Biomedical subjects

M Roach

Publications and source records attributed to M Roach.

At least 19 recordsLinked to original sources

PubMed2006

The use of megavoltage cone-beam CT to complement CT for target definition in pelvic radiotherapy in the presence of hip replacement.

In Europe and the USA combined, over half a million people had a hip joint replaced in 2005, contributing to the increasing number of radiotherapy patients with metallic hip prostheses. The treatment plan for external beam radiation therapy is based on the delineation of the anatomy in the planning CT scan. When implanted objects of high atomic number (Z) material are present, however, severe image artefacts are generated in conventional CT, strongly hindering the ability to delineate some organs. This is particularly the case for the planning of prostate patients with hip prostheses. This short communication presents the use of a new imaging modality, megavoltage cone-beam CT, to complement the regular CT for target definition of prostate cancer treatment of patients with hip replacements.

Hip Prosthesis↗

PubMed2006

[Megavoltage cone-beam CT: Recent developments and clinical applications].

The Megavoltage cone-beam (MV CBCT) system consists of a new a-Si flat panel adapted for MV imaging and an integrated workflow application allowing the automatic acquisition of projection images, cone-beam CT image reconstruction, CT to CBCT image registration and couch position adjustment. This provides a 3D patient anatomy volume in the actual treatment position, relative to the treatment isocenter, moments before the dose delivery, that can be tightly aligned to the planning CT, allowing verification and correction of the patient position, detection of anatomical changes and dose calculation. In this paper, we present the main advantages and performance of this MV CBCT system and summarize the different clinical applications. Examples of the image-guided treatment process from the acquisition of the MV CBCT scan to the correction of the couch position and dose delivery will be presented for spinal and lung lesions and for head and neck, and prostate cancers.

Head and Neck Neoplasms↗

PubMed2004

Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: Radiation Therapy Oncology Group Trial 92-02.

PURPOSE: The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT) -treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. PATIENTS AND METHODS: There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. RESULTS: Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P =.08), BF (P =.0445), DM (P <.0001), CSD (P <.0001), and OD (P =.0094). When categoric variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The 7.1% cut point was related to BF (P =.09), DM (P =.0008), and CSD (P =.017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. CONCLUSION: Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.

Adult↗

PubMed2004

The use of hormonal therapy with radiotherapy for prostate cancer: analysis of prospective randomised trials.

In 1901, Wilhelm Conrad Röntgen won the Nobel prize in Physics for his discovery of the Röntgen rays or, as he himself called them, X-rays. In 1966, Dr Charles Brenton Higgins won the Nobel Prize in Medicine for his breakthroughs concerning hormonal treatment of prostatic cancer. After 31 years, in 1997, the first prospective randomised trials of the combination of hormonal therapy and radiation therapy were published, showing increased survival when compared to radiation therapy alone for patients with prostate cancer. Since 1997, many investigators have published trials combining hormonal and radiation therapy for prostate cancer. This minireview will address the largest and most influential of these trials, and attempt to guide physicians in selecting the appropriate patients for this combined approach.

Antineoplastic Agents, Hormonal↗

PubMed2004

Outcomes research in cancer clinical trial cooperative groups: the RTOG model.

BACKGROUND: The Radiation Therapy Oncology Group (RTOG), a National Cancer Institute sponsored cancer clinical trials research cooperative, has recently formed an Outcomes Committee to assess a comprehensive array of clinical trial endpoints and factors impacting the net effect of therapy. METHODS: To study outcomes in a consistent, comprehensive and coordinated manner, the RTOG Outcomes Committee developed a model to assess clinical, humanistic, and economic outcomes important in clinical trials. RESULTS: This paper reviews how the RTOG incorporates outcomes research into cancer clinical trials, and demonstrates utilization of the RTOG Outcomes Model to test hypotheses related to non-small-cell lung cancer (NSCLC). In this example, the clinical component of the model indicates that the addition of chemotherapy to radiotherapy (RT) improves survival but increases the risk of toxicity. The humanistic component indicates that esophagitis is the symptom impacting quality of life the greatest and may outweigh the benefits in elderly (> or =70 years) patients. The economic component of the model indicates that accounting for quality-adjusted survival, concurrent chemoRT for the treatment of NSCLC is within the range of economically acceptable recommendations. CONCLUSION: The RTOG Outcomes Model guides a comprehensive program of research that systematically measures a triad of endpoints considered important to clinical trials research.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Evaluation of ultrasound-based prostate localization for image-guided radiotherapy.

