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Michael Lock

Publications and source records attributed to Michael Lock.

17 recordsLinked to original sources
PubMed2006

A comparison of prostate IMRT and helical tomotherapy class solutions.

The purpose of this study was to assess a variety of potential IMRT class solutions as compared to a helical tomotherapy (HT) class solution for localized prostate cancer. Target and critical structures were contoured on 10 prostate cancer patient CT datasets. HT treatment plans were compared to four different IMRT approaches by paired t-tests. HT prostate planning generally provided treatment plans with excellent target homogeneity and favorable critical structure sparing when compared to conventional IMRT.

Humans↗
PubMed2006

Immunogenicity and tolerance of ascending doses of a recombinant protective antigen (rPA102) anthrax vaccine: a randomized, double-blinded, controlled, multicenter trial.

BACKGROUND: We report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine. METHODS: Hundred healthy volunteers were randomized in a 4:1 ratio to receive intramuscular doses of rPA102 in the following formulations: 5, 25, 50, or 75 microg of rPA102 in 82.5 microg aluminum hydroxide adjuvant at 0, 4, and 8 weeks; or the US licensed Anthrax Vaccine Adsorbed (AVA) at weeks 0 and 4. FINDINGS: Local reactogenicity (mostly pain) was more common with AVA than with rPA102 following the first (94.7% versus 44.4%; p < 0.001) and the second (84.2% versus 35.4%; p < 0.001) vaccinations. Systemic reactogenicity (mostly headache) was more common among rPA102 vaccinees, but only following the first vaccination (49.4% versus 15.8%; p = 0.025). A dose-response relationship for anti-PA antibodies was present after the 2nd and 3rd vaccinations. Two weeks following the 2nd vaccination, the geometric mean titers (GMT) for lethal toxin neutralization activity (TNA), for the 5, 25, 50 and 75 microg rPA102 and AVA groups were 38.6, 75.4, 373.9, 515.3, and 855.2, respectively. The geometric mean concentrations (GMC) measured by anti-PA IgG ELISA were 3.7, 11.5, 25.9, 44.1, and 171.6, respectively. Two weeks following the 3rd vaccination, TNA GMTs for the four rPA102 groups, were: 134.7, 719.7, 2116.6, 2422.4; and ELISA GMCs were: 22.9, 104.7, 196.4, and 262.6, respectively. INTERPRETATION: No clinically serious or dose-related toxicity or reactogenicity was observed. The TNA response after two injections of the 75 microg dose of rPA102 was similar to the response after two injections of AVA. The third rPA102 vaccination substantially increased the antibody response.

Adjuvants, Immunologic↗
PubMed2006

Prostate contouring uncertainty in megavoltage computed tomography images acquired with a helical tomotherapy unit during image-guided radiation therapy.

PURPOSE: To evaluate the image-guidance capabilities of megavoltage computed tomography (MVCT), this article compares the interobserver and intraobserver contouring uncertainty in kilovoltage computed tomography (KVCT) used for radiotherapy planning with MVCT acquired with helical tomotherapy. METHODS AND MATERIALS: Five prostate-cancer patients were evaluated. Each patient underwent a KVCT and an MVCT study, a total of 10 CT studies. For interobserver variability analysis, four radiation oncologists, one physicist, and two radiation therapists (seven observers in total) contoured the prostate and seminal vesicles (SV) in the 10 studies. The intraobserver variability was assessed by asking all observers to repeat the contouring of 1 patient's KVCT and MVCT studies. Quantitative analysis of contour variations was performed by use of volumes and radial distances. RESULTS: The interobserver and intraobserver contouring uncertainty was larger in MVCT compared with KVCT. Observers consistently segmented larger volumes on MVCT where the ratio of average prostate and SV volumes was 1.1 and 1.2, respectively. On average (interobserver and intraobserver), the local delineation variability, in terms of standard deviations [Deltasigma = radical(sigma2MVCT-sigma2KVCT)], increased by 0.32 cm from KVCT to MVCT. CONCLUSIONS: Although MVCT was inferior to KVCT for prostate delineation, the application of MVCT in prostate radiotherapy remains useful.

Humans↗
PubMed2006

Highly attenuated smallpox vaccine protects rabbits and mice against pathogenic orthopoxvirus challenge.

