized by ultrasound (US) in lateral (left/right), vertical (anteroposterior), and longitudinal (superior/inferior) dimensions and then by fiducial seed marker (SM) kV X-ray. Assuming initial setup to skin marks as the origin, the mean suggested shifts (for all dimensions) were hypothesized to be similar and within 1 mm of the origin. The three-dimensional distance discrepancy between suggested SM and US shift points was calculated. We hypothesized a mean discrepancy >5 mm as clinically significant. RESULTS: From 40 patients, 1019 US/SM measurements were obtained. Lateral, vertical, and longitudinal dimensional comparisons reveal statistically significant differences in mean shifts (p < 0.0001 for all). US dimensional shifts reveal significantly greater variability. The US three-dimensional vector is greater and more variable than the SM vector (p < 0.0001). The mean US/SM three-dimensional distance discrepancy is 8.8 mm (significantly >5 mm, p < 0.0001). CONCLUSIONS: Ultrasound and SM methods suggest different shifts. US data reveal greater systematic/random error vs. SM data. The US data suggest larger PTV expansion margins (approximately 9 mm) are necessary for US IGRT vs. SM IGRT (approximately 3 mm). The hypotheses that US and SM methods suggest similar shifts and that the mean US/SM three-dimensional distance discrepancy is < or =5 mm are rejected.
BACKGROUND: Disparities in cancer outcome among different subsets of the American population related to ethnic background have been well documented. Clinical trials represent the most powerful strategy for improving cancer treatments, but racial and ethnic minority patients are frequently underrepresented among patients accrued to these protocols. Proof of comparable efficacy for a promising cancer therapy in different groups of patients requires diversity in the clinical trial populations so that study results will be generalizable. Appropriate targets for accrual of minority ethnicity patients have not previously been defined. METHODS: The National Cancer Database (NCDB) is maintained jointly by the American Cancer Society and the American College of Surgeons. Information submitted by tumor registries throughout the United States represents an estimated 70% of newly diagnosed cancer cases. The authors analyzed NCDB reports on ethnic distribution of patients with breast, prostate, nonsmall cell lung, and colorectal cancer, stratified by stage of disease at diagnosis. RESULTS: African Americans with cancer of the breast and prostate had the most notable patterns of disproportionate representation among populations with advanced-stage disease. The authors compiled a table of suggested accrual targets for selected solid-organ cancers based on NCDB stage-specific reports. CONCLUSIONS: Clinical trial results will be more meaningful if participating patients reflect the site- and stage-specific populations that are under study. The authors recommended that clinical trial investigators incorporate accrual targets for minority ethnicity populations into the study design.
Although the incidence of gastric cancer has been decreasing in the United States, it remains a leading cause of cancer death in the world, only lung cancer causes more deaths worldwide. The combination of relatively low prevalence, lack of pathognomonic symptoms, and lack of defined risk factors are associated with a delay in diagnosis leading to a dismal prognosis. For localized disease, surgery remains a cornerstone of treatment but much controversy remains regarding optimal peri-operative therapy. For advanced disease, several new agents and new combination chemotherapies have offered encouraging results. This paper seeks to review the major topics surrounding gastric cancer and cover the results of recently reported and ongoing trials.
The management of Pancoast tumors has challenged surgeons and radiation and medical oncologists over several decades. Retrospective studies have raised a greater awareness of the importance of positive N2 lymph nodes in terms of prognosis and treatment decision making. While patients with positive N2 lymph nodes have generally been excluded from trials of preoperative chemoradiation for superior sulcus tumors, the potential of surgery for these patients is still being evaluated. The role of PET for initial staging as well as for assessment of disease response to induction therapy continues to evolve. The use of combined treatment modalities has enhanced the progress in successfully treating Pancoast tumors. The historical data showing improved results with a combination of surgery and radiation compared with surgery alone for patients with positive N2 nodes provides the basis for several important clinical trials that integrate the use of chemotherapy into the treatment paradigm. The Southwest Oncology Group and Japanese Clinical Oncology Group have shown dramatic improvements in complete resection rates following a neoadjuvant course of combined chemotherapy and radiation therapy compared with historical series. We discuss relevant ongoing clinical trials that include consolidative taxane-based chemotherapy and the role of prophylactic cranial irradiation in complete responders. Future potential areas of investigation, including the role of surgery for patients with N2-positive disease and the use of imaging to assess response after induction therapy, are discussed.