To evaluate the use of the ultrasound-based BAT system for daily prostate alignment. Prostate alignments using the BAT system were compared with alignments using radiographic images of implanted radiopaque markers. The latter alignments were used as a reference. The difference between the BAT and marker alignments represents the displacements that would remain if the alignments were done using ultrasonography. The inter-user variability of the contour alignment process was assessed. On the basis of the marker alignments, the initial displacement of the prostate in the AP, superoinferior, and lateral direction was -0.9 +/- 3.9, 0.1 +/- 3.9, and 0.2 +/- 3.4 mm respectively. The directed differences between the BAT and marker alignments in the respective directions were 0.2 +/- 3.7, 2.7 +/- 3.9, and 1.6 +/- 3.1 mm. The occurrence of displacements >/=5 mm was reduced by a factor of two in the AP direction after the BAT system was used. Among eight users, the average range of couch shifts due to contour alignment variability was 7, 7, and 5 mm in the antero-posterior (AP), superoinferior, and lateral direction, respectively. In our study, the BAT alignments were systematically different from the marker alignments in the superoinferior, and lateral directions. The remaining random variability of the prostate position after the ultrasound-based alignment was similar to the initial variability. However, the occurrence of displacements >/=5 mm was reduced in the AP direction. The inter-user variation of the contour alignment process was significant.

Humans↗

PubMed2003

Loss of p16 expression is of prognostic significance in locally advanced prostate cancer: an analysis from the Radiation Therapy Oncology Group protocol 86-10.

PURPOSE: The retinoblastoma (RB) cell cycle regulatory pathway is known to be deregulated in virtually all known human tumors. The protein product of the RB gene, pRB, and its upstream regulator, p16, are among the most commonly affected members of this pathway. We investigated the prognostic significance of both pRB and p16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86-10. MATERIALS AND METHODS: Sixty-seven cases from RTOG 86-10 had immunohistochemically stained slides, judged interpretable for both p16 and pRB, available for analysis. Median follow-up was 8.9 years (range, 6.0 to 11.8 years) for surviving patients. Staining for each marker was then correlated with overall survival, local progression, distant metastasis, and disease-specific survival. RESULTS: Loss of p16 expression, as defined by expression was significantly associated with reduced overall survival (P =.039), disease-specific survival (P =.006), and higher risk of local progression (P =.0007) and distant metastasis (P =.026) in the univariate analysis. In the multivariate analysis, loss of p16 was significantly associated with reduced disease-specific survival (P =.0078) and increased risk of local failure (P =.0035) and distant metastasis (P =.026). A borderline association with reduced overall survival (P =.07) was also evident. Loss of pRB was associated with improved disease-specific survival on univariate (P =.028) and multivariate analysis (P =.043), but carried no other significant outcome associations. CONCLUSION: Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer.

Adult↗

PubMed2003

Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413.

PURPOSE: This trial tested the hypothesis that combined androgen suppression (CAS) and whole-pelvic (WP) radiotherapy (RT) followed by a boost to the prostate improves progression-free survival (PFS) by 10% compared with CAS and prostate-only (PO) RT. This trial also tested the hypothesis that neoadjuvant and concurrent hormonal therapy (NCHT) improves PFS compared with adjuvant hormonal therapy (AHT) by 10%. MATERIALS AND METHODS: Eligibility included localized prostate cancer with an elevated prostate-specific antigen (PSA) < or = 100 ng/mL and an estimated risk of lymph node (LN) involvement of 15%. Between April 1, 1995, and June 1, 1999, 1,323 patients were accrued. Patients were randomly assigned to WP + NCHT, PO + NCHT, WP + AHT, or PO + AHT. Failure for PFS was defined as the first occurrence of local, regional, or distant disease; PSA failure; or death for any cause. RESULTS: With a median follow-up of 59.5 months, WP RT was associated with a 4-year PFS of 54% compared with 47% in patients treated with PO RT (P =.022). Patients treated with NCHT experienced a 4-year PFS of 52% versus 49% for AHT (P =.56). When comparing all four arms, there was a progression-free difference among WP RT + NCHT, PO RT + NCHT, WP RT + AHT, and PO RT + AHT (60% v 44% v 49% v 50%, respectively; P =.008). No survival advantage has yet been seen. CONCLUSION: WP RT + NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT, and compared with WP RT + AHT in patients with a risk of LN involvement of 15%.

