Clinical and dosimetric factors associated with a prolonged feeding tube requirement in patients treated with chemoradiotherapy (CRT) for head and neck cancers.

BACKGROUND: Patients treated with chemoradiotherapy (CRT) for head and neck cancers often require feeding tubes (FTs) due to toxicity. We sought to identify factors associated with a prolonged FT requirement. PATIENTS AND METHODS: We retrospectively reviewed 80 patients treated with CRT for head and neck cancers. The pharyngeal constrictors (PCs), supraglottic larynx (SGL), and glottic larynx (GL) were contoured and the mean radiation doses and the volumes of each receiving >40, 50, 60, and 70 Gy (V40, V50, V60, and V70) were determined. RESULTS: A total of 33 of 80 patients required a FT either before or during the course of CRT. Fifteen patients required the FT for > or = 6 months. On univariate analysis, significant factors associated with a prolonged FT requirement were mean PC dose, PC-V60, PC-V70, SGL dose, SGL-V70, and advanced T3-T4 disease. Multivariate analyses found both PC-V70 and T3-T4 disease as significant factors .The proportions of patients requiring a FT > or = 6 months were 8% and 28% for treatment plans with PC-V70 <30% and > or = 30%, respectively. CONCLUSIONS: Increased radiation dose to the PCs is associated with a higher risk of a prolonged FT need. Dose sparing of the PC muscles may reduce this risk.

The rates of second lung cancers and the survival of surgically-resected second primary lung cancers in patients undergoing resection of an initial primary lung cancer.

BACKGROUND: The Lung Cancer Screening Trial demonstrated improved overall survival (OS) and lung cancer specific survival (LCSS), likely due to finding early-stage NSCLC. The purpose of our investigation is to evaluate whether long-term surveillance strategies (4+ years after surgical resection of the initial lung cancer(1LC)) would be beneficial in NSCLC patients by assessing the rates of second lung cancers(2LC) and the OS/LCSS in patients undergoing definitive surgery in 1LC as compared to 2LC (>48 months after 1LC) populations. METHODS: SEER13/18 database was reviewed for patients during 1998-2013. Log-rank tests were used to determine the OS/LCSS differences between the 1LC and 2LC in the entire surgical group(EG) and in those having an early-stage resectable tumors (ESR, tumors <4 cm, node negative). Joinpoint analysis was used to determine rates of second cancers 4-10 year after 1LC using SEER-9 during years 1985-2014. RESULTS: The rate of 2LCs was significantly less than all other second cancers until 2001 when the incidence of 2LCs increased sharply and became significantly greater than all other second cancers in females starting in year 2005 and in men starting in year 2010. OS/LCSS, adjusted for propensity score by using inverse probability weighting, demonstrated similar OS, but worse LCSS for 2LCs in the EG, but similar OS/LCSSs in the ESR group. CONCLUSION: Because the rate of 2LCs are increasing and because the OS/LCSS of the 1LC and 2LC are similar in early-stage lesions, we feel that continued surveillance of patients in order to find early-stage disease may be beneficial.

CT versus MR Imaging in Estimating Cochlear Radiation Dose during Gamma Knife Surgery for Vestibular Schwannomas.