Randomized prospective trials have shown the benefits of adjuvant radiotherapy in decreasing local recurrence rates in stage II and stage III rectal cancer. However, some patients with stage II lesions have relatively low risks of local recurrence when treated with modern surgery alone. This article will discuss important prognostic, diagnostic, and therapeutic factors including depth of tumor invasion, tumor location, improvements in staging with endorectal ultrasound and magnetic resonance imaging, enhanced surgical technique with total mesorectal excision, circumferential tumor margin, and lymph node dissection that may help to better define a subset of stage II rectal cancer patients in which pelvic radiation may be safely omitted.
BACKGROUND: While colorectal cancer (CRC) incidence and mortality rates have declined slightly over the past decade, there remain marked differences by ethnicity. Our aim was to investigate ethnic differences in occurrence, clinical presentation and outcome of CRC at a tertiary university center that serves a predominantly Hispanic population. METHODS: Prospectively collected data from the tumor registry on patients diagnosed with colorectal cancer from 1985 through 2001 was examined. Age at diagnosis, mode of presentation, sex, tumor location, ethnicity, TNM stage, and survivals were assessed and ethnic differences were sought. RESULTS: Records from 453 patients with CRC were reviewed. There were 296 (65%) patients that were Hispanics, 112 (25%) non-Hispanic Whites, 37 (8%) African Americans, and 8 (2%) of other or unknown ethnicity. Compared with non-Hispanic Whites, Hispanics presented at a younger age (58.5 +/- 14 versus 53.6 +/- 12.73, respectively; P < 0.01), with a significantly greater incidence of stage IV disease (19% versus 32%, respectively; P = 0.02). They had significantly poorer age-adjusted survival (median survival of 92 months for <55 years and 77 months for >55 years versus 48 months for <55 years and 48 months for >55 years, respectively; adjusted log rank P = 0.045). There were no differences in tumor location, mode of presentation or adjuvant treatment received. CONCLUSIONS: Hispanic patients with CRC in our catchment area present at a younger age with more metastatic disease and have a poorer survival than non-Hispanic Whites. Modification of screening criteria and treatment paradigms may be required for Hispanics.
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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Squamous cell carcinoma (SCC) of the anal canal is a rare condition with increasing incidence rates in the United States population in the past several decades. This review article provides a complete overview of the etiology, anatomy and the approach to the multidisciplinary management of the patient with anal SCC. Chemoradiation therapy for the treatment of SCC of the anal canal provides excellent disease control and survival while preserving anal sphincter function in the majority of patients. The surgeon plays a key role in the diagnosis and follow-up of this disease. Surgical salvage with APR for disease persistence or recurrence in carefully selected patients can result in reasonable 5-year survivals.
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BACKGROUND: Gangliocytic paraganglioma are rare neoplasms that predominantly arise in periampulary region. Though considered benign the disease can spread to regional lymphatics. CASE PRESENTATION: A 49 year old woman presented with melena and was found to have a periampullary mass. Endoscopic evaluation and biopsy demonstrated a periampullary paraganglioma. The tumor was resected with pylorus-preserving pancreaticoduodenectomy and was found to represent a gangliocytic paraganglioma associated with nodal metastases. In a controversial decision, the patient was treated with adjuvant external beam radiation therapy. She is alive and well one year following resection. The authors have reviewed the current literature pertaining to this entity and have discussed the biologic behavior of the tumor as well as the rationale for treatment strategies employed. CONCLUSION: Paraganglioma is a rare tumor that typically resides in the gastrointestinal tract and demonstrates low malignant potential. Due to rarity of the disease there is no consensus on the adjuvant treatment even though nearly 5% of the lesions demonstrate the malignant potential.