Induction and concurrent paclitaxel/carboplatin every 3 weeks with thoracic radiotherapy in locally advanced non-small-cell lung cancer: an interim report.

The paclitaxel/carboplatin combination has demonstrated promising activity in metastatic non-small-cell lung cancer (NSCLC); therefore, we mounted an exploratory study of these agents with thoracic radiation (TRT) in locally advanced NSCLC. Eligibility stipulated a Karnofsky performance status >or= 70%, weight loss or= 2 esophagitis has corresponded to length (> 16 cm) of esophagus in the radiation treatment field (Fisher's exact test, P = 0.006). The partial response rate to induction therapy was 40% and to the combined modality therapy was 60%. The median survival for all 49 patients is 15.3 months, with a median disease-free survival (DFS) of 7.8 months. In the subset of 22 patients treated on the phase I portion of the study, the median survival and DFS were 18.5 months and 13.5 months, respectively. Induction therapy with paclitaxel and carboplatin followed by concurrent chemoradiotherapy with the same agents is an active and well-tolerated treatment approach in locally advanced NSCLC. To date, paclitaxel 175 mg/m2 plus carboplatin AUC 5 administered at 3-week intervals for 2 cycles is safe in combination with TRT.

Reduced-dose radiosurgery for vestibular schwannomas.

OBJECTIVE: To evaluate tumor control and complications associated with low-dose radiosurgery for vestibular schwannomas. METHODS: Between December 1993 and January 2000, 47 patients with vestibular schwannomas were treated at our center with gamma knife radiosurgery. The marginal tumor doses ranged from 7.5 to 14.0 Gy (median, 12.0 Gy) for patients treated after microsurgery and from 10.0 to 15.0 Gy (median, 12.0 Gy) for patients in whom radiosurgery was the primary treatment. The median maximum tumor diameter was 18 mm (range, 3-50 mm). Evaluation included audiometry, neurological examination, and serial imaging tests. A survey was conducted at the time of analysis. RESULTS: Follow-up data were available for 45 patients and ranged from 1 to 7 years (median, 3.6 yr). In 43 patients (96%), tumor control (no radiographic progression or surgical resection) was observed. All 33 previously untreated patients had tumor control. Transient facial weakness, experienced in two patients (4%), had resolved completely within 6 months. No patient developed trigeminal neuropathy. Hearing was diminished from baseline in 12% of patients with useful hearing (Gardner-Robertson Class III). However, all patients with pretreatment hearing Gardner-Robertson Class I or II maintained testable hearing (Class I to III) at the most recent examination. CONCLUSION: Low-dose radiosurgery in this series provided comparable local control and decreased incidences of complications in relation to other reports. Additional follow-up will allow more definitive conclusions to be reached regarding the ultimate rates of tumor control and hearing preservation. Nevertheless, the current dose used for vestibular schwannomas at the University of Maryland Medical Center is 12.0 Gy to the tumor periphery.

Variation of clinical target volume definition in three-dimensional conformal radiation therapy for prostate cancer.

PURPOSE: Currently, three-dimensional conformal radiation therapy (3D-CRT) planning relies on the interpretation of computed tomography (CT) axial images for defining the clinical target volume (CTV). This study investigates the variation among multiple observers to define the CTV used in 3D-CRT for prostate cancer. METHODS AND MATERIALS: Seven observers independently delineated the CTVs (prostate +/- seminal vesicles [SV]) from the CT simulation data of 10 prostate cancer patients undergoing 3D-CRT. Six patients underwent CT simulation without the use of contrast material and serve as a control group. The other 4 had urethral and bladder opacification with contrast medium. To determine interobserver variation, we evaluated the derived volume, the maximum dimensions, and the isocenter for each examination of CTV. We assessed the reliability in the CTVs among the observers by correlating the variation for each class of measurements. This was estimated by intraclass correlation coefficient (ICC), with 1.00 defining absolute correlation. RESULTS: For the prostate volumes, the ICC was 0.80 (95% confidence interval [CI]: 0.56-0.96). This changed to 0.92 (95% CI: 0.75-0.99) with the use of contrast material. Similarly, the maximal prostatic dimensions were reliable and improved. There was poor agreement in defining the SV. For this structure, the ICC never exceeded 0.28. The reliability of the isocenter was excellent, with the ICC exceeding 0.83 and 0.90 for the prostate +/- SV, respectively. CONCLUSIONS: In 3D-CRT for prostate cancer, there was excellent agreement among multiple observers to define the prostate target volume but poor agreement to define the SV. The use of urethral and bladder contrast improved the reliability of localizing the prostate. For all CTVs, the isocenter was very reliable and should be used to compare the variation in 3D dosimetry among multiple observers.

A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma.

PURPOSE: A phase I dose escalation of hypofractionated stereotactic radiotherapy (H-SRT) in recurrent or persistent malignant gliomas as a means of increasing the biologically effective dose and decreasing the high rate of reoperation due to toxicity associated with single-fraction stereotactic radiosurgery (SRS) and brachytherapy. MATERIALS AND METHODS: From November 1994 to September 1996, 25 lesions in 20 patients with clinical and/or imaging evidence of malignant glioma persistence or recurrence received salvage H-SRT. Nineteen patients at the time of initial diagnosis had glioblastoma multiforme (GBM) and one patient had an anaplastic astrocytoma. All of these patients with tumor persistence or recurrence had received initial fractionated radiation therapy (RT) with a mean and median dose of 60 Gy (44.0-72.0 Gy). The median time from completion of initial RT to H-SRT was 3.1 months (0.7-45.5 months). Salvage H-SRT was delivered using daily 3.0-3.5 Gy fractions (fxs). Three different total dose levels were sequentially evaluated: 24.0 Gy/3.0 Gy fxs (five lesions), 30.0 Gy/3.0 Gy fxs (10 lesions), and 35.0 Gy/3.5 Gy fxs (nine lesions). Median treated tumor volume measured 12.66 cc (0.89-47.5 cc). The median ratio of prescription volume to tumor volume was 2.8 (1.4-5.0). Toxicity was judged by RTOG criteria. Response was determined by clinical neurologic improvement, a decrease in steroid dose without clinical deterioration, and/or radiologic imaging. RESULTS: No grade 3 toxicities were observed and no reoperation due to toxicity was required. At the time of analysis, 13 of 20 patients had died. The median survival time from the completion of H-SRT is 10.5 months with a 1-year survival rate of 20%. Neurological improvement was found in 45% of patients. Decreased steroid requirements occurred in 60% of patients. Minor imaging response was noted in 22% of patients. Using Fisher's exact test, response of any kind correlated strongly to total dose (p = 0.0056). None of six lesions treated with 21 Gy or 24 Gy responded, whereas there was a 79% response rate among the 19 lesions treated with 30 or 35 Gy. Tumor volumes < or =20 cc were associated with a higher likelihood of response (p = 0.053). CONCLUSIONS: H-SRT used in this cohort of previously irradiated patients with malignant glioma was not associated with the need for reoperation due to toxicity or grade 3 toxicity. This low toxicity profile and encouraging H-SRT dose-related response outcome justifies further evaluation and dose escalation.