Aged↗

PubMed2003

What does postradiotherapy PSA nadir tell us about freedom from PSA failure and progression-free survival in patients with low and intermediate-risk localized prostate cancer?

OBJECTIVES: To determine whether the post-external beam radiotherapy (RT) prostate-specific antigen nadir (nPSA) improves our ability to predict freedom from PSA failure, progression-free survival (PFS), and overall survival. Controversy regarding the importance of nPSA after external beam RT as a prognostic indicator for patients with localized prostate cancer has continued. METHODS: This analysis was based on the data from 748 patients with low and intermediate-risk localized prostate cancer treated with external beam RT alone. Patients were categorized by nPSA quartile groups with cutpoints of less than 0.3, 0.3 to less than 0.6, 0.6 to less than 1.2, and 1.2 ng/mL or greater. Both univariate and multivariate analyses were used to determine the significance of nPSA on PSA failure (American Society for Therapeutic Radiology Oncology consensus definition), PFS (death after PSA failure), and overall survival (death from any cause). RESULTS: Freedom from PSA failure was strongly associated with nadir quartile groups (P <0.0001). PFS was also significantly different statistically among nadir quartile groups (P = 0.02). No statistically significant difference was found in overall survival associated with nPSA at this point. CONCLUSIONS: nPSA is a strong independent predictor of freedom from PSA failure and PFS in patients with low and intermediate-risk localized prostate cancer treated with RT alone. Longer follow-up and larger patient numbers are required to confirm these observations.

Adenocarcinoma↗

PubMed2001

Changing face and different countenances of prostate cancer: racial and geographic differences in prostate-specific antigen (PSA), stage, and grade trends in the PSA era.

The purpose of this investigation was to examine changes in pretreatment prostate-specific antigen (PSA), stage, and grade over the past decade as a function of race and geographic region. A multiinstitutional database representing 6,790 patients (1,417 African-American, 5,373 white) diagnosed with nonmetastatic prostate cancer between 1988 and 1997 was constructed. PSA, stage, and grade data were tabulated by calendar year and region, and time trend analyses based on race and region were performed. There was an overall decline of PSA of 0.8%/year, which was significant (P = 0.0001), with a faster rate of decline in African-Americans (1.9%/year) than for whites (0.6%/year). The odds ratio (OR) for a stage shift was 1.09, which was significant (P < 0.0001), and this shift was greater in whites. The OR for an overall grade shift was 1.15, which was significant (P < 0.0001). Although grade and PSA trends were similar for the different regions, there were significant regional differences in stage trends. The implications are that the face of prostate cancer has changed over the past decade; i.e., the distributions of stage, grade, and PSA (the most important prognosticators) have changed. In addition, the countenances of that face are different for whites and African-Americans. For African-Americans, this is good news: the stage, grade, and PSA distributions are more favorable now than before. For whites, the trends are more complex and more dependent on region. These findings should be used for future clinical and health-policy decisions in the screening and treatment of prostate cancer.

Black People↗

PubMed2001

Forward or inversely planned segmental multileaf collimator IMRT and sequential tomotherapy to treat multiple dominant intraprostatic lesions of prostate cancer to 90 Gy.

PURPOSE: To investigate the technical feasibility of using forward or inversely planned segmental multileaf collimator (SMLC) intensity-modulated radiotherapy and sequential tomotherapy (ST) to escalate to a dose of 90 Gy to multiple dominant intraprostatic lesions within the prostate gland while delivering a dose of 75.6 Gy to the remaining prostate. METHODS AND MATERIALS: A selected case with one dominant intraprostatic lesion located at the left base and a second dominant intraprostatic lesion at the right apex of the prostate was planned using three different intensity modulation techniques. Two plans were generated with inverse treatment planning, using either SMLC or ST with a special multivane collimator. The third plan also employed SMLC but was generated using forward planning. All three plans were compared based on dose-volume histograms, isodose distributions, and doses to sensitive normal structures. RESULTS: All three plans meet and exceed the desired dose constraints, limiting doses to the rectum and bladder to an estimated RTOG Grade 2 complication rate of <10%. The ST plan achieved the best dose conformality, whereas the inverse SMLC plan gave the lowest dose to the rectal wall, and the forward SMLC plan obtained the best dose homogeneity inside the targets. CONCLUSIONS: Using any of the three intensity-modulated techniques, it is technically feasible to concurrently treat multiple selected high-risk regions within the prostate to 90 Gy and the remaining prostate to 75.6 Gy, while keeping the doses to the rectum and the bladder significantly lower than those associated with a Grade 2 complication rate of 10%.

Feasibility Studies↗

PubMed2001

Clinical staging of prostate cancer: reproducibility and clarification of issues.

The American Joint Committee on Cancer (AJCC) staging system for prostate cancer adopted in 1992 is based on tumor-node-metastasis (TNM) designations. It has been widely accepted for use in local and advanced disease. The purpose of this study was to assess reproducibility of staging among observers and to help clarify staging issues. Twelve prostate cancer cases were sent to 20 physicians with special expertise in prostate cancer including eight urologists, eight radiation oncologists, and four medical oncologists. Physicians were asked to assign a stage based on the 1992 AJCC clinical staging. The most frequently reported stage assigned to each case was taken to be the consensus. Agreement was the percentage of physicians who reported that particular stage. Seventy-five percent of the physicians responded. The overall agreement for assignment of T stage was 63.9%. Differences were found by specialty for inclusion of available information in designating a T stage. The overall agreement for N stage was 73.8%. The most common designation was Nx regardless of availability of a computed tomography scan. The overall agreement for M stage was 76.6%. Without a bone scan the most common designation was Mx regardless of Gleason grade or prostate-specific antigen (PSA). A frequent comment was that PSA was more indicative of disease extent than current clinical staging. The reproducibility of the 1992 clinical AJCC staging is poor even among experts in the field. This problem arises primarily from disagreement regarding which studies are included in assigning a stage. Some of these difficulties are addressed in the 1997 revision. However, the clinical staging does not address the true biological significance of disease in many instances.

Humans↗

PubMed2001

Toxicity following high-dose three-dimensional conformal and intensity-modulated radiation therapy for clinically localized prostate cancer.

OBJECTIVES: To report the toxicity profile of patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) receiving doses of 82 Gy or more to portions of their prostate. METHODS: Forty-four patients treated with radiation therapy for prostate cancer between June 1992 and August 1998 at the University of California, San Francisco received a maximal dose within the target volume (Dmax) of 82 Gy or more. Eighteen patients were boosted selectively to a limited portion of their prostate using IMRT, whereas 26 patients were treated with 3D-CRT and had unselected "hot spots" within their prostate. The Radiation Therapy Oncology Group (RTOG) acute and late toxicity scales were used to score gastrointestinal (GI) and genitourinary (GU) morbidity. RESULTS: Median follow-up and Dmax were 23.1 months (range 10.0 to 84.7) and 84.5 Gy (range 82.0 to 96.7), respectively. Of the patients, 59.1% and 34.1% developed some level of acute GU and GI toxicity, respectively. One patient experienced grade 3 acute GI toxicity. No other grade 3 or greater acute toxicity was observed. The 2-year actuarial rates for freedom from late GI and GU morbidity were 77.1% (95% confidence interval [CI] 60.4% to 87.5%) and 79.5% (95% CI 62.7% to 89.3%), respectively. Although no grade 3 or greater late GU morbidity has been observed to date, 3 patients experienced grade 3 late GI morbidity. However, these cases involved rectal bleeding and were effectively managed with laser coagulation/fulguration. CONCLUSIONS: Doses of 82 Gy or more to a portion of the prostate gland can be tolerated with acceptable morbidity. This observation supports the continued investigation of IMRT as a means for improving disease control in prostate cancer.

Aged↗

PubMed2001

Dose of radiation received by the bulb of the penis correlates with risk of impotence after three-dimensional conformal radiotherapy for prostate cancer.

