Richard L. Crownover

Stereotactic radiosurgery for lung tumors: Preliminary report of a phase I trial

BACKGROUND Stereotactic radiosurgery is well established for the treatment of intracranial neoplasms but its use for lung tumors is novel. METHODS Twenty-three patients with biopsy-proven lung tumors were recruited into a two-institution, dose-escalation, phase I clinical trial using a frameless stereotactic radiosurgery system (CyberKnife). Fifteen patients had primary lung tumors and 8 had metastatic tumors. The age range was 23 to 87 years (mean, 63 years). After undergoing computed tomography-guided percutaneous placement of two to four small metal fiducials directly into the tumor, patients received 1,500 cGY of radiation in a single fraction using a linear accelerator mounted on a computer-controlled robotic arm. Safety, feasibility, and efficacy were studied. RESULTS Nine patients were treated with a breath-holding technique, and 14 with a respiratory-gating, automated, robotic technique. Tumor size ranged from 1 to 5 cm in maximal diameter. There were four complications related to fiducial placement: three pneumothoraces requiring chest tube insertion and one emphysema exacerbation. There were no grade 3 to 5 radiation-related complications. Follow-up ranged from 1 to 26 months (mean, 7.0 months). Radiographic response was scored as complete in 2 patients, partial in 15, stable in 4, and progressive in 2. Four patients died of non-treatment-related causes at 1, 5, 9, and 11 months after radiation. CONCLUSIONS Single-fraction stereotactic radiosurgery is safe and feasible for the treatment of selected lung tumors. Additional studies are planned to investigate the optimal radiation dose, best motion-suppression technique, and overall treatment efficacy.

Results of whole brain radiotherapy in patients with brain metastases from breast cancer: a retrospective study

PURPOSE To analyze the factors that affect survival in patients with brain metastases (BM) from breast cancer who were treated with whole brain radiotherapy (WBRT). METHODS AND MATERIALS We identified 116 women with breast cancer who were treated with WBRT alone between February 1984 and September 2000. All patients had treatment and follow-up data available in their medical charts, which we extracted for this retrospective study. We evaluated a number of potential predictors of survival after WBRT: age, primary tumor stage, control of primary tumor, presence of other systemic metastases, site of systemic metastases, Karnofsky performance status, Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, total dose of WBRT, and number of BM. Eighteen patients received a total dose >3000 cGy and 7 received a partial brain boost. RESULTS For the entire cohort, the median survival from the start of WBRT was 4.2 months. The 1-year survival rate was 17%, and the 2-year survival rate was 2%. Using univariate analysis, only Karnofsky performance status (p = 0. 0084), recursive partitioning analysis class (p = 0. 0147), and total WBRT dose (p = 0.0001) were predictive of longer survival. In multivariate analysis, Karnofsky performance status was the only significant predictor. CONCLUSION Overall survival in breast cancer patients with BM treated with WBRT is poor. We recommend breast cancer patients with BM be enrolled in prospective trials to improve results.

Treatment and prognosis of primary breast lymphoma: A review of 13 cases

Primary non-Hodgkins lymphoma (NHL) of the breast is a rare entity that does not have a well-defined treatment strategy. At presentation, most patients are clinically thought to have a primary breast carcinoma, and the diagnosis of lymphoma is made at biopsy. Once the diagnosis of lymphoma is made, patients are treated with some combination of chemotherapy, radiation therapy, and surgery. We review The Cleveland Clinic Foundation experience with primary breast lymphoma. Between 1980 and 1996, 17 patients with primary breast lymphoma were seen at The Cleveland Clinic Foundation, and 13 had follow-up information available. All patients underwent a staging workup including computed tomography (CT) scan of the chest, abdomen, and pelvis, as well as bilateral bone marrow biopsies; all patients staged IE (breast involvement only) or IIE (limited to the breast and ipsilateral axilla) were included. We did not include patients with more extensive supradiaphragmatic nodal involvement who were stage IIE. Patients received some combination of surgery, radiation, and chemotherapy. The median follow-up was 34 months, with a range of 7 to 138 months. There was an equal incidence of right- versus left-sided lesions. Five patients survived at least 5 years from the time of diagnosis. Long-term survival in patients with primary NHL of the breast is possible. We recommend treating patients with aggressive NHL of the breast with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, followed by involved field radiation and treating those patients with indolent lymphoma with involved field radiation alone.

Very low temperature spectroscopy: The pressure broadening coefficients for CH3F between 4.2 and 1.9 K

Pressure broadening parameters and cross sections for the CH3F–He system have been measured between 4.2 and 1.9 K by means of a recently developed technique based on collisional cooling in a cryogenic cell. The cross sections for the K=0 and K=1 components of the J=1–2 transition were found to be 75.2 and 66.6 A2, respectively, at 4.2 K and 55.5 and 54.5 A2, respectively, at 1.9 K. The cross sections at 4.2 K are about 50% larger than the 300 K values. These results are compared with earlier experimental and theoretical results obtained for the CO–He system.

Phase II Trial of Liposomal Doxorubicin (Doxil®) in Advanced Soft Tissue Sarcomas

AbstractPurpose: To assess the objective response rate, toxicityexperienced, progression-free survival, and overall survival ofpatients with previously untreated advanced soft tissue sarcomastreated with a liposomal doxorubicin formulation (Doxil). Methods: Patients with metastatic or recurrent soft tissuesarcoma who had received no prior chemotherapy for advanceddisease were treated with liposomal doxorubicin (Doxil) accordingto a two stage accrual design. Doxil was administered at 50mg/m2 every 4 weeks. A total of 15 patients were treated andare evaluable for response and toxicity. Results: The male/female ratio was 7/8, the median age was60 years (34–75) and the ECOG performance status was 0-1 in>90% of patients. Leiomyosarcoma (7/15) and malignant fibroushistiocytoma (2/15) were the most common histologic diagnoses.No objective responses were observed in the 15 evaluablepatients. No lethal toxicity occurred. Grade 3–4 leukopenia orneutropenia were reported in 3/15 (20%) patients. Grade 3mucositis or hand-foot syndrome occurred in 2/15 (13%) and 1/15(7%) patients respectively and seemed more severe in olderpatients. The median time to progression was 1.9 months (range0.9–6.2). Twelve patients have now died. The Kaplan-Meierestimate of median overall survival is 12.3 months. As called forin the study design, accrual was terminated because no responseswere obtained in the first 15 patients. Conclusion: Though well-tolerated, Doxil given accordingto this dose and schedule to patients with advanced soft tissuesarcoma had no significant therapeutic activity. A correlationbetween older age and skin/mucosal toxicity of Doxil is suggestedin this study but needs confirmation. Future investigations ofDoxil in soft tissue sarcomas should use a different schedule anddose.

Potency following high-dose three-dimensional conformal radiotherapy and the impact of prior major urologic surgical procedures in patients treated for prostate cancer

PURPOSE To assess the impact of high-dose three-dimensional conformal radiotherapy (3DCRT) on potency in patients treated for clinically localized prostate cancer and to identify factors that might predict the outcome of sexual function following treatment. METHODS AND MATERIALS One hundred twenty-four consecutive patients treated with 3DCRT for localized prostate cancer at UCSF between 1991-1993 were included in this retrospective analysis. Patient responses were obtained from a mailed questionnaire, telephone interviews, or departmental records. Medial follow-up was 21 months. RESULTS Sixty patients reported having sexual function prior to 3DCRT, including 47 who were fully potent and 13 who were marginally potent. Of the remaining 64 patients, 45 were impotent, 7 were on hormones, 1 was status-postorchiectomy, and 11 were not evaluable. Following 3DCRT, 37 of 60 patients (62%) retained sexual function sufficient for intercourse. Of those with sexual function before irradiation, 33 of 47 (70%) of patients fully potent and 4 of 13 (31%) of patients marginally potent maintained function sufficient for intercourse (p < 0.01). Potency was retained in 6 of 15 (40%) patients with a history of a major urologic surgical procedure (MUSP) and in 31 of 45 (69%) with no history of a MUSP (p < 0.04). Transurethral resection of the prostate was the MUSP in eight of these patients, with four (50%) maintaining sexual function. CONCLUSIONS Patients who receive definitive 3DCRT for localized prostate cancer appear to maintain potency similar to patients treated with conventional radiotherapy. However, patients who are marginally potent at presentation or who have a history of a MUSP appear to be at increased risk of impotence following 3DCRT.

The rotational spectrum of nitric acid - The first five vibrational states

Abstract With the work reported here, we have completed a series of rotational analyses of the v 9 , v 7 , v 6 , and v 8 vibrational states of the important atmospheric species nitric acid. In this paper, we report the details of our work on the v 8 vibrational state, which arise from the NO 2 out of plane vibration. For this state, over 210 transitions have been measured in the millimeter and submillimeter spectral region and analyzed with Watsons A reduced centrifugal distortion Hamiltonian. In the course of our work on the excited vibrational states, a number of additional lines of the ground state have been observed and a more complete analysis of the ground state is provided. Also included in this work is a comparison of all these spectra and an overview of the millimeter and submillimeter spectra associated with these states. Although at the high sensitivity available in laboratory experiments, many additional lines are observable, all arise from vibrational states whose populations are more than 100 times lower than the ground state. The most prominent of these are due to the states which give rise to the perturbed 2 v 9 and v 5 bands near 11μm. These results provide a significant data base for both atmospheric remote sensing experiments and spectral analyses of data in other spectral regions, especially the infrared (i.r.).

Flutamide-induced liver toxicity including fatal hepatic necrosis

PURPOSE To describe hepatic injuries in three patients who received flutamide prior to and during radiation treatment to make radiation oncologists aware of the need for careful monitoring of liver function during use of this drug. METHODS AND MATERIALS The records of three patients who developed abnormal liver function tests while undergoing total androgen suppression (TAS), as well as the literature concerning flutamide toxicity were reviewed and summarized. RESULTS Three of 34 patients treated with a TAS regimen incorporating flutamide developed significant hepatic abnormalities: elevated transaminases [2] and fatal hepatic necrosis [1]. Following the discontinuation of flutamide, two patients recovered fully. Unfortunately, the third patients hepatic function continued to deteriorate, which culminated in his death. Transient elevations in serum transaminases, which do not exceed four times the upper limits of normal, are common and apparently without clinical significance. Unfortunately, idiosyncratic serious and/or fatal liver damage can occur. Significant liver toxicity may be obviated by monitoring of liver function tests (LFT) early in the course of flutamide therapy. CONCLUSION The incidence of hepatic toxicity associated with flutamide may be higher than previously suggested. To prevent the development of serious hepatic dysfunction, all patients receiving flutamide should be monitored clinically for signs and symptoms referable to hepatic injury and with serial LFT. We recommend baseline LFT followed by serial LFT at weeks 2, 4, 6, and 8 from the start of treatment with flutamide. Flutamide should be stopped promptly if significant liver abnormalities are detected.

Study of the ν3 and 2ν3 ← ν3 bands of 12CH3F by infrared laser sideband and submillimeter-wave spectroscopy

Abstract An infrared laser sideband spectrometer operating in the CO 2 laser region with 8- to 18-GHz sidebands has been used to record 266 transitions in the ν 3 band and 84 transitions in the 2 ν 3 ← ν 3 band of 12 CH 3 F. The accuracy of the measured frequencies is estimated to be 1–3 MHz. A millimeter/submillimeter-wave spectrometer has been used to record the spectra of 48 pure rotational transitions in the ground vibrational state and 55 transitions in the v 3 = 1 vibrational state with an accuracy of 20–90 kHz. The new measurements have been combined with previous radio frequency and infrared laser results to derive sets of constants for the ground, v 3 = 1, and v 3 = 2 states for this molecule. Tables of the vibrational dependence of the parameters and of the near coincidences of the ν 3 and 2 ν 3 ← ν 3 band transitions with CO 2 laser frequencies are given.

Reducing scatter radiation to the contralateral breast with a mobile, conformal shield during breast cancer radiotherapy

During a standard course of breast radiotherapy, the contralateral breast generally receives approximately 2.5 to 6.0 Gy of scattered radiation. Although most studies have not found an overall increase in metachronous contralateral breast cancers in patients undergoing radiotherapy, a cohort of younger women may be genetically more susceptible to radiation-induced breast cancers and may thus be adversely affected by the scattered radiation. We are attempting to develop a simple, convenient, effective mechanism for minimizing the scattered radiation to the contralateral breast during the process of clinical breast radiotherapy. We therefore designed a conformal, platform-based breast shield consisting of 2.5 cm of molded lead in a mobile counterweighted polystyrene casing. This shield was intended to serve as a physical barrier to prevent both low and high energy scattered photons from the medial and lateral tangential fields. We conducted a prospective trial of 20 women, each woman serving as her own control. Each woman received breast radiotherapy with and without shield, and an array of thermoluminescent dosimeters was positioned across the contralateral breast to evaluate the in vivo dosimetry and the impact of the breast shield on surface absorption of scattered radiation. We found that the use of the breast shield reduced the median dose of scattered radiation by approximately 60% (p < 0.0001). This represented a median dose reduction of approximately 300 cGy at the nipple. The shield was easily positioned and added < 1 min to daily setup time. We conclude that the use of this sort of surface barrier shielding technique was feasible, effective, and practical for clinical use. The degree of scatter reduction accomplished through the use of this breast shield may be biologically significant, especially for those patients with biologic or epidemiologic risk factors that may predispose them to the development of radiogenic breast cancers.