The possible reemergence of smallpox through bioterrorism requires the preparation of adequate stockpiles of vaccine. Dryvax, the only US-licensed vaccinia virus smallpox vaccine, has an unacceptable safety profile in the pre-event setting. LC16m8 is a Japanese-licensed attenuated vaccinia virus strain that has been safely used in over 50,000 persons. Until now, efficacy of this vaccine was unproven. Using two animal models, we show that LC16m8 and Dryvax elicit comparable humoral immune responses after a single vaccination and equivalently protect against lethal poxvirus disease. Thus, LC16m8 shows promise as a safe and effective smallpox vaccine with the potential for replacing Dryvax.

Animals↗
PubMed2006

Clinical implementation of adaptive helical tomotherapy: a unique approach to image-guided intensity modulated radiotherapy.

Image-guided IMRT is a revolutionary concept whose clinical implementation is rapidly evolving. Methods of executing beam intensity modulation have included individually designed compensators, static multi-leaf collimators (MLC), dynamic MLC, and sequential (serial) tomotherapy. We have developed helical tomotherapy as an innovative solution to overcome some of the limitations of other IMRT systems. The unique physical design of helical tomotherapy allows the realization of the concepts of adaptive radiotherapy and conformal avoidance. In principle, these advances should improve normal tissue sparing and permit dose reconstruction and verification, thereby allowing significant biologically effective dose escalation. Recent radiobiological findings can be translated into altered fractionation schemes that aim to improve the local control and long-term survival. This strategy is being tested at the University of Wisconsin using helical tomotherapy with its highly precise delivery and verification system along with meticulous and practical forms of immobilization. Innovative techniques such optical guidance, respiratory gating, and ultrasound assessments are being designed and tailored for helical tomotherapy use. The intrinsic capability of helical tomotherapy for megavoltage CT (MVCT) imaging for IMRT image-guidance is being optimized. The unique features of helical tomotherapy might allow implementation of image-guided IMRT that was previously impossible or impractical. Here we review the technological, physical, and radiobiological rationale for the ongoing and upcoming clinical trials that will use image-guided IMRT in the form of helical tomotherapy; and we describe our plans for testing our hypotheses in a rigorous prospective fashion.

Humans↗
PubMed2006

High-precision radiotherapy: where are we going and how do we get there?

In January 2006, physicians with an interest in urologic cancers met to discuss patient care at the 4th Annual Current Problems in Urology Conference. A portion of the meeting was focused on technical issues in prostate cancer radiotherapy. This portion of the meeting sought to answer the questions: where are we going? And how can we get there? Work performed at the Princess Margaret Hospital (PMH) and the London Regional Cancer Program (LRCP) served as the basis for discussion and to present examples of options for implementation of new techniques. The response to the first question reviewed the issue of improved outcomes with dose escalation and the preliminary implementation of hypofractionated treatment. The impact on toxicity was reviewed in detail. The response to the second question revolved around the options available to ensure adequate tumor localization. As dose is increased, the need to localize the prostate accurately has become more important in order to ensure tumor control and to avoid toxicity. Selection of appropriate margins around the prostate is determined by a center's ability to localize the target. Options to localize organs including three-dimensional ultrasound, fiducial markers, megavoltage CT and cone beam CT were discussed. The basic research to enable selection and implementation of these options were presented.

Humans↗
PubMed2006

Controversies in prostate cancer staging implementation at a tertiary cancer center.