OBJECTIVES: To evaluate the effect of the dose to the bulb of the penis on postradiation potency. METHODS: Twenty-one patients reporting potency before three-dimensional conformal radiotherapy had the dose delivered to the bulb of the penis evaluated. This was then compared with the patient assessments of post-treatment sexual function to determine whether a dose-volume relationship exists. RESULTS: Among the patients analyzed to date, a strong dose-volume relationship and the likelihood of remaining potent after treatment seems to exist. Patients receiving a dose of less than 40 Gy to 70% of the bulb of the penis appear to have a much greater likelihood of maintaining potency. Patients receiving 70 Gy or more to 70% of the bulb of the penis appear to be at very high risk of experiencing radiation-induced impotence (P = 0.03). CONCLUSIONS: More studies are needed to confirm these observations. If confirmed, these data suggest that by using three-dimensional-based treatment planning and carefully designed treatment fields, the potency of men treated with radiotherapy might be substantially improved.

Aged↗

PubMed2001

Brachytherapy for prostate cancer: endorectal MR imaging of local treatment-related changes.

PURPOSE: To determine the local treatment-related endorectal magnetic resonance (MR) imaging findings after brachytherapy for prostate cancer. MATERIALS AND METHODS: Endorectal MR imaging was performed in 35 consecutive patients at a mean interval of 12 months (range, 1-31 months) after brachytherapy for prostate cancer. Transverse T1-weighted and high-spatial-resolution transverse and coronal T2-weighted images were acquired. Two readers reviewed MR image quality and findings, with discrepancies resolved by consensus. Posttreatment urinary symptoms in patients (n = 24) were documented by using chart review. RESULTS: All studies were of diagnostic quality. On T2-weighted images, prostatic findings consisted of diffuse low signal intensity (n = 35) and indistinct zonal anatomy (n = 34). Intra- and extraprostatic seed locations could be distinguished. The most common extraprostatic site of seed implantation was the neurovascular bundles (n = 35, bilateral in 32). The most common extraprostatic tissue finding was increased signal intensity on T2-weighted images in the levator ani muscle (n = 34) and the genitourinary diaphragm (n = 28). Postbrachytherapy urinary symptoms showed no demonstrable correlation with periurethral or genitourinary diaphragm seed implantation or with signal intensity change in the genitourinary diaphragm. CONCLUSION: Endorectal MR imaging can be used to evaluate seed distribution and to demonstrate treatment-related changes after brachytherapy for prostate cancer.

Brachytherapy↗

PubMed2001

The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure.

The lipid mediator prostaglandin E2 (PGE2) has diverse biological activity in a variety of tissues. Four different receptor subtypes (EP1-4) mediate these wide-ranging effects. The EP-receptor subtypes differ in tissue distribution, ligand-binding affinity, and coupling to intracellular signaling pathways. To identify the physiological roles for one of these receptors, the EP1 receptor, we generated EP1-deficient (EP1-/-) mice using homologous recombination in embryonic stem cells derived from the DBA/1lacJ strain of mice. The EP1-/- mice are healthy and fertile, without any overt physical defects. However, their pain-sensitivity responses, tested in two acute prostaglandin-dependent models, were reduced by approximately 50%. This reduction in the perception of pain was virtually identical to that achieved through pharmacological inhibition of prostaglandin synthesis in wild-type mice using a cyclooxygenase inhibitor. In addition, systolic blood pressure is significantly reduced in EP1 receptor-deficient mice and accompanied by increased renin-angiotensin activity, especially in males, suggesting a role for this receptor in cardiovascular homeostasis. Thus, the EP1 receptor for PGE2 plays a direct role in mediating algesia and in regulation of blood pressure.

Animals↗

PubMed2001

Stage II (N1) lung cancer.

As therapies evolve and mature, the authors predict that the next 20 years will see significant advances in the understanding of non-small-cell lung cancer (NSCLC), in molecular stratification of NSCLC, and significant improvement in survival and cure rates. This survival will be achieved through early detection and combined treatments using effective surgical interventions, improved radiotherapeutics, and especially significantly enhanced, rationally designed systemic therapies.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study.

OBJECTIVE: To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder. SUBJECTS AND METHODS: The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline. RESULTS: A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups. CONCLUSIONS: Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.

Aged↗