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Biomedical subjects

W J Curran

Publications and source records attributed to W J Curran.

At least 109 records · Page 6Linked to original sources
PubMed1992

Observations on the predictive value of perfusion lung scans on post-irradiation pulmonary function among 210 patients with bronchogenic carcinoma.

As a component of treatment planning for thoracic irradiation (RT), 210 bronchogenic carcinoma patients seen at the Fox Chase Cancer Center from 1983 to 1990 underwent quantitative perfusion scans, superimposition of their RT treatment fields onto these scans, and pulmonary function testing. These studies were used to prospectively estimate the influence of the planned thoracic irradiation on pulmonary function, as measured by the forced expiratory volume in one second (FEV1). Among the 156 patients with unresected lesions, the mean pre-RT FEV1 was 1.71 +/- 0.67 liters (+/- standard deviation), and the mean percentage of total lung perfusion within the treatment field was 31.0 +/- 12.1%. Mean values for the 54 patients treated post-operatively were 1.79 liters (pre-RT FEV1) and 28.8% (% perfusion within RT field). Using this technique, the prospectively predicted post-RT FEV1 is the product of the pre-RT FEV1 (1% of total lung perfusion within the treatment field). The mean predicted post-treatment FEV1 for the nonoperative patients was 1.15 +/- 0.43 liters and 1.25 +/- 0.41 liters for the postoperative patients. Forty-three nonoperative and 19 postoperative patients had FEV1 determinations following RT, at a mean post-RT interval of 11 months for nonoperative patients and 23 months for post-operative patients. Among nonoperative patients, 53% had no change in post-RT FEV1, 19% improved, while 22% had readings declining toward the predicted value. Only 5% had readings below predicted. Among postoperative patients, 37% had no change or improvement, 37% declined toward the predicted, 10% declined to predicted, and 11% had values worse than predicted. This technique of superimposing RT fields onto lung perfusion scans predicts for a degree of pulmonary impairment which is observed in only a minority of patients (10%) and which is rarely exceeded (6%).

Carcinoma, Bronchogenic↗
PubMed1992

Adverse influence of younger age on outcome in patients with non-small cell lung carcinoma (NSCLC) treated with radiation therapy (RT) alone.

Treatment outcome of 63 patients younger than 50 years of age initiated on a course of once-daily definitive radiation therapy without concurrent or preirradiation chemotherapy for clinical Stages I-III unresected non-small cell lung carcinoma from 1978 to 1988 was compared to the outcome of 695 patients over the age of 50. Follow-up ranged from 24-110 months with follow-up until death in 88% of patients. The actuarial overall survival rate for all patients was 22% at 2 years with a median survival time of 11.5 months. Patients less than 50 and greater than or equal to 50 years old were similar in male:female ratio, distribution of histologic subtype, performance status, and extent of weight loss. Poorly differentiated histologic grade was more prevalent among the younger patients (59% vs 41%, p = .005). Ninety-four percent of younger patients and 86% of older patients had clinical stage III disease (p = NS). Survival was significantly worse for patients who were younger than 50 years old (p = .05), with a median survival time of 7.8 months. Median survival time for those patients 50 years of age or older was 12.4 months. Poorer survival outcome among young patients was most pronounced among patients with unfavorable characteristics of poor performance status (greater than or equal to 2) or weight loss (greater than 5%) (p = .002). Distant failure (p = .029) and brain failure (p = .003) as initial site of relapse was more common among younger patients. Among young patients, poor histologic grade was associated with both distant failure (p = .003) and brain metastasis (p = .002). The difference in distribution of histologic grade, incidence of distant failure, particularly in the brain, and poorer survival outcome among patients less than 50 may be indicative of more aggressive tumor behavior in the younger patients. These results indicate that patients less than 50 may require alternate treatment strategies. Age should be considered a stratification variable in non-operative randomized trials of non-small cell lung carcinoma which include patients with non-favorable characteristics.

Adult↗
PubMed1991

Comparison of the Radiation Therapy Oncology Group and American Joint Committee on Cancer staging systems among patients with non-small cell lung cancer receiving hyperfractionated radiation therapy. A report of the Radiation Therapy Oncology Group protocol 83-11.