BACKGROUND AND PURPOSE: Leksell stereotactic radiosurgery is an effective option for patients with vestibular schwannomas. Some centers use a combination of stereotactic CT fused with stereotactic MR imaging to achieve an optimal target definition as well as minimize the radiation dose delivered to adjacent structures that correlate with hearing outcomes. The present prospective study was designed to determine whether there is cochlear dose variability between MR imaging and CT. MATERIALS AND METHODS: Fifty consecutive patients underwent stereotactic radiosurgery for vestibular schwannomas. Dose-planning was performed using high-definition fused stereotactic MR imaging and stereotactic CT images. The 3D cochlear volume was determined by delineating the cochlea on both CT and T2-weighted MR imaging. The mean radiation dose, maximum dose, and 3- and 4.20-Gy cochlear volumes were identified using standard Leksell Gamma Knife software. RESULTS: The median mean radiation dose delivered to the cochlea was 3.50 Gy (range, 1.20-6.80 Gy) on CT and 3.40 Gy (range, 1-6.70 Gy) on MR imaging (concordance correlation coefficient = 0.86, r 2 = 0.9, P ≤ .001). The median maximum dose delivered to the cochlea was 6.7 Gy on CT and 6.6 Gy on MR imaging (concordance correlation coefficient = 0.89, r 2 = 0.90, P ≤ .001). Dose-volume histograms generated from CT and MR imaging demonstrated a strong level of correlation in estimating the 3- and 4.20-Gy volumes (concordance correlation coefficient = 0.81, r 2 = 0.82, P ≤ .001 and concordance correlation coefficient = 0.87, r 2 = 0.89, P ≤ .001). CONCLUSIONS: Both MR imaging and CT provide similar cochlear dose parameters. Despite the reported superiority of CT in identifying bony structures, high-definition MR imaging alone is sufficient to identify the radiation doses delivered to the cochlea.

Principles and practice of gamma knife radiosurgery: a review.

OBJECTIVES: To determine the physics, biology, outcomes and risks of gamma knife radiosurgery (GKRS) in treating brain tumours, arteriovenous malformations (AVMs), pain and movement disorders. DATA SOURCES: A retrospective MEDLINE search was used to find all gamma knife radiosurgery studies published from 1967 to 12th March 2005 and strict inclusion criteria were applied. STUDY SELECTION: Limited to the review articles in the human study with the key word of gamma knife radiosurgery. DATA EXTRACTION: In each subject, both authors reviewed related articles separately. DATA SYNTHESIS: Adding up data and compare the results. CONCLUSIONS: The GKRS represents one of the most advanced means available to treat brain tumours, arteriovenous malformations (AVMs), pain and movement disorders safely and effectively. At present, the long-term results after GKRS procedures remain to be documented. The physics, biology, current indications and expected outcomes after GKRS are discussed.

Sensitivity to radiation-induced apoptosis and neuron loss declines rapidly in the postnatal mouse neocortex.

Therapeutic brain irradiation can cause progressive decline in cognitive function, particularly in children, but the reason for this effect is unclear. The study explored whether age-related differences in apoptotic sensitivity might contribute to the increased vulnerability of the young brain to radiation. Postnatal day 1 (P1) to P30 mice were treated with 0-16 Gy whole-body X-irradiation. Apoptotic cells were identified and quantified up to 48 h later using the TdT-UTP nick end-labelling method (TUNEL) and immunohistochemistry for activated caspase-3. The number of neuron-specific nuclear protein (NeuN)-positive and -negative cells were also counted to measure neuronal and non-neuronal cell loss. Significantly greater TUNEL labelling occurred in the cortex of irradiated P1 animals relative to the other age groups, but there was no difference among the P7, P14 and P30 groups. Irradiation decreased the %NeuN-positive cells in the mice irradiated on P1, whereas in P14 animals, irradiation led to an increase in the %NeuN-positive cells. These data demonstrate that neocortical neurons of very young mice are more susceptible to radiation-induced apoptosis. However, this sensitivity decreases rapidly after birth. By P14, acute cell loss due to radiation occurs primarily in non-neuronal populations.

Cranial nerve preservation after stereotactic radiosurgery for small acoustic tumors.

OBJECTIVE: To assess those factors associated with and predictive of cranial nerve preservation after stereotactic radiosurgery in patients with small acoustic tumors identified by magnetic resonance imaging. DESIGN: We performed a retrospective analysis of our experience with 31 patients with preserved hearing and acoustic tumors measuring 10 mm or smaller (pons-to-petrous dimension). All patients underwent clinical and audiologic evaluations varying from 6 to 48 months (mean, 20 months) after stereotactic radiosurgery performed with use of the 201 source cobalt 60 gamma unit. RESULTS: Stabilization or reduction in tumor volume was achieved in 29 of 31 patients. One patient required delayed microsurgical resection. Useful hearing (pure tone average < or = 50 dB and speech discrimination score > or = 50%) preservation was achieved in 10 of 10 patients immediately postoperatively, eight of 10 patients at 6 months, six of 10 patients at 1 year, and five of 10 at 2 years. Preservation of some measurable hearing was possible in all patients immediately after radiosurgery, in 84% and in more than half of patients at 2 years. Preoperative facial nerve function was preserved in 19 of 20 patients at 2 years after radiosurgery. All patients returned to their preoperative employment status within 2 to 5 days after radiosurgery. CONCLUSION: Stereotactic radiosurgery performed with current technology (multiple radiation isocenters and magnetic resonance imaging guidance) is a safe and effective management strategy for patients with small acoustic tumors. The risk of facial and trigeminal neuropathy after gamma knife radiosurgery is low, and useful hearing can be preserved in up to 50% of patients with useful preoperative hearing. Stereotactic radiosurgery is a valuable alternative strategy to surgical removal for many patients with newly diagnosed small acoustic tumors.

Gamma knife radiosurgery for trigeminal neuralgia: results and expectations.

BACKGROUND: Trigeminal neuralgia is a disabling pain syndrome responsive to both medical and surgical therapies. Stereotactic radiosurgery using the gamma knife can be used to inactivate a specified volume in the brain by cross firing 201 photon beams. We evaluated pain relief and treatment morbidity after trigeminal neuralgia radiosurgery. METHODS: All evaluable patients (n = 106) had medically or surgically refractory trigeminal neuralgia. A single 4-mm isocenter of radiation was focused on the proximal trigeminal nerve just anterior to the pons. For follow-up an independent physician who was unaware of treatment parameters contacted all patients. RESULTS: After radiosurgery, 64 patients (60%) became free of pain and required no medical therapy (excellent result), 18 (17%) had a 50% to 90% reduction (good result) in pain severity or frequency (some still used medications), and 9 (9%) had slight improvement. At last follow-up (median, 18 months; range, 6-48 months), 77% of patients maintained significant relief (good plus excellent results). Only 6 (10%) of 64 patients who initially attained complete relief had some recurrent pain. Radiosurgery dose (70-90 Gy), age, surgical history, or facial sensory loss did not correlate with pain relief. Poorer results were found in patients with multiple sclerosis. Twelve patients developed new or increased facial paresthesias after radiosurgery (10%). No patient developed anesthesia dolorosa. There was no other procedural morbidity. CONCLUSIONS: Gamma knife radiosurgery is a minimally invasive technique to treat trigeminal neuralgia. It is associated with a low risk of facial paresthesias, an approximate 80% rate of significant pain relief, and a low recurrence rate in patients who initially attain complete relief. Longer-term evaluations are warranted.

Stereotactic radiosurgery of residual or recurrent craniopharyngioma, after surgery, with or without radiation therapy.

This study evaluated the role of stereotactic radiosurgery in the multimodality management of craniopharyngioma patients whose prior therapies failed. Ten consecutive patients (3 males and 7 females) had radiosurgery for craniopharyngioma during a 10-year interval. Their ages ranged from 9 to 64 years (median, 14.5 years). The median interval between diagnosis and radiosurgery was 46.5 months. In total, 12 stereotactic radiosurgical procedures were performed to control the solid component of the tumor (2 intrasellar and 10 suprasellar tumors). The median tumor volume was 1.35 cm3. One to 9 isocenters with different beam diameters were used; the median marginal dose was 16.4 Gy; and the dose to the optic apparatus was limited to less than 8 Gy. Clinical and imaging follow-up data were obtained at a median of 63 months (range, 13-150 months) from radiosurgery. Overall, 7 of 12 tumors became smaller or vanished within a median of 8.5 months. Prior visual defects objectively improved in 6 patients. One patient with prior visual defect deteriorated further and lost vision 9 months after radiosurgery. Multimodality therapy is often necessary for patients with refractory solid and cystic craniopharyngiomas. Stereotactic radiosurgery is a reasonable option in select patients with small recurrent or residual craniopharyngioma.

An integrated logistic formula for prediction of complications from radiosurgery.

An integrated logistic model for predicting the probability of complications when small volumes of tissue receive an inhomogeneous radiation dose is described. This model can be used with either an exponential or linear quadratic correction for dose per fraction and time. Both the exponential and linear quadratic versions of this integrated logistic formula provide reasonable estimates of the tolerance of brain to radiosurgical dose distributions where there are small volumes of brain receiving high radiation doses and larger volumes receiving lower doses. This makes it possible to predict the probability of complications from stereotactic radiosurgery, as well as combinations of fractionated large volume irradiation with a radiosurgical boost. Complication probabilities predicted for single fraction radiosurgery with the Leksell Gamma Unit using 4, 8, 14, and 18 mm diameter collimators as well as for whole brain irradiation combined with a radiosurgical boost are presented. The exponential and linear quadratic versions of the integrated logistic formula provide useful methods of calculating the probability of complications from radiosurgical treatment.

Radiotherapy and multimodality management of cholangiocarcinoma.

PURPOSE: To evaluate the results of radiotherapy in cholangiocarcinoma patients managed with various combinations of chemotherapy and surgical resection with selective liver transplantation. METHODS AND MATERIALS: From January 1990 to December 1995, 61 patients with histologically confirmed biliary duct adenocarcinoma were seen in the Radiation Oncology Department of the University of Pittsburgh. Median follow-up was 22 months (1 to 91 months). The extent of surgery was complete resection in 23 patients (including 17 with orthotopic liver transplant), partial resection in 4, and biopsy in 34. All patients had radiotherapy; median dose was 49.5 Gy. Thirty patients received chemotherapy: 5-fluorouracil (5-FU)-leucovorin with interferon alpha (IFNalpha) in 27, and taxol in 3. RESULTS: The median survival was 20 months (95% CI 15-25 months). The 5-year actuarial survival was 23.8 +/- 6.8%. The only significant variable in multivariate analysis was achieving a complete resection with negative margins through conventional surgery or liver transplantation (p = 0.001, hazard rate ratio [HRR] = 0.25, 95% CI 0.12-0.54). Patients with complete resections had a 5-year actuarial survival of 53.5 +/- 10.9%. CONCLUSION: Combined modality therapy that includes complete surgical resection with or without transplantation can be curative in the majority of patients with biliary duct carcinoma. Further study is needed to better define the roles of chemotherapy and radiotherapy in cholangiocarcinoma.

Repeat megavoltage irradiation of pituitary and suprasellar tumors.

From 1965 to 1984, ten patients with suprasellar or pituitary tumors received repeat courses of radiation therapy at the Joint Radiation Oncology Center of the University of Pittsburgh. The radiation doses varied between 36.00 to 53.65 Gy for the first treatment course and from 35.00 to 49.60 Gy for retreatment. Six patients were treated for pituitary tumors, two for germinoma, one for optic glioma, and one for craniopharyngioma. One died of disease progression 19 years after a second course of radiation. Two patients were dead of intercurrent disease 0.2 and 1.5 years after repeat radiation. The remainder are free of disease progression 1.6 to 20.5 years after repeat irradiation. Optic neuropathy developed in one patient 1.3 years following a second course of treatment to 40 Gy in 20 fractions administered 7.5 years after initial treatment to 46 Gy in 23 fractions. Neither the Nominal Standard Dose nor the Neuret formula provided an adequate estimate of the repair of radiation. An estimation that 40% of the original radiation dose effect is still present appears to be a reasonable "rule of thumb" guideline to account for prior radiotherapy.

Cranial nerve length predicts the risk of delayed facial and trigeminal neuropathies after acoustic tumor stereotactic radiosurgery.