OBJECTIVE: To assess accuracy of recorded prostate cancer stage after implementation of a quality assurance staging improvement plan. METHODS AND MATERIALS: Genitourinary multidisciplinary TNM staging guidelines were prospectively implemented. Educational programs for health records technicians (HRT) and clinicians preceded implementation of the new guidelines. Patient stage information was entered into the Oncology Patient Information System (OPIS) as part of the usual operations of the cancer center by an HRT. Physician and HRT auditors performed a subsequent quality assurance audit on 97 prostate cancer patients seen over a 2-month period. Assessment of staging accuracy and reasons for discrepancies between the OPIS stage and auditor stage were analyzed and reported. RESULTS: Fifty-four (52%) charts showed discrepancies between auditors. Of the fifty-four, twelve (22%) had discrepancies between OPIS and auditor, thirty (56%) showed discrepancies between auditors, and twelve (22%) had discrepancies between OPIS, physician auditor, and HRT auditor. Forty-three (41%) cases had no discrepancies. Reasons for discrepancies included: misinterpretation of the digital rectal examination (16/54), inappropriate use of TRUS/MRI (9/54) in staging, stage not assigned at initial diagnosis (9/54), misinterpretation of pathology (7/54), TNM staging confusion (4/54), OPIS update not performed (3/54), inappropriate use of biopsy data (3/54), disagreement between consultants (2/54), and misinterpretation of TURP result (1/54). Overall staging accuracy was 76% for OPIS, 65% for the physician auditor and 62% for the HRT auditor. CONCLUSIONS: Despite guidelines and educational interventions, computer registry staging accuracy remains an issue. On-going audit procedures are proposed to identify and correct both published and institutional staging guidelines.

Canada↗
PubMed2005

Consolidative abdominopelvic radiotherapy after surgery and carboplatin/paclitaxel chemotherapy for epithelial ovarian cancer.

PURPOSE: To assess the feasibility and morbidity of sequential cytoreductive surgery, carboplatin/paclitaxel chemotherapy, and consolidative abdominopelvic radiotherapy (APRT) in ovarian cancer. METHODS AND MATERIALS: Between 1998 and 2000, 29 patients with optimally cytoreduced epithelial ovarian cancer were treated with carboplatin (135 mg/m2) and paclitaxel (area under the curve [AUC] of 6) followed by APRT in a prospective protocol. All patients were clinically, radiographically, and biochemically (CA-125) free of disease at the completion of chemotherapy. Abdominopelvic radiotherapy was delivered using 6 MV anterior-posterior photon fields to encompass the peritoneal cavity. Median follow-up was 4 years. RESULTS: Two patients experienced Radiation Therapy Oncology Group Grade 3 gastrointestinal toxicity during APRT; 6 patients, Grade 3 or 4 neutropenia; and 3 patients, Grade 3 or 4 thrombocytopenia. Overall, 10 patients had Grade 3 or 4 acute toxicity. All of the acute side effects resolved after treatment was completed, and there were no serious consequences such as sepsis or hemorrhage. Abdominopelvic radiotherapy was abandoned prematurely in 3 patients. Late side effects were seen in 5 patients, including 1 small bowel obstruction, 2 symptomatic sacral insufficiency fractures, 1 case of severe dyspareunia, and 1 case of prolonged fatigue. All resolved with supportive management. The 4-year actuarial disease-free survival was 57%, and the overall survival was 92%. Eleven of 12 patients who relapsed received salvage chemotherapy, which was well tolerated. CONCLUSIONS: Abdominopelvic radiotherapy after optimal surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late side effects and does not limit subsequent salvage chemotherapy. Consolidative APRT warrants further investigation as a means of improving the outcome of patients with ovarian cancer.

Adult↗
PubMed2005

Intensity-modulated arc therapy for treatment of high-risk endometrial malignancies.

PURPOSE: We developed an intensity-modulated arc therapy (IMAT) technique for the treatment of women with high-risk endometrial malignancies. In the context of multimodality therapy, nodal and tumor bed irradiation was delivered while respecting tolerance doses for critical structures. METHODS AND MATERIALS: Five patients were planned and treated with the IMAT technique after hysterectomy. Computed tomographic (CT) scans for treatment planning were acquired with the tumor bed contoured as the clinical target volume (CTV(tumor_bed)) and the iliac and presacral vessels contoured as the gross tumor volume (GTV). In 2 patients the lower para-aortic nodes were included into the GTV. The small bowel, iliac crests, femoral heads, bladder, and rectum were contoured as critical organs. For the nodes, a CTV(nodes) was generated with a 7-10-mm margin around the vessels, and the planning target volume (PTV(nodes)) was generated by a further 5-mm expansion. For the tumor bed, the PTV(tumor_bed) was generated with a margin of 7-10 mm around CTV(tumor_bed). Planning constraints included adequate coverage of the tumor bed (>95% receiving > or =45 Gy) and nodes (> or =95% receiving > or =40 Gy). Arc combinations with different extents were tested, and the final plan was generated based on the balance between complexity (number of arcs), PTV coverage, and critical structure sparing. Conventional and 8-field intensity-modulated radiation therapy (IMRT) plans were generated for each patient for comparison purposes. All patients were treated with IMAT. RESULTS: We found that two anterior intensity-modulated arcs (300 degrees to 30 degrees and 330 degrees to 60 degrees ) adequately treated the PTVs. Furthermore, this IMAT technique allowed sparing of small bowel and the iliac crests (marrow space) to a similar degree as the 8-field IMRT. The 8-field IMRT yielded better dose uniformity than IMAT in the target volumes; however, neither technique was as uniform as the conventional plan. In the 5 patients, IMAT treatment was well tolerated and completed as planned. CONCLUSIONS: We successfully piloted an optimized intensity-modulated arc technique to treat 5 high-risk endometrial cancer patients undergoing multimodality treatment. This allowed a significant reduction in dose to bone marrow and small bowel compared with conventional techniques and was simpler to deliver than multifield IMRT.

Bone Marrow↗
PubMed2004

Prediction of radiation pneumonitis by dose - volume histogram parameters in lung cancer--a systematic review.

BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy. METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data were abstracted from the various reports to calculate operating characteristics and odds ratios for the different DVH metrics. RESULTS: A total of 12 published studies and two abstracts were identified. Eleven studies assessed V(dose), seven assessed MLD, and eight assessed NTCP. Nine studies exclusively analyzed the association between various DVH metrics and RP risk. Five studies also analyzed other patient, tumor, and treatment variables in conjunction with standard DVH metrics. A direct comparison between studies and the generation of summary statistics (i.e. meta-analysis) could not be achieved due to significant predictive and outcome variable heterogeneity. Most studies did show an association between DVH parameters and RP risk. However, overall accuracy, sensitivity, specificity, and positive predictive value were generally poor to fair for all three classes of DVH metrics. CONCLUSIONS: An association between DVH parameters and RP risk has been demonstrated in the literature. However, the ideal DVH metric with excellent operating characteristics, either alone or in a model with other predictive variables, for RP risk prediction has not yet been identified. Several recommendations for reporting and conduct of future research into the association between DVH metrics and RP risk are provided.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Megavoltage computed tomography imaging: a potential tool to guide and improve the delivery of thoracic radiation therapy.

Helical tomotherapy is an innovative means of delivering intensity-modulated radiation therapy (IMRT) using a device that merges features of a linear accelerator and a helical computed tomography (CT) scanner. The tomotherapy unit can generate CT images from the megavoltage radiation it uses for treatment as often as needed during a course of radiation therapy. These megavoltage CT (MVCT) images offer verification of patient position prior to and potentially during radiation therapy, and provide considerably more anatomical detail than the conventional radiation therapy port films used for patient set-up verification. Also, MVCT imaging may enable reconstruction of the radiation dose delivered, thereby providing unprecedented verification of the actual treatment. These key features of helical tomotherapy distinguish it from other IMRT approaches. We report results from a pilot feasibility trial of 10 patients with non-small-cell lung cancer (NSCLC) on whom we obtained MVCT images using a prototype helical tomotherapy system. All patients underwent conventional CT imaging for radiation therapy treatment planning. Specific aims were to subjectively compare MVCT and conventional CT images and then to objectively compare the 2 modalities by contouring tumors and performing a volumetric comparison. Seven patients had disease located primarily in the lung parenchyma, 2 primarily in the mediastinum, and 1 in both. When evaluated by location, all 7 patients with lesions primarily in the lung parenchyma had subjectively high-quality MVCT images. Objectively, the volumetric agreement between conventional and MVCT for parenchymal lesions was excellent in 5 of the 7 patients. Megavoltage CT imaging via the helical tomotherapy prototype provided adequate information for use in verification of patient position and dose reconstruction for lesions within the pulmonary parenchyma, but presently appears suboptimal for primarily mediastinal disease. Further studies are ongoing to optimize MVCT imaging and better define its utility in patients with NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Determination of laboratory reference ranges for lymphocyte immunophenotype subsets in healthy adult Japanese using flow cytometry.