Since 1973, the Radiation Therapy Oncology Group (RTOG) has staged and stratified patients in non-small cell lung cancer (NSCLC) protocols according to the RTOG staging system. In 1985, the American Joint Committee on Cancer (AJCC) revised its lung cancer staging system, with the principle differences from the RTOG system being the staging of involvement of the chest wall and of contralateral mediastinal and hilar lymph nodes. To determine if the AJCC system discriminated outcome differently than the RTOG system in a nonoperative series, all 850 evaluable patients treated with hyperfractionated radiation therapy (RT) on the RTOG protocol 83-11 were restaged by the AJCC system. There was 67% agreement in patient distribution between the following comparable stages in each system: RTOG Stage II/AJCC Stage II; RTOG Stage III/AJCC Stage IIIA; and RTOG Stage IV/AJCC Stage IIIB. Both systems successfully predicted for survival (P less than 0.001), although the RTOG staging was more discriminating (relative risk ratios, 1.59 versus 1.38). Among the 507 favorable patients (those with less than or equal to 5% weight loss and Karnofsky performance status [KPS] of 70 to 100), the RTOG staging was also more predictive (P = 0.004 versus P = 0.01). When RTOG Stage III (462 patients) was divided into those without contralateral mediastinal or hilar adenopathy (AJCC Stage II/IIIA) and those with (AJCC Stage IIIB), a significant survival (P = 0.0001) was noted with 2-year survival rates of 26% versus 4%, respectively. When AJCC Stage IIIA (348 patients) was divided into the patients without chest wall invasion (RTOG Stage II/III) and those with (RTOG Stage IV), a difference in 2-year survival of 22% versus 10% was observed (P = 0.002). Although both staging systems independently predict for survival, a fusion of both staging systems is the most discriminating of outcome. Future nonoperative studies in locally advanced NSCLC should stratify for contralateral nodal involvement (per AJCC staging) and chest wall invasion (per RTOG staging).

Carcinoma, Non-Small-Cell Lung↗
PubMed1991

A descriptive study of learned food aversions in radiotherapy patients.

While animal studies have documented the efficacy of ionizing radiation as a conditioning stimulus for food aversion learning, little is known about the incidence or nature of aversions that form in cancer patients administered radiation therapy. Forty-nine newly diagnosed patients with a variety of cancer types were monitored for the duration of their treatment or up to six months. Aversions were identified by questionnaires and responses to an experimental food administered at stipulated time points. Fifty-nine percent of patients formed new aversions after initiating treatment and for 53% of patients, this involved items in their customary diet. A wide array of items were targeted, but there was direct relationship between exposure frequency and aversion formation. The aversions were highly specific (median = 2.5 items/afflicted patient). The onset time was approximately 1-2 weeks, and they were transient, generally lasting 1-3 weeks. There was no evidence of a discrepant incidence among patients treated in different sites. Aversion incidence was not significantly associated with age, gender or other selected patient characteristics.

Abdomen↗
PubMed1991

Technique, pharmacokinetics, toxicity, and efficacy of intratumoral etanidazole and radiotherapy for treatment of spontaneous feline oral squamous cell carcinoma.

The histologic appearance, locoregional recurrence, and rate/site of metastases of spontaneous feline oral squamous cell carcinoma are similar to head and neck cancer in humans. A feasibility study of intratumoral Etanidazole, a hypoxic cell sensitizer, and radiation therapy were instituted in this model. Eleven cats with feline squamous cell carcinoma were treated with intratumoral Etanidazole and radiation therapy. Total Etanidazole doses were 1.5-24.0 gms/m2 (0.5-6.9 gms). The tumor partial response rate was 100% (11/11); the median volume regression was 70%. All cats have died as a result of tumor recurrence or tumor-related complications. Median survival was 116 days. Ten cats have been autopsied. Non-necrotic and necrotic tumor cells were identified at the treatment site in all cats. Pharmacokinetic studies were performed in six cats. Following intravenous infusion, the plasma elimination of the Etanidazole was biexponential. The systemic availability following intratumoral administration was 61.2 +/- 21.1%. Peak plasma Etanidazole levels were observed 14 minutes following intratumoral injection, after which elimination was biexponential. Thirty minutes following intratumoral Etanidazole administration, tumor Etanidazole levels were 62.8% of plasma levels. Feline squamous cell carcinoma appears to be a useful model of human head and neck cancer. Cats tolerate substantial doses of intratumoral and intravenous Etanidazole. Etanidazole and radiation therapy cause rapid regression, but not cure, of feline squamous cell carcinoma. There is a similarity between the intravenous kinetics of Etanidazole in humans and cats. Further studies in this model are planned.

Animals↗
PubMed1991

Decreasing gastrointestinal morbidity with the use of small bowel contrast during treatment planning for pelvic irradiation.

Small bowel tolerance is a major dose-limiting factor in treating the pelvis with radiation therapy (RT). The use of small bowel contrast during RT simulation is one technique used to localize the bowel and identify the treatment plan that would exclude the greatest volume. To determine the influence of treatment planning with oral contrast on gastrointestinal injury, acute and chronic small bowel morbidity was analyzed in 115 patients with endometrial and rectal carcinoma who received postoperative radiation therapy at the Fox Chase Cancer Center. Mean and median time of follow-up were 31 and 27 months, respectively. Acute diarrhea was seen in 82% of the patient population. Ten percent of patients experienced major complications requiring hospitalization. Ninety-three percent of patients simulated without contrast experienced side effects compared to 77% of patients simulated with contrast (p = .026). There was an increased incidence of chronic complications in patients who were not simulated with contrast dye (50% vs 23%, p = .014). Median duration of minor side effects was 4 months for patients planned without oral contrast and 1 month for patients who had contrast at the time of simulation (p = .036). The superior aspect of the treatment field was determined to be at a more inferior location in patients simulated with contrast, thereby excluding small bowel from treatment. Seventy-four percent of patients simulated without contrast had the upper border of the field placed at the superior aspect of the sacroiliac joint or above, compared to only 40% of patients planned with oral contrast (p = .002). This study has demonstrated decreased complications (both overall and chronic) as well as a change in the location of the treatment field with the use of small bowel contrast. Multivariate analysis revealed that both the use of oral contrast (p = .026) and a lower superior border of the treatment field (p = .007) were predictive for fewer sequelae to RT, indicating that planning with contrast leads to changes in the technical delivery of RT other than field placement (e.g., block placement). The reduced incidence and duration of small bowel morbidity may be in part caused by alterations of the treatment plan made when the small bowel is visualized at the time of simulation. It is therefore recommended that oral small bowel contrast be used during treatment planning for pelvic irradiation.

Adult↗
PubMed1991

Elapsed treatment days--a critical item for radiotherapy quality control review in head and neck trials: RTOG report.

For all randomized trials since 1978, the Radiation Therapy Oncology Group has required the study chairman for radiation therapy to review the treatment given to each patient. The chairman scores the compliance of the treatment borders, total dose, fraction, and total elapsed time relative to the protocol prescription at the primary site, regional nodes, and any critical structure. The individual parameters are then considered together to derive an "overall" treatment score. For two RTOG head and neck studies in patients with moderately and very advanced carcinomas, the "overall" treatment was classified as unacceptable if the treatment at primary was scored unacceptable with respect to dose, fractionation, and field borders. However, prolonged elapsed treatment was not included. Analysis of these studies with 426 evaluable patients was performed to assess the relationship of unacceptable "overall" treatment compliance with outcome. Patients with prolonged treatment elapsed days (14 days beyond the protocol prescription) exhibited significantly poorer loco-regional control (13% vs. 27% at 3 years with p = .007) and absolute survival (13% vs. 26% at 3 years with p = .01). As a result, the criteria for unacceptable "overall" treatment were revised to include prolonged elapsed treatment days. Further multivariate analyses showed the revised criteria identified patients with significantly poorer loco-regional control and absolute survival even after adjusting for other prognostic factors.

Carcinoma, Squamous Cell↗
PubMed1991

Improvements observed in care and outcome in carcinoma of the larynx.

The 1978 Patterns of Care Studies (PCS) survey of carcinoma of the larynx reviewed the process (pre-treatment evaluation and treatment) and outcome of 521 patients. When compared to results from the 1973 PCS survey, several important changes have been observed. The use of surgery in conjunction with radiation therapy (RT) increased in Stage III cases from less than 30% to greater than 60% and in Stage IV cases from 48% to greater than 70%. This change in therapy was associated with a decline in locoregional failure in this patient group. Among Stage I and II supra- and subglottic carcinomas, an improvement in 3-year local tumor control (Stage I: 78 to 100% and Stage II: 54 to 74%) and overall freedom from recurrence (Stage I: 78 to 100% and Stage II: 45 to 73%) was seen over this 5-year period with no identifiable change in process for this subgroup. Also noted was an improvement in the freedom from recurrence rate for Stage III and IV patients receiving treatment at facilities with low process scores. The 1978 PCS survey confirmed the presence of superior patient outcome in several subgroups and the relationship of this improvement to patient process.

Clinical Protocols↗
PubMed1990

Recurrent intracranial ependymomas in children. Survival, patterns of failure, and prognostic factors.

Thirty-six pediatric patients (ages 0.8-16.8 years) with recurrent intracranial ependymoma were treated for a total of 52 separate cases of relapse from 1970 to 1989. Therapy consisted of surgery in 33 cases and chemotherapy in 38 cases. Twelve patients received radiation at the time of first relapse, and five of these 12 who had initially been treated with surgery and chemotherapy alone were irradiated to full dose. The 2-year actuarial survival and progression-free survival (PFS) rates are 29% and 23%, respectively. Two-year survival after treatment of first relapse is 39%. Of the 52 cases, there have been 44 subsequent relapses (and one septic death), three of which have occurred in the five patients treated with definitive radiation. Twenty-seven relapses have occurred exclusively with local disease. Eight patients failed with disease outside as well as in the primary site. Survival was better for patients who had histologically benign lesions at relapse (53% versus 9%, P less than 0.02), and for patients in first versus subsequent relapse (p less than 0.005). Cisplatin and etoposide (VP-16) appeared to be the most active chemotherapeutic agents. The authors conclude that some patients with histologically benign ependymoma at first relapse may benefit from aggressive therapy, with occasional long-term, progression-free survival possible. Patients with malignant lesions, or patients who relapse a second time, are less likely to benefit from conventional therapy for a significant period of time.

Actuarial Analysis↗
PubMed1990

Analysis of the influence of elective nodal irradiation on postirradiation pulmonary function.

Irradiation (RT) field selection for bronchogenic carcinoma is based on such factors as extent of disease, pulmonary function, and the perceived need for elective nodal irradiation (ENI). A technique of superimposing a patient's RT treatment film onto his quantitative perfusion lung scan can predict the fractional volume of perfused lung receiving RT and has been shown to reliably estimate the minimum post-RT pulmonary function as measured by the forced expiratory volume in one second (FEV1). This technique has been applied to 20 patients with nonresected clinically staged T1-4N0M0 lesions to quantify the pulmonary impact of varying degrees of ENI. The five treatment volumes selected were as follows: (1) tumor volume plus a 2-cm margin; (2) volume 1 plus ipsilateral hilum; (3) volume 2 plus mediastinum; (4) volume 3 plus supraclavicular fossae; and (5) volume 4 plus contralateral hilum. The median pre-RT FEV1 was 2.0 l, and the median predicted minimal post-RT FEV1 for each proposed field was field 1, 1.7 l; field 2, 1.5 l; field 3, 1.3 l; field 4, 1.1.; and field 5, 1.0 l. The decline in median predicted FEV1 with each increase in field size ranged from 2% to 12%, with a broad range of declines for each field. Such quantification can aid in decisions regarding ENI for patients with impaired pulmonary function.

Carcinoma, Bronchogenic↗
PubMed1990

Influence of grade, histologic subtype, and timing of radiotherapy on outcome among patients with stage II carcinoma of the endometrium.

In 1988, the Federation of International Gynecologic Oncologists (FIGO) adopted a new staging system mandating preradiotherapy surgical staging in endometrial cancer. To evaluate the potential impact of this recommendation on patients with cervical involvement (stage II), an analysis of 184 consecutive patients with clinical or pathologic stage II carcinoma of the endometrium treated with definitive intent at three institutions was performed. Median follow-up time was 5.7 years. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with preoperative radiation therapy (RT) (54%), postoperative RT (37%), or both (1%); definitive RT (7%); or radical hysterectomy (1%). The median total RT dose for combined intracavitary and external beam or either alone was 70.6 Gy with a range of 32.4-105.0 Gy. The overall 5-year survival rate and disease-free survival (DFS) rate at 5 years were 70 and 79%, respectively. Of patients treated with surgery and adjuvant radiation, 13% (22/168) had infield pelvic failure (PF) and 18% (31/168) had distant metastases (DM). Patterns of failure in patients receiving preoperative and postoperative radiotherapy are presented. Univariate analysis of pretreatment and treatment factors, including histology, grade, clinical stage, extent of cervical involvement, and timing of adjuvant radiation, revealed histology and grade to be significant predictors of DFS, PF, and DM. Clinical stage was a significant predictor of DFS only in univariate analysis. Multivariate analysis found only histology (P less than 0.001) and grade (P = 0.002) to be predictors of DFS. From this review, we conclude that histology and grade are independent predictors of DFS, and more aggressive treatment should be directed at patients with stage II endometrial cancer found to have high grade adenocarcinoma or papillary serous/clear cell histologic variants. The timing of radiotherapy was not an independent predictor of outcome; therefore, preradiotherapy surgical staging should not impact on DFS and should provide surgicopathologic information to tailor treatment and predict prognosis. The FIGO clinical staging system used in this analysis was not an independent predictor of outcome, and future multivariate analyses will be necessary to test the predictive value on outcome of the new 1988 FIGO surgical staging.

