Comparison of 3D conformal radiation therapy and intensity-modulated radiation therapy in patients with endometrial cancer: efficacy, safety and prognostic analysis.

Introduction: Adjuvant whole-pelvic radiation therapy (WPRT) improves locoregional control for high-intermediate stages I-III endometrial cancer patients. Intensity modulated radiation therapy (IMRT) tends to replace the standard 3D conformal radiation therapy (3DCRT) technique used in trials. Material and methods: Consecutive patients with stages I-IIIc endometrial cancer treated between 2008 and 2014 in our department with post-operative 3DCRT or IMRT WPRT were studied retrospectively. Patients with cervical involvement underwent additional low-dose rate vaginal brachytherapy. The impact of the WPRT technique on local control, tolerance, disease-free survival (DFS) and overall survival (OS) was assessed. Clinicians evaluated routinely acute radiation toxicity each week during radiation therapy and late toxicity during standard follow-up consultations. Results: Median follow-up was 50 months (range: 6-158). Among the 83 patients included, 47 were treated with 3DCRT and 36 with IMRT. There was no difference in patient characteristics between groups. The 5-year locoregional control and DFS rates were 94.5% and 68%, respectively. No significant difference was found between the 3DCRT and IMRT groups in terms of survival, with 5-year OS rates of 74.6% and 78%, respectively. In multivariate analysis, age over 68, stage > T1 and grade 3 were independently associated with shorter DFS and OS. Seven patients (8.4%) had grades 3-4 acute gastrointestinal (GI) toxicity with five patients (10.6%) and two (5.4%) in the 3DCRT and IMRT groups, respectively (p = .69). One case (1.2%) of late grade 3 GI toxicity was observed treated in 3DCRT. Conclusions: IMRT seems to be a safe technique for the treatment of endometrial cancer with a trend towards decreased acute GI toxicities. Results of the phase 3 RTOG 1203 trial are needed to confirm these results.

External validation of leukocytosis and neutrophilia as a prognostic marker in anal carcinoma treated with definitive chemoradiation.

PURPOSE: To validate the prognostic value of leukocyte disorders in anal squamous cell carcinoma (SCC) patients receiving definitive concurrent chemoradiation. MATERIALS AND METHODS: Bi-institutional clinical records from consecutive patients treated between 2001 and 2015 with definitive chemoradiation for anal SCC were retrospectively reviewed. Prognostic value of pretreatment leukocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as leukocyte or neutrophil count exceeding 10G/L and 7G/L, respectively. RESULTS: We identified 133 patients, treated in two institutions. Eight% and 7% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year overall survival (OS) and progression-free survival (PFS) were 88% and 77%, respectively. In univariate analysis, both leukocytosis and neutrophilia were associated with worse OS, PFS (p<0.01), locoregional control (LRC) and Distant Metastasis Control (DMC) (p<0.05), also after stratification by each institution. In multivariate analysis, leukocytosis and neutrophilia remained as independent risk factors associated with poorer OS, PFS, LRC and DMC (p<0.05). CONCLUSION: This study validates leukocytosis and neutrophilia as independent prognostic factors in anal SCC patients treated with definitive chemoradiation. Although prospective confirmation is warranted, it is suggested that the leukocyte and neutrophil count parameters are clinically relevant biomarkers to be considered for further clinical investigations.

Chemoradiation in rectal squamous cell carcinoma: Bi-institutional case series.

BACKGROUND AND PURPOSE: Primary rectal squamous cell carcinoma (SCC) is an uncommon disease. Early reports stated that surgery is the most effective treatment. However, recent publications suggest conservative strategy with chemoradiation provides satisfactory results. PATIENTS AND METHODS: We have retrospectively studied the medical charts of 23 patients treated for a rectal SCC in two teaching hospitals in France between 1992 and 2013. Twenty-one patients received an exclusive chemoradiotherapy (CRT) and two a pre-operative CRT followed by a planned surgery. Patients received pelvic irradiation with a dose ranging from 36-45 Gy followed by a boost of 15-23 Gy. Twenty-two patients received a concurrent chemotherapy. RESULTS: After CRT, the rate of clinical complete response was 83%. With a median follow-up of 85 months, 5-year overall survival rate was 86%. Five patients presented with a relapse. The 5-year disease-free survival rate was 81%. The 5-year colostomy-free survival rate was 65%. Three patients (13%) presented with grade III-IV late rectal toxicity. CONCLUSIONS: Although retrospective, this is the largest cohort of patients treated with CRT for a rectal SCC. Exclusive CRT could result in high local control rate and prolonged survival in rectal SCC patients with a high rate of organ preservation.

Efficacy and safety of vinorelbine in heavily pretreated recurrent/metastatic head and neck squamous cell carcinoma patients.

The aim of this study was to evaluate the efficacy and tolerance of vinorelbine as a single agent in the treatment of recurrent/metastatic head and neck squamous cell carcinoma. Patients were treated with oral or intravenous vinorelbine according to the pluridisciplinary tumor board's decision. Efficacy and safety outcomes were analyzed retrospectively. Twenty-three patients were included in the study. Sixteen patients (69%) had received at least two previous lines of chemotherapy. The disease control rate was 19%. The median progression-free survival was 2.6 months and the median overall survival was 3.4 months. The rate of grade 3-4 side effects was low (13%). Only one patient discontinued treatment because of side effects. Vinorelbine seems to be a well-tolerated regimen in heavily pretreated patients. However, this regimen does not seem to be efficient enough to be recommended.

Neuronal immunoexpression and a distinct subtype of adult primary supratentorial glioblastoma with a better prognosis.

OBJECT: In this study, the authors address whether neurofilament protein (NFP) expression can be used as an independent prognostic factor in primary glioblastoma multiformes (GBMs). METHODS: Three hundred and two consecutive adult patients with newly diagnosed supratentorial primary GBMs were analyzed (January 2000-August 2008). Detailed data regarding clinical, imaging, and pathological findings, oncological treatments, and outcomes were recorded. Neurofilament protein immunoexpression served to identify NFP-positive tumor cells (normal entrapped neurons and mature ganglion-like cells excluded). RESULTS: Neurofilament-positive cells were identified in 177 GBMs (58.6%). Patients with NFP-positive GBMs were younger (p < 0.0001), and their GBMs presented with more temporal lobe tumor localization (p = 0.029) and more cortical involvement (p = 0.0003). Neurofilament-negative GBMs presented with more ventricular contact (p < 0.0001) and more tumor midline crossing (p = 0.03). Median overall survival and progression-free survival (PFS) were 13.0 and 7.6 months, respectively, for NFP-positive GBMs, and 7.0 and 5.1 months, respectively, for NFP-negative GBMs. Multivariate analysis revealed NFP immunoexpression, tumor midline crossing, complete resection, and radiotherapy combined with chemotherapy as independent factors associated with overall survival. Neurofilament protein-positive immunoexpression was associated with longer overall survival (hazard ratio [HR] 0.54, 95% CI 0.40-0.74; p < 0.0001) and longer PFS (HR 0.71, 95% CI 0.53-0.96; p = 0.02). CONCLUSIONS: Neurofilament protein-positive immunoexpression represents a strong, therapeutically independent prognostic factor for primary supratentorial GBM clinical outcome among adult patients. Neurofilament protein-GBM's unique pathological features are not only associated with distinct clinical and anatomical behavior, but are also predictive of overall patient survival and PFS. Neurofilament protein immunoexpression may help identify a distinct subgroup of primary GBMs with a favorable prognosis, which should be considered in the design of future targeted therapies.

Dynamic imaging response following radiation therapy predicts long-term outcomes for diffuse low-grade gliomas.

Quantitative imaging assessment of radiation therapy (RT) for diffuse low-grade gliomas (DLGG) by measuring the velocity of diametric expansion (VDE) over time has never been studied. We assessed the VDE changes following RT and determined whether this parameter can serve as a prognostic factor. We reviewed a consecutive series of 33 adults with supratentorial DLGG treated with first-line RT with available imaging follow-up (median follow-up, 103 months). Before RT, all patients presented with a spontaneous tumor volume increase (positive VDE, mean 5.9 mm/year). After RT, all patients demonstrated a tumor volume decrease (negative VDE, mean, -16.7 mm/year) during a mean 49-month duration. In univariate analysis, initial tumor volume (>100 cm(3)), lack of IDH1 expression, p53 expression, high proliferation index, and fast post-RT tumor volume decrease (VDE at -10 mm/year or faster, fast responders) were associated with a significantly shorter overall survival (OS). The median OS was significantly longer (120.8 months) for slow responders (post-RT VDE slower than -10.0 mm/year) than for fast responders (47.9 months). In multivariate analysis, fast responders, larger initial tumor volume, lack of IDH1 expression, and p53 expression were independent poor prognostic factors for OS. A high proliferation index was significantly more frequent in the fast responder subgroup than in the slow responder subgroup. We conclude that the pattern of post-RT VDE changes is an independent prognostic factor for DLGG and offers a quantitative parameter to predict long-term outcomes. We propose to monitor individually the post-RT VDE changes using MRI follow-up, with particular attention to fast responders.

The protective status of subtotal obliteration of arteriovenous malformations after radiosurgery: significance and risk of hemorrhage.

OBJECTIVE: Arteriovenous malformations (AVMs) treated by radiosurgery with complete obliteration of the nidus but a persisting early draining vein on follow-up angiography can be termed subtotally obliterated. However, these are persistent circulating AVMs. The significance of these lesions, their hemorrhage rate, and their management are analyzed. METHODS: In a series of 862 consecutive patients with AVMs treated by radiosurgery, 121 patients (14%) achieved subtotal obliteration (STO). The angiographic evolution and rate of obliteration were studied. The pretreatment angiographic features, dosimetric parameters, and postradiosurgery hemorrhage rate were compared with those in the rest of the treated population. Finally, the options for follow-up and treatment were analyzed. RESULTS: Of 121 subtotally obliterated AVMs, the bleeding rate was 0%; 53% of patients achieved complete obliteration. This occurred in 71% of those who had STO at 1 year. In the cases in which STO was detected at 2, 3, and 4 years, total obliteration eventually occurred in 43%, 28.5%, and 0%, respectively. Comparative analysis with AVMs in which a part of the nidus persisted showed a significant difference in the bleeding rate. Except for volume, no significant statistical difference in angiographic and dosimetric parameters was found between the STO group and the rest of the studied population with residual nidus. Six cases received further treatment, resulting in 2 cures and 2 treatment-related complications. CONCLUSION: Subtotally obliterated AVMs are different from other partially obliterated AVMs, with a 0% bleeding rate. Their complete obliteration is a function of delay of appearance on follow-up angiography. Invasive follow-up and further treatment of these AVMs do not seem warranted.

Radiosurgery with or without A 2-mm margin for 93 single brain metastases.

PURPOSE: Retrospective comparison of Linac radiosurgery (RS) in 93 single brain metastases with or without a 2-mm margin. PATIENTS AND METHODS: A total of 153 patients had Linac RS (between April 1992 and June 2004), with 139 patients (90.8%) evaluable in June 2005. Sixty-one patients (44%) had extracranial lesions and 65 patients had neurologic symptoms (47%). RS alone: 105 patients (66%); RS +whole brain radiotherapy: 34 patients (24%). Single metastasis: 93/139 patients; classic RS: 42/93 patients; 2-mm margin: 51/93 patients; 30 multiple lesions patients were excluded. TREATMENT: 15 Mv X-ray Linac, circular minibeams, 8-30 mm, four to six noncoplanar coronal arcs. Isodose was 60-80%; doses were 10-20 Gy. FOLLOW-UP: 12 months-13 years; median, 14 months. RESULTS: Local control (LC) was not improved in 51 margin patients vs. 42 classic RS patients: 1 year: 69.1% and 72.4%. Two-year LC rate: 64% and 54.7%, respectively. Survival: median classic RS: 11.3 months; margin RS, 19 months (p = 0.34) and 1 year, 41.6% and 60.2%, respectively. Margin RS patients had a significantly higher rate of severe parenchymal complications: 19.6% vs. 7.1% (p = 0.02); surgery was necessary in 4 of 51 cases vs. 1 of 42 classic RS cases. CONCLUSION: No increase of 1- and 2-year LC rate in margin RS or survival and median survival: 11.3 vs. 19 months (NS) 2-mm margin associated with more severe parenchymal complications (p = 0.02). This procedure is therefore not recommended. Late CT images and 1-mm margin as recommended by pathologists, use of three-dimensional magnetic resonance imaging and fuzzy method to calculate volumes may yield better results. Stereotactic hypofractionation requires further studies.

Microsurgery or radiosurgery for cerebral arteriovenous malformations? A study of two paired series.

OBJECTIVE: To detect parameters that may augment the therapeutic strategy in patients with a cerebral arteriovenous malformation (AVM) that is considered equally suitable for treatment by neurosurgery or radiosurgery, we compared the efficacy and risks of these two methods in a paired series with similar patient and AVM characteristics. PATIENTS AND METHODS: Two series of patients with AVM were studied, including a series of 39 patients treated using microsurgery (MS) and another series of 39 patients treated via radiosurgery (RS). These series were paired for age and sex, initial symptoms, size, location and Spetzler-Martin grade, and presence of embolization preceding treatment. We compared the posttreatment outcome in the two groups with respect to obliteration rate, neurological status, mortality rate, and recurrent bleeding. Statistical analysis was performed using paired Student's t test. RESULTS: The Glasgow Outcome Scale values and Modified Rankin Scores measured at discharge and 12 to 24 months were significantly better in the RS series than in the MS series. The obliteration rate tended to be higher in the MS series (91% versus 81%; P = 0.10, not significant), whereas the rate of neurological deficit was higher in the MS series than in the RS series (P < 0.001). The mortality rate was not significantly different in the two series, but the rate of recurrent bleeding was higher in the RS group (10% versus 0%; P = 0.04). CONCLUSIONS: Although the rate of cure was similar for patients treated with MS and RS, neurological morbidity was higher after MS and recurrent bleeding was more frequent after RS.

[PET and malignant cerebral tumors]. / La TEP dans les tumeurs malignes cérébrales.

Normal biodistribution of FDG includes intense physiologic uptake in the brain, which consumes glucose. The high background therefore makes it difficult to detect the foci taking up glucose, which correspond to malignant lesions. FDG PET is nevertheless clinically useful for detecting high-grade gliomas, cerebral lymphomas and, in some cases, unexpected brain metastases in whole-body PET examinations. As an adjunct to CT and MRI, FDG-PET can make stereotactic radiosurgery more precise in targeting primary or secondary brain cancers and can differentiate necrotic fibrosis from viable cancer tissue during follow-up in cases of abnormal or equivocal MRI results. When available, methionine-(11C) PET delineates low grade gliomas accurately. Several fluorine (18F)-labeled radiopharmaceuticals have been proposed in this setting, with FET and FDOPA apparently the most effective. Four original clinical cases illustrating performances of FET and FDOPA PET in this setting are presented.

Bleeding after radiosurgery for cerebral arteriovenous malformations.

OBJECTIVE: Obliteration is progressive after radiosurgery (RS) for cerebral arteriovenous malformation (AVM), and until it is complete, there is still a risk of hemorrhage. The aim of our study was to evaluate the severity of hemorrhage after RS, the actuarial risk of hemorrhage, and the parameters associated with hemorrhage. METHODS: Of 756 patients treated by linear accelerator RS for AVM, 51 (6.5%) had one or more hemorrhages after the RS. We studied the clinical, anatomic, and dosimetric parameters and obliteration rate before hemorrhage and then calculated the actuarial risk per patient and per hemorrhage before and after RS. Correlations between parameters and risk were studied by univariate and multivariate analysis using Kaplan-Meier hemorrhage-free survival curves and the Cox model. RESULTS: Apart from one exclusively ventricular hemorrhage, which caused the death of the patient, only parenchymal hemorrhages were associated with morbidity and neurological deficits (64.5% of all cases of hemorrhage had neurological deficits, 45% had a permanent deficit). The overall mortality rate per hemorrhage was 7.14%. The overall morbidity rate was 47.6%, 26.2% with a permanent deficit. In all but one patient, the AVM was not cured before hemorrhage; thus, the mean obliteration rate before hemorrhage was 24%. The actuarial hemorrhage rates were 3.08% per year per patient and 3.31% per year per hemorrhage. The actuarial rate per patient increased from 1.66% the 1st year to 3.87% in the 5th year after RS but was not statistically different from the rate before radiosurgery. The parameters found to be correlated with hemorrhage risk after RS using multivariate analysis were intranidal or paranidal aneurysms, complete coverage, and minimum dose. CONCLUSION: The risk of hemorrhage after RS would seem to be the sum of hemorrhage risk factors of the AVM and factors predicting a poor level of obliteration. These factors can be predicted in some cases but rarely avoided.

Radiosurgery of cerebral arteriovenous malformations in children: a series of 57 cases.

PURPOSE: To evaluate the efficacy and outcome of Linac radiosurgery (RS) as treatment of cerebral arteriovenous malformations (cAVM) in a series of 57 children. METHODS AND MATERIALS: Between 1984 and 2000, we used Linac radiosurgery to treat 792 patients with cAVM. This series included 57 children (7.2%) under the age of 15 years at the time of RS (range = 7-15 years, median = 12 years). We were able to evaluate 49 of the children (86%) by angiography, 21 boys and 28 girls (sex ratio = 0.75). First symptoms were: hemorrhage, 34 patients (69.4%); seizures, 6 patients (12.5%); headache, 6 patients (12.5%); and progressive neurologic deficit, 1 patient (2.1%). Nidus size ranged from 5 to 50 mm (median = 20 mm). Nidus volume ranged from 0.6 to 16 cc (median = 3.5 cc). Patient distribution according to Spetzler-Martin grade was as follows: Grade 1, n = 5 (11%); Grade 2, n = 18 (35%); Grade 3, n = 21 (40%,); Grade 4, n = 5 (14%); and Grade 5, n = 0%. Twenty-seven patients (55.1%) had other treatment before RS: embolization, n = 14 (31.1%); neurosurgery, n = 9 (20.5%); embolization and neurosurgery, n = 3 (6.1%). RS was performed with the system used for adults. Patients were seated in a Betti armchair. Circular 15 MV X-ray minibeams (6 to 20 mm) were delivered in coronal arcs by a GECGR Saturne 43 Linac. Planification and dosimetry were carried out using the Associated Target Methodology and Dosigray TPS dosimetric systems. The dose at the peripheral isodose (50-70%) ranged from 18 to 28 Gy. Median and mean doses were 25 Gy and 23.8 Gy. Mono-isocentric planification was used in 25 patients (53.2%) and multi-isocentric in 24 patients (2 to 5 isocenters). The overall follow-up ranged from 7 to 172 months (mean 40 months, median 34 months). RESULTS: The overall rate of obliteration (OR) was 30/49 (61.2%). Mean time to obliteration was 34 months (range = 7 to 172 months). OR varied according to nidus size and volume: OR was 80% for nidus <15 mm, 67% for nidus between 15 and 25 mm, and 42% for nidus >25 mm (p = 0.058). OR was 100% for nidus <1 cc, 73% for nidus between 1 and 4 cc, and 40% for nidus of 4 to 10 cc (p = 0.019). OR according to patient gender was 84.2% for boys and 40% for girls. OR according to minimum dose (Dmin) was 44% for Dmin < 15 Gy (p = 0.01), 89% for D min from 15 to 20 Gy, and 100% for Dmin > 20 Gy (p = 0.01). OR was 62% in nonembolized AVM and 58% in previously embolized AVM (NS). OR according to the number of isocenters was 68.2%, 55.6%, 80%, 50%, and 0% for 1, 2, 3, 4, and 5 isocenters, respectively. After multivariate analysis, only Dmin closely correlated with OR (beta = 0.462; SE = 0.244, p = 0.057). Of the 6 patients with seizures before RS, 5 (80%) were seizure-free without medication after RS. One patient died of pneumonia. MORBIDITY: Four patients (8.2%) had bleeding after RS at 39, 45, 51, and 59 months. No new neurologic deficit was found during the follow-up period. Twenty-nine patients underwent magnetic resonance imaging. Thirteen patients (44.8%) showed no parenchymal changes. Thirteen patients (44.8%) had Grade 2 changes, that is, T2 hypersignals. Two patients (6.9%) had Grade 3 changes, and 1 patient (3.4%) had Grade 4 "necrosis-like" changes. CONCLUSION: In our experience, Linac RS has proven to be a safe and effective method to treat cerebral AVM in children <15 years, whether used alone or in association with embolization and/or neurosurgery.

Results of definitive irradiation in a series of 305 epidermoid carcinomas of the anal canal.

PURPOSE: To evaluate our data concerning the prognostic factors for locoregional control, survival, late complications, and sphincter conservation in a series of epidermoid cancers of the anal canal without clinical evidence of metastasis. METHODS AND MATERIALS: Between June 1972 and January 1997, 305 patients were treated with curative-intent radiotherapy (RT). The T stage according to the 1987 International Union Against Cancer classification was T1 in 26, T2 in 141, T3 in 104, and T4 in 34. Forty-nine patients had nodal involvement at presentation. The pretreatment anal function score, according to our in-house system, was 0 for 22 patients, 1 for 182, 2 for 74, 3 for 7, and 4 for 11 patients; for 9 patients, scores were unavailable. The treatment started with external beam radiotherapy (EBRT) in 303 patients (median dose 45 Gy). After a rest period of 4-6 weeks, a boost of 20 Gy was delivered by EBRT in 279 patients and by interstitial (192)Ir brachytherapy in 17 patients. Seven patients received only one course of EBRT (mean dose 49.5 Gy), and 2 patients were treated with interstitial (192)Ir brachytherapy alone (55 Gy and 60 Gy). Concomitant chemotherapy (5-fluorouracil and either mitomycin C or cisplatin) was delivered to 19 patients. The mean follow-up was 103 months (median 84). RESULTS: At the end of RT, the local tumor clinical complete response rate was 96% for T1, 87% for T2, 79% for T3, and 44% for T4. Of the 61 locally progressive tumors, 27 (44%) were salvaged with abdominoperineal resection. The rate of local tumor relapse was 12%. Among 37 local tumor relapses, 20 (54%) were salvaged with abdominoperineal resection and one with interstitial (192)Ir brachytherapy. The overall local control rate (with or without salvage local therapy) was 84%. The local control rate with good anal function (score 0 or 1) was 56.5%. Of 181 available patients with their anus preserved, 94% had good anal function. For a subgroup of 15 patients with a tumor length of <2 cm and without nodal involvement, the clinical complete response rate after RT completion was 100%, the local control rate with or without local salvage treatment was 100%, and among 13 available patients with their anus preserved, the anal function score was good in 12 patients (92%). The 10-year disease-free survival rate was 74%. After multivariate analysis, three independent predictive factors significantly influenced disease-free survival: the interval between the two courses of RT (>38 days vs. < or =38 days, p = 0.0025), pretreatment anal function score (0 vs. 1 vs. 2 vs. 3 vs. 4, p = 4.4.10(-6)), and clinical complete response after RT completion (no complete response vs. complete response, p = 2.5.10(-14)). CONCLUSION: We confirm the excellent results with RT in T1 and T2 lesions. However, to improve survival without colostomy with good anal sphincter function, chemoradiotherapy should be preferred for tumors > or =2 cm in length and for locally advanced tumors.

Repeat linear accelerator radiosurgery for cerebral arteriovenous malformations.

PURPOSE: To evaluate repeat radiosurgery (RS2) for cerebral arteriovenous malformations (AVMs) after failure of initial radiosurgery (RS1). METHODS AND MATERIALS: Between 1986 and 2000, 41 patients underwent RS2. Nine patients were not assessable: seven had insufficient follow-up (RS2 in 1999 and 2000) and two had no recent control angiography data. Thus, 32 (78%) of 41 patients were assessed. Most lesions (29 [90%] of 32) were supratentorial: 22 (69%) on the left, 8 (25%) on the right, and 2 on the midline (6%). The patients had Spetzler-Martin Grade 1-5 (median Grade 3). The symptoms before RS1 included hemorrhage in 20 (63%), epilepsy in 10 (31%), progressive neurologic deficits in 2 (6%), and headaches in 6 (19%). Five patients had two or more symptoms. Twenty-two patients (69%) had received other treatment before RS1, including neurosurgery in 3 patients (9%) and one to six embolizations in 19 patients. At RS1, the median largest nidus dimension was 2.7 cm (range 0.8-5). The median volume was 2.7 cm(3) (range 1.2-9.9). The median time from RS1 to RS2 was 52 months (range 12-126). Between RS1 and RS2, 7 (22%) of 32 patients experienced bleeding. The same irradiation technique was used for RS1 and RS2, except for 2 patients who underwent RS2 at another institution. Circular 15-MV X-ray minibeams (range 6-20 mm) and coronal arcs were used. RS1 was monoisocentric in 75% of cases and multiisocentric in 25%. At RS2, the median largest nidus dimension was 3 cm (range 1.4-5). The median volume was 4.2 cm(3) (range 0.8-13.4). RS2 was monocentric in 72% of cases and multiisocentric in 28%. After RS2, the median follow-up was 19.5 months (range 0-79; mean 25.3). RESULTS: After RS2, the obliteration rate was 59.3% (19 of 32). The median time to arteriographic obliteration was 21 months (range 12-96). The survival rate was 97% (31 of 32). Five of the 13 patients with a nonobliterated nidus experienced complications; 3 had bleeding (9%) and 2 without prior neurologic deficits developed partially regressive neurologic deficits. One patient with a previously existing deficit developed an additional new partially regressive neurologic deficit after an episode of bleeding. Thus, 3 (9%) of 32 patients had neurologic complications. Moderate-grade parenchymal changes at MRI increased after RS2 (88.2% vs. 57.7% after RS1; p = 0.10, not significant). However, necrosis-like changes did not significantly increase. After RS1 failure, salvage may be attempted by embolization, neurosurgery, or RS2. RS2 should be considered after the second successive annual angiogram if reduction of the nidus is <25%. CONCLUSION: The results after RS2 are encouraging. A multidisciplinary approach is mandatory to reduce the initial failure rate and to choose the modality and timing of salvage treatment.

Prediction of AVM obliteration after stereotactic radiotherapy using radiobiological modelling.

This study was carried out in order to derive the radiobiological parameters of the dose-response relation for the obliteration of arteriovenous malformation (AVM) following single fraction stereotactic radiotherapy. Furