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W J Curran

Publications and source records attributed to W J Curran.

At least 19 recordsLinked to original sources
PubMed1996

Final report of a phase I/II trial of hyperfractionated and accelerated hyperfractionated radiation therapy with carmustine for adults with supratentorial malignant gliomas. Radiation Therapy Oncology Group Study 83-02.

BACKGROUND: Efforts to improve local control and survival by increasing the dose of once-daily radiation therapy beyond 70 Gray (Gy) for patients with malignant gliomas has yet been unsuccessful. Hyperfractionated radiation therapy (HF) should allow for delivery of a higher total dose without increasing normal tissue late effects, whereas accelerated hyperfractionated radiation therapy (AHF) may minimize tumor repopulation by shortening overall treatment time. The Radiation Therapy Oncology Group (RTOG) conducted a randomized Phase I/II study of escalating doses of HF and AHF either carmustine (bis-chlorethyl nitrosourea [BCNU]) fro adults with supratentorial glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA). Primary study endpoints were overall survival and acute and chronic treatment-related toxicity. METHODS: From 1983 to 1989, 786 patients with supratentorial gliomas (81% with GBM and 19% with AA) were stratified by histology, age, and performance status and randomized to receive partial brain irradiation, utilizing either HF (1.2 Gy twice daily to doses of 64.8, 72, 76.8, or 81.6 Gy) of AHF (1.6 Gy twice daily to doses of 48 or 54.4 Gy). All patients received carmustine. The distinction of pronistic factors was similar on all arms. RESULTS: There were 747 eligible and analyzable patients among 786 enrolled patients (95%). Two patients had a Grade 5 and 65 patients had a Grade 4 chemotherapy toxicity. Two patients in the 81.6 Gy arm experienced late Grade 4 radiation toxicity and there was 1 late radiation-associated death in the 54.4 Gy arm. The rate of Grade 3 of worse radiation toxicity at 5 years, calculated by the delivered does level, was 3% in the lowest total dose arms (48 and 54.4 Gy), 4% in the intermediate dose arms (64.8 and 72 Gy), and 5% in the highest dose arms (76.8 and 81.6 Gy) (p = 0.54). Survival rates at 2 and 5 years were: 21% and 11%, and 4%, respectively, for GBM patients. There were no significant differences between the treatment arms with regard to median survival time (MST), when analyzed by the originally assigned dose. The MST for all patients varied between 10.8 months and 12.7 months (P = 0.59); between 9.6 months and 11 months for patients with GBM (P = 0.43); and between 30.4 months and 85.8 months for patients with AA (P = 0.78). Analysis of the survival rates for all patients by dose received rather than by dose assigned revealed a 14% 5-year survival rate for the lower HF doses (64.8 and 73 Gy), 11% for the higher doses (76.8 and 81.6 Gy), and 10% for the AHF doses (48 and 54.4 Gy) (P = 0.1). The subgroup a AA patients had a better MST (49.9 months) in the lower received HF doses than in the higher HF doses (34.6 months) (P = 0.35). In contrast, GM patients who received the higher HF doses had survival superior to the patients in the AHF arms (MST of 11.6 months and 10.2 months, respectively, P = 0.04). CONCLUSIONS: The use of HF with BCNU and dose escalation up to 81.6 Gy is both feasible and tolerable, although late toxicity increases slightly with increasing dose. The best MST with the least toxicity were observed for AA in the lower received HF doses (72 and 64.8 Gy). Accordingly, 72 Gy in two 1.2 Gy fractions was used as the investigational arm of a completed Phase III trial (RTOG 90-06). In contrast, for GBM patients, longer survival times were noted in the higher received HF doses (78.6 and 81.6 Gy), suggesting the role for further dose escalation. The low toxicity rate with AHF arms suggest that further dose escalation is possible and is currently occurring in RTOG 94-11.

Adolescent↗
PubMed1996

Do overall treatment time, field size, and treatment energy influence local control of T1-T2 squamous cell carcinomas of the glottic larynx?