PURPOSE: To test the hypothesis that length of cranial nerve irradiated is a major factor predicting the risk of cranial nerve injury following radiosurgery and to identify any other significant related treatment factors. METHODS AND MATERIALS: Ninety-two patients (93 acoustic tumors) were treated with a 201 source Cobalt-60 gamma unit from 1987 to 1990 and prospectively followed. The range of minimum tumor dose was 12-20 Gy and maximum dose 24-50 Gy. Univariate and multivariate analyses were used to evaluate any correlations between tumor measurements and treatment factors, with the development of trigeminal and facial neuropathies following radiosurgery. RESULTS: The risks of trigeminal and facial neuropathy following radiosurgery were associated with the pon-petrous distance and mid porous transverse tumor diameters respectively (anatomically related to the irradiated length of cranial nerves V and VII respectively) in both univariate (p = .002 for V and p = .026 for VII) and multivariate (p = .004 for V and p = .055 for VII) analyses. Tumor volume, other tumor measurements, maximum dose, minimum tumor dose, and tumor dose inhomogeneity were not significantly related to either trigeminal or facial neuropathy in univariate and multivariate analyses. CONCLUSION: Within a minimum tumor dose range of 12-20 Gy, the incidence of delayed trigeminal or facial neuropathy depended more on the estimated length of nerve irradiated than the tumor dose or tumor volume. In the future, the risk of delayed facial or trigeminal cranial neuropathy may be reduced significantly by performing radiosurgery when the tumor still has both a small mid-porous transverse diameter and a small pons-petrous distance.

Potential human error in setting stereotactic coordinates for radiosurgery: implications for quality assurance.

PURPOSE: The error frequency in setting stereotactic coordinates for gamma knife radiosurgery was investigated to determine what quality assurance safeguards are necessary. METHODS AND MATERIALS: A prospective study of 200 consecutive isocenter settings for gamma knife radiosurgery was analyzed to identify the frequency of spontaneous errors in setting and checking stereotactic coordinates (corrected prior to treatment). An additional 25 coordinate errors were introduced at random among the next 200 consecutive isocenter settings to provide additional data on identification of errors. RESULTS: Stereotactic coordinates required resetting in 12% (24/200) of the isocenters treated due to errors of 0.25-0.50 mm (8%) and 1-20 mm (4%). This comprised 2.2% (26/1200) of the individual coordinate settings. The frequency of these errors was significantly related to the specific directional coordinate set (p = 0.0004) and experience (p = 0.016). Errors were identified by 83.5% (91/109) of the observers checking the settings (60.0% of 0.25 mm errors, 94.6% of errors > or = 0.5 mm, p = 0.0000). Verification of stereotactic coordinates by two observers reduces the probability of an undetected error > or = 0.25 mm to 1/1,392 and to 1/154,712 for errors > or = 1 mm. CONCLUSION: Errors in setting stereotactic coordinates are common (12% prior to checking) but are corrected with a high degree of confidence by a quality assurance policy requiring coordinate verification by a minimum of two observers.

Stereotactic radiosurgery for chordoma and chondrosarcoma: further experiences.

PURPOSE: Skull base chordomas and chondrosarcomas pose management challenges owing to their critical location, locally aggressive nature, and high recurrence rate despite multimodality treatment. We used stereotactic radiosurgery as primary or adjuvant therapy to achieve safe and effective therapeutic irradiation. METHODS AND MATERIALS: At an average of 4 years (range 1-7), we evaluated 15 patients (nine with chordomas and six with chondrosarcomas) who had gamma-knife radiosurgery as an adjunct (13 patients) or as an alternative to microsurgical resection (two patients). Patient age varied from 7 to 70 years (mean 38). There was a distinct male preponderance (2:1). Thirteen patients had undergone between one and four resections. Using conformal radiosurgical planning, a maximum tumor dose of 24-40 Gy (mean 36) and a tumor margin dose of 12-20 Gy (mean 18) was given to a mean tumor volume of 4.6 ml. RESULTS: Eight patients showed clinical improvement, three remained stable, and four died. Two of the four patients who died had tumor progression remote from the radiosurgery volume; two patients died of unrelated disorders. Among 11 surviving patients, follow-up imaging showed a reduction in tumor size in five, no further tumor growth in five, and an increase in the size of the tumor in one. The patient with further tumor growth after radiosurgery subsequently underwent repeat resection. CONCLUSION: Despite the formidable management challenge posed by these neoplasms, our long-term evaluation has shown that radiosurgery is a safe and effective treatment for patients with small volume tumors.