This study represents a comprehensive evaluation of normative values for lymphocyte immunophenotype subsets using flow cytometry techniques in a Japanese population. Lymphocyte reference ranges were determined for percentage and absolute count of T, B, and NK cells in healthy adult Japanese using an extensive two-color immunophenotyping panel and consistently applied quality control methodology. Reference values were also determined for activation markers on CD3+ lymphocytes CD3+/CD25+, CD3+/CD38+ and CD3+/HLA-DR+. Differences in age and gender were observed for specific lymphocyte subsets. Comparison of the Japanese study with a Thai multi-center study that used similar methodology also demonstrated ethnic differences in lymphocyte reference ranges. The results in this study strongly suggest that reference values derived from studies in one population may not be applied to another population even when similar protocols for reagents, instruments and procedures are used although such studies do appear useful for epidemiological comparisons.

ADP-ribosyl Cyclase↗
PubMedDate not supplied

Minimal decrease in hot flashes desired by postmenopausal women in family practice.

OBJECTIVE: To determine the minimal important difference in the frequency and severity of hot flashes that postmenopausal women desire from a nonhormonal agent. DESIGN: Women recorded their number of hot flashes daily, along with their degree of severity, using a diary for 1 week and completed the Menopause-Specific Quality of Life Questionnaire. Women were asked to report the percentage reduction in hot flashes that they would find clinically important. Distribution-based estimates were used to estimate the minimal important difference. RESULTS: Approximately 69% of the postmenopausal women who reported their hot flashes as moderate to severe responded that they wanted a nonhormonal agent that provided at least a 50% mean reduction in the frequency of hot flashes (95% CI, 32% to 66%). Median hot flash reduction for all respondents was 50%. CONCLUSIONS: The minimal clinically important difference in hot flashes is approximately 50%. This estimate can provide the basis to calculate sample size in clinical trials of anti-hot flash agents and in selecting possible candidates for investigation.

Aged↗
PubMedDate not supplied

Oxybutynin for refractory hot flashes in cancer patients.

OBJECTIVE: There is little information available on the treatment of hot flashes in patients refractory to pharmaceutical interventions. Anecdotal evidence led to the use of oxybutynin for the management of hot flashes in refractory cancer patients; therefore, we performed a retrospective chart review of such patients to determine the effect of oxybutynin in treating hot flashes and to observe the side effects of the drug in these patients. DESIGN: A prospective database of all patients treated for hot flashes was started in July 2004 and was retrospectively analyzed as of March 2006. Also included were individual charts preceding July 2004. Fifty-two patient charts were examined. Demographic information was obtained along with baseline severity and frequency of hot flashes, dose and duration of treatment with oxybutynin, patient response to oxybutynin, and side effects. RESULTS: More than 90% of patients analyzed were refractory to hot flash treatments before starting oxybutynin. Seventy percent of patients showed a partial or excellent response to oxybutynin. The duration of oxybutynin use ranged from 2 weeks to 5 years with more than half of patients currently on oxybutynin or taking oxybutynin for longer than 6 months. Of those patients who experienced an excellent or partial response to treatment, 12% stopped because of documented oxybutynin-related side effects within 4 weeks. CONCLUSION: Oxybutynin seems promising in the management of hot flashes with tolerable side effects in the majority of refractory patients. A placebo-controlled, randomized study is being developed to look more closely at the effectiveness of oxybutynin in reducing hot flashes.

Adult↗
PubMedDate not supplied

[Evaluation of atypical stab and incision wounds in a case of combined suicidal injuries].

A fatal case of stabbing and cutting is reported which involved a 37-year-old male who suffered from depressive disorder and had already attempted suicide in the past. The postmortem examination revealed 12 lacerations of the scalp, 5 deep incised wounds on the flexor surface of the right forearm, 3 stab wounds of the back of the head, 12 stab wounds of the chest (with cutting of ribs but no injury of heart and lungs), 35 stab wounds of the abdomen and deep incised wounds of both sides of the neck with hesitation marks and incision of the left internal jugular vein. The significance of criteria to properly establish the manner of death like localization, axis and pattern of the wounds, hesitation marks, defense wounds, pulling aside the clothing to expose the target area, sustained capacity of physical activity and potential lethal effects of the single injuries as well as conclusions from the scene of death are discussed.

Adult↗