PURPOSE: To evaluate treatment and patient related prognostic factors that may influence local control in the treatment of T1-T2 squamous cell carcinoma of the glottic larynx. METHODS AND MATERIALS: One hundred nine patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx were treated with curative intent with radiotherapy at the Fox Chase Cancer Center between June 1980 and November 1991. Follow-up ranged from 26-165 months (mean 83 months). RESULTS: The 2-year local control rates for patients with T1 and T2 lesions were 89% and 80%, respectively. The 2-year local control rate for patients whose overall treatment time was < 50 days was 92% vs. 82% for patients whose overall treatment time was > 50 days (p = 0.07). The 2-year local control rate for patients treated with an irradiated area < 36 cm(2) was 90% compared to 86% in patients who were treated to an area > or = 36 cm(2). The 2-year local control rate for patients treated with 60Co was 83% vs. 92% for patients treated with 6 MV x-ray. Cox proportional hazards regression analysis was performed using the following variables: treatment energy, irradiated area, gender, tobacco pack years, tumor differentiation, overall treatment time, total dose, dose per fraction, and T stage. Overall treatment time (p = 0.05) was the only variable that significantly influenced local control. CONCLUSION: Extending the overall treatment time was found to adversely influence local control. Neither the irradiated area nor treatment energy was found to influence local control in early stage vocal cord carcinoma.

Adult↗
PubMed1996

Race and prognosis of brain tumor patients entering multicenter clinical trials. A report from the Radiation Therapy Oncology Group.

We investigated the possible influence of race on the survival of patients with malignant gliomas enrolled in three consecutive trials of the Radiation Therapy Oncology Group (RTOG) retrospectively using the group's statistical database. There were no statistical differences between the survival rates for black patients with glioblastoma multiforme (GBM) and those for the white patients. The limited influence of therapy on this disease may be responsible in part for this result.

Adult↗
PubMed1996

Concurrent chemoradiation therapy with oral etoposide and cisplatin for locally advanced inoperable non-small-cell lung cancer: radiation therapy oncology group protocol 91-06.

PURPOSE: Patients with locally advanced inoperable non-small-cell lung cancer (NSCLC) have a poor clinical outcome. We conducted a prospective study to evaluate the merit of chemotherapy administered concurrently with hyperfractionated thoracic radiation therapy. PATIENTS AND METHODS: Seventy-nine patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Treatment consisted of two cycles of oral etoposide 100 mg/d (50 mg/d if body-surface area [BSA] < 1.70 m2), intravenous cisplatin 50 mg/m2 on days 1 and 8, and hyperfractionated radiation therapy 5 days per week (1.2 Gy twice daily > 6 hours apart; total 69.6 Gy). RESULTS: Seventy-six assessable patients with a Karnofsky performance status > or = 60 and adequate organ function who had received no prior therapy were evaluated for clinical outcome and toxic effects. After a minimum follow-up duration of 21 months, the 1- and 2-year survival rates and the median survival duration were 67%, 35%, and 18.9 months overall; they were 70%, 42%, and 21.1 months for patients with weight loss of < or = 5%. Toxicity was significant; 57% developed grade 4 hematologic toxicity, 53% grade 3 or 4 esophagitis, and 25% grade 3 or 4 lung toxicity. However, only 6.6% of patients had grade 4 or lethal nonhematologic toxicity, which included three treatment-related deaths (two of pneumonitis and one of renal failure). CONCLUSION: Concurrent chemoradiation therapy with oral etoposide and cisplatin plus hyperfractionated radiation therapy is feasible. The survival outcome from this regimen compares favorably with that of other chemoradiation trials and even of multimodality trials that have included surgery.

Administration, Oral↗
PubMed1995

Central pathology review in clinical trials for patients with malignant glioma. A Report of Radiation Therapy Oncology Group 83-02.

BACKGROUND: Confounding biologic factors, including histologic grade, may influence the outcome of adult patients with malignant gliomas more than may modifications in therapeutic approach. Any clinical trial design for malignant gliomas in adults must account for such biologic factors, including the accurate identification of the two histologic subgroups astrocytoma with anaplastic foci (AAF) or glioblastoma multiforme (GBM), which are associated with distinctly different survival outcomes. This paper examines the need for a central pathology review before entry of patients in cooperative group clinical trials stratified by histologic grade. METHODS: Pathology slides from Radiation Therapy Oncology Group (RTOG) trial 83-02, a randomized Phase II study of hyperfractionated and accelerated hyperfractionated radiation therapy and carmustine for malignant gliomas, provided 747 analyzable cases, with 680 (91%) available for central pathology review. This review was performed by a single pathologist according to RTOG/Eastern Cooperative Oncology Group histopathologic criteria. The kappa statistic was used to measure agreement between the institutional and central classification of AAF and GBM. The influence of misclassification was examined using computer simulation of varying clinical trial sizes (n = 25, 50, or 200). The effect on the statistical power of trials (n = 200) with varying mixtures of AAF and GBM tumors was investigated using computer simulations. RESULTS: Of 159 tumors classified as AAF by institutional pathology review, only 66% (105) were classified as AAF (AAF/AAF) by central review, and 54 of these cases (34%) were classified as GBM (GBM/AAF), whereas 96% (501) of 521 institutionally classified as GBM (GBM/GBM) were similarly classified by central review. Computer simulations demonstrated a 59% underestimation in the median survival (1.82 vs. 4.49 years) for trials of patients with institutionally defined AAF compared to patients with centrally defined AAF in studies of 200 patients, resulting from the addition of poor prognosis of GBM in the trial. Misclassification can also substantially reduce the statistical power of a clinical trial. In one of the simulation studies, statistical power was reduced from 65% to 14% if 50% of the patients were to receive an inaccurate histologic classification. Even greater losses in power are possible in many plausible clinical settings. CONCLUSIONS: This examination of a central versus an institutional pathology review demonstrates a low level of agreement on AAF classification and a high level of concordance on GBM classification. The results indicate the need to adjust sample size for trials of both AAF and GBM tumors to have adequate statistical power. A central pathology review remains essential for trial entry for patients with AAF and could be omitted for trials enrolling patients with GBM only.

Adult↗
PubMed1995

Results of an RTOG phase III trial (RTOG 85-27) comparing radiotherapy plus etanidazole with radiotherapy alone for locally advanced head and neck carcinomas.

PURPOSE: The objectives of this study were to determine the efficacy and toxicity of Etanidazole (ETA), a hypoxic cell sensitizer, when combined with conventional radiotherapy (RT) in the management of advanced head and neck carcinomas. METHODS AND MATERIALS: From March 1988 to September 1991, 521 patients who had Stage III or IV head and neck carcinomas were randomized to receive conventional RT alone (66 Gy in 33 fractions to 74 Gy in 37 fractions, 5 fractions per week) or RT+ETA (2.0 g/m2 thrice weekly for 17 doses), of whom 504 were eligible and analyzable. Treatment assignments were stratified before randomization according to the primary site (oral cavity + hypopharynx vs. supraglottic larynx + oropharynx + nasopharynx), T-stage (T1-3 vs. T4), and N-stage (N0-2 vs. N3). Pretreatment characteristics were balanced. In the RT-alone arm, 39% of patients had T3 and 34% had T4 disease, whereas in the RT+ETA arm, 42% of patients had T3 and 33% had T4 disease. Thirty-eight percent of the RT-alone patients and 37% of the RT+ETA patients had N3 disease. The median follow-up of surviving patients was 3.38 years, with a range between 0.96 and 5.63 years. RESULTS: One hundred and ninety-four of the 252 (77%) RT+ETA patients received at least 14 doses of the drug. Overall RT protocol compliance rate was 82% in the RT-alone arm and 86% in the RT+ETA arm. No Grade 3 or 4 central nervous system or peripheral neuropathy was observed in the RT+ETA arm. Eighteen percent of the patients developed Grade 1 and 5% developed Grade 2 peripheral neuropathy. Other drug related toxicities included nausea/vomiting (27%), low blood counts (15%), and allergy (9%). Most of these toxicities were Grade 1 and 2. The incidence of severe acute and late radiation effects were similar between the two arms. The 2-year actuarial local-regional control rate (LCR) was 40% for the RT-alone arm and 40% for the RT+ETA arm. Two-year actuarial survival was 41% for the RT-alone arm and 43% for the RT+ETA arm (p = 0.65). Multivariate analyses were performed to investigate the influence of covariates on treatment effects. A strong treatment interaction with N-stage was revealed: LCR (50% vs. 40% at 2 years), RT+ETA improved for patients with N0-2 disease but not for N3 patients (22% for RT+ETA and 40% for RT). Further analyses showed that RT+ETA was more advantageous in N0-1 patients, with a 2-year LCR of 55% for RT+ETA vs. 37% for RT only (p = 0.03). A similar phenomenon was observed when using survival as the end point. CONCLUSION: The results showed that adding Etanidazole to conventional RT produced no global benefit for patients who had advanced head and neck carcinomas. There was a suggested benefit for patients who had N0-1 disease, and that needs to be confirmed by another study.

Carcinoma, Squamous Cell↗
PubMed1995

Concurrent hyperfractionated irradiation and chemotherapy for unresectable nonsmall cell lung cancer. Results of Radiation Therapy Oncology Group 90-15.

BACKGROUND: Clinical trials of hyperfractionated radiation therapy and induction chemotherapy followed by standard radiation therapy have shown improved survival in patients with unresectable nonsmall cell lung cancer (NSCLC). Radiosensitization may improve local tumor control when chemotherapy is given concurrently with hyperfractionated radiation therapy, but also may increase toxicity. A Phase I/II trial, Radiation Therapy Oncology Group 90-15, was designed to evaluate whether this strategy could improve survival with acceptable toxicity and be part of a Phase III trial of chemoradiation sequencing. METHODS: Vinblastine (5 mg/M2 weekly x 5 weeks) and cisplatin (75 mg/M2 days 1, 29, and 50) were given during twice-daily irradiation (1.2 Gy, 6 hours apart) to 69.6 Gy in 58 fractions in 6 weeks. Eligible patients had American Joint Committee on Cancer (AJCC) Stage II (unresected) or IIIA-B NSCLC and Karnofsky performance status 70 or greater; there were no weight loss restrictions. RESULTS: Of 42 eligible patients, 76% had greater than 5% weight loss, 45% had T4 primary tumors, and 62% were Stage IIIB. All protocol treatment was completed in 53%. Acute toxicity was predominantly hematologic with 19 of 42 (45%) having Grade 4 toxicity or higher, three (7%) with septic death. Ten of 42 (24%) had Grade 3 or higher esophagitis. There were two (4.7%) patients with Grade 3 or higher (1 lung and 1 esophagus) and two (4.7%) with Grade 4 or higher (1 lung and 1 hematologic) late toxicities. Median survival time was 12.2 months, with an overall 1-year survival of 54%, an estimated 2 year survival of 28% and a 1-year progression free survival of 38%. CONCLUSIONS: For patients with unresectable nonsmall cell lung cancer, who were not selected on the basis of weight loss, concurrent hyperfractionated irradiation and chemotherapy had more intense acute toxicity than hyperfractionation alone, but late toxicity was acceptable. One and 2-year survival rates were 54 and 28%, respectively.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Quality-adjusted survival analysis of malignant glioma. Patients treated with twice-daily radiation (RT) and carmustine: a report of Radiation Therapy Oncology Group (RTOG) 83-02.

PURPOSE: To quantify the quality of life of malignant glioma patients treated on a randomized Phase I/II trial of twice-daily radiation therapy (RT) and carmustine, using a modified quality adjusted survival (QAS) model, and to compare the QAS among assigned treatment arms. MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) accrued 786 malignant glioma patients to a Phase I/II randomized dose escalation trial of twice-daily RT with carmustine from 1983 to 1989. Patients were randomized to one of four arms of hyperfractionated RT in 1.2 Gy twice daily (BID) fractions (64.8 Gy, 72.0 Gy, 76.8 Gy, or 81.6 Gy) or to either of two accelerated hyperfractionated RT arms in 1.6 Gy BID fractions (48.0 or 54.4 Gy). Although preliminary toxicity and survival data have been published, little information is available regarding the quality of these patients' lives during and following such therapy. QAS is a refinement of the methodology for assessing survival quality among breast cancer patients receiving adjuvant chemotherapy. The QAS method allows for inclusion of both improvement and decline in neurologic functional status. Patients were scored by the presence or absence of 15 neurologic signs and symptoms at on-study and at every follow-up. Within each category were gradations of severity, with the quality survival time (Q-TIME) adjusted according to any changes in these neurologic findings. The summation of all changes in signs and symptoms were weighted by 1/15th and incorporated into the QAS model as QAS = Q-TIME-TOX-RRX. TOX was the time spent with treatment-related toxicities, and RRX was the time spent in recovery from subsequent therapy. RESULTS: Of 747 evaluable patients, the average QAS time was 18.5 months. The average QAS for the hyperfractionated arms of 64.8 Gy, 72.0 Gy, 76.8 Gy, and 81.6 Gy were 15.6, 20.8, 10.0, and 13.7 months, respectively. For the accelerated hyperfractionated RT arms of 48.0 and 54.4 Gy, the average QAS times were 13.1 and 13.4 months. The QAS time of the 72.0 Gy arm was significantly longer than that of all other groups, except the 64.8 Gy arm. As expected, the QAS times were strongly discriminated by both age and Karnofsky Performance Scores (KPS) (p < 0.001). Younger patients and patients with high KPS benefited most from assignment to the 72.0 Gy arm; QAS time was not significantly longer in any treatment arm among patients over age 50 or with KPS scores of 80 or less. CONCLUSIONS: This quality-adjusted survival methodology can be successfully applied to malignant glioma patients and permits a quantitative assessment of the influence of investigational therapies on patient quality of life. This analysis confirms the potential benefit of intermediate dose (72.0 Gy) hyperfractionated RT for selected malignant glioma patients.

Adult↗
PubMed1995

Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer.

BACKGROUND: Regionally advanced, surgically unresectable non-small-cell lung cancer represents a disease with an extremely poor prognosis. External-beam irradiation to the primary tumor and regional lymphatics is generally accepted as standard therapy. The use of more aggressive radiation regimens and the addition of cytotoxic chemotherapy to radiotherapy have yielded conflicting results. Recently, however, results from clinical trials using innovative irradiation delivery techniques or chemotherapy before irradiation have indicated that patients treated with protocols that incorporate these modifications may have higher survival rates than patients receiving standard radiation therapy. PURPOSE: On the basis of these results, the Radiation Therapy Oncology Group (RTOG)-Eastern Cooperative Oncology Group (ECOG) elected to conduct a phase III trial comparing the following regimens: 1) standard radiation therapy, 2) induction chemotherapy followed by standard radiation therapy, and 3) twice-daily radiation therapy. METHODS: Patients with surgically unresectable stage II, IIIA, or IIIB non-small-cell lung cancer were potential candidates. Staging was nonsurgical. Patients were required to have a Karnofsky performance status of 70 or more and weight loss less than 5% for 3 months prior to entry into the trial, to be older than 18 years of age, and to have no metastatic disease. Of the 490 patients registered in the trial, 452 were eligible. The disease in 95% of the patients was stage IIIA or IIIB. More than two thirds of the patients had a Karnofsky performance status of more than 80. Patients were randomly assigned to receive either 60 Gy of radiation therapy delivered at 2 Gy per fraction, 5 days a week, over a 6-week period (standard radiation therapy); induction chemotherapy consisting of cisplatin (100 mg/m2) on days 1 and 29 and 5 mg/m2 vinblastine per week for 5 consecutive weeks beginning on day 1 with cisplatin, followed by standard radiation therapy starting on day 50; or 69.6 Gy delivered at 1.2 Gy per fraction twice daily (hyperfractionated radiation therapy). RESULTS: Toxicity was acceptable, with four treatment-related deaths. Three patients subsequently died of chronic pulmonary complications. Compliance with protocol treatment was acceptable. One-year survival (%) and median survival (months) were as follows: standard radiation therapy--46%, 11.4 months; chemotherapy plus radiotherapy--60%, 13.8 months; and hyperfractionated radiation therapy--51%, 12.3 months. The chemotherapy plus radiotherapy arm was statistically superior to the other two treatment arms (logrank P = .03). CONCLUSIONS: In "good-risk" patients with surgically unresectable non-small-cell lung cancer, induction chemotherapy followed by irradiation was superior to hyperfractionated radiation therapy or standard radiation therapy alone, yielding a statistically significant short-term survival advantage.

Adult↗
PubMed1995

Influence of a sampling review process for radiation oncology quality assurance in cooperative group clinical trials--results of the Radiation Therapy Oncology Group (RTOG) analysis.

The Radiation Therapy Oncology Group (RTOG) designed a random sampling process and observed its influence upon radiotherapy review mechanisms in cooperative group clinical trials. The method of sampling cases for review was modeled from sampling techniques commonly used in pharmaceutical quality assurance programs, and applied to the initial (on-study) review of protocol cases. 'In control' (IC) status is defined for a given facility as the ability to meet minimum compliance standards. Upon achieving IC status, activation of the sampling process was linked to the rate of continued patient accrual for each participating institution in a given protocol. The sampling design specified that > or = 30% cases not in compliance would be detected with 80% power. A total of 458 cases was analyzed for initial review findings in four RTOG Phase III protocols. Initial review findings were compared with retrospective (final) review results. Of the 458 cases analyzed, 370 underwent initial review at on-study, while 88 did not require review as they were enrolled from institutions that had demonstrated protocol compliance. In the group that had both initial and final review, 345/370 (93%) were found to have followed the protocol or had a minor variation. Of the exempted cases, 79/88 (90%) were found to be per protocol or a minor variant. The sampling process proved itself to be cost-effective and resulted in a noticeable reduction in the workload, thus providing an improved approach to resource allocation for the group. Continued evaluation of the sampling mechanism is appropriate as study designs and participants vary over time, and as more data become available to study.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Protocols↗
PubMed1995

Use of multiplanar reformatted radiographic and digitally reconstructed radiographic images for planning conformal radiation therapy.

A three-dimensional treatment planning system capable of gantry, collimator, and table rotations is required for a noncoplanar conformal therapy. Unfortunately, such a system is not widely available. A method in which multiplanar reformatted radiographic (MPR) and digitally reconstructed radiographic (DRR) images are used is presented for conformal treatment of brain tumors. A head phantom containing a target volume was scanned on a computed tomographic (CT) simulator. The coronal MPR images were digitized on a treatment planning system to create a conformal block of the planned treatment field. The DRR images were generated on the CT simulator with the setup parameters calculated from the treatment planning system. A second set of conformal blocks was generated based on DRR images of the fields. The accuracy of the MPR- and DRR-generated blocks was verified on the vertex field. The differences between the actual planning target volume and the field edges of the MPR and DRR blocks were within +/- 4 mm and +/- 2 mm, respectively. The authors conclude that the MPR and DRR images could be successfully used to generate conformal blocks and for treatment planning of noncoplanar beams in radiation therapy.

Brain Neoplasms↗
PubMed1995

Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx.

PURPOSE: A number of reports have documented the relationship between pretreatment hemoglobin level and local control and/or survival in the treatment of cervix, bladder, and advanced head and neck tumors. Consideration of correcting anemia before initiation of radiation therapy may prove increasingly important as clinical trials use intensive induction chemotherapy in the treatment of head and neck carcinomas. Neoadjuvant chemotherapy may produce anemia, which in turn may reduce the effectiveness of subsequent irradiation. MATERIALS AND METHODS: One hundred nine patients with T1-2N0 squamous cell carcinoma of the glottic larynx were treated with definitive radiotherapy at the Fox Chase Cancer Center between June 1980 and November 1990. Follow-up times ranged from 26 to 165 months (median, 82). RESULTS: The 2-year local control rate for patients who presented with a hemoglobin level < or = 13 g/dL was 66%, compared with 95% for patients with a hemoglobin level more than 13 g/dL (P = .0018). The 2-year survival rate for patients with a hemoglobin level < or = 13 g/dL was 46%, compared with 88% for patients with a hemoglobin level more than 13 g/dL (P < .001). Cox proportional hazards regression analysis showed that hemoglobin level (P = .0016) was the only variable that significantly influenced local control (P = .0016) and survival (P < .0001). CONCLUSION: Patients who presented with hemoglobin levels more than 13 g/dL had significantly higher local control and survival rates. The strong apparent correlation between hemoglobin level, local control, and survival supports consideration of correcting anemia before initiation of radiation therapy.

Actuarial Analysis↗
PubMed1995

New therapeutic strategies involving radiation therapy for patients with non-small cell lung cancer.

Recent notable developments have occurred involving radiation therapy (RT) for patients with non-small cell lung cancer (NSCLC). For patients with good performance status with unresected thoracic tumors, induction cisplatin-based chemotherapy followed by RT has resulted in a significant survival advantage over RT alone in two North American trials. However, the best sequence of administration of these two modalities in NSCLC remains to be determined. For palliation of tumor-related symptoms, efforts under way to improve control of brain metastases include the use of twice-daily cranial RT to a higher total dose, the use of focused radiation boost techniques like stereotactic radiosurgery to small metastatic deposits, and increased use of neurosurgical extirpation. For patients with NSCLC with symptomatic bone metastases, use of wider-field irradiation may benefit selected patients. Metastases to the adrenal gland, liver, and subcutaneous tissues can be palliated successfully by brief courses of RT. Intrathoracic tumor symptoms are well palliated by brief courses of thoracic RT. As adjuvant therapy following curative surgery, RT reduces the intrathoracic tumor recurrence rate among patients with metastatic tumor foci in hilar or mediastinal lymph nodes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

White matter changes are correlated significantly with radiation dose. Observations from a randomized dose-escalation trial for malignant glioma (Radiation Therapy Oncology Group 83-02).

BACKGROUND: A Phase I/II randomized dose-seeking trial was performed to document the severity, time course, and significance of white matter changes seen on serial imaging scans (magnetic resonance imaging, computed tomography) associated with bis-chlorethyl nitrosourea (BCNU) and hyperfractionated cranial irradiation. METHODS: Long term survivors (> or = 18 months) were identified from a prospective randomized dose-escalation Phase I/II trial designed to evaluate twice-daily radiotherapy for supratentorial high grade malignant gliomas. All scans were reviewed by a neuroradiologist who had no information about the prescribed dose and fractionation. In the trial, patients were assigned to receive 64.8 Gy, 72.0 Gy, 76.8 Gy, or 81.4 Gy (all fractionated as 1.2 Gy twice a day [bid]), or 48.0 Gy or 54.4 Gy (both in 1.6-Gy bid fractions). Bis-chlorethyl nitrosourea was administered every 8 weeks for 1 year. Of 747 randomized patients, 177 had analyzable scans. The scans reviewed were those acquired preoperatively, immediately postoperatively, 3, 6, 12, and 18 months after radiotherapy. Radiographic endpoints included no white matter change (Grade 0), minimal patchy white matter foci (Grade 1), start of confluence of white matter disease (Grade 2), large confluent areas (Grade 3), confluence with cortical/subcortical involvement (Grade 4), leukoencephalopathy (Grade 5), and possible necrosis (Grade 6) according to the classification of F. Fazekas et al. The effects were scored relative to the baseline preoperative scans. The dose pairs of 48 Gy and 54.4 Gy, 64.8 Gy and 72 Gy, and 76.8 Gy and 81.4 Gy were grouped together for analysis (low, intermediate, and high dose, respectively). Toxicity was analyzed in three ways: Grade 2 or worse, Grade 3 or worse, and Grade 6. RESULTS: Grade 2 or worse changes were observed in 26.6, 27.6, and 40.4% of patients in the low, intermediate, and high dose groups, respectively. Grade 3 or worse changes were observed in 8.3, 20.0, and 36.5% of patients in the low, intermediate, and high dose groups, respectively. Grade 6 changes were observed in 1.6, 4.6, and 19.2% of patients in the low, intermediate, and high dose groups, respectively. No statistically significant differences were observed among treatment groups when toxicity was evaluated as Grade 2 or worse. For toxicity of Grade 3 or worse, an chi-square test revealed P values of 0.04 (low vs. intermediate dose), 0.09 (intermediate vs. high dose), and 0.0005 (low vs. high dose). With the endpoint of possible necrosis (Grade 6), P values were 0.21 (low vs. intermediate dose), 0.05 (intermediate vs. high dose), and 0.003 (low vs. high dose). The median time to radiographic appearance of an effect (15 months) was not influenced by total dose or fraction size. CONCLUSIONS: A well described toxicity scale for white matter injury was applied successfully to patients with malignant glioma treated with definitive irradiation. Severe white matter changes continued to increase significantly as the total dose of hyperfractionated cranial irradiation was escalated. The time to onset of the white matter abnormalities appeared to be independent of dose. An ongoing Radiation Therapy Oncology Group study will allow correlation of white matter injury with prospective neuropsychometric testing.

Brain↗
PubMed1993

Report of phase II trial of concurrent chemoradiotherapy with radical thoracic irradiation (60 Gy), infusional fluorouracil, bolus cisplatin and etoposide for clinical stage IIIB and bulky IIIA non-small cell lung cancer.

PURPOSE: To assess the response rate, median and long-term survival of patients (pts) with locally advanced, initially inoperable non-small cell lung cancer (NSCLC) treated on a phase II study of radical thoracic radiotherapy (TRT) and concurrent radiosensitizing chemotherapy. METHODS AND MATERIALS: From 3/87 to 7/90, 41 previously untreated patients at Fox Chase Cancer Center with locally advanced non-small cell lung cancer, 24 with bulky clinical Stage IIIA, and 17 with IIIB disease, received concurrent thoracic radiotherapy (60 Gy/2.0 Gy/d in 6 weeks) and 2 cycles of infusional 5FU (640-800 mg/m2/24 hrs x 5 d); cisplatin (20 mg/m2 qd x 5); and etoposide (50 mg/m2 d 1, 2, 5) administered days 1 and 28 of TRT. RESULTS: Forty of 41 were evaluable. Response rate was 90%, with radiographic CR in 20%. Thirteen pts (33%) underwent thoracotomy and complete resection with clinical downstaging in 10, including three pathologic CR's. Overall median survival was 14 months and 2-year survival was 38% with no difference between CS IIIA and IIIB pts (p = 0.2224). At median potential follow-up of 42 months, 8/40 pts. (20%) are alive and progression-free, including 4 of 13 resected pts. The chief toxicity was esophagitis, occurring in 32 pts. (80%), Grade 3-4 in 21 (52%), with 13 (33%) requiring hospitalization and 7 (18%) needing TPN. Grade 3-4 granulocytopenia was noted in 20 pts. (50%) with ten episodes of fever mandating intravenous antibiotics. Cardiac ischemia was documented in 2 (5%). Of 13 thoracotomy pts, six underwent lobectomy without perioperative mortality; 3 of 7 pneumonectomy pts died post-operatively, two from broncopleural fistula, and one from ARDS. CONCLUSION: This aggressive regimen produced a 2-year survival (38%) comparable to the best arm of cancer and leukemia groups B study 8433, which administered radical thoracic radiotherapy after protoadjuvant vinblastine and cisplatin in similar and earlier stage non-small cell lung cancer patients. Toxicity, particularly esophagitis, was severe, but of short duration. An unacceptably high complication rate was seen following pneumonectomy, but not lobectomy.

Adult↗
PubMed1993

Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials.

PURPOSE: The influence of tumor site, size, and extent of surgery on the survival of patients with glioblastoma multiforme treated on three consecutive prospectively randomized Radiation Therapy Oncology Group trials employing surgery and irradiation plus or minus chemotherapy was studied. METHODS AND MATERIALS: Six hundred forty-five patients with a diagnosis of glioblastoma multiforme on central pathological review were analyzed for survival with respect to known prognostic factors, that is, age and Karnofsky Performance Status, as well as extent of surgery, site, and size. Surgical treatment consisted of biopsy only in 17%, partial resection in 64%, and total resection in 19%. Tumors were located in frontal lobe in 43%, temporal lobe in 28%, and parietal lobe in 25%. Maximum tumor diameter as determined on computed tomography or magnetic resonance imaging scans was less than 5 cm for 38%, between 5-10 cm for 56% and greater than 10 cm for 6% of patients. The extent of surgical therapy was the same for tumors greater than 5 or greater than 10 cm, whereas total resection was more often performed for tumors less than 5 cm. The extent of surgery did not appear to vary with age or site. RESULTS: Patients undergoing total resection had a median survival of 11.3 months compared to 6.6 months for patients with a biopsy only. A significant difference in median survival was also found for partial resection versus biopsy only treatment (10.4 vs. 6.6 months). There was no difference in survival for the different tumor sizes. Patients with frontal lobe tumors survived longer than those with temporal or parietal lobe lesions (11.4 months, 9.1 months, and 9.6 months, respectively) (p = 0.01). A Cox multivariate model confirmed a significant correlation of age, Karnofsky Performance Status, extent of surgery, and primary site with survival. The best survival rates occurred in patients who had at least three of the following features: < 40 years of age, high Karnofsky Performance Status, frontal tumors, and total resection (17 months median). CONCLUSION: We conclude that biopsy only yields inferior survival to more extensive surgery for patients with glioblastoma multiforme treated with surgery and radiation therapy.

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