Biomedical subjects

W Curran

Publications and source records attributed to W Curran.

At least 19 recordsLinked to original sources

PubMed2000

Predictors of severe esophagitis include use of concurrent chemotherapy, but not the length of irradiated esophagus: a multivariate analysis of patients with lung cancer treated with nonoperative therapy.

PURPOSE: To identify in a multivariate analysis treatment-related factors predisposing patients (pts) with lung cancer to acute esophagitis, expressed as a severity grade or Esophagitis Index (EI). METHODS AND MATERIALS: Acute esophagitis is prospectively scored as an RTOG Grade in our institution during and after thoracic radiotherapy. Charts, toxicity forms and digitally reconstructed radiographs (DRRs) of all pts with lung cancer who received thoracic radiotherapy (RT) between 11/95 and 1/99 were reviewed. Esophagitis grades for each time point were verified by review of weekly physician and nursing treatment notes, hospital discharge summaries and referring physician notes and then plotted on graph against time. The area under the curve was calculated for each patient's graph and was defined as an Esophagitis Index. The length of esophagus was measured on each anterior DRR while assuming that esophagus overlies the vertebral bodies on the anterior films and projects over the edge of the vertebral body on the oblique DRRs. This assumption was confirmed in 10 pts by digitizing esophagus on CT simulator-derived slices and visualizing its position on DRRs. To compare RT doses delivered with different fractionation schemes to standard fractionated doses, the equivalent RT doses were calculated using the linear-quadratic formula and alpha/beta ratio of 10. Univariate and multivariate analyses of several factors potentially influencing the maximum esophagitis grade, as well as EI, were performed. RESULTS: A total of 277 pts were identified. Pts were included in the analysis (n = 105) if they fulfilled the following criteria: chart, toxicity form and DRRs were all available; parallel opposed fields (no multiple fields) were used for both the initial and off cord/cone down fields; and an equivalent dose of 45.0 Gy or more was delivered. Seventy-eight pts had Stage III; 32, Stage IV, and the remainder, Stages I, II, or recurrent lung cancer (85 non-small cell and 18, small cell). Seventy-four pts were treated with definitive intent. Chemotherapy was given concurrently with RT in 58 pts (in 7 pts, with twice daily, or b.i.d., RT) and as induction treatment, in 11. Only 2 pts required a treatment break of more than 1 week. Median total and equivalent RT doses, fraction size, and anterior esophageal length were as follows: 59.9 Gy, 59.9 Gy, 2.0 Gy, and 14 cm (range, 4.2-21). The following maximum grades of esophagitis were recorded: 1, in 54 pts; 2, in 17 pts; 3, in 13 pts, and 4, in 1 pt. The mean EI for all pts; pts treated with standard RT alone; induction chemotherapy and standard RT; concurrent chemotherapy and standard (QD) RT; and b.i.d. RT with concurrent chemotherapy, was 41. 5 (range, 0-317); 13.6; 24.5; 52.4; and 132.1, respectively (p < 0. 001). Three pts developed an esophageal stricture within 3 months beginning RT. In multivariate analysis, the following factors were significantly associated with increasing EI: concurrent chemotherapy with QD RT and concurrent chemotherapy with b.i.d. RT (p < 0.001, considered jointly). Both factors were also associated with increasing maximum esophagitis grade (p = 0.011). Esophageal length was not associated with increasing EI or esophagitis grade in either univariate or multivariate analyses. CONCLUSION: Concurrent chemotherapy and twice daily radiotherapy, especially if combined together, were associated with the highest acute maximum esophagitis grade and esophagitis index in pts with lung cancer. The duration of acute esophagitis was also longest in the concurrent chemotherapy/twice daily radiotherapy group. Esophagitis Index appeared to be a more sensitive measure of acute esophagitis than the maximum esophagitis grade. The increasing length of esophagus in the radiation field did not predict for the severity of acute esophagitis.

Adult↗

PubMed2000

Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) previously developed three prognostic classes for brain metastases using recursive partitioning analysis (RPA) of a large database. These classes were based on Karnofsky performance status (KPS), primary tumor status, presence of extracranial system metastases, and age. An analysis of RTOG 91-04, a randomized study comparing two dose-fractionation schemes with a comparison to the established RTOG database, was considered important to validate the RPA classes. METHODS AND MATERIALS: A total of 445 patients were randomized on RTOG 91-04, a Phase III study of accelerated hyperfractionation versus accelerated fractionation. No difference was observed between the two treatment arms with respect to survival. Four hundred thirty-two patients were included in this analysis. The majority of the patients were under age 65, had KPS 70-80, primary tumor controlled, and brain-only metastases. The initial RPA had three classes, but only patients in RPA Classes I and II were eligible for RTOG 91-04. RESULTS: For RPA Class I, the median survival time was 6. 2 months and 7.1 months for 91-04 and the database, respectively. The 1-year survival was 29% for 91-04 versus 32% for the database. There was no significant difference in the two survival distributions (p = 0.72). For RPA Class II, the median survival time was 3.8 months for 91-04 versus 4.2 months for the database. The 1-year survival was 12% and 16% for 91-04 and the database, respectively (p = 0.22). CONCLUSION: This analysis indicates that the RPA classes are valid and reliable for historical comparisons. Both the RTOG and other clinical trial organizers should currently utilize this RPA classification as a stratification factor for clinical trials.

Age Factors↗

PubMed2000

Common toxicity criteria: version 2.0. an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy.

In 1997, the National Cancer Institute (NCI) led an effort to revise and expand the Common Toxicity Criteria (CTC) with the goal of integrating systemic agent, radiation, and surgical criteria into a comprehensive and standardized system. Representatives from the Radiation Therapy Oncology Group (RTOG) participated in this process in an effort to improve acute radiation related criteria and to achieve better clarity and consistency among modalities. CTC v. 2.0 replaces the previous NCI CTC and the RTOG Acute Radiation Morbidity Scoring Criteria and includes more than 260 individual adverse events with more than 100 of these applicable to acute radiation effects. One of the advantages of the revised criteria for radiation oncology is the opportunity to grade acute radiation effects not adequately captured under the previous RTOG system. A pilot study conducted by the RTOG indicated the new criteria are indeed more comprehensive and were preferred by research associates. CTC v. 2.0 represents an improvement in the evaluation and grading of acute toxicity for all modalities.

Antineoplastic Agents↗

PubMed2000

Continuity-based and discontinuity-based segmentation in transparent and spatially segregated global motion.

The mechanisms underlying the parsing of a spatial distribution of velocity vectors into two adjacent (spatially segregated) or overlapping (transparent) motion surfaces were examined using random dot kinematograms. Parsing might occur using either of two principles. Surfaces might be defined on the basis of similarity of motion vectors and then sharp perceptual boundaries drawn between different surfaces (continuity-based segmentation). Alternatively, detection of a high gradient of direction or speed separating the motion surfaces might drive the process (discontinuity-based segmentation). To establish which method is used, we examined the effect of blurring the motion direction gradient. In the case of a sharp direction gradient, each dot had one of two directions differing by 135 degrees. With a shallow gradient, most dots had one of two directions but the directions of the remainder spanned the range between one motion-defined surface and the other. In the spatial segregation case the gradient defined a central boundary separating two regions. In the transparent version the dots were randomly positioned. In both cases all dots moved with the same speed and existed for only two frames before being randomly replaced. The ability of observers to parse the motion distribution was measured in terms of their ability to discriminate the direction of one of the two surfaces. Performance was hardly affected by spreading the gradient over at least 25% of the dots (corresponding to a 1 degrees strip in the segregation case). We conclude that detection of sharp velocity gradients is not necessary for distinguishing different motion surfaces.

Discrimination, Psychological↗

PubMed2000

Speed and direction of locally-paired dot patterns.

Phenomenal transparency in random-dot kinematograms is abolished when two motion directions are 'locally-balanced' by pairing limited-lifetime dots at each location [Qian, Andersen and Adelson (1994). Journal of Neuroscience, 14, 7357-7366]. Qian et al. also report that locally-paired stimuli appear as directionless flicker when the paired dots differ in their directions by 90 degrees or more. They attribute this to local inhibition between motion detectors more than 45 degrees apart. We investigated perceived motion in such displays, by requiring subjects to make direction and speed judgements with locally-paired stimuli containing two directions 60, 90 or 120 degrees apart. Subjects perceived coherent motion in these displays and made reliable direction judgements, indicating that the two motions are combined rather than interfering destructively. Our results show that the judged motion of locally-paired stimuli is in the vector-average direction of the two components. This vector-averaging rule also applies when the two sets of component dots differ in their velocity. Similarly, speed judgements comply with a vector-averaging rule for a range of speeds as well as for mixed-speed stimuli. These results suggest that the abolition of transparency does not necessarily imply abolition of a global motion percept. The local interaction abolishing transparency is not exclusively inhibitory, at least for directions up to 120 degrees apart, but generates a vector combination of the superimposed motions.

Humans↗

PubMed2000

Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group.

STUDY OBJECTIVES: The purpose of this phase III clinical trial was to test whether chemotherapy followed by radiation therapy resulted in superior survival to either hyperfractionated radiation or standard radiation in surgically unresectable non-small cell lung cancer. DESIGN: Patients were prospectively randomized to 2 months of cisplatin, vinblastine chemotherapy followed by 60 Gy of radiation at 2.0 Gy per fraction or 1.2 Gy per fraction radiation delivered twice daily to a total dose of 69.6 Gy, or 2.0 Gy per fraction of radiation once daily to 60 Gy. Patients were enrolled from January 1989 through January 1992, and followed for a potential minimum period of 5 years. SETTING: This trial was an intergroup National Cancer Institute-funded trial within the Radiation Therapy Oncology Group, the Eastern Cooperative Oncology Group, and the Southwest Oncology Group. PATIENTS: Patients with surgically unresectable non-small cell lung cancer, clinical stage II, IIIA, and IIIB, were required to have a Karnofsky Performance Status of > or = 70 and a weight loss of < 5% for 3 months before study entry. Four hundred ninety patients were registered on trial, of which 458 patients were eligible. CONCLUSION: Overall survival was statistically superior for the patients receiving chemotherapy and radiation vs the other two arms of the study. The twice-daily radiation therapy arm, although better, was not statistically superior in survival for those patients receiving standard radiation. Median survival for standard radiation was 11.4 months; for chemotherapy and irradiation, 13.2 months; and for hyperfractionated irradiation, 12 months. The respective 5-year survivals were 5% for standard radiation therapy, 8% for chemotherapy followed by radiation therapy, and 6% for hyperfractionated irradiation.

Adult↗

PubMed1999

What motion distributions yield global transparency and spatial segmentation?

We have examined the ability of observers to parse bimodal local-motion distributions into two global motion surfaces, either overlapping (yielding transparent motion) or spatially segregated (yielding a motion boundary). The stimuli were random dot kinematograms in which the direction of motion of each dot was drawn from one of two rectangular probability distributions. A wide range of direction distribution widths and separations was tested. The ability to discriminate the direction of motion of one of the two motion surfaces from the direction of a comparison stimulus was used as an objective test of the perception of two discrete surfaces. Performance for both transparent and spatially segregated motion was remarkably good, being only slightly inferior to that achieved with a single global motion surface. Performance was consistently better for segregated motion than for transparency. Whereas transparent motion was only perceived with direction distributions which were separated by a significant gap, segregated motion could be seen with abutting or even partially overlapping direction distributions. For transparency, the critical gap increased with the range of directions in the distribution. This result does not support models in which transparency depends on detection of a minimum size of gap defining a bimodal direction distribution. We suggest, instead, that the operations which detect bimodality are scaled (in the direction domain) with the overall range of distribution. This yields a flexible, adaptive system that determines whether a gap in the direction distribution serves as a segmentation cue or is smoothed as part of a unitary computation of global motion.

Computer Graphics↗

PubMed1999

Development of illusory-contour perception in infants.

We investigated whether infants from 8-22 weeks of age were sensitive to the illusory contour created by aligned line terminators. Previous reports of illusory-contour detection in infants under 4 months old could be due to infants' preference for the presence of terminators rather than their configuration. We generated preferential-looking stimuli containing sinusoidal lines whose oscillating, abutting terminators give a strong illusory contour in adult perception. Our experiments demonstrated a preference in infants 8 weeks old and above for an oscillating illusory contour compared with a stimulus containing equal terminator density and movement. Control experiments excluded local line density, or attention to alignment in general, as the basis for this result. In the youngest age group (8-10 weeks) stimulus velocity appears to be critical in determining the visibility of illusory contours, which is consistent with other data on motion processing at this age. We conclude that, by 2 months of age, the infant's visual system contains the nonlinear mechanisms necessary to extract an illusory contour from aligned terminators.

Child Development↗

PubMed1999

Prognostic factors and survival in patients with spinal cord gliomas after radiation therapy.

The purpose of this study was to determine the impact of various prognostic factors on survival in spinal cord gliomas treated with radiation. Fifty-three patients with spinal cord gliomas irradiated at three major institutions were studied. Fifty-one patients were classified as having ependymoma, astrocytoma, or both. Two patients were classified as having gliomas (otherwise unspecified). Eleven patients had complete resection of their tumor. Biopsy or partial resection was done in the remaining patients. All patients received external beam radiation. Information on these patients was placed in a central database file and analyzed for the effect of several prognostic factors on survival. Overall survival of the entire group was 76.9% and 61.5% at 5 and 10 years, respectively. Pathologic status significantly affected survival (p = 0.03). Patients with ependymomas had a 5-year survival of 93.8% and a 10-year survival of 67.5%. Patients with astrocytoma had a 5-year survival of 64.2% and a 10-year survival of 54%. Univariate analysis showed pathology and the presence of cysts (p = 0.038) to significantly affect survival. Age, sex, location of the primary, extent of surgery radiation dose, and number of involved segments did not affect survival. On multivariate analysis, astrocytic pathology, involvement of more than five segments, male sex, and the absence of cysts (in or adjacent to the tumor) were associated with a significantly inferior survival. This study confirms the importance of pathology and number of segments involved in determining outcome or survival. The presence of cysts adjacent to or within the tumor was found to be associated with an improvement in survival.

Adolescent↗

PubMed1998

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

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.

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