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Biomedical subjects

K J Stelzer

Publications and source records attributed to K J Stelzer.

At least 19 recordsLinked to original sources
PubMed1999

A new technique for performing Syed template interstitial implants for anterior vaginal tumors using an open retropubic approach.

The Syed template (Alpha-Omega Services, Bellflower, CA) has been established as an advance in interstitial gynecologic brachytherapy. Unfortunately, enthusiasm for the technique is often tempered by certain tumor geometries which require blind insertion of the interstitial needles, potentially risking inaccurate placement of the radioactive sources and viscus perforation. These concerns arise particularly in the management of anterior vaginal tumors where difficulties in negotiating the pubic arch can prevent optimal needle placement. In answer to this problem, a technique utilizing an open retropubic approach for Syed template interstitial implants in anterior vaginal tumors under direct visualization is described. To date, six procedures have been performed. The disease entities include advanced cervical squamous cell carcinoma, clear cell carcinoma of the vagina, recurrent vaginal carcinoma, recurrent endometrial carcinoma, and urethral adenocarcinoma. Complete response was noted in five of six patients but persistent local control of disease was achieved in only one of five complete responses over a relatively short follow-up interval. Complications included paravaginal abscess (n = 1), postoperative deep venous thrombosis (n = 1), abdominal incision cellulitis (n = 1), and radiation enteritis (n = 1). An open retropubic approach allows direct visualization of the bladder and urethra during interstitial implantation of anterior vaginal malignancies and facilitates negotiation of the pubic arch. In our experience, this technique results in improved needle positioning and is thus intuitively likely to aid in avoiding injury to surrounding normal tissues. Additional accrual of a larger cohort will be necessary to arrive at any meaningful objective conclusions regarding the technique's benefit over current modalities.

Adult↗
PubMed1998

Concurrent cisplatin, prolonged oral etoposide, and vincristine plus chest and brain irradiation for limited small cell lung cancer: a phase II study of the Southwest Oncology Group (SWOG-9229).

PURPOSE: The primary objectives of the study were to evaluate the efficacy and safety of prolonged oral (PO) etoposide as part of cisplatin-based chemotherapy plus concurrent chest/brain irradiation induction, followed by CAV consolidation, in the treatment of patients with limited-stage small cell lung cancer (SCLC-LD) within a cooperative group setting. METHODS AND MATERIALS: Fifty-six eligible patients with SCLC-LD received three 28-day cycles of cisplatin 50 mg/m2 i.v. (days 1, 8; 29, 36; and 57, 64), PO etoposide 50 mg/m2 (days 1-14, 29-42, and 57-70), and vincristine 2 mg i.v. (days 1, 29, and 57). Thoracic irradiation (TRT) was administered at 1.8 Gy in 25 daily fractions to a total dose of 45 Gy via an AP:PA arrangement, to begin concomitantly with induction chemotherapy. Prophylactic cranial irradiation (PCI) was started on day 15 of induction therapy. Fifteen daily fractions of 2.0 Gy were administered to the entire brain to a total dose of 30 Gy to finish at approximately the same time as TRT. Two 21-day cycles of consolidation cyclophosphamide 750 mg/m2 i.v., doxorubicin 50 mg/m2 i.v., and vincristine 2 mg i.v. (all on days 1 and 22), were given beginning on day 106 or week 16, from the start of induction therapy. RESULTS: Among 56 eligible patients, 93% had SWOG performance status 0-1. All had adequate organ function and had not received prior therapy. The overall confirmed response rate was 46%, including 16% complete responders and 30% partial responders. After a minimum follow-up duration of 17 months, the Kaplan-Meier median progression-free (PFS) and overall survival (OS) were 10 and 15 months, respectively. Two-year survival is 28%. Only 28 of 56 patients (50%) completed chemotherapy per protocol, while 52 of 56 patients (93%) completed radiation per protocol. Eleven patients (20%) discontinued secondary to toxicity and two patients died from treatment. The major toxicity was hematologic. The two deaths were secondary to infection. Of the nonhematologic toxicities, there were 10 cases of pulmonary fibrosis (including one Grade 3) and six cases of pneumonitis (including one Grade 3). CONCLUSION: Concomitant chemoradiation with oral etoposide as part of a platinum-based chemotherapy and TRT induction regimen is toxic. The CR rate is not better than our prior best group-wide experience. The progression-free and overall survival are similar to published trials utilizing short-course i.v. etoposide. As in chemotherapy for extensive-stage SCLC, there is no apparent advantage to prolonged exposure to etoposide, and toxicity resulted in an inferior therapeutic index compared to programs with shortened exposure.

Administration, Oral↗
PubMed1998

Fast neutrons in prostatic adenocarcinomas: worldwide clinical experience.

Primary tumor control remains a major problem in the treatment of locally advanced prostate carcinoma. Clinical local failure rates approach 30-40% and may be significantly higher when results of prostatic biopsy or prostate-specific antigen (PSA) levels are considered. The low growth rate and cycling fraction of prostate adenocarcinoma suggest potential therapeutic advantage for the high linear energy transfer (LET) of neutrons. The Radiation Therapy Oncology Group (RTOG) performed a multi-institutional randomized trial (RTOG 77-04) comparing mixed beam (neutron plus photon) irradiation to conventional photon irradiation for the treatment of locally advanced prostate cancer. A subsequent trial by the Neutron Therapy Collaborative Working Group (NTCWG 85-23) compared pure neutron irradiation to standard photon irradiation. Both randomized trials demonstrate significant improvement in locoregional control with neutron irradiation compared to conventional photon irradiation in the treatment of locally advanced prostate carcinoma. To date, only the mixed beam trial has shown a significant survival benefit. Future analysis of the larger NTCWG trial at the 10-year point should confirm whether or not improved locoregional control translates into a survival advantage. These findings have significant implications for all local treatment strategies including dose-escalated conformal photon irradiation, prostate implantation, and neutron radiation. Given the large numbers of patients afflicted with this disease, a positive survival advantage for neutrons or mixed beam therapy would provide a strong incentive for the development of economically feasible clinical neutron facilities.

Adenocarcinoma↗
PubMed1997

Boron neutron capture enhanced fast neutron radiotherapy for malignant gliomas and other tumors.

Both fast neutron radiotherapy and boron neutron capture therapy have been investigated as new radiation treatment techniques for patients with malignant gliomas. While each of these techniques individually has shown the potential for pathological eradication of malignant glioma, to date neither has evolved into an accepted, improved method of treatment. We have recently begun a research program investigating the feasibility of combining the benefits of both types of therapy. As a fast neutron beam penetrates tissue some of the particles are degraded to thermal energies. These can be captured by 10B or other suitable isotopes resulting in a highly-localized release of additional energy during a course of fast neutron radiotherapy. In this article we will review the rationale for such an approach, and review the underlying physics as well as in vitro, in vivo, and early human studies testing its feasibility. If appropriate carrier agents can be found that preferentially-localize in tumor cells, this approach ena be applied to many different tumor systems.

Animals↗
PubMed1996

Operation and permanent low activity 125I brachytheraphy for recurrent high-grade astrocytomas.

Twenty-two adult patients with recurrent high grade astrocytomas [18 glioblastoma multiforme (GBM) and 4 anaplastic astrocytoma (AA) at time of implant] underwent therapy at the University of Washington from October 1991 through March 1995, with repeat craniotomy, maximal debulking of tumor, and placement of permanent low activity 125I seeds. Median age was 41 years and median Karnofsky performance status was 90. Median survival for the entire group was 65 weeks from the time of implant. For the subgroup of GBM patients, median survival was 64 weeks from the time of implant. One-year survival from the date of implant was 57% for the entire group and 59% for those with GBM. The site of first failure after implant was local (within 2 cm of the resection cavity) in 70%, distant (noncontiguous, beyond 2 cm) in 18% and concurrently local and distant in 12%. There was one case of symptomatic radiation injury that resolved with steroid therapy, and no patient required repeat craniotomy for parenchymal necrosis. For patients with recurrent GBM, treatment with resection and permanent low activity 125I brachytherapy yielded improved survival compared to an internal historical control group treated with resection and chemotherapy (p = 0.023). Craniotomy with maximal tumor debulking and placement of low activity 125I seeds yields encouraging results with minimal morbidity in patients with recurrent high-grade astrocytomas.

Adolescent↗
PubMed1996

Clinical trials of neutron radiotherapy in the United States.

The development of clinical neutron facilities in the 1980s, capable of delivering high energy neutrons spurred full scale phase III testing of neutron beam radiotherapy in a number of tumors including salivary gland, head and neck, prostate, and non small-cell lung cancer. The Radiation Therapy Oncology Group (RTOG) and the Medical Research Council (MRC) jointly sponsored a randomized trial for the treatment of advanced stage salivary gland tumors comparing neutron to conventional photon and/or electron radiotherapy. Although no improvement in survival was seen, the study demonstrated a striking and statistically significant difference in the local-regional control of unresectable salivary gland tumors (56 vs 17%), favoring neutron beam irradiation. Subsequent clinical trials of neutron beam irradiation were initiated by the Neutron Therapy Collaborative Working Group (NTCWG) sponsored by the National Cancer Institute (NCI). A phase III trial comparing neutron to photon radiotherapy for inoperable regional non-small cell lung cancer showed no overall improvement in survival. However, a statistically significant improvement in survival was observed in the subset of patients with squamous cell histology. The NTCWG trial comparing fast-neutron therapy versus conventional photon irradiation in the treatment of advanced squamous cell carcinomas of the head and neck showed a statistically significant improvement in initial complete response (70 vs 52%) favoring neutrons. However, subsequent failures erased any difference in ultimate local-regional control rates and survival curves were essentially the same in both arms. The randomized study of the NTCWG for locally advanced prostate cancer demonstrated a significant decrease in local-regional failure (11 vs 32%) at 5 years, favoring the neutron arm. Furthermore, biochemical measures of disease control also favored the neutron arm with prostate specific antigen (PSA) levels elevated in 17% of the neutron-treated patients compared to 45% of the photon-treated patients at 5 years. At the 5-year analysis, no significant difference in survival was observed between the two arms; however, longer follow-up is necessary to assess the ultimate impact of improved local-regional control on survival. An analysis of complications in this series revealed the importance of beam shaping and treatment planning capabilities in maintaining long-term sequelae following neutron irradiation at an acceptably low level.

Actuarial Analysis↗
PubMed1996

Expanded pelvic radiotherapy fields for treatment of local-regionally advanced carcinoma of the cervix: outcome and complications.

OBJECTIVE: Recent anatomic and radiographic studies have indicated that standard external beam radiation portals may not adequately treat the volume at risk in patients with local-regionally advanced cervical cancer. A feasibility study was undertaken to evaluate toxicity, outcome, and patterns of failure in patients with advanced cervical cancer treated by expanded pelvic radiation fields. STUDY DESIGN: Thirty-eight women with stages IIB and III cancers of the cervix confined to the pelvis were irradiated with curative intent with expanded pelvic radiation portals. Anteriorly and posteriorly, the median field length and width were 20 and 17.5 cm, respectively. Lateral fields had a median width of 16.5 cm, and the posterior border encompassed the entire sacral silhouette. The median external beam whole-pelvis dose was 4140 cGy, with overall point A dose boosted by brachytherapy to 8315 cGy. RESULTS: Stage IIB patients (n = 22) had a 4-year actuarial local control rate of 70%, freedom from distant metastases rate of 62%, and disease-specific survival rate of 76%. In stage III disease (n = 16), the 4-year actuarial local control, freedom from distant metastases, and disease-specific survival rates were 80%, 48%, and 53%, respectively. Radiographically determined nodal status was an important predictor of disease-specific survival and distant metastases but not local control. The 4-year disease-specific survival rate was 40% in 11 patients with nodal disease compared with 71% in 27 node-negative patients (p < 0.01). The rate of freedom from distant metastases was 36% in node-positive patients versus 67% in node-negative cases (p < 0.01). The actuarial overall 4-year severe late complication rate was 14.8%. CONCLUSION: This study has demonstrated that expanded fields for pelvic radiotherapy is feasible, well tolerated, and therapeutic. The pelvic field design concepts presented should be integrated into radiation oncology practice.

Antineoplastic Agents↗
PubMed1996

Effects of irradiation geometry on treatment plan optimization with linac-based radiosurgery.

A comparison was made of different treatment plans to determine the effect on the three-dimensional dose distributions of varying the allowed parameters in linac-based stereotactic radiosurgery with circular collimators; these parameters are arc position, length, and weighting, and collimator diameter. For the class of eccentrically shaped target volumes that are not so irregular as to require several separate isocenters, it was found that superior dose distributions could be achieved by varying arc length, arc position, arc weighting, and collimator diameter. An analysis of the results achieved with an automated planning program indicates that, in general, the variables of arc position and arc length are of greater importance than collimator size or beam weighting. However, there are cases where varying these latter two parameters does result in markedly better dose distributions. A deeper investigation into the effects of multiple collimators on the dose distribution in the area of steepest gradient demonstrated that multiple collimator sizes do not significantly degrade the dose falloff, which is in fact mostly determined by the effects of intersecting arcs.

Brain Neoplasms↗
PubMed1995

Effect of pentoxifylline on radiation-induced lung and skin toxicity in rats.

PURPOSE: There is currently substantial clinical interest in pentoxifylline as an inhibitor of radiation-related normal tissue injury. To further assess this drug's potential toxicity-sparing effects, pentoxifylline was studied in rats using a radiation-induced lung injury model. METHODS AND MATERIALS: Adult male rats were exposed to either sham irradiation or a single fraction of 21 Gy delivered to the left hemithorax. Four study groups were defined: those that received neither radiation nor pentoxifylline, those that received pentoxifylline (500 mg/L in drinking water) but no irradiation, those that underwent irradiation without pentoxifylline, and those that received both pentoxifylline and radiation. Lung injury was measured by changes in relative left:right lung perfusion ratios derived from quantitative gamma camera imaging of 99mTechnetium-macroaggregated albumin uptake in the pulmonary circulation. Serial scans were done over a 40-week period following radiation. Skin toxicity was also assessed. After 40 weeks, the animals were killed, and lung tissue was assayed for angiotensin converting enzyme activity as a marker for endothelial cell damage. RESULTS: Both groups of radiated (with or without pentoxifylline) rats showed equivalent acute sharp decreases in left:right lung perfusion ratios compared to the nonirradiated groups, reaching a mean nadir value of 0.29 at week 4. Irradiated lung perfusion in subsequent weeks in the radiation-only group showed minimal recovery, with a plateau mean ratio of 0.37 (0.36-0.39). However, there was apparent later recovery of lung perfusion in the radiation with pentoxifylline group from weeks 14 through 40, to a mean ratio of 0.47 (0.43-0.52) (p < 0.01 compared to the radiation-only group). Angiotensin converting enzyme activity correlated closely with lung perfusion data. No effect of pentoxifylline on acute or late skin toxicity was detected. CONCLUSIONS: This study suggests that pentoxifylline does not have any measurable effect on acute lung injury following hemithoracic irradiation in rats, but does result in sparing of later lung toxicity.

Animals↗
PubMed1995

The use of intraoperative radiation therapy in radical salvage for recurrent cervical cancer: outcome and toxicity.

OBJECTIVE: Our purpose was to evaluate the contribution of intraoperative radiation therapy in the management of recurrent cervical cancer. STUDY DESIGN: Twenty-two patients were treated with electron beam intraoperative radiation therapy for recurrent cervical cancers that were confined to the pelvis but were too extensive to be adequately treated by radical surgery alone. All patients underwent extensive surgical dissection for exposure and maximal tumor resection. Doses of intraoperative radiation therapy ranged from 14 to 27.8 Gy (median 22 Gy). Twelve patients received intraoperative radiation therapy to address gross residual disease, and 10 patients were treated for microscopically positive or close surgical margins. RESULTS: The five-year disease-specific survival and local control rates were 43% and 48%, respectively. There were trends toward better local control and disease-specific survival in patients with microscopic residual disease compared with those with gross residual disease. Seven patients had peripheral neuropathy related to treatment, and four of these cases resolved. CONCLUSION: In carefully selected cases intraoperative radiation therapy contributes to radical salvage of patients with recurrent cervical cancer involving the pelvic wall.

Combined Modality Therapy↗
PubMed1995

Radiation therapy for sarcoid of the thalamus/posterior third ventricle: case report.

There are a limited number of previously reported cases involving the use of radiation therapy for sarcoid of the brain. The case of a 22-year-old man with a thalamic/posterior third ventricle sarcoid mass that grew despite steroid medication is presented. The patient was treated with external beam radiation to a total dose of 20 Gy, with 2-Gy fractions over 14 elapsed days. A complete radiographic response was achieved 4 months after radiation was completed. Radiographic follow-up through 8 months postradiation shows no evidence of disease recurrence. Fractionated radiation therapy in low-to-moderate doses appears to be efficacious in steroid-refractory sarcoid of the brain.

Adult↗
PubMed1994

Caffeine consumption is associated with decreased severe late toxicity after radiation to the pelvis.

PURPOSE: Recent studies have suggested that pentoxifylline, a methylxanthine, can prevent or ameliorate late radiation injury in animals and humans. Caffeine is a commonly consumed methylxanthine that provides a model for evaluating the impact of this category of drugs on radiation injury. A retrospective study was undertaken to determine if there is an association between caffeine consumption and a lower incidence of late radiation toxicity. METHODS AND MATERIALS: From 1984 through 1990, 82 patients with cervical cancer and 53 patients with endometrial cancer were treated with primary or adjuvant radiation therapy at the University of Washington. Patients were interviewed regarding ingestion of caffeine-containing beverages, and average daily caffeine consumption during the time of radiotherapy was estimated. The evaluable patients (42 cervical, 31 endometrial) were stratified by quantity of caffeine consumption for correlation with the incidence of radiation toxicity. RESULTS: Acute radiation toxicity was not associated with caffeine consumption for cervical or endometrial cancer. There was a nonstatistically significant trend toward a decrease in overall late radiation toxicity with increased caffeine intake for cervical cancer patients. Subgroup analysis revealed this trend to be attributable to a decreased incidence of severe late radiation injury in cervical cancer patients who consumed higher levels of caffeine at the time of their radiotherapy (p = 0.02). This relationship was not observable for late toxicity in the endometrial cancer patients due to the low incidence of severe late injury following radiation for that disease. CONCLUSIONS: This investigation is supportive of previous studies showing a radioprotective effect for pentoxifylline, and suggests that the mechanisms of radioprotection may be common to methylxanthines as a drug class.

Caffeine↗
PubMed1994

Stereotactic radiosurgery: a review and comparison of methods.

PURPOSE: Stereotactic radiosurgery (SRS) is an evolving modality for treating well-circumscribed intracranial lesions. Different physical methods have been developed to deliver highly localized dose distributions accurately. We review the different methods and the documented clinical results to present a coherent view of radiosurgery, and to aid physicians and physicists in the appropriate use of this modality. DESIGN: A review of the medical physics and clinical literature was conducted. The physical aspects of the different methods and their impact on treatment were summarized. Results were compiled from those individual clinical series with adequate follow-up data to compare the various modalities with respect to treatment outcome for benign tumors, metastases, and vascular malformations. RESULTS: The physical accuracy was comparable between radiosurgical methods. Differences between gamma radiation and linear accelerator methods had little effect on the dose distribution for single isocenter treatments. Charged particle methods could produce better dose localization for large lesions (> 25 cm3) than was possible with photon methods. Clinical results indicate similar lesion control rates between all radiosurgical methods. There was a progressive increase in the median size of treated lesions for gamma radiation, linear accelerator, and charged particle methods. CONCLUSION: For small lesions (< 5 cm3), physical dose distributions are similar for the photon methods, but linear accelerator methods offer more flexibility for the treatment of intermediate-sized (5 to 25 cm3) lesions in applying future technical developments. More clinical results are needed before firm conclusions can be drawn on the type of lesions to be treated, and the dose-volume parameters to be used.

Brain Neoplasms↗
PubMed1994

Runaway pacemaker during high-energy neutron radiation therapy.

Runaway pacemaker occurred in a patient undergoing high-energy neutron radiation therapy despite adherence to published safety guidelines. The very low estimated dose of 0.9 Gy received by the pacemaker demonstrates the extreme sensitivity of integrated circuits to this new modality of radiation therapy.

Adenocarcinoma↗
PubMed1994

Fast neutron radiotherapy. The University of Washington experience.

An overview of the University of Washington neutron radiotherapy facility is presented. The utility of the multi-leaf, programmable, variable collimator is emphasized. Due to success in the treatment of salivary gland tumors, such patients comprise an ever increasing portion of the patients being treated. A cooperative randomized clinical trial for the treatment of salivary gland tumors was undertaken comparing fast neutrons against photon/electron radiation. At ten years, there was a statistically significant improvement in local/regional control for the neutron group (56% vs 25%, p = 0.009), but there was no improvement in survival (15% vs 25%, p = n.s.). Distant metastases were the primary reason for the failure of improved local/regional control to impact survival in the neutron group. The University of Washington experience is summarized with special emphasis on the treatment of adenoid cystic carcinomas. Excellent local/regional control can be achieved with neutrons even for large tumors arising in the paranasal sinuses. We conclude that the potential morbidity of a surgical debulking procedure is not warranted in most clinical situations.

Adult↗
PubMed1994

Fast neutron radiation therapy. Results of phase III randomized trials in head and neck, lung, and prostate cancers.

The results of phase III trials comparing neutrons to photons for head and neck squamous cell cancers, non-small cell lung cancers, and prostate adenocarcinomas are reviewed, with emphasis given to the most recent U.S. National Cancer Institute sponsored randomized clinical studies in which fast neutrons were delivered using modern, hospital-based, high-energy, isocentric-capable cyclotrons. In locally advanced squamous cell head and neck cancers, neutrons showed no convincing advantage over photons. Fast neutron radiotherapy may have provided a therapeutic benefit in selected patients with inoperable non-small cell lung cancers. For locally advanced prostate adenocarcinomas, neutron therapy resulted in significantly superior clinical and histological loco-regional tumor control, which may translate to improved survival with additional follow-up. In general, severe late complications were more frequent with neutrons, especially in patients treated on older physics laboratory-based equipment. Even with modern state-of-the-art neutron generators, careful beam collimation and treatment planning are required to minimize side effects.

Adenocarcinoma↗