PubMed HealthSearch

Biomedical subjects

W Curran

Publications and source records attributed to W Curran.

At least 19 recordsLinked to original sources

Influence of bromodeoxyuridine radiosensitization on malignant glioma patient survival: a retrospective comparison of survival data from the Northern California Oncology Group (NCOG) and Radiation Therapy Oncology Group trials (RTOG) for glioblastoma multiforme and anaplastic astrocytoma.

PURPOSE: To examine the effect of treatment using Bromodeoxyuridine (BrdU) during radiation therapy on malignant glioma patient survival by comparing historical survival data from several large clinical trials. METHODS: A retrospective analysis of patient data from Radiation Therapy Oncology Group (RTOG) trials 74-01, 79-18, and 83-02 and the Northern California Oncology Group (NCOG) study 6G-82-1 was conducted. Patient data was supplied by both groups, and analyzed by the RTOG. Pretreatment characteristics including age, extent of surgery, Karnofsky Performance Status (KPS), and histopathology were collected; the only treatment variable evaluated was the use of BrdU during radiation therapy. Radiation dose, dose-fractionation schedule, use of chemotherapy, and/or type of chemotherapy was not controlled for in the analyses. Univariate and multivariate analyses were conducted to examine the potential treatment effect of BrdU on patient survival. RESULTS: Data from 334 patients treated with BrdU on NCOG 6G-82-1 and 1743 patients treated without BrdU on 3 RTOG studies was received. Patients were excluded from the review if confirmation of eligibility could not be obtained, if the patient was ineligible for the study they entered, if central pathology review was not done, or if radiotherapy data was not available. Patients treated according to the RTOG studies had to start radiotherapy within 4 weeks of surgery; no such restriction existed for the NCOG studies. To ensure comparability between the studies, patients from the NCOG studies who began treatment longer than 40 days from surgery were also excluded. The final data set included 296 cases from the NCOG studies (89%) and 1478 cases from the RTOG studies (85%). For patients with glioblastoma multiforme (GBM) the median survival was 9.8 months in the RTOG studies and 13.0 months in the NCOG trial (p < 0.0001). For patients with AA the median survival was 35.1 months for the RTOG studies and 42.8 months in the NCOG trial (p = 0.126). Univariate results showed consistent results favoring BrdU among patients over 30 years of age, across the extent of surgery, and for GBM patients. A proportional hazards regression model that included treatment, histopathology, KPS, age, and extent of surgery demonstrated that treatment with BrdU was included in the best model only for the GBM group of patients (risk ratio 0.83). CONCLUSIONS: Because of the heterogeneity of the treatment groups, including potentially important differences in pathology reviewers assessment of nonglioblastoma cases, differences in radiation dose and schedules, and chemotherapy during or after radiation, these analyses cannot provide the definitive answer as to whether BrdU given during radiation therapy improves survival in patients with malignant glioma. There does appear to be a favorable treatment effect seen in patients with GBM, with a lesser effect in patients with AA.

Adolescent

A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104.

PURPOSE: To compare 1-year survival and acute toxicity rates between an accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis. METHODS AND MATERIALS: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionation vs. standard fractionation from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastasis were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. For AH, 32 Gy in 20 fractions over 10 treatment days (1.6 Gy twice daily) was delivered to the whole brain. A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margin. RESULTS: The average age in both groups was 60 years; nearly two-thirds of all patients had lung primaries. Of the 429 eligible and analyzable patients, the median survival time was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in the AH arm. No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms. Recursive partitioning analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 years of age, and brain metastases only (RPA class I), had a 1-year survival of 35% in the AF arm vs. 25% in the AH arm (p = 0.95). In a multivariate model, only age, KPS, extent of metastatic disease (intracranial metastases only vs. intra- and extracranial metastases), and status of primary (controlled vs. uncontrolled) were statistically significant (at p < 0.05). Treatment assignment was not statistically significant. Overall Grade III or IV toxicity was equivalent in both arms, and one fatal toxicity at 44 days secondary to cerebral edema was seen in the AH arm. CONCLUSION: Although a previous RTOG Phase I/II report had suggested a potential benefit in patients with limited metastatic disease, a good Karnofsky performance status, or neurologic function when treated with an AH regimen, this randomized comparison could not demonstrate any improvement in survival when compared to a conventional regimen of 30 Gy in 10 fractions. Therefore, this accelerated hyperfractionated regimen to 54.4 Gy cannot be recommended for patients with intracranial metastatic disease.

Adult

Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02.

PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. RESULTS: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. CONCLUSION: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis.

Antineoplastic Agents, Alkylating

Quality of life and neuropsychological evaluation for patients with malignant astrocytomas: RTOG 91-14. Radiation Therapy Oncology Group.

UNLABELLED: With increasingly aggressive neurosurgical and radiation therapy modalities (gamma knife, external beam stereotactic radiation and interstitial brachytherapy with or without hyperthermia) offered to patients with malignant astrocytomas (MA), increasing national demand for medical outcome studies and rising health care costs amidst public, business, and governmental debate to cut spending, we as physicians are obligated to continue our research to find effective treatments for malignant astrocytoma (MA) and a cost-effective means to study their impact upon the patient's quality of life (QOL). PURPOSE: We report data that was collected within the Radiation Therapy Oncology Group (RTOG) on 126 patients with MA who were enrolled in RTOG 91-14. This study was undertaken to prospectively test the feasibility of performing quality of life (QOL) and neuropsychological evaluation (NPE) and collecting this data within the RTOG. RESULTS: The NPE and QOL parameters that were used in this study are cost effective. They are not only much cheaper than formal cognitive and memory testing, but also provide additional information regarding the patients' day to day functional abilities that are not provided by the current routinely used means, such as KPS. The Mini-Mental Status Exam (MMSE) provides greater sensitivity to patients' differences in neurological status and may be preferable to NFS as an eligibility criteria.

Activities of Daily Living

Randomized study of chemotherapy/radiation therapy combinations for favorable patients with locally advanced inoperable nonsmall cell lung cancer: Radiation Therapy Oncology Group (RTOG) 92-04.

PURPOSE: The purpose of this study was to compare the severity and distribution of the toxicities associated with the two different combinations of chemotherapy and radiotherapy. METHODS AND MATERIALS: This prospective randomized trial studied toxicities associated with induction chemotherapy followed by concurrent treatment (Arm 1) vs. immediate concurrent chemotherapy/radiotherapy (CT/RT) (Arm 2). Arm 1 consisted of vinblastine (VB), 5 mg/M2 I.V. bolus weekly, weeks 1-5 and cisplatin (DDP), 100 mg/M2 days 1 and 29, DDP 75 mg/M2, days 50, 71, and 92. Daily RT started on day 50; a total dose of 63 Gy was given in 34 fractions in 7 weeks. In Arm 2 RT started day 1; a total dose of 69.6 Gy was given in 58 fractions of 1.2 Gy bid, 5 days per week for 6 weeks with DDP 50 mg/M2 i.v. days 1 and 8, and oral VP-16 50 mg b.i.d. during the first 10 days of RT. DDP/VP-16 were repeated beginning day 29. Survival was used as the Phase II endpoint. RESULTS: Between July 1992 and February 1994, 168 patients were randomized; 162 evaluable patients had minimum follow-up of 20 months. Eighty patients were registered to Arm 1 and 82 to Arm 2. Pretreatment characteristics were distributed evenly. Arm 1 had significantly more Grade 4 hematologic toxicity (62%) than Arm 2 (33%) (p = 0.021). Acute nonhematologic Grade 3+ toxicity was also greater (p = 0.018) in Arm 2 than Arm 1 due mainly to esophagitis (38 vs. 6%; p < 0.0001). Grade 3+ late esophageal toxicity was 12% on Arm 2 compared to 3% on Arm 1 (p = 0.006). There were no differences between the two arms in compliance with protocol specifications for either RT or CT. At 1 year, 31.7% of patients had in-field progression on Arm 1 compared to 19.8% on Arm 2 (p = 0.042), but overall progression-free survival rates were nearly identical; 50 and 49% for Arms I and II, respectively, at 12 months. One-year and median survivals were 65% and 15.5 months on Arm 1 compared to 58% and 14.4 months on Arm 2. CONCLUSION: Whereas hematologic toxicity was greater in Arm 1, esophageal toxicity, both acute and late, was greater in Arm 2. Infield progression was lower in Arm 2, but overall progression rates were similar and there were no significant differences in survival between the two arms. A 3-arm randomized Phase III study is underway in the RTOG to compare sequential and concurrent CT/RT.

Antineoplastic Combined Chemotherapy Protocols

Induction paclitaxel and carboplatin followed by concurrent chemoradiotherapy in patients with unresectable, locally advanced non-small cell lung carcinoma: report of Fox Chase Cancer Center study 94-001.

The paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/carboplatin combination has demonstrated promising activity in patients with incurable non-small cell lung cancer (NSCLC). Our exploratory study is designed to evaluate the efficacy of this combination as induction therapy in patients with locally advanced NSCLC, to determine the maximally tolerated doses of paclitaxel and carboplatin administered every 3 weeks during radical thoracic radiation after induction treatment, and to determine the efficacy of granulocyte colony-stimulating factor (G-CSF) priming before induction treatment, followed by conventional G-CSF, compared with conventional G-CSF alone. Eligibility stipulated Karnofsky performance status > or =70%, < or =5% weight loss, and stages IIIB or bulky IIIA NSCLC. Induction treatment consisted of two cycles of paclitaxel 175 to 225 mg/m2 infused over 3 hours combined with carboplatin (target area under the concentration-time curve of 7.5) given on days 1 and 22. On days 2 through 15 and 23 through 36, all patients received G-CSF 5 microg/kg; half were randomized to receive priming G-CSF daily for 5 days before day 1 of treatment. On day 43, thoracic radiation (60 Gy in 30 2-Gy fractions daily, 5 days a week for 6 weeks) was initiated. At dose level 1, patients received carboplatin dosed to a target area under the concentration-time curve of 3.75 and paclitaxel 67.5 mg/m2 over 3 hours on days 43 and 64. In the absence of dose-limiting toxicity, phase I escalation in three-patient cohorts proceeded to a maximum carboplatin area under the concentration-time curve of 5.0 and a paclitaxel dose of 175 mg/m2, delivered over 3 hours. To date, 35 patients (83% stage IIIB) have received induction treatment, 29 of whom are evaluable for response. Myelosuppression and neurotoxicity have been mild during induction treatment, prompting a paclitaxel dose increase to 225 mg/m2 on days 1 and 22 after the first seven patients were accrued. The phase III portion of the study evaluating G-CSF priming remains coded. Sixteen patients have received concurrent thoracic radiation and chemotherapy and are evaluable for response and toxicity. In sequential cohorts, the paclitaxel dose on days 43 and 64 has been escalated to 175 mg/m2 with only one episode each of grade 4 granulocytopenia and grade 3 anemia. In the first 13 patients evaluated, the severity of esophagitis corresponded to the length of the esophagus in the radiation treatment field: grade 1 in all six patients with esophageal exposure < or =16 cm and grade > or =2 in six of seven patients with > or =16 cm of the esophagus irradiated. Three episodes of grade > or =2 steroid-responsive pulmonary toxicity have occurred 2 to 6 months after the conclusion of concurrent thoracic radiation and chemotherapy. The major response rate is 38% to induction treatment and 59% to combined-modality treatment. Of the first 21 patients accrued, 62% survived 1 year. Induction paclitaxel/carboplatin therapy is active and well tolerated by patients with locally advanced NSCLC. The maximum tolerated doses of paclitaxel and carboplatin during concurrent thoracic radiation and the role of G-CSF priming are not yet established. Severity of esophagitis corresponds to the extent of esophagus irradiated during concurrent thoracic radiotherapy and chemotherapy.

Adult

Phase III study of interstitial thermoradiotherapy compared with interstitial radiotherapy alone in the treatment of recurrent or persistent human tumors. A prospectively controlled randomized study by the Radiation Therapy Group.

PURPOSE: The objectives of this randomized trial were to determine if interstitial thermoradiotherapy (ITRT) improves tumor regression/control in accessible lesions in comparison with interstitial radiotherapy (IRT) alone and to assess the skin and soft tissue complications with either modality. METHODS AND MATERIALS: From January 1986 to June 1992, 184 patients with persistent or recurrent tumors after previous radiotherapy and/or surgery, which were amenable to interstitial radiotherapy, were accessioned to a protocol developed by the Radiation Therapy Oncology Group (RTOG). One hundred seventy-three cases were analyzed (87 patients in the IRT group and 86 in the ITRT arm). The two arms were well balanced regarding stratification criteria. Most tumors were in the head and neck (40% in the IRT group and 46% in the ITRT group), and pelvis (42% and 43%, respectively). Eighty-four percent of patients in both arms had prior radiation therapy (> or = 40 Gy); 50% and 40%, respectively, had prior surgery, and 34% in each arm had prior chemotherapy. The dose of radiation therapy administered was dependent on the previous radiation dose and did not exceed a total cumulative dose of 100 Gy. Hyperthermia was delivered in one or two sessions, either before or before and after interstitial implant. The intended goal of the hyperthermia was to maintain a minimal tumor temperature of 42.5 degrees C for 30 to 60 min. RESULTS: There was no difference in any of the study end points between the two arms. Complete response (CR) was 53% and 55% in both arms. Two-year survival was 34% and 35%, respectively. Complete response rate for persistent lesions was 69% and 63% in the two treatment arms as compared with 40% and 48% for recurrent lesions. A set of minimal adequacy criteria for the delivery of hyperthermia was developed. When these criteria were applied, only one patient had an adequate hyperthermia session. Acute Grade 3 and 4 toxicities were 12% for IRT and 22 % for ITRT. Late Grade 3 and 4 toxicities were 15% for IRT and 20% for ITRT. The difference was not significant. CONCLUSIONS: Interstitial hyperthermia, as applied in this randomized study, did not show any additional beneficial effects over interstitial radiotherapy alone. Delivery of hyperthermia remains a major obstacle (since only one patient met the basic minimum adequacy criteria as defined in this study). The benefit of hyperthermia in addition to radiation therapy still remains to be proven in properly randomized prospective clinical trials after substantial technical improvements in heat delivery and dosimetry are achieved.

Adult

The effect of illuminant position on perceived curvature.

In shaded scenes surface features can appear either concave or convex, depending upon the viewer's judgement about the direction of the prevailing illumination. If other curvature cues are added to the image this ambiguity can be removed. However, it is not clear to what extent, if any, illuminant position exerts an influence on the perceived magnitude of surface curvature. Subjects were presented with pairs of spherical surface patches in a curvature matching task. The patches were defined by shading and texture cues. The perceived curvature of a standard patch was measured as a function of light source position. We found a clear effect of light source position on apparent curvature. Perceived curvature decreased as light source tilt increased and as light source slant decreased. We also found that the strength of this effect is determined partly by a surface's reflectance function and partly by the relative weight of the texture cue. When a specular component was added to the stimuli, the effect of light source orientation was weakened. The weight of the texture cue was manipulated by disrupting the regular distribution of texture elements. We found an inverse relationship between the strength of the effect and the weight of the texture cue: lowering the texture cue weight resulted in an enhancement of the illuminant position effect.

Cues

Investigating shape-from-shading illusions using solid objects.

Recent growth in the shape-from-shading psychophysics literature has been paralleled by an increasing availability of computer graphics hardware and software, to the extent that most psychophysical studies in this area now employ computer lighting algorithms. The most widely used of these algorithms in shape-from-shading psychophysics is the Phong lighting model. This model, and other shading models of its genre, produce readily interpretable images of three-dimensional scenes. However, such algorithms are only approximations of how light interacts with real objects in the natural environment. Nevertheless, the results from psychophysical experiments using these techniques have been used to infer the processes underlying the perception of shape-from-shading in natural environments. It is important to establish whether this substitution is ever valid. We report a series of experiments investigating whether two recently reported illusions seen in computer-generated, Phong shaded images occur for solid objects under real illuminants. The two illusions investigated are three-dimensional curvature contrast and the illuminant-position effect on perceived curvature. We show that both effects do occur for solid objects, and that the magnitude of these effects are equivalent regardless of whether subjects are presented with ray traced or solid objects.

Algorithms

Three-dimensional curvature contrast--geometric or brightness illusion?

Simultaneous contrast effects have been found across a wide range of visual dimensions. We describe a simultaneous contrast effect--three-dimensional curvature contrast--in which the apparent curvature of a surface defined by shading and texture information is influenced by the curvature of a surrounding surface. The effect is strong and easily measurable. We asked whether the effect depends upon the presence of contrast at the level of the internal representation of surface curvature or whether it could be better explained in terms of local changes in the apparent brightness of regions within the test patches induced by luminance transitions at the borders. The experimental results suggest that, while these luminance-contrast-induced effects do contribute to the observed changes in perceived curvature, there are additional influences. In particular changes in perceived curvature induced by a pattern of curved patches were eliminated or considerably weakened when the inducing pattern was transformed into a photographic negative, a procedure which disrupts the apparent three-dimensional structure of the surface patches without changing their brightness contrast. This suggests a component of the illusion involves comparisons at the level of representation of surface curvature. The observation that three-dimensional curvature contrast persists when the inducing surfaces are spatially separate from the test surface suggests that shape perception involves global, as well as local, operations.

Depth Perception

Integration of shading and texture cues: testing the linear model.

One of the first attempts to develop a formal model of depth cue integration is to be found in Maloney and Landy's [(1989) Proceedings of the SPIE: Visual communications and image processing, Part 2 (pp. 1154-1163)] "human depth combination rule". They advocate that the combination of depth cues by the visual system is best described by a weighted linear model. The present experiments tested whether the linear combination rule applies to the integration of texture and shading. As would be predicted by a linear combination rule, the weight assigned to the shading cue did not vary as a function of its curvature value. However, the weight assigned to the texture cue varied systematically as a function of the curvature values of both cues. Here we describe a non-linear model which provides a better fit to the data. Redescribing the stimuli in terms of depth rather than curvature reduced the goodness of fit for all models tested. These results support the hypothesis that the locus of cue integration is a curvature map, rather than a depth map. We conclude that the linear combination rule does not generalize to the integration of shading and texture, and that for these cues it is likely that integration occurs after the recovery of surface curvature.

Cues

Phase I/II trial of accelerated fractionation in brain metastases RTOG 85-28.

PURPOSE: Radiation Therapy Oncology Group 85-28 represents a Phase I/II trial of accelerated fractionation in patients with brain metastases. METHODS AND MATERIALS: Patients entered had controlled or absent primary with metastases other than brain which were stable or only brain metastases with the primary uncontrolled. Karnosfky status was required to be greater than 60. Patients received 1.6 Gy twice daily separated by 4-8 hr delivered 5 days a week. The entire brain was treated to 32.0 Gy and the boost dose escalated from 16.0 Gy to 22.40 Gy and subsequently 32.00 Gy and 42.40 Gy. RESULTS: We observed no undue toxicity with escalating dose of irradiation. An incremental, although not statistically significant improvement in survival was noted with escalating doses. Median survival ranged from 4.2 months to 6.4 months with escalating dose of irradiation. Median survival also increased in patients with controlled primary tumors, non-lung primaries and solitary metastasis. CONCLUSION: The incremental improvement in survival in patients with good prognostic factors appeared encouraging. The Radiation Therapy Oncology Group will test the 54.4 Gy study against 30 Gy in 2 weeks in a Phase III trial based on the results of this trial.

Adult

Free magnesium levels in normal human brain and brain tumors: 31P chemical-shift imaging measurements at 1.5 T.

We have studied a series of normal subjects and patients with brain tumors, by using 31P three-dimensional chemical shift imaging to obtain localized 31P spectra of the brain. A significant proportion of brain cytosolic ATP in normal brain is not complexed to Mg2+, as indicated by the chemical shift delta of the beta-P resonance of ATP. The ATP beta-P resonance position in brain thus is sensitive to changes in intracellular free Mg2+ concentration and in the proportion of ATP complexed with Mg because this shift lies on the rising portion of the delta vs. Mg2+ titration curve for ATP. We have measured the ATP beta-P shift and compared intracellular free Mg2+ concentration and fractions of free ATP for normal individuals (n = 6) and a limited series of patients with brain tumors (n = 5). In four of the five spectra obtained from brain tissue containing a substantial proportion of tumor, intracellular free Mg2+ was increased, and the fraction of free ATP was decreased, compared with normal brain.

Adenosine Triphosphate

Comparison of three animal viruses with circular single-stranded DNA genomes.

No common antigenic determinants and no DNA sequence homologies were detected when three animal viruses, chicken anaemia agent (CAA), porcine circovirus (PCV), and psittacine beak and feather disease virus (PBFDV), all of which possess circular single-stranded DNA genomes, were compared. Negative contrast electron microscopy showed that PCV and PBFDV particles were 30% smaller than CAA particles and lacked the surface structure of CAA.

Animals

Concomitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous cell carcinoma of the head and neck. Long-term results of the Radiation Therapy Oncology Group study 81-17.

One hundred twenty-four eligible patients with advanced mucosal squamous cell carcinoma of the head and neck were entered into a pilot study of concomitant cisplatin (100 mg/m2 given every 3 weeks for three doses) and standard irradiation. The initial complete response (CR) was 71% with an additional two cases salvaged by surgery for an overall 73% CR. When no keratin was identified in the histologic specimen (41 patients) the CR was 90%. The nasopharynx showed the best CR (89%) among the sites. At 4 years after treatment, the estimated locoregional tumor control rate was 43% and the survival, 34%. When no keratin was present in the specimen, the estimated locoregional control of tumor was superior (56% versus 38% with keratin identified, P = 0.02) and the estimated survival was also superior (48% versus 26%, P = 0.008). Acute treatment-related toxicities included one death due to renal damage and two patients with life-threatening renal damage. The delivery of radiotherapy was not altered. Late toxicity included necrosis -3%, fibrosis -4%, and one fistula. The results of this study justify a randomized trial for the comparison of this combination of cisplatin and radiotherapy versus radiotherapy alone in advanced mucosal carcinomas of the head and neck.

Carcinoma, Squamous Cell