Shari Rudoler

Immediate side effects of stereotactic radiotherapy and radiosurgery.

PURPOSE Despite increased utilization of fractionated stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS), the incidence and nature of immediate side effects (ISE) associated with these treatment techniques are not well defined. We report immediate side effects from a series of 78 patients. MATERIALS AND METHODS Intracranial lesions in 78 adult patients were treated with SRT or SRS, using a dedicated linear accelerator. Those lesions included 13 gliomas, 2 ependymomas, 19 metastatic tumors, 15 meningiomas, 12 acoustic neuromas, 4 pituitary adenomas, 1 optic neuroma, 1 chondrosarcoma, and 11 arteriovenous malformations (AVM). SRT was used in 51 and SRS in 27 patients. Mean target volume was 9.0 cc. Eleven patients received prior external-beam radiation therapy within 2 months before SRT/SRS. Any side effects occurring during and up to 2 weeks after the course of radiation were defined as ISE and were graded as mild, moderate, or severe. The incidence of ISE and the significance of their association with several treatment and pretreatment variables were analyzed. RESULTS Overall, 28 (35%) of 78 patients experienced one or more ISE. Most of the ISE (87%) were mild, and consisted of nausea (in 5), dizziness/vertigo (in 5), seizures (in 6), and new persistent headaches (in 17). Two episodes of worsening neurological deficit and 2 of orbital pain were graded as moderate. Two patients experienced severe ISE, requiring hospitalization (1 seizure and 1 worsening neurological deficit). ISE in 6 cases prompted computerized tomography of the brain, which revealed increased perilesional edema in 3 cases. The incidence of ISE by diagnosis was as follows: 46% (6 of 13) for gliomas, 50% (6 of 12) for acoustic neuromas, 36% (4 of 11) for AVM, 33% (5 of 15) for meningiomas, and 21% (4 of 19) for metastases. A higher incidence of dizziness/vertigo (4 of 12 = 33%) was seen among acoustic neuroma patients than among other patients (p< 0.01). There was no significant association of dizziness/vertigo with either a higher average and maximum brainstem dose (p = 0.74 and 0.09, respectively) or with 2-Gy equivalents of the average and maximum brainstem doses (p = 0.28 and 0.09, respectively). Higher RT dose to the margin and higher maximum RT dose were associated with a higher incidence of ISE (p = 0.05 and 0.01, respectively). However, when RT dose to the margin was converted to a 2-Gy dose-equivalent, it lost its significance as predictor of ISE (p = 0.51). Recent conventional external-beam radiation therapy, target volume, number of isocenters, collimator size, dose inhomogeneity, prescription isodose, pretreatment edema, dose of prior radiation, fraction size (2.0-7.0 Gy with SRT and 13.0-21.0 Gy with SRS), fractionation schedule, and dose to brainstem were not significantly associated with ISE. ISE occurred in 26% (8) of 31 patients taking corticosteroids prior to SRT/SRS and in 20 (42%) of 47 patients not taking them (p = 0.15). CONCLUSION ISE occur in one third of patients treated with SRT and SRS and are usually mild or moderate and self-limited. Dizziness/vertigo are common and unique for patients with acoustic neuromas and are not associated with higher brainstem doses. We are unable to detect a relationship between ISE and higher margin or maximum RT doses. No specific conclusion can be drawn with regard to the effect of corticosteroids, used prior to SRS/SRT, on the occurrence of ISE.

External beam irradiation for choroid metastases: Identification of factors predisposing to long-term sequelae

PURPOSE To improve overall quality of life, palliative treatments should attempt to minimize associated complications while effectively controlling specific symptoms. We reviewed our experience treating posterior uveal metastases with external beam radiotherapy (EBRT) to determine the complication rate and to identify the relationship between patient, tumor, or treatment-related factors and the development of ocular complications. METHODS AND MATERIALS 483 consecutive patients (pts) (578 eyes) were diagnosed with intraocular metastatic disease from solid tumors between 1972-1995. Of these, 233 eyes (188 pts) had lesions of the posterior uveal tract and received EBRT. Median follow-up time was 5.8 months (range: 0.7-170.0 months). Follow-up information regarding the development of complications was documented for 230 eyes. Complete EBRT details were available for 189 eyes. Seventy-two percent of the patients received 30.0-40.0 Gy in 2.0-3.0 Gy fractions. Biologically effective dose (BED) was calculated to allow meaningful comparisons between various fractionation regimens and total doses. Concurrent chemotherapy and/or hormonal therapy was used for 101 eyes (44%). RESULTS Median BED was 61 Gy3 (range, 6.7-105 Gy3), and 80% of treated eyes received BED 50-70 Gy3. EBRT energies included photons (70%), 60Co (19%), electrons (6%), mixed energies (3%), and orthovoltage (2%). Lens-sparing techniques were used in 136 eyes (71%). At last follow-up 28 eyes (12%) developed one or more significant complications, including cataracts (16 eyes), radiation retinopathy (6 eyes), optic neuropathy (5 eyes), exposure keratopathy (5 eyes), and neovascularization of the iris (4 eyes). Two eyes developed narrow-angle glaucoma, and one of these required enucleation. On univariate analysis, Caucasian race (vs. Black/Hispanic, p = 0.03), increased intraocular pressure at diagnosis (>21 mmHg, p = 0.02), and diagnosis by biopsy (vs. no biopsy, p = 0.03) predisposed toward the development of complications. Factors not correlated with complications included BED (p = 0.18), energy type (p = 0.81), lens-sparing technique (versus whole globe, p = 0.57), and concurrent systemic treatment (p = 0.60). The small number of complications did not support a multivariate analysis. CONCLUSIONS Despite the employment of a variety of EBRT treatment techniques and the proximity of choroidal metastases to radiosensitive structures, significant complications of palliative EBRT were infrequent. Although complications do occur, they are related to host factors and do not appear to be a function of irradiation parameters. We conclude that the potential benefits of vision and globe preservation after palliative EBRT outweigh the small risk of treatment induced complications.

Functional vision is improved in the majority of patients treated with external-beam radiotherapy for choroid metastases : A multivariate analysis of 188 patients

PURPOSE Metastatic deposits are the most common intraocular malignancies. We evaluated the efficacy of external-beam radiotherapy (EBRT) in the palliation of posterior uveal metastases in terms of clinically relevant outcomes: functional vision, tumor control, and globe preservation. PATIENTS AND METHODS Four hundred eighty-three consecutive patients (578 eyes) were diagnosed with intraocular metastatic disease from solid tumors between 1972 and 1995. Of these, 233 eyes (188 patients) had lesions of the posterior uveal tract and received EBRT. Best-corrected visual acuity (VA) was documented pre- and post-EBRT. Visual function was considered excellent if VA < or = 20/50, navigational if 20/60 to 20/200, and legally blind if > or = 20/400. Most patients received 30 to 40 Gy in 2- to 3-Gy fractions to the posterior or entire globe. RESULTS Fifty-seven percent of all assessable eyes had improved visual function or maintained at least navigational vision following EBRT. Thirty-six percent of legally blind eyes regained useful vision. Ninety-three percent experienced no clinical evidence of tumor progression and the globe preservation rate was 98%. The following characteristics independently predicted improvement to or maintenance of excellent vision on multivariate analysis: excellent vision pre-EBRT (P = .001), age less than 55 years (P = .004), white race (v black/Hispanic) (P = .003), and tumor base diameter less than 15 mm (P < .001). CONCLUSION EBRT effectively restores and maintains useful vision in patients with choroid metastases, with a globe preservation rate of 98%. Patients less than 55 years with pretreatment VA better than 20/60 and tumor diameter less than 15 mm are most likely to benefit from this therapeutic intervention.

Patterns of tumor progression after radiotherapy for low-grade gliomas: analysis from the computed tomography/magnetic resonance imaging era.

Postoperative radiotherapy for low-grade gliomas has been shown in retrospective series to improve survival, compared with surgery alone. To determine the proper radiotherapy treatment volume and dose, an understanding of the patterns of failure with current radiotherapy techniques is necessary. We studied 30 consecutive patients who had a pathologic diagnosis of low-grade nonpilocytic glioma treated in our department between 1975 and 1994. Before radiotherapy, 5 patients underwent biopsy, 22 had subtotal resection, and 3 had gross total excision. All had pre- and posttreatment computed tomographic (CT) or magnetic resonance imaging (MRI) scanning. Megavoltage radiotherapy was delivered to shrinking partial (22 patients) or whole-brain (8 patients) fields. Median dose was 59.4 Gy (range, 46.4-64 Gy) in 1.8- to 2-Gy fractions. Median follow-up was 44 months (3-215 months) for the cohort and 105 months for survivors. For the entire series, 5-year overall survival and relapse-free survival rates were 50% and 41%, respectively. Sixteen patients (53%) progressed at a median of 30 months. At the time of failure, 71% (5 of 7) of pathologically evaluated tumors were of high grade. Recurrence originated within the field in all patients. Higher 5-year overall survival and relapse-free survival rates were associated (p < 0.001) with preradiotherapy functional status 1 versus functional status 2 through 4 (60% vs. 0% and 55% vs. 0%, respectively). Seizure as initial presentation was favorable over other symptoms (5-year overall survival, 64% versus 14%; p = 0.057). We conclude that 1) low-grade nonpilocytic gliomas can transform to high-grade lesions after treatment with conventional radiotherapy, 2) recurrence uniformly occurs within the treatment volume, and 3) pretreatment functional status correlates prognostically with survival. The local pattern of failure suggests that radiotherapy dose escalation within conformal fields could improve results.

Impact of Her-2 Neu overexpression on outcome of elderly women treated with wide local excision and breast irradiation for early stage breast cancer: an exploratory analysis.

Objective:The purpose of this study was to investigate the prognostic significance of Her-2 neu status in elderly patients managed with breast conservation strategy for stage I–II breast cancer. Methods:We conducted an IRB approved retrospective review of 153 women age 70 and older with stage I–II breast cancer, managed with wide local excision and breast radiation between January 1997 and December 2002. The subset of 106 patients had a known Her-2 neu status and was analyzed for primary patient and tumor characteristics. These characteristics were correlated with cause specific survival (CSS), overall survival (OS), and combined nodal and distant failure (NDF). Her-2 neu positivity was confirmed with FISH HercepTestTM. Statistical tests included Cox regression, contingency table and Kaplan-Meier analysis. Results:Median follow-up was 55 months and patients median age was 76. Twenty two percent of patients were Her-2 neu positive and 78% were Her-2 neu negative. Her-2 neu positivity was significantly associated with high histologic grade (P = 0.008), T2 stage (P = 0.001) and positive axillary lymph nodes (P = 0.02) among 73 patients who had surgical assessment of axilla. Overall, only 15 patients (14%) received chemotherapy. There were no recurrences in the breast. Her-2 neu positivity predicted for NDF and CSS on multivariate analysis. Projected 5-year freedom from NDF was 70% for Her-2 neu positive and 97% for Her-2 neu negative patients (P < 0.01, log-rank). CSS was 86% for Her-2 neu positive and 98% for Her-2 neu negative patients (P < 0.01, log-rank). OS was no different between Her-2 neu positive and Her-2 neu negative patients (80% versus 85%, P = 0.25). Conclusions:Her-2 neu amplification predicts development of NDF and negatively influences CSS, but not local control or OS in elderly patients treated with breast conservation. Similar to the trend in younger patients, Her-2 neu positivity may be used in the future to consider more aggressive treatment strategies in elderly patients.

Emergent/urgent therapeutic irradiation in pediatric oncology: patterns of presentation, treatment, and outcome.

PURPOSE We reviewed all pediatric cases referred for emergent/urgent therapy (requiring treatment within 48 hours) to identify frequency, patterns of presentation, and efficacy of therapy. We defined five categories of emergent/urgent therapy based on irradiated site and/or signs: Group I, spinal cord compression; Group II, respiratory compromise; Group III, infradiaphagmatic distress; Group IV, intracranial signs; Group V, pain. MATERIALS AND METHODS From 2/1/88-3/1/ 94, 104 children with 115 problems were referred by specialists at the Childrens Hospital of Philadelphia. Diagnosis, nature of the emergency, and response were examined. Responses were categorized as complete resolution, improvement or stabilization, and progression. RESULTS The 104 children represented 12% of referrals during the study period. The most common tumors were CNS PNET and gliomas (20%); and neuroblastoma (20%). Forty-five problems occurred with newly diagnosed tumors and 70 after progression. Ninety-one episodes were managed with radiation therapy and 24 with other modalities. Patients with spinal cord/cauda equina (n = 33) compression improved (55%) or stabilized (30%). Patients with respiratory compromise from thoracic (n = 14) or abdominal (n = 5) disease had a response rate of 72%. Eight patients in group III had a 66% response. In Group IV (n = 16), 63% had complete responses and 19% had stabilization. Group V (n = 15) patients had a complete or partial response of 93%. CONCLUSION Approximately 10% of children referred for radiation therapy required emergent/urgent treatment. Eighty percent of patients achieved stabilization or showed improvement in signs and symptoms, indicating that radiotherapy is a valuable and reliable component of multimodal care in such situations.

Radiation Therapy of Uveal and Orbital Metastases

Metastatic deposits in every subsite of the eye and orbit have been described in the literature. It is now widely accepted that metastatic lesions are the most common intraocular malignancy (Eliassi-Rad et al. 1996; Ferry and Font 1974; Shields et al. 1997b). Autopsy studies estimate the incidence at 4–12% in patients with solid tumors of all histologies, and greater than one third in breast cancer patients (Bloch and Gartner 1971; Eliassi-Rad et al. 1996; Ferry and Font 1974; Nelson et al. 1983). This chapter will exclude discussion of childhood cancers and ocular manifestations of systemic cancers such as lymphoma, leukemia and myeloma, focusing on metastatic disease from distant solid tumors.

SU‐E‐T‐480: Can PTV Density Be Overridden for SBRT Lung Planning?

Purpose: To demonstrate a PTV density overridden method that may reduce planned MU while still delivering sufficient dose to the tumor for SBRT lung planning. Methods: The tumor motion inside the planning target volume (PTV) during treatment changes the density distribution inside the PTV. The worst case scenario occurs when CTV fills the PTV at the same moment, so the PTV density becomes the same as the CTV density. Our hypothesis is that the MU calculated with appropriate PTV density should be sufficient for delivering the prescription dose to the tumor. To find support for this, the plan MU with the PTV density assigned as 0.8g/cm3 were recalculated using Pinnacle planning software for twelve patients. Three of those patients had four CTV structures copied and manually placed at the border of the PTV. The new CTV density was overridden to 1g/cm3 and the density of the PTV, excluding new CTV, was overridden to 0.2 g/cm3. The plans were recalculated using the MU from the PTV density overridden plan. Each new plan with the CTV coverage and dose distribution was compared to the plan with the original density. Results: MU was reduced by more than 10% for three patients whose CTV sizes were smaller than 1.2cc. For the remaining patients, MU was reduced by an average of 3%. Without considering density redistribution due to tumor relocation, the new CTVs of those three patients only had 58%, 74%, and 47% of their volumes receiving the prescription dose. However, the coverage of the CTVs increased to 95% in average if density redistribution was applied. The prescription isodose line changed with the CTV location. Conclusion: This work finds support for a significant reduction in MU for very small CTV lung SBRT plan, while still delivering sufficient dose to the tumor.

Serum testosterone changes in patients treated with radiation therapy alone for prostate cancer on NRG oncology RTOG 9408

Objectives We reviewed testosterone changes for patients who were treated with radiation therapy (RT) alone on NRG oncology RTOG 9408. Methods and materials Patients (T1b-T2b, prostate-specific antigen <20 ng/mL) were randomized between RT alone and RT plus 4 months of androgen ablation. Serum testosterone (ST) levels were investigated at enrollment, RT completion, and the first follow-up 3 months after RT. The Wilcoxon signed rank test was used to compare pre- and post-treatment ST levels in patients who were randomized to the RT-alone arm. Results Of 2028 patients enrolled, 992 patients were randomized to receive RT alone and 917 (92.4%) had baseline ST values available and completed RT. Of these 917 patients, immediate and 3-month post-RT testosterone levels were available for 447 and 373 patients, respectively. Excluding 2 patients who received hormonal therapy off protocol after RT, 447 and 371 patients, respectively, were analyzed. For all patients, the median change in ST values at completion of RT and at 3-month follow-up were −30.0 ng/dL (p5-p95; −270.0 to 162.0; P < .001) and −34.0 ng/dL (p5-p95, −228.0 to 160.0; P < .01), respectively. Conclusion RT for prostate cancer was associated with a median 9.2% decline in ST at completion of RT and a median 9.3% decline 3 months after RT. These changes were statistically significant.

Thoracic surgeon performed electromagnetic navigational bronchoscopy: new modality, new diagnosis

Electromagnetic navigational bronchoscopy (ENB) is a promising novel technique, which enables physicians to access pulmonary lesions, previously inaccessible, for both biopsy and fiducial placement. The use of ENB has also not been limited to the realm of the interventional pulmonologist, and success has been had in large academic centers with its performance by thoracic surgeons. The flexibility of ENB is without added risk, and may even decrease risks, as ENB has been documented to have a more favorable safety profile than other forms of biopsy and placement of fiducials. With ENB’s increasing ability for diagnosis via biopsy, this may have an influence on prognosis and treatment, and the following case is representative of that impact. Case