Female↗
PubMed1990

The influence of tumor size and pre-treatment staging on outcome following radiation therapy alone for stage I non-small cell lung cancer.

From 1970 through 1987, 77 patients with Stage I lung cancer were treated with definitive radiation therapy (RT) alone at the Fox Chase Cancer Center or the Hospital of The University of Pennsylvania. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidates for surgical resection because of premorbid medical problems or patient refusal. The median age was 72 years, although 10 patients were over 80. The histologic cell type was squamous in 44, adenocarcinoma in 15, large cell in 3, adenosquamous in 1, non-small cell in 11, and bronchioli-alveolar in 3. Tumor size was retrievable in 75 patients and 25 were less than or equal to 3 cm, 41 from 3-6 cm, and 9 greater than 6 cm. Diagnostic staging varied during the study period. Twelve patients, evaluated with a CT scan of the chest, including the liver, and a bone scan were classified as having "excellent" staging, 24 patients with conventional tomography, liver-spleen scan and a bone scan had "good" staging, and 41 patients were staged less rigorously. The RT was of megavoltage energy in all patients. The median dose was 60 Gy. The mediastinum was treated in all but eight patients who had poor pulmonary function. Survival was measured from the date of pathologic diagnosis. The actuarial 3-year survival rate of the entire group of patients is 17% with a median survival time of 20 months. Of the 61 deaths, 51 were due to disease and 10 were due to intercurrent disease without evidence of tumor recurrence. The actuarial 3-year disease-specific survival (DSS) was 22%. The 3-year disease-specific survival for patients with tumors less than 3 cm and from 3-6 cm was 30% and 17%, respectively. All nine patients with tumors greater than 6 cm were dead of disease. Local progression occurred in 33 patients, resulting in a 44%, 3-year actuarial freedom from local progression. The median time to local failure was 28 months and there were no local failures after 3 years in the 18 patients eligible for observation beyond this point. Of the patients with "excellent" staging, only 2 of 12 were dead of disease compared with 22 of 24 with "good" staging and 30 of 41 of the remainder. In this large group of Stage I non-small cell lung cancer, thorough pre-treatment staging and smaller tumor size are associated with a more favorable outcome.

Aged↗
PubMed1990

Intracranial ependymomas in children.

Between 1970 and 1988, 51 children with intracranial ependymal tumors (33-infratentorial, 18-supratentorial received initial treatment at the University of Pennsylvania. Therapy consisted of total or near total tumor resection in 15 patients and partial resection or biopsy in 36. Postoperative irradiation alone was given to 18, chemotherapy to 4, and a combination of these two modalities to 26. Patients have been followed for a median period of 7.75 years. The 5-year actuarial survival and progression-free survival (PFS) rates are 46% and 30%, respectively. Of the 30 patients who have progressed, 29 did so locally and one died before the site of failure could be determined. Six patients also had disease outside the primary site at relapse; three of them had received craniospinal irradiation. Local control was significantly better for patients whose tumor dose exceeded 4500 cGy (32% vs. 0%, p = .01) and for Caucasian patients (34% vs. 15%, p =.05). Survival was better for patients who were over 4 years of age at diagnosis (55% vs. 30%, p = .04), for patients who received local radiation doses above 4500 cGy (51% vs. 18%, p = .01), and for Caucasian patients (43% vs. 14%, p = .01). Extent of resection, histology, location, the use of cranial or craniospinal irradiation, and the use of chemotherapy did not significantly impact on survival. We conclude that the inability to control local disease remains the single most important factor leading to treatment failure. Older age, higher local radiation dose, and Caucasian race appear to be the only favorable prognostic factors.

Adolescent↗