Analysis of neurological sequelae from radiosurgery of arteriovenous malformations: how location affects outcome.

PURPOSE/OBJECTIVE: To elucidate how the risks of developing temporary and permanent neurological sequelae from radiosurgery for arteriovenous malformations (AVM) are related to AVM location, the addition of stereotactic magnetic resonance (MR) imaging to angiographic targeting, and prior hemorrhage or neurological deficits. MATERIALS AND METHODS: We evaluated follow-up imaging and clinical data in 332 AVM patients who received gamma knife radiosurgery at the University of Pittsburgh between 1987 and 1994. All patients had regular clinical or imaging follow-up for a minimum of 2 years (range: 24-96 months, median = 45 months). There were 83 patients with MR-assisted planning, 187 with prior hemorrhages, and 143 with prior neurological deficits. RESULTS: Symptomatic postradiosurgery sequelae (any neurological problem including headache) developed in 30 (9%) of 332 patients. Symptoms resolved in 58% of patients within 27 months with a significantly greater proportion (p = 0.006) resolving in patients with Dmin < 20 Gy vs. > or = 20 Gy (89 vs. 36%). The 7-year actuarial rate for developing persistent symptomatic sequelae was 3.8%. We first evaluated the relative risks for different locations to construct a postradiosurgery injury expression (PIE) score for AVM location. Multivariate logistic regression analysis of symptomatic postradiosurgery sequelae identified independent significant correlations with PIE location score (p = 0.0007) and 12 Gy volume (p = 0.008), but with none of the other factors tested (p > 0.3), including the addition of MR targeting, average radiation dose in 20 cc, prior hemorrhage, or neurological deficit. We used these results to construct a risk prediction model for symptomatic postradiosurgery sequelae. The risk of radiation necrosis was significantly correlated with PIE score (p < 0.048), but not with 12-Gy volume. CONCLUSION: The risks of developing complications from AVM radiosurgery can be predicted according to location with the PIE score, in conjunction with the 12-Gy treatment volume. Further study of factors affecting persistence of these sequelae (progression to radiation necrosis) is needed.

A dose-response analysis of arteriovenous malformation obliteration after radiosurgery.

PURPOSE: Although radiosurgery is effective in obliterating the pathologic vessels of intracranial arteriovenous malformations (AVM), the relationships of both dose and volume to obliteration have not been well defined. METHODS AND MATERIALS: The results of radiosurgery in 197 AVM patients with 3-year angiographic follow-up were analyzed. Volume varied from 0.06-18 cc (median: 4.1 cc), and minimum target dose (Dmin) varied from 12.0-25.6 Gy (median: 20.0 Gy). RESULTS: Follow-up angiography revealed complete AVM obliteration in 142 out of 197 patients (72%). The targeted AVM nidus failed to obliterate in 20 patients (10%), but in-field obliteration was complete in the remaining 35 patients (18%) discovered to have residual untargeted AVM nidus. Multivariate logistic regression analysis of in-field obliteration revealed a significant independent correlation with Dmin (p = 0.04), but not with volume or maximum dose. A sigmoid dose-response curve for in-field obliteration was constructed that significantly differed from the dose-volume-response relationships that would have been expected from overall obliteration data. CONCLUSIONS: The success rate for in-field obliteration of AVM after radiosurgery depends on Dmin but does not appear to change appreciably with volume or maximum dose. Success rates for complete obliteration additionally are limited by problems defining the complete AVM nidus.

Evolution in technique for vestibular schwannoma radiosurgery and effect on outcome.

PURPOSE: To define changes in treatment technique for vestibular schwannoma radiosurgery and to relate them to changes in outcome, a large single institution experience was reviewed. METHODS AND MATERIALS: Two hundred seventy-three patients with unilateral vestibular schwannomas underwent Gamma knife radiosurgery: 118 with computed tomography (CT) treatment planning during 1987-1991, and 155 with magnetic resonance imaging (MR) treatment planning in 1991-1994. Mean treatment parameters differed between the CT and MR groups: minimum tumor dose (D(min)) was 17 vs. 14 Gy, number of isocenters was 3.4 vs. 5.8, and volume was 3.5 vs 2.7 cc., respectively. RESULTS: The actuarial 7-year clinical tumor control rate (no requirement for surgical intervention) for the entire series was 96.4 +/- 2.3%, with a radiographic tumor control rate of 91.0 +/- 3.4%; these rates were similar for the CT and MR groups. Significantly lower rates of postradiosurgery facial, trigeminal, and auditory neuropathy were observed in the MR group compared to the CT group. Multivariate analyses found significant independent correlations of increasing rates of facial and trigeminal neuropathy with increasing transverse tumor diameter and D(min), as well as with CT treatment planning (compared to MR). Decreased hearing was similarly correlated with diameter and CT planning but not with D(min). CONCLUSIONS: Changes in radiosurgery technique and the use of lower doses improved the outcome after vestibular schwannoma radiosurgery by decreasing cranial neuropathy rates. MR-based treatment planning appears to have significantly contributed to this improvement. Despite decreases in radiation dose, no change in the high rate of tumor control has yet been observed.

Split course radiation therapy for adenocarcinoma of the pancreas.

Ninety-five patients with biopsy proven adenocarcinoma of the pancreas were treated with split course radiation therapy. Fifty-five patients had disease confined to the peripancreatic tissues and lymph nodes. Forty patients had metastatic disease. The intended radiation therapy scheduled consisted of two courses of 25 Gy in 10 fractions each followed by a 3 to 4 week rest period. Depending on the response and the patient's clinical status, another 10 Gy in 5 fractions was administered as a final boost. The median survival in patients with metastatic disease was 3 months and the median survival in patients with localized disease was 8 months. Twenty-seven of the fifty-five patients with localized disease received chemotherapy (5 FU or FAM) combined with radiotherapy. There was no significant difference in median survival between the patients treated with radiation alone and those with combined radiation and chemotherapy. The median survival for patients with localized disease receiving 25, 50, and 60 Gy were 3, 7, and 12 months respectively. After a dose of 50 Gy in 20 fractions, CT scan showed no evidence of tumor in 6%, smaller tumor size in 31%, stable tumor size in 41%, and tumor growth in 22% of patients. The split course radiation therapy was well tolerated and no late complications were detected. The medical and economic advantages of using split course radiation therapy and in using CT scan response to plan boost therapy are discussed.

Estimation of complications for linear accelerator radiosurgery with the integrated logistic formula.

Radiosurgery techniques permit high doses of single fraction irradiation to be administered to small volumes of tumor with relative sparing of surrounding brain tissue. The tolerance of surrounding normal brain tissue to dose distributions from linear accelerator radiosurgery with different collimator sizes is an important factor that must be estimated by anyone using these treatment techniques. The exponential and linear quadratic versions of the integrated logistic formula were used to estimate the probability of brain necrosis at different doses for radiosurgical dose distributions administered by a 6 MV linear accelerator with a 5 arc technique for collimator sizes from 12.5 to 30 mm in diameter. Dose-volume isoeffect curves for a 3% risk of brain necrosis from linear accelerator radiosurgery were then calculated. These curves approximate those calculated for gamma knife radiosurgery and a published 1% dose-volume isoeffect line predicted for proton beam irradiation. Similar dose-volume isoeffect curves were calculated for single fraction radiosurgery boosts administered after 30 Gy of whole brain irradiation in 12 fractions. The integrated logistic formula appears to be a useful tool for estimating tolerance and providing guidelines for prescribing radiation doses for linear accelerator radiosurgery.