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For children, craniospinal irradiation (CSI) with photons is associated with significant toxic effects. The use of electrons for spinal fields is hypothesized to spare anterior structures but the long-term effects remain uncertain. We studied late effects of CSI using electrons for spinal radiation therapy (RT).Records of 84 consecutive patients treated with CSI using electrons for the spine at a single institution between 1983 and 2014 were reviewed. Median age at RT was 5 (range, 1-14) years. The most common histologies were medulloblastoma/primitive neuroectodermal tumor (59%) and ependymoma (8%). The median prescribed dose to the entire spine was 30 Gy (range, 6-45). A subset of 48 (57%) patients aged 2 to 14 at RT with clinical follow-up for ≥5 years was analyzed for late effects. Height z scores adjusted for age before and after CSI were assessed using stature-for-age charts and compared with a t test.At median follow-up of 19 years (range, 0-38 years), the median survival was 22 years (95% confidence interval, 12-28 years) after RT, with 47 patients (56%) alive at last follow-up. On subset analysis for late effects, 19 (40%) patients developed hypothyroidism and 5 (10%) developed secondary malignancies. Other complications reported were esophageal stricture and periaortic hemorrhage in 1 and restrictive pulmonary disease in 1 patient. Median height z score before treatment was -0.4 (36th percentile; interquartile range, -1.0 to 0.0) and at last follow-up was -2.2 (first percentile; interquartile range, -3.1 to -1.6; P.001). Of 44 patients with spinal curvature assessments, 15 (34%) had scoliosis with median Cobb angle 15° (range, 10°-35°) and 1 (2%) required surgery.Frequent musculoskeletal toxic effects and predominantly decreased height were seen with long-term follow-up. Scoliosis and hypothyroidism were each seen in at least one-third of long-term survivors. However, clinically evident esophageal, pulmonary, and cardiac toxic effects were infrequent.

PURPOSE/OBJECTIVE(S) Craniospinal irradiation (CSI) with photons is associated with significant toxicities. The use of electrons for spinal fields is hypothesized to spare anterior structures but its long-term effects remain poorly characterized. We studied late effects of CSI using electrons for spinal radiotherapy (RT). MATERIALS/METHODS Records of 84 consecutive patients treated with CSI using electrons for the spine at a single institution from 1983-2014 were reviewed. Median age at RT was 5 (range, 1-14) years with 60% male. Most common histologies were medulloblastoma/PNET (59%) and ependymoma (8%). Most commonly used electron energies were 16 (44%) and 20 (25%) MeV (range, 12-21). Median prescribed dose to the entire spine was 30 (range 6-45) Gy. A spinal boost was used in 14%. A subset of 47 (56%) patients was analyzed for late effects with the following inclusion criteria: 1) age between 2 and 14 years at time of CSI, and 2) clinical and radiographic follow-up for ≥ 5 years. Height z-scores adjusted for age before and after CSI were assessed using CDC stature-for-age charts and compared with a t-test. A Cobb angle of > 10° was used to identify scoliosis. RESULTS At a median follow-up of 18 (range, 0-37) years, the median survival was 22 (95% confidence interval [CI], 12-28) years with 50 patients (60%) alive at last follow up. On subset analysis for late effects, 18 (38%) patients developed hypothyroidism and 4 (9%) developed secondary malignancies possibly attributable to spine RT (3 papillary thyroid cancer, 1 renal cell carcinoma) at a median 26 (range, 10-33) years after RT. Chronic pulmonary issues were seen in 2 patients (restrictive lung disease, recurrent pneumonia) and 1 patient developed esophageal strictures and periaortic hemorrhage. No patients developed myelopathy or cardiotoxicity. Median height z-score prior to treatment was -0.3 (37th percentile; interquartile range [IQR], -1.0 to +0.1) and at last follow up after RT was -2.2 (1st percentile; IQR, -3.1 to -1.5; P < 0.001). Of 42 patients with spinal curvature assessments, 14 (33%) had scoliosis with median Cobb angle 16° (IQR, 14-18°). CONCLUSION Long-term follow-up of children treated with CSI using electron spinal fields showed frequent musculoskeletal toxicity, predominantly decreased height. Scoliosis and hypothyroidism were seen in at least a third of long-term survivors. Esophageal, pulmonary, cardiac and spinal cord toxicities were infrequent.

Primary and metastatic tumors of the central nervous system are a heterogeneous group of neoplasms with varied outcomes and management strategies. Recently, improved survival observed in 2 randomized clinical trials established combined chemotherapy and radiation as the new standard for treating patients with pure or mixed anaplastic oligodendroglioma harboring the 1p/19q codeletion. For metastatic disease, increasing evidence supports the efficacy of stereotactic radiosurgery in treating patients with multiple metastatic lesions but low overall tumor volume. These guidelines provide recommendations on the diagnosis and management of this group of diseases based on clinical evidence and panel consensus. This version includes expert advice on the management of low-grade infiltrative astrocytomas, oligodendrogliomas, anaplastic gliomas, glioblastomas, medulloblastomas, supratentorial primitive neuroectodermal tumors, and brain metastases. The full online version, available at NCCN. org, contains recommendations on additional subtypes.

Purpose To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. Patients and Methods Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point. Results Five hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio [HR], 0.75; 95% CI, 0.59 to 0.95; P = .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P = .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemotherapy (HR, 1.25; 95% CI, 0.98 to 1.61; P = .08). Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT (HR, 0.58; 95% CI, 0.37 to 0.89; P = .0050) and over RT alone (P < .001), whereas induction PF followed by RT was not better than treatment with RT alone (HR, 1.26; 95% CI, 0.88 to 1.82; P = .35). No difference in late effects was detected, but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% v 20.8% with induction chemotherapy and 16.9% with RT alone). Conclusion These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS. Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone. New strategies that improve organ preservation and function with less morbidity are needed.

Object. The authors report data concerning the safety, effectiveness, and patterns of failure obtained in a Phase I/II study of stereotactic body radiotherapy (SBRT) for spinal metastatic tumors. Methods. Sixty-three cancer patients underwent near-simultaneous computed tomography–guided SBRT. Spinal magnetic resonance imaging was conducted at baseline and at each follow-up visit. The National Cancer Institute Common Toxicity Criteria 2.0 assessments were used to evaluate toxicity. Results. The median tumor volume of 74 spinal metastatic lesions was 37.4 cm3 (range 1.6–358 cm3). No neuropathy or myelopathy was observed during a median follow-up period of 21.3 months (range 0.9–49.6 months). The actuarial 1-year tumor progression–free incidence was 84% for all tumors. Pattern-of-failure analysis showed two primary mechanisms of failure: 1) recurrence in the bone adjacent to the site of previous treatment, and 2) recurrence in the epidural space adjacent to the spinal cord. Grade 3 or 4 toxicities were limited to acute Grade 3 nausea, vomiting, and diarrhea (one case); Grade 3 dysphagia and trismus (one case); and Grade 3 noncardiac chest pain (one case). There was no subacute or late Grade 3 or 4 toxicity. Conclusions. Analysis of the data obtained in the present study supports the safety and effectiveness of SBRT in cases of spinal metastatic cancer. The authors consider it prudent to routinely treat the pedicles and posterior elements using a wide bone margin posterior to the diseased vertebrae because of the possible direct extension into these structures. For patients without a history of radiotherapy, more liberal spinal cord dose constraints than those used in this study could be applied to help reduce failures in the epidural space.

Purpose: To evaluate the spatial relationship between peritumoral edema and recurrence pattern in patients with glioblastoma (GBM). Methods and Materials: Forty-eight primary GBM patients received three-dimensional conformal radiotherapy that did not intentionally include peritumoral edema within the clinical target volume between July 2000 and June 2001. All 48 patients have subsequently recurred, and their original treatment planning parameters were used for this study. New theoretical radiation treatment plans were created for the same 48 patients, based on Radiation Therapy Oncology Group (RTOG) target delineation guidelines that specify inclusion of peritumoral edema. Target volume and recurrent tumor coverage, as well as percent volume of normal brain irradiated, were assessed for both methods of target delineation using dose–volume histograms. Results: A comparison between the location of recurrent tumor and peritumoral edema volumes from all 48 cases failed to show correlation by linear regression modeling (r2 = 0.0007; p = 0.3). For patients with edema >75 cm3, the percent volume of brain irradiated to 46 Gy was significantly greater in treatment plans that intentionally included peritumoral edema compared with those that did not (38% vs. 31%; p = 0.003). The pattern of failure was identical between the two sets of plans (40 central, 3 in-field, 3 marginal, and 2 distant recurrence). Conclusion: Clinical target volume delineation based on a 2-cm margin rather than on peritumoral edema did not seem to alter the central pattern of failure for patients with GBM. For patients with peritumoral edema >75 cm3, using a constant 2-cm margin resulted in a smaller median percent volume of brain being irradiated to 30 Gy, 46 Gy, and 50 Gy compared with corresponding theoretical RTOG plans that deliberately included peritumoral edema.

Purpose: The aim of this study was to determine whether recombinant human interferon β-1a (rhIFN-β), when given after radiation therapy, improves survival in glioblastoma. Methods and Materials: After surgery, 109 patients with newly diagnosed supratentorial glioblastoma were enrolled and treated with radiation therapy (60 Gy). A total of 55 patients remained stable after radiation and were treated with rhIFN-β (6 MU/day i.m., 3 times/week). Outcomes were compared with the Radiation Therapy Oncology Group glioma historical database. Results: RhIFN-β was well tolerated, with 1 Grade 4 toxicity and 8 other patients experiencing Grade 3 toxicity. Median survival time (MST) of the 55 rhIFN-β–treated patients was 13.4 months. MST for the 34 rhIFN-β–treated in RPA Classes III and IV was 16.9 vs. 12.4 months for historical controls (hazard ratio [HR] = 1.27, 95% confidence interval [CI] = 0.89–1.81). There was also a trend toward improved survival across all RPA Classes comparing the 55 rhIFN-β treated patients and 1,658 historical controls (HR = 1.24, 95% CI = 0.94–1.63). The high rate of early failures (54/109) after radiation and before initiation of rhIFN-β was likely caused by stricter interpretation of early radiographic changes in the current study. Matched-pair and intent-to-treat analyses performed to try to address this bias showed no difference in survival between study patients and controls. Conclusion: RhIFN-β given after conventional radiation therapy was well tolerated, with a trend toward survival benefit in patients who remained stable after radiation therapy. These data suggest that rhIFN-β warrants further evaluation in additional studies, possibly in combination with current temozolomide-based regimens.

This study was undertaken to determine the disease outcomes in patients treated with surgery alone or surgery and adjuvant radiotherapy (RT) for myxopapillary ependymoma (MPE) of the spine. The medical records of 35 patients with MPE treated at The University of Texas M.D. Anderson Cancer Center between December 1968 and July 2002 were reviewed. The endpoints analyzed were progression-free survival (PFS), overall survival, and local control. The median age of patients was 35 years (range, 14–63 years), and the male to female ratio was 2.5:1. In total, 21 (60%) patients underwent a gross total resection, 13 (37%) a subtotal resection, and 1 (3%) a biopsy only; 22 of them (63%) also received adjuvant RT. The median follow-up was 10.7 years. The 10-year overall survival, PFS, and local control rates for the entire group were 97%, 62%, and 72%, respectively. Of 11 patients 5 (45%) who had undergone gross total resection alone had recurrence. A total of 12 (34%) patients had disease recurrence, all in the neural axis; 8 of them had treatment failure at the primary site only, 3 in the distant neural axis only, and 1 at the primary site and in the distant neural axis. Patient age (> 35 years; P = 0.002) and adjuvant RT (P = 0.04) significantly affected PFS. The long-term patient survival duration for MPE managed with surgery and adjuvant RT is favorable. Regardless of the extent of resection, adjuvant RT appears to significantly reduce the rate of tumor progression. Failures occurred exclusively in the neural axis, mainly at the primary site.

Object. The role of stereotactic radiosurgery (SRS) for recurrent glioblastoma multiforme (GBM) was evaluated in a case—control study. Methods. All patients who underwent SRS for recurrent GBM before March 2003 formed the case group. A control group of patients who did not undergo SRS was created from an institutional database, and each case was matched for known prognostic factors in GBM. The medical and neuroimaging records of all the patients were reviewed, and survival and treatment outcomes were recorded. The case and control groups were well matched with regard to demographics and pre-SRS interventions. In the control group, the date on which magnetic resonance imaging identified a recurrent lesion that would have been eligible for SRS was deemed the “SRS” date. The number of surgeries performed in the control group was statistically higher than that in the case group. The median duration of overall survival from diagnosis was 26 months in the case group and 23 months in the control group. From the date of SRS or “SRS”, the median duration of survival was 11 months in the case group and 10 months in the control group, a difference that was not statistically significant. Conclusions. It appears that a subgroup of patients with GBMs has a higher than expected median survival duration despite the initial prognostic factors. In patients with localized recurrences, survival may be prolonged by applying aggressive local disease management by using either SRS or resection to equal advantage.

Purpose: YKL-40 is a secreted protein that has been reported to be overexpressed in epithelial cancers and gliomas, although its function is unknown. Previous data in a smaller sample set suggested that YKL-40 was a marker associated with a poorer clinical outcome and a genetically defined subgroup of glioblastoma. Here we test these findings in a larger series of patients with glioblastoma, and in particular, determine if tumor YKL-40 expression is associated with radiation response. Experimental Design: Patients (n = 147) with subtotal resections were studied for imaging-assessed changes in tumor size in serial studies following radiation therapy. An additional set (n = 140) of glioblastoma patients who underwent a gross-total resection was tested to validate the survival association and extend them to patients with minimal residual disease. Results: In the subtotal resection group, higher YKL-40 expression was significantly associated with poorer radiation response, shorter time to progression and shorter overall survival. The association of higher YKL-40 expression with poorer survival was validated in the gross-total resection group. In multivariate analysis with both groups combined (n = 287), YKL-40 was an independent predictor of survival after adjusting for patient age, performance status, and extent of resection. YKL-40 expression was also compared with genetically defined subsets of glioblastoma by assessing epidermal growth factor receptor amplification and loss at chromosome 10q, two of the common recurring aberrations in these tumors, using fluorescent in situ hybridization. YKL-40 was significantly associated with 10q loss. Conclusions: The findings implicate YKL-40 as an important marker of therapeutic response and genetic subtype in glioblastomas and suggest that it may play an oncogenic role in these tumors.

Purpose To evaluate in a Phase I study the safety, feasibility, and patient-positioning accuracy of treating patients with intensity-modulated, near-simultaneous, computed tomographic (CT) image-guided stereotactic body radiotherapy (SBRT). Patients and methods Fifteen consecutive patients with metastatic spinal disease who met protocol eligibility criteria were entered into a Phase I clinical trial. Each patient received five treatments of intensity-modulated, near-simultaneous CT image-guided SBRT, for a total of 75 treatments with 90 isocenter setups during the course of the study. Patients uniformly received 30 Gy (if possible) of radiotherapy in 5 fractions to the clinical target volume. The total dose was constrained by limiting the spinal cord to a maximum dose of 10 Gy. To verify correct daily patient positioning before each treatment and to determine the daily treatment setup error after radiation delivery, axial CT scans were taken before and immediately after each treatment without moving the patient from the treatment position, for comparison with the planning CT scan. Toxicity was measured using the Common Toxicity Criteria, the Late Effects of Normal Tissue scoring system and a neurologic function scale. Follow-up was conducted 4 weeks after completion of SBRT, and then 2, 3, 6, 9, 12, and every 6 months thereafter. Results The procedure was technically feasible to perform in all patients. No neurologic toxicity was observed in any patient. The median follow-up time was 9 months (range 6–16). The Clopper-Pearson upper bound on the probability of paralysis with 95% confidence is no greater than 0.181. The positional setup error was determined to be within 1 mm of planning isocenter. Conclusions This Phase I study shows that intensity-modulated, near simultaneous, CT image-guided SBRT is a feasible, and highly precise technique for the noninvasive treatment of spinal metastases. Although no paralysis has developed in the 15 patients treated, continued monitoring for spinal cord toxicity is warranted, as larger numbers of patients will be needed to more precisely define the upper bound on the probability of spinal cord myelopathy.

Purpose Recently, considerable attention has been directed toward computed tomography radiation doses (estimated 1 to 4 cGy) received by pediatric patients, because of the potential for increasing a pediatric patient's risk for developing a secondary malignancy. However, minimal attention has been given to the radiation exposure outside the treatment field resulting from the use of portal films to visualize surrounding anatomy. The objective of this study was to quantify the radiation dose from portal imaging delivered within and outside the radiation treatment field during a course of radiation therapy. Methods and materials A retrospective review was conducted of the port film dose for 56 consecutive pediatric patients who underwent definitive radiation therapy between January 2001 and January 2002. Treatment locations were classified as brain, 27 patients; abdomen, 11 patients; extremities, 9 patients; pelvis, 6 patients; and thorax, 3 patients. Using the dose per monitor unit and total number of port films taken, the total port film dose for each patient was calculated. In addition, port film dose was quantified for 5 pediatric patients undergoing intensity modulated radiation therapy. Results The mean total port dose varied from a maximum of 46 cGy for brain to a minimum of 17 cGy for thorax. The mean total port dose as a percentage of prescribed dose was less than 1.25% for all locations in this study; however, most of the port dose is a result of the open-field dose from the double-exposure technique. Conclusions Care should be exercised while exposing port films of pediatric patients to minimize both the number of films and corresponding radiation exposure without compromising the quality of treatment delivery. Specifically, the number of monitor units used to image regions outside the treatment field should be kept to a minimum, because such exposure could lead to an increased risk of development of secondary neoplasms.

To report on the outcome of patients with melanoma brain metastases treated with stereotactic radiosurgery (SRS).One hundred three patients with 153 intracranial melanoma metastases consecutively underwent Linac-based SRS between November 1991 and October 2001. The Kaplan-Meier method, univariate comparisons with log-rank test, and multivariate analyses with classification and regression tree models were performed. Calculations were based on last imaging date rather than the date of the last visit.Median age was 51 years (range, 18-93 years). Median Karnofsky performance status was 90. Sixty-one patients (59%) had single brain metastasis at presentation. Treatment sequence was SRS alone (61 patients), SRS + whole-brain radiotherapy (WBRT) (12 patients), and salvage SRS after WBRT (30 patients). The median tumor volume was 1.9 cm(3) (range, 0.06-22.3 cm(3)). The median SRS minimum peripheral dose and isodose was 18 Gy (range, 10-24 Gy) and 85% (range, 60%-100%), respectively. The median follow-up was 6 months for all patients and 13 months (range, 2-46 months) for patients alive at the time of analysis. The 1-year local control (LC) for all patients treated with SRS was 49%. Among the patients treated with initial SRS alone, the 1-year LC was better for patients with tumorsor =2 cm(3) than with tumors2 cm(3): 75.2% vs. 42.3% (p0.05). The 1-year distant brain metastasis-free survival incidence was 14.7% for the 73 patients receiving either initial SRS alone or SRS +WBRT. The initial number of brain lesions (single vs. multiple) was the only factor with a significant effect on distant brain metastasis-free survival at 1 year: 23.5% for single metastases and 0% for multiple lesions (p0.05). The 1-year overall survival was 25.2%. Stratification by Score Index for Radiosurgery (SIR) revealed a significant effect on survival, which was 29% at 1 year for SIR6 and 10% for SIR==6 (relative hazard ratio, 2.1; p0.05) in classification and regression-tree multivariate analysis involving age, Karnofsky performance status, primary tumor control, tumor volume, SRS dose, SIR (6 vs.or =6), and systemic disease status.Initial SRS alone was an effective treatment modality for smaller cerebral melanoma metastases, achieving a 75% incidence of 1-year LC foror =2 cm(3) single brain metastases and should be considered in patients with SIR6. The role of WBRT in melanoma brain metastases cannot be addressed, owing to retrospective bias toward administering this treatment to patients with more aggressive disease. A prospective study is needed to assess the role of WBRT in patients with melanoma brain metastasis.

BACKGROUND The current retrospective study was undertaken to evaluate the treatment outcomes of patients with meningeal hemangiopericytoma (M-HPC), to define the role of radiotherapy in the management of the disease, and to report on the patterns of failure. METHODS The medical records of 29 patients with nonmetastatic M-HPC treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between August 1979 and March 1999 were reviewed. Fifteen patients (52%) underwent macroscopic total resection (‘gross total resection’ [GTR]), 10 (34%) underwent subtotal resection (STR), and 4 (14%) had unknown extent of surgery. Ten of 24 patients received adjuvant radiotherapy. RESULTS The 5, 10, and 15-year overall survival rates were 85%, 68%, and 43%, respectively. The local control rates at 5 and 10 years were 68% and 22%, respectively. Two patients experienced disease recurrence at another intracranial site. Sixteen patients (55%) developed extraneural metastases. Four patients (14%) developed spinal metastases. The 5-, 10-, and 15-year distant metastasis–free survival rates were 80%, 46%, and 21%, respectively. The 5-year local control rates for patients treated with GTR and STR were 84% and 38%, respectively (P = 0.003). Of the 15 patients treated with GTR, 3 received adjuvant radiotherapy as part of their initial treatment. Malignant disease did not recur locally in these three patients. However, the effect of the adjuvant radiotherapy on local control was not statistically significant. CONCLUSIONS M-HPCs can recur locally or distantly in the neural axis or as extraneural distant metastases. Based on literature review and the patterns of failure in the current series, attempting to perform GTR followed by limited-field radiotherapy appeared to represent a reasonable approach for the initial management of M-HPC. Cancer 2004;100:1491–7. © 2004 American Cancer Society.

Induction chemotherapy with cisplatin plus fluorouracil followed by radiotherapy is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of adding chemotherapy to radiotherapy and the optimal timing of chemotherapy are unknown.We randomly assigned patients with locally advanced cancer of the larynx to one of three treatments: induction cisplatin plus fluorouracil followed by radiotherapy, radiotherapy with concurrent administration of cisplatin, or radiotherapy alone. The primary end point was preservation of the larynx.A total of 547 patients were randomly assigned to one of the three study groups. The median follow-up period was 3.8 years. At two years, the proportion of patients who had an intact larynx after radiotherapy with concurrent cisplatin (88 percent) differed significantly from the proportions in the groups given induction chemotherapy followed by radiotherapy (75 percent, P=0.005) or radiotherapy alone (70 percent, P0.001). The rate of locoregional control was also significantly better with radiotherapy and concurrent cisplatin (78 percent, vs. 61 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 56 percent with radiotherapy alone). Both of the chemotherapy-based regimens suppressed distant metastases and resulted in better disease-free survival than radiotherapy alone. However, overall survival rates were similar in all three groups. The rate of high-grade toxic effects was greater with the chemotherapy-based regimens (81 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 82 percent with radiotherapy with concurrent cisplatin, vs. 61 percent with radiotherapy alone). The mucosal toxicity of concurrent radiotherapy and cisplatin was nearly twice as frequent as the mucosal toxicity of the other two treatments during radiotherapy.In patients with laryngeal cancer, radiotherapy with concurrent administration of cisplatin is superior to induction chemotherapy followed by radiotherapy or radiotherapy alone for laryngeal preservation and locoregional control.

To report treatment setup data from an emerging technique using near-simultaneous computed tomography (CT) image-guided stereotactic radiotherapy for the treatment of spinal and paraspinal tumors.A targeting system that integrates a CT-on-rails scanner with a linear accelerator (LINAC) was evaluated in the lead-in portion of a Phase I/II protocol for treating patients with paraspinal metastases. Patients were immobilized in supine position by a moldable body cushion vacuum wrapped with a plastic fixation sheet. Planning CT and immediately repeated CT were performed on the LINAC/CT-on-rails unit to assess respiratory-related vertebral body motion. Coplanar intensity-modulated radiotherapy (IMRT) using 7-9 beams was used to deliver 30 Gy in five fractions to the target volume, while limiting the spinal cord dose to10 Gy. Pretreatment CT scans were fused with the planning CT scans to determine the correct target isocenter by accounting for any translational and roll (axial) rotational discrepancies from the planning CT. (Corrections caused by yaw and pitch rotations have not yet been implemented.) The reproducibility of the treatment isocenter as compared with the planned isocenter was measured with digitally reconstructed radiographs (DRRs), portal film imaging, and immediate post-treatment verification CT scans. Phantom measurements were taken for dose verification for each IMRT plan.Based on a total of 36 CT scans (3 for planning, 3 for respiration study, 15 pretreatment, and 15 post-treatment) from 3 patients, no respiration-associated vertebral body motion was seen. A comparison of the corrected daily anterior-posterior (AP) and lateral (LAT) digital portal images with the planning AP and LAT DRRs confirmed that the isocenter setup accuracy for the 15 treatments was within 1 mm of the planning isocenter. The results from the immediate post-treatment CT scans reconfirmed the findings from the portal images and verified the absence of spinal movement during the treatment. The ion-chamber measurement for the high-dose region was within 2% of the planning dose for three patient treatment plans. Film dose measurement in an IMRT quality assurance phantom demonstrated good agreement from 90% to 30% isodose lines between the planned and measured results.Preliminary experience suggests that the near-simultaneous CT image-guided verification technique can be used as a new platform technology for extracranial applications of stereotactic radiotherapy and radiosurgery to spinal and paraspinal tumors.

A modified 3-field technique was designed with opposed cranial fields and a single spinal field encompassing the entire spinal axis. Two methods of plan verifications were performed before the first treatment. First, a system of orthogonal rulers plus the thermoplastic head holder was used to visualize the light fields at the craniospinal junction. Second, film phantom measurements were taken to visualize the gap between the fields at the level of the spinal cord. Treatment verification entailed use of a posterior-anterior (PA) portal film and placement of radiopaque wire on the inferior border of the cranial field. More rigorous verification required a custom-fabricated orthogonal film holder. The isocenter positions of both fields when they matched were recorded using a record-and-verify system. A single extended distance spinal field collimated at 42 degrees encompassed the entire spinal neuraxis. Data were collected from 40 fractions of craniospinal irradiation (CSI). The systematic error observed for the actual daily treatments was -0.5 mm (underlap), while the stochastic error was represented by a standard deviation of 5.39 mm. Measured data across the gapped craniospinal junction with junction shifts included revealed a dose ranging from 89.3% to 108%. CSI can be performed without direct visualization of the craniospinal junction by using the verification methods described. While the use of rigorous film verification for supine technique may have reduced the systematic error, the inability to visualize the supine craniospinal junction on skin appears to have increased the stochastic error compared to published data on such errors associated with prone craniospinal irradiation.

Beside a few known radiosensitive syndromes, a patient's reaction to radiotherapy is difficult to predict. In this report we describe the management of a pediatric cancer patient presented with a family history of radiosensitivity and cancer proneness. Laboratory investigations revealed a chromosomal fragility syndrome and an increased cellular radiosensitivity in vitro. AT gene sequencing revealed no mutations. The patient was treated with reduced radiation doses to avoid the presumed increased risks of toxicity to normal tissues. The patient tolerated well the treatment with no significant acute or late radiation sequelae. Five years later, the patient remains both disease and complications free. While an accurate laboratory test for radiosensitivity is still lacking, assessments of chromosomal fragility, cell survival and clinical medicine will continue to be useful for a small number of patients.

Neoplastic meningitis usually occurs late in the natural history of cancer. Adequate staging and assessment of the patient's overall reserves and prognosis are crucial in determining whether aggressive treatment is justified. Although radiotherapy remains the single most effective treatment, it is considered palliative for epithelial cancers and is generally directed to sites of bulky disease that obstruct the flow of cerebrospinal fluid or cause neurologic dysfunction. Such diseases as leukemia, medulloblastoma, and germinoma are exceptions that can be treated definitively with craniospinal irradiation. Innovations in conformal therapy may help to reduce the significant amount of myelosuppression associated with spinal irradiation. The main long-term toxicity associated with whole-brain irradiation (WBI) is dementia resulting from leukoencephalopathy, which may be exacerbated when WBI is given in combination with chemotherapy. A case report highlighting the use of radiotherapy for palliation in a patient with neoplastic meningitis is presented at the end of this article.

The planning target volume (PTV) includes the clinical target volume (CTV) to be irradiated and a margin to account for uncertainties in the treatment process. Uncertainties in miniature multileaf collimator (mMLC) leaf positioning, CT scanner spatial localization, CT‐MRI image fusion spatial localization, and Gill‐Thomas‐Cosman (GTC) relocatable head frame repositioning were quantified for the purpose of determining a minimum PTV margin that still delivers a satisfactory CTV dose. The measured uncertainties were then incorporated into a simple Monte Carlo calculation for evaluation of various margin and fraction combinations. Satisfactory CTV dosimetric criteria were selected to be a minimum CTV dose of 95% of the PTV dose and at least 95% of the CTV receiving 100% of the PTV dose. The measured uncertainties were assumed to be Gaussian distributions. Systematic errors were added linearly and random errors were added in quadrature assuming no correlation to arrive at the total combined error. The Monte Carlo simulation written for this work examined the distribution of cumulative dose volume histograms for a large patient population using various margin and fraction combinations to determine the smallest margin required to meet the established criteria. The program examined 5 and 30 fraction treatments, since those are the only fractionation schemes currently used at our institution. The fractionation schemes were evaluated using no margin, a margin of just the systematic component of the total uncertainty, and a margin of the systematic component plus one standard deviation of the total uncertainty. It was concluded that (i) a margin of the systematic error plus one standard deviation of the total uncertainty is the smallest PTV margin necessary to achieve the established CTV dose criteria, and (ii) it is necessary to determine the uncertainties introduced by the specific equipment and procedures used at each institution since the uncertainties may vary among locations. PACS number(s): 87.53.Kn, 87.53.Ly

Nuclear workers, oil well loggers, astronauts, air flight crews, and frequent fliers can be exposed to low doses of neutrons, but the long-term human health consequences of neutron exposure are unknown. While few of these exposed populations are suitable for studying the effects of neutron exposure, patients treated with neutron-beam therapy might be a source of information. To assess the feasibility of conducting a multi-center international study of the late effects of neutron therapy, we surveyed 23 cancer centers that had used neutron beam therapy. For the 17 responding institutions, only 25% of the patients treated with neutrons (2,855 of 11,191) were alive more than 2 years after treatment. In a two-center U.S. pilot study of 484 neutron-treated cancer patients, we assessed the feasibility of obtaining radiotherapy records, cancer incidence and other follow-up data, and of estimating patient organ doses. Patients were treated with 42 MeV neutrons between 1972 and 1989. Applying a clinical equivalence factor of 3.2 for neutrons, total average organ doses outside the treatment beam ranged from 0.14 to 0.29 Gy for thyroid, 0.40 to 2.50 Gy for breast, 0.63 to 2.35 Gy for kidney, and 1.12 to 1.76 Gy for active bone marrow depending upon the primary cancer treatment site. We successfully traced 97% of the patients, but we found that patient survival was poor and that chemotherapy was not confirmable in a quarter of the patients. Based on our findings from the international survey and the feasibility study, we conclude that a large investigation could detect a fivefold or higher leukemia risk, but would be inadequate to evaluate the risk of solid cancers with long latent periods and therefore would likely not be informative with respect to neutron-related cancer risk in humans.

Dissemination of malignant glioma to the fourth ventricle with metastatic deposits and intractable vomiting is rare. Leptomeningeal extension of malignant glioma is an uncommon condition that has been reported in patients with end-stage disease and is usually unresponsive to any treatment modality. We describe 3 patients with progressing recurrent glioblastoma multiforme in whom leptomeningeal invasion manifested itself as intractable vomiting due to tumor metastases in the floor of the fourth ventricle. All patients received additional radiation therapy focused to the posterior fossa, with complete resolution of vomiting occurring within 10 days after irradiation. The remission of symptoms in these patients persisted until their death 3-4 months after the repeat radiation therapy. These reports indicate that additional focused radiation should be considered because of its significant therapeutic effect in alleviating intractable nausea and vomiting in patients with glioma metastasized to the posterior fossa.

Background The role of radiotherapy after surgery for myxopapillary ependymoma (MPE) is unclear. Objective To review long-term outcomes after surgery, with or without radiation, for spinal MPE. Methods Fifty-one patients with spinal MPE treated from 1968 to 2007 were included. Associations between clinical variables and overall survival (OS), progression-free survival (PFS), and local control (LC) were tested with Cox regression analysis. Results The median age at diagnosis was 35 years (range, 8-63 years). Twenty patients (39%) had surgery alone, 30 (59%) had surgery plus radiotherapy (RT), and 1 (2%) had RT only. At a median follow-up of 11 years (range, 0.2-37 years), 10-year OS, PFS, and LC for the entire group were 93%, 63%, and 67%, respectively. Nineteen patients (37%) had disease recurrence, and the recurrence was mostly local (79%). Twenty-eight of 50 patients who had surgery (56%) had gross total resection; 10-year LC was 56% after surgery vs 92% after surgery and RT (log-rank P = .14); the median time of LC was 10.5 years for patients receiving gross total resection plus RT, and 4.75 years for gross total resection only (P = .03). Among 16 patients with subtotal resection and follow-up data, 10-year LC was 0% after surgery vs 65% for surgery plus RT (log-rank P = .008). On multivariate analyses adjusting for resection type, age older that 35 years at diagnosis and receipt of adjuvant radiation were associated with improved PFS (hazard ratio [HR]: 0.14, P = .003 and HR: 0.45, P = .009) and LC (HR: 0.22, P = .02 and HR: 0.45, P = .009). Conclusion Postoperative radiotherapy after resection of MPE was associated with improved PFS and LC.

This study was conducted to determine prognostic factors for tumor response and patient survival after stereotactic radiosurgery (SRS) for brain metastasis. Eighty-four patients with brain metastasis underwent SRS at a single institution. After fixation of the head with a stereotactic frame, computed tomography treatment planning was performed. The metastatic lesion was treated with multiple arcs to a median dose of 19 Gy. Forty-seven patients (56%) had a solitary brain lesion. Fifty-nine patients (70%) had evidence of extracranial disease at the time of SRS. The median survival duration from SRS was 7 months. Sixty-three percent of the patients had an objective radiographic response to SRS, which in turn was associated with superior central nervous system control. Age, collimator size, number of arcs, tumor location, and histology did not influence objective response rates. Patients who had a solitary lesion or who received treatment within 2 weeks after diagnosis were more likely to have an objective response than were those who did not (P < 0.05). Progressive brain disease accounted for 37% of the deaths. Nineteen patients (23%) had an in-field relapse. Four severe complications were attributed to SRS. This study confirms the role of SRS as an acceptable treatment option for patients with solitary or limited brain metastases. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 157–162 (2000). © 2000 Wiley-Liss, Inc.

BACKGROUND The prognosis of patients with brain metastasis as the only manifestation of an undetected primary tumor generally is considered to be poor. Therefore, most treatment is palliative. The authors reviewed the clinical outcomes and treatment results of patients presenting with brain metastasis from an undetected primary tumor at The University of Texas M. D. Anderson Cancer Center. METHODS Between 1977-1996, 220 patients were referred to the study department for the treatment of brain metastasis from an undetected primary tumor. The patients' records were reviewed to identify those for whom brain metastasis was the only manifestation of the primary tumor. The majority of patients were excluded from the current analysis because extracranial metastasis also were present. Thirty-nine patients qualified for this retrospective review. The level of neurosurgical excision varied, but all patients received radiotherapy. Tumor control in the brain and survival were analyzed by various tumor-related and treatment-related factors. RESULTS In 31 patients, the brain metastasis were adenocarcinomas, whereas the remaining patients had tumors of various other histologies. In 12 patients, the primary tumor eventually was found, most commonly in the lung. The median survival time for all patients was 13.4 months. Overall survival rates (OS) at 1, 3, and 5 years were 56%, 19%, and 15%, respectively. Intracranial disease control was 72% at 5 years. Patients who received gross total resection (GTR) and radiotherapy had significantly better OS than patients who received radiotherapy alone. The OS of patients whose primary tumor was identified was similar to that of patients in whom the primary tumor remained occult. CONCLUSIONS Brain metastasis as the only manifestation of an unknown primary tumor is a distinct clinical entity. The prognosis for patients with this presentation is better than that of patients with brain metastasis in general. Although the majority of patients die of extracranial disease, a few will achieve long term survival. Treatment to the brain is effective in controlling local disease; aggressive treatment with GTR and radiotherapy is recommended. Cancer 1998;83:2181-2184. © 1998 American Cancer Society.

Purpose: To review the long-term clinical effects of unilateral kidney irradiation on overall renal function and blood pressure in patients with gastric lymphoma. Methods and Materials: In the study were 27 patients with Stage I or II gastric lymphoma who had undergone irradiation of at least 24 Gy to ≥1/3 of the left kidney. They include 16 women and 11 men, aged 31 to 77, with a mean age of 57.6 years (median 56). Fifteen patients had Stage I and 12 had Stage II disease. In 13 patients the whole kidney had been irradiated, and 14 had had partial kidney irradiation, at doses ranging between 24 and 40.5 Gy. All patients received combined chemotherapy with various drugs: all patients received corticosteroids, and five received cis-platinum. Their follow-up ranged between 0.7 and 7.8 years (mean 3.4 years). Data on possible effects of the treatment on blood pressure, renal function as assessed by blood urea and creatinine, and kidney shrinkage as seen by serial computed tomography scanning were collected on all patients. Results: Three patients had persistent, mild elevations of urea and creatinine levels, which did not require special treatment. All three also received cis-platinum. Ipsilateral kidney shrinkage was evident in most patients. In 19 patients the craniocaudal measurement of the kidney shrank by ≥1.6 cm. Shrinkage in other dimensions was also evident. The degree of atrophy was related to the volume of kidney irradiated. Only two patients developed hypertension, both at a low level of 150/90; one patient had had 40 Gy to the whole kidney, the other 40 Gy to half the kidney. Neither patient had elevated urea or creatinine. Conclusions: Notwithstanding the shrinkage to the irradiated part of the kidney, the treatment did not lead to clinically significant hypertension or renal dysfunction. The administration of cis-platinum to patients with gastric lymphoma that requires kidney irradiation should be further evaluated.

Purpose: Approximately 10% of patients with metastatic renal cell carcinoma are diagnosed with brain metastases. Most of these patients receive palliative radiotherapy and die of progressive brain metastatic disease. This retrospective study examines the M. D. Anderson Cancer Center experience with such patients who received only whole brain radiation therapy ( WBRT) . Methods and Materials: Records of 200 patients with brain metastases from renal carcinoma who were treated at M. D. Anderson Cancer Center between 1976 and 1993 were reviewed. Of these patients, 119 received WBRT only and constitute the basis of this study. Different prognostic factors were analyzed. Results: Overall median survival time from diagnosis of the brain metastases was 4.4 months. Multiple brain tumors were treated in 70 patients (58.8% ) who had a survival of 3.0 months compared with 4.4 months for patients having a single brain metastasis (p = 0.043). Among 117 patients the causes of death were neurologic in 90 (76% ), systemic cancer in 19 ( 16% ), and unknown in 9 (8% ). Survival rates at 6 months, 1 year, and 2 years, were 33.6,16.8, and 5.9%, respectively. Patients in whom brain metastases were diagnosed synchronously with a renal primary (n = 24) had a median survival time of 3.4 months compared with 3.2 months for those 95 who were diagnosed metachronously (p < 0.79, NS). In the Cox multivariate analysis of 13 possible prognostic factors, only a single brain metastasis @ = 0.0329), lack of distant metastases at the time of diagnosis @ = 0.0056)) and tumor diameter zz 2 cm (p < 0.0016) were statistically significant. Conclusion: These unsatisfactory results with WBRT suggest that more aggressive approaches, such as surgery or radlosurgery should be applied whenever possible. 0 1997 Elsevier Science Inc.

Purpose: A prototype Miniature Multi-Leaf Collimator (MMLC) designed specifically for radiosurgery and small field radiotherapy has been fabricated and evaluated at the University of Texas M. D. Anderson Cancer Center (UTMDACC). This work demonstrates the advantages of a computer-controlled MMLC vs. conventional circular collimation for the treatment of an irregularly shaped target volume in the brain. Methods and Materials: Two patients treatments were selected for this comparison from 38 intracranial tumors treated with radiosurgery at UTMDACC from 8/6/91 to 5/10/94. Target contours and critical structures defined for one of the patients was used to create a simulated target volume and critical structures in a spherical head phantom. Computer simulations were performed using traditional single isocenter treatment with a circular collimator for a set of six arcs. The same arc paths were used to compute the dose distribution for the MMLC and conformed beam geometries were defined using a three-dimensional (3D) treatment planning system with beam's eye view capabilities. Then, the calculated dose distribution for a single isocente, conformal treatment was delivered to the spherical head phantom under static conditions by shaping the MMLC to conform the target volume shape projected as a function of couch rotation and gantry angle. Planar dose distributions through the target volume were measured using therapy verification film located in the phantom. The measurements were used to verify that the 3D treatment planning system was capable of simulating the MMLC technique. For the second patient with a peanut-shaped tumor, the 3D treatment planning calculations were used to compare dose distributions for the MMLC and for traditional single and multiple isocenter treatments using circular collimators. The resulting integral dose-volume histograms (DVHs) for the target volume, normal brain, and critical structures for the three treatment techniques were compared. Results: (a) Analysis of the film dosimetry data exemplified the degree of conformation of the high-dose region to the target shape that is possible with a computer-controlled MMLC. (b) Comparison of measured and calculated dose distributions indicates that the 3D treatment planning system can simulate the MMLC treatment. (c) Comparison of DVHs from the single isocenter MMLC and circular collimator treatments shows similar coverage of the target volume with increased dose to the brain for circular collimation (4). Comparison of DVHs from the single isocenter MMLC with the multiple isocenter circular collimator treatment approach shows a more inhomogeneous dose distribution through the target volume and increased dose to the brain for the latter. Conclusion: Dosimetry data for single isocenter treatments using computer-controlled field shaping with a MMLC demonstrate the ability to conform the dose distribution to an irregularly shaped target volume. DVHs validated that the single isocenter MMLC treatment is preferable to both single and multiple isocenter, circular collimator treatment because it provides a more uniform dose distribution to an irregularly shaped target volume and reduces the dose to surrounding brain tissue for the example cases.

Because of a substantial overall recurrence rate of meningiomas, the role of surgery as the sole treatment for every case must be evaluated. Also, occasionally, the patient's age and/or the location of the tumor precludes considering him/her as a candidate for surgery. In these instances, radiotherapy or radiosurgery may be advisable. The article presents two cases treated at M. D. Anderson Cancer Center, those of a 65-year-old male with a tumor in the left temporal lobe and 74-year-old female with a tumor in the right petroclival region. It also reviews the roles that radiotherapy plays in treating patients with meningiomas. Retrospective analyses of outcomes provide ample evidence that conventional radiation after incomplete resection reduces the incidence of progression of tumor over a long period. Information on patients who have had only external radiation is meager, since most patients have at least a partial resection. Complete resection for benign meningiomas is sufficient. For malignant meningiomas, adjuvant radiation should be administered, regardless of the extent of surgical excision. When surgery poses a high risk of morbidity or mortality, radiation therapy and radiosurgery are promising alternatives.

Purpose : To establish the feasibility of performing split-course accelerated hyperfractionation (AHFX-S) and concomitant boost accelerated fractionation radiotherapy (AFX-C) for advanced head and neck cancer in a multi-institutional cooperative trial setting and to evaluate the tumor clearance rate and acute and late toxicity of these fractionation schedules. Methods and Materials : Between February 1989 and January 1990, 75 patients with Stage III or IV squamous cell carcinoma of the head and neck were randomized to receive : (a) AHFX-S : 1.6 Gy/fraction, twice daily (6-h interval), 5 days/week, to a total dose of 67.2 Gy/42 fractions/6 weeks, with a 2-week rest after 38.4 Gy ; or (b) AFX-C : 1.8 Gy/fraction/day, 5 daily fractions/week to 54 Gy/30 fractions/6 weeks to a large field and 1.5 Gy/fraction/day to a boost field, 6 h after large field treatment during the last 11 treatment days, to a total dose of 70.5 Gy/41 fractions/6 weeks. Acute and late toxicities were scored according to the RTOG normal tissue reaction scales and tumor clearance was evaluated at completion of therapy and at regular intervals thereafter. Results : Of the 70 analyzable patients, 38 received AHFX-S and 32 received AFX-C. The two arms were balanced with respect to sex, age, T-stage, and Karnofsky Performance Status (KPS). However, the AHFX-S arm had a higher proportion of oropharyngeal primaries (63% vs. 44%), and Stage IV disease (82% vs. 50%) and lower proportion of oral cavity lesions (3% vs. 22%) and N0 disease (16% vs. 31%) than the AFX-C arm. The median follow-up was 2 years (range : 0.03-4.87 years). Tolerance of both variants of accelerated fractionated radiotherapy was satisfactory. There was no significant difference in local-regional control, disease-free survival, or survival between the two arms. The 2-year local-regional failure rate, survival, and disease-free survival was 50, 50, and 40%, respectively, for the entire group of patients. Acute radiation mucositis was increased in both arms. There was no significant difference in the incidence of grade 3 acute toxicities (63% vs. 56%) and grade 3 (14% vs. 14%) or grade 4 (6% vs. 17%) late toxicities. Permanent grade 4 late toxicity was observed in 6 and 7% of the patients, respectively. Conclusion : Results of this randomized Phase I/II trial showed that the two accelerated fractionated schedules studied can be successfully given in a multi-institutional cooperative trial. There was no significant difference in acute or late toxicities, local-regional control, disease-free survival, or survival in this small scale study. Therefore, a Phase III trial comparing the relative efficacy of these two accelerated fractionation schedules against standard fractionation and hyperfractionation has been activated.

Purpose: To compare the efficacy of fast neutron radiotherapy versus conventional photon and/or electron radiotherapy for unresectable, malignant salivary gland tumors a randomized clinical trial comparing was sponsored by theRadiation Therapy Oncology Group in the United States and the Medical Research Council in Great Britain. Methods and Materials: Eligibility criteria included either inoperable primary or recurrent major or minor salivary gland tumors. Patients were stratified by surgical status (primary vs. recurrent), tumor size (less than or greater than 5 cm), and histology (squamous or malignant mixed versus other). After a total of 32 patients were entered onto this study, it appeared that the group receiving fast neutron radiotherapy had a significantly improved local/regional control rate and also a borderline improvement in survival and the study was stopped earlier than planned for ethical reasons. Twenty-five patients were study-eligible and analyzable. Results: Ten-year follow-up data for this study is presented. On an actuarial basis, there continues to be a statistically significant improvement in local/regional control for the neutron group (56% vs. 17%, p = 0.009) but there is no improvement in overall survival (15010 vs. 25010, p = n . s .). Patterns of failure are analyzed and it is shown that distant metastases account for the majority of failures on the neutron arm and local/regional failures account for the majority of failures on the photon arm. Long-term, treatment-related morbidity is analyzed and while the incidence of morbidity graded "severe" was greater on the neutron arm, there was no significant difference in "life-threatening" complications. This work is placed in the context of other series of malignant salivary gland tumors treated with definitive radiotherapy. Conclusions: Fast neutron radiotherapy appears to be the treatment-of-choice for patients with inoperable primary or recurrent malignant salivary gland tumors.

Purpose : This study was designed to determine in a prospective randomized trial the optimal dose of conventionally fractionated postoperative radiotherapy for advanced head and neck cancer in relation to clinical and pathologic risk factors. Methods and Materials : Between January 1983 and March 1991, 302 patients were enrolled on the study. This analysis is based on the first 240 patients entered through September 1989, of whom 221 (92%) had AJC Stage III or IV cancers of the oral cavity, oropharynx, hypopharynx, or larynx. The patients were stratified by postulated risk factors and randomized to one of three dose levels ranging between 52.2 Gy and 68.4 Gy, all given in daily doses of 1.8 Gy. Patients receiving ≥ 57.6 Gy had a field reduction at this dose level such that boosts were only given to sites of increased risk. Results : The overall crude and actuarial 2-year local-regional recurrence rates were 25.4% and 26%, respectively. Patients who received a dose of ≤ 54 Gy had a significantly higher primary failure rate than those receiving >- 57.6 Gy (p = 0.02). No significant dose response could be demonstrated above 57.6 Gy except for patients with extracapsular nodal disease in the neck in whom the recurrence rate was significantly higher at 57.6 Gy than at ≥ 63 Gy. Analysis of prognostic factors predictive of local-regional recurrence showed that the only variable of independent significance was extracapsular nodal disease. However, clusters of two or more of the following risk factors were associated with a progressively increased risk of recurrence: oral cavity primary, mucosal margins close or positive, nerve invasion, ≥ 2 positive lymph nodes, largest node > 3 cm, treatment delay greater than 6 weeks, and Zubrod performance status ≥ 2. Moderate to severe complications of combined treatment occurred in 7.1% of patients; these were more frequent in patients who received ≥ 63 Gy. Conclusion : With daily fractions of 1.8 Gy, a minimum tumor dose of 57.6 Gy to the whole operative bed should be delivered with a boost of 63 Gy being given to sites of increased risk, especially regions of the neck where extracapsular nodal disease is present. Treatment should be started as soon as possible after surgery. Dose escalation above 63 Gy at 1.8 Gy per day does not appear to improve the therapeutic ratio.

Background. Radiation port dermatophytosis (RPD) is an uncommon condition in which patients receiving radiation therapy concurrently have tinea corporis that is confined primarily to the irradiated skin. Methods. The case of a 33-year-old man is reported who was receiving cobalt-60 radiation therapy for a nasopharyngeal carcinoma. During therapy, a dermatophyte infection developed in the treated field. Results. Including this patient, there have been only three cases of RPD reported in the world literature. The clinical characteristics of patients with RPD are reviewed. The diagnosis, management, and pathogenesis of this condition are discussed. Conclusions. Because the cutaneous manifestations of RPD may be misinterpreted clinically as acute radiation-induced dermatitis, this condition may be more prevalent than the paucity of published reports suggests.

Between 1955 and 1986, 25 children (aged 2 weeks to 15 years) were treated for intracranial ependymoma at M.D. Anderson Cancer Center. Nine patients had supratentorial primaries (5 high-grade, 4 low-grade), and 16 had infratentorial primaries (9 high-grade, 7 low-grade). Five patients had gross complete resection and 20 had incomplete resection. Seven patients received craniospinal irradiation (25-36 Gy to the neuro-axis, 45-55 Gy to tumor bed), 12 received local field irradiation (29-60 Gy, median 50 Gy). Five infants had adjuvant chemotherapy without radiotherapy, and 6 children had post-radiotherapy adjuvant chemotherapy, and 12 patients had salvage chemotherapy with various agents and number of courses. Eight patients are alive, disease-free and without relapse from 1 year to 12 1/2 years from diagnosis (median 42 months). The primary failure pattern was local recurrence. The data suggest that 1) the long-term cure rate of children with ependymoma is suboptimal; 2) histologic grade may be of prognostic importance for supratentorial tumors; 3) prognosis appears worse for girls and infants under 3 years of age; 4) in well-staged patients routine spinal irradiation could be omitted; 5) the role of adjuvant chemotherapy is unclear.

Normal tissue reactions limit the use of radiotherapy in the management of patients with head and neck neoplasms. Customized intraoral stents can help prevent unnecessary irradiation of various normal tissues thus reducing severity of reactions. Two basic types of devices, referred to as shielding and positional stents, are presented. The fabrication and the application of such devices are illustrated through five case reports. Recommendations on use of these tools and the possibility of combining these means with methods to improve dose distribution within the target volume containing air gaps are provided. Close collaboration between the attending radiotherapist and dentist is essential for designing appropriate devices for individual patients. However, when properly designed and used, these stents are effective in reducing treatment morbidity.

The use of an amorphous silicon electronic portal imaging device (EPID) and Monte Carlo calculations were investigated for pretreatment fluence verification in intensity modulated stereotactic radiotherapy (IMSRT). Monte Carlo calculations were performed using BEAM, a general purpose Monte Carlo code to simulate radiation beams from radiotherapy units. The dose distribution to the EPID phosphor was calculated by BEAM and then converted to pixel value using a pixel calibration curve. The calibration correlated calculated pixel dose to the measured pixel value for a range of open fields. Points within the region bounded by the photon jaws were extracted for comparison. Criteria for successful verification were 5% local percent difference in high dose regions, 1 mm distance to agreement in high gradient regions, or 2% of the Monte Carlo calculated central axis pixel value in low dose regions. Software was written to quantitatively compare the measured and calculated EPID images. Successful verification of the modulated field required that ≥ 95% of compared points fall within the comparison criteria. Dose response of the EPID was found to be linear with Monte Carlo calculated doses over the dose ranges examined in this work Comparison of the measured and calculated EPID dose distributions showed good agreement with 97% of the points passing criteria. The sensitivity of the methodology to detect field shaping errors was tested by introducing positioning errors in segments of the modulated field. These sensitivity tests indicate that the comparison software designed for this work can detect a 1 mm positioning error in a single segment of the composite IMSRT field. It should be noted, however, that the work presented here is a proof of concept and currently not a clinically viable QA tool. It represents a limited evaluation using a single IMSRT field, and verification of additional fields will be required for a comprehensive evaluation of the described methods before broad conclusions can be drawn. Additionally, the results of this work are subject to the comparison criteria that were used. Clinical implementation of the proposed technique should be evaluated for the specific institutional criteria where it will be employed.

Summary Background It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction. Methods Patients with one to three newly diagnosed brain metastases were randomly assigned using a standard permutated block algorithm with random block sizes to SRS plus WBRT or SRS alone from Jan 2, 2001, to Sept 14, 2007. Patients were stratified by recursive partitioning analysis class, number of brain metastases, and radioresistant histology. The randomisation sequence was masked until assignation, at which point both clinicians and patients were made aware of the treatment allocation. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test–Revised (HVLT-R) total recall at 4 months. An independent data monitoring committee monitored the trial using Bayesian statistical methods. Analysis was by intention-to-treat. This trial is registered at www.ClinicalTrials.gov, number NCT00548756. Findings After 58 patients were recruited (n=30 in the SRS alone group, n=28 in the SRS plus WBRT group), the trial was stopped by the data monitoring committee according to early stopping rules on the basis that there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function (mean posterior probability of decline 52%) at 4 months than patients assigned to receive SRS alone (mean posterior probability of decline 24%). At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from CNS recurrence at 1 year, compared with 27% of patients who received SRS alone (p=0·0003). In the SRS plus WBRT group, one case of grade 3 toxicity (seizures, motor neuropathy, depressed level of consciousness) was attributed to radiation treatment. In the group that received SRS, one case of grade 3 toxicity (aphasia) was attributed to radiation treatment. Two cases of grade 4 toxicity in the group that received SRS alone were diagnosed as radiation necrosis. Interpretation Patients treated with SRS plus WBRT were at a greater risk of a significant decline in learning and memory function by 4 months compared with the group that received SRS alone. Initial treatment with a combination of SRS and close clinical monitoring is recommended as the preferred treatment strategy to better preserve learning and memory in patients with newly diagnosed brain metastases. Funding No external funding was received.

Between January 1982 and June 1986, 60 consecutive patients with high-grade astrocytomas [39 glioblastoma multiforme (GBM), 21 anaplastic astrocytoma (AA)] were treated with radiation therapy after biopsy (13 patients) or resection (47 patients). Fifty-three patients were treated with limited-volume irradiation, and seven patients received whole-brain irradiation. The mean tumor dose was 65.4 Gy. In 35 patients, chemotherapy was given as part of their initial treatment. The 1- and 2-year survivals for GBM patients were 40 and 14%, respectively. Survival figures for AA patients were 76 and 52% at 1 and 2 years, respectively. The progression-free rate at 1 year was 13% in GBM and 29% in AA patients. Thirty-four of 48 patients who received limited-volume irradiation had evidence of progression on postirradiation CT scans. Six patients (3 GBM, 3 AA) had evidence of a new intracranial metastatic site on CT scan. In three patients the metastasis was within the previously irradiated volume, and in the other three patients, it was outside this volume. All six had evidence of progression of their primary tumor at the original location on CT scan prior to the discovery of the metastatic site. Twenty-one patients (15 GBM, 6 AA) had at least one postirradiation reoperation for a recurrent mass. Nineteen patients had recurrent tumors in the primary site, and two patients had necrosis but no tumor. Patients who received limited-volume irradiation for high-grade astrocytomas achieved the same survival results as patients treated previously with whole brain irradiation. New intracranial metastases did not influence the outcome, since these were always antedated by tumor progression at the primary site.

Five hundred and fifty patients were entered into a set of dose-searching studies designed to determine normal tissue tolerances to high energy (42–66 MeV reactions) fast neutrons delivered in 12 equal fractions over 4 weeks. Participating institutions included: The Fermilab (66 MeVp+ → Be), The University of Washington (50 MeVp+ → Be), U.C.L.A. (45 MeVHdash → Be), M.D. Anderson Hospital (42 MeVHdash → Be), and The Cleveland Clinic (42 MeVp+ → Be). Patients were stratified by treatment facility and then randomized to receive 16, 18 or 20 Gy for tumors located in the upper abdomen or pelvis, and 18, 20 or 22 Gy for tumors located in the head and neck, thorax or extremities. Following completion of the randomized protocols, additional patients were studied at the 20.4 Gy level in the head and neck, thorax and pelvis. Normal tissue effect scoring was accomplished using the RTOG-EORTC acute and late normal tissue effect scales. Acute Grade 3 + toxicity rates in the head and neck were 19% for 20/20.4 Gy and 20% for 22 Gy. Time adjusted late toxicity rates in the head and neck at 12 months were 15% for 20/20.4 Gy and 0% for 22 Gy. The 18 Gy treatment arm of the head and neck protocol was dropped early in the study after only two patients were accrued. For cases treated in the thorax, acute Grade 3 + toxicity rates were 6% for 18 Gy, 15% for 20/20.4 Gy and 7% for 22 Gy. Late toxicity rates at 12 months were 0% for 18 Gy, 11% for 20/20.4 Gy and 18% for 22 Gy. Acute Grade 3 + toxicity rates in the upper abdomen were 0% for 16 Gy, 8% for 18 Gy and 12% for 20 Gy. There were no Grade 3 + late toxicities in the upper abdomen. In the pelvis, acute Grade 3 + toxicity rates were 0% for 16 Gy, 3% for 18 Gy and 3% for 20/20.4 Gy. Late Grade 3 + toxicities at 24 months were 20% for 16 Gy, 5% for 18 Gy and 24% for 20/20.4 Gy. In extremities, acute Grade 3 + toxicity rates were 7% for 20 Gy and 21% for 22 Gy while at 12 months, late Grade 3 + toxicity rates were 14 and 35%, respectively. The 18 Gy treatment arm of the extremities protocol was dropped early in the study after only two patients were accrued. Factors associated with normal tissue effects in addition to treatment dose are discussed.

From 1956 to 1988, 57 children and young adults (age 4-21 years) with a diagnosis of nasopharyngeal carcinoma were treated at The University of Texas M.D. Anderson Cancer Center (42 patients) and Stanford University Medical Center (15 patients). The male to female ratio was 2:1. Forty-three patients had lymphoepithelioma, seven had undifferentiated neoplasms, and seven had squamous cell carcinoma. Two patients had Stage III disease and the remainder had Stage IV disease at the time of presentation. All patients were treated with primary radiotherapy, and 14 patients also had chemotherapy with combinations of the following drugs: dactinomycin, doxorubicin, bleomycin, cisplatin, cyclophosphamide, fluorouracil, methotrexate, and vincristine. Twenty-six patients are alive 6 to 178 months from the first day of treatment (median 93 months). The 5- and 10-year actuarial survival rates are 51% and 36%, respectively, and the corresponding disease specific survival rates were 51% and 51%. There were no recurrences after 42 months. The patterns of failure were as follows: distant metastasis only, 21 patients; locoregional metastasis only, 1; both, 5. Distant metastases most commonly occurred in bones, lungs, liver, and mediastinal lymph nodes. Chronic treatment-related morbidity was encountered in a significant number of long term survivors. Trends in the data not reaching statistical significance suggest a more favorable prognosis for a) females, b) patients less than or equal to 15 years of age, c) lymphoepithelioma or undifferentiated histologies, d) stages T3-4 NO-1 vs T1-2 N2-3 vs T3-4 N2-3, e) primary tumor dose greater than or equal to 65 Gy and f) patients who received chemotherapy.

From January 1963 through December 1979, 103 patients with Stage T1N0 and T2N0 squamous cell carcinomas of the oral tongue were treated with definitive radiotherapy. The primary was Stage T1 in 18 patients and T2 in 85 patients. Therapy to the primary consisted of interstitial therapy only in 18 patients, 16-37 Gy in 2.4-4.0 Gy fractions followed by interstitial therapy to doses of 38-55 Gy in 31 patients, external therapy of 40-50 Gy with interstitial therapy of 20-40 Gy in 46 patients, and external beam only to doses of 45-82 Gy in 8 patients. Follow-up ranged from 2 to 290 months (median 159 months). Five of the 8 patients treated with external therapy alone and 6 of the 18 patients treated with interstitial therapy failed at the primary site. In those patients treated with a combination of external and interstitial therapy the 2-year local control rate was 92% for patients treated with external therapy to doses of less than 40 Gy combined with a moderately high dose of brachytherapy, compared with 65% for patients who received external therapy to doses of greater than or equal to 40 Gy with lower brachytherapy doses (p = .01). Conversely the risk of failure in the neck was directly related to the dose delivered by external beam therapy. In field recurrence occurred in 44% of patients receiving no therapy to the neck. 27% in those receiving less than 40 Gy, and 11% in those patients with neck treatment to greater than or equal to 40 Gy. Eleven of 87 (13%) of patients who were at risk for complications for greater than or equal to 24 months developed severe complications; severe complications were more likely to occur in the group who received most of their therapy with external beam irradiation. These data show that a high dose of interstitial therapy is necessary to secure optimum local control of early primary tongue cancer. Because of the high frequency of moderate to severe late complications in this series we have adopted a policy of initial surgery for most oral tongue cancers with postoperative radiotherapy if indicated by pathological features predictive of a high rate of local-regional failure.

Thirty-four patients with stages IE and IIE gastric lymphoma were treated with chemotherapy and radiotherapy combinations without stomach resection. In 20 patients, the diagnosis was established by endoscopic biopsy only; the other 14 had laparotomy and biopsy. No patient had a gastrectomy before treatment. Nineteen patients had stage IE disease and 15 had stage IIE. Lymphoma diagnoses were: diffuse large-cell, 26; immunoblastic, three; diffuse well-differentiated, three; nodular mixed, one; and unclassified, one. The treatment plan was to deliver an initial four cycles of chemotherapy, followed by radiotherapy, and finally, more chemotherapy. Thirty-three patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo). Four patients with stage IIE disease received cyclophosphamide, methotrexate, etoposide, and dexamethasone (CMED). Twenty-three patients (68%) never had a relapse. Three patients had successful salvage therapy, one for local recurrence and two for tumor dissemination. Five patients died of recurrent abdominal disease, and one died of tumor dissemination. Two died of treatment-related complications, one of sepsis during treatment with CMED and one of bleomycin-induced lung fibrosis. No patient developed stomach perforation or bleeding as a result of chemotherapy or radiotherapy. Twenty-four of the 26 surviving patients were able to retain their stomachs. One patient required a gastrectomy for progressive disease during chemotherapy, and another required a subtotal gastrectomy for relief of an obstruction caused by cicatrization. These data show that surgery is not a necessary procedure in gastric lymphoma. Favorable results can be achieved by combining effective chemotherapy and local radiation.

This study was undertaken to evaluate the outcome of patients undergoing stereotactic radiosurgery (SRS) as primary or salvage treatment of brain metastases arising from breast cancer.Between July 2000 and September 2005, the medical records of 49 breast cancer patients who underwent SRS for 84 brain metastases were reviewed retrospectively. Thirty-four patients received SRS as primary brain metastasis treatment and 15 patients received SRS as salvage treatment of brain metastasis recurrence following prior whole-brain radiation therapy. The Kaplan-Meier method, univariate comparisons with log-rank test, and multivariate analysis were performed.Median follow-up was 12 months (range, 5-50 months) and median survival was 19 months for all patients. The 1- and 2-year overall survival (OS) rates were 60%, 56%, and 55%, 23% for initial SRS alone and SRS salvage groups, respectively (P = 0.99). A multivariate analysis showed that a high KPS score (KPSor =90 vs.90; P = 0.02), a higher SIR value (SIRor =6 vs.6; P = 0.001), postmenopausal status (P = 0.003), and positive estrogen receptor status (P = 0.04) were predictive of better survival. The 1- and 2-year local control rates were 79%, 49%, and 77%, 46% for SRS alone and SRS salvage group, respectively.SRS can be used as primary treatment of brain metastases or salvage of recurrences after whole-brain radiation therapy to achieve good local control on the order of close to 80% at 1 year. The median survival of brain metastasis patients with breast cancer of 19 months appears favorable compared with the general brain metastasis population.

OBJECTIVE: Whether to administer or omit adjuvant whole-brain radiation therapy in conjunction with stereotactic radiosurgery (SRS) in the initial management of patients with one to three newly diagnosed brain metastases is the subject of debate. This report provides data from a pilot study in which neurocognitive function (NCF) was prospectively measured for patients with one to three newly diagnosed brain metastases treated with initial SRS alone. METHODS: Fifteen patients were prospectively treated with initial SRS alone. Assessment of NCF and magnetic resonance imaging scans were performed. RESULTS: At baseline, 67% of the patients had impairment on one or more tests of NCF. The domains most frequently impaired at baseline were executive function, motor dexterity, and learning/memory with an incidence of 50, 40, and 27% respectively. Brain metastasis volume (>3 cm 3 ) measured at the time of initial SRS treatment was associated with worse performance on a measure of attention (P< 0.05). At 1 month, declines in the learning/memory and motor dexterity domains were most common. In a subgroup of five patients still alive 200 days after enrollment, four patients (80%) demonstrated stable or improved learning/memory, three (60%) demonstrated stable or improved executive function, and three (60%) demonstrated stable or improved motor dexterity relative to their baseline evaluation. CONCLUSION: Although two-thirds of the brain metastasis patients had impaired NCF at baseline, the majority of five long-term survivors had stable or improved NCF performance across executive function, learning/memory, and motor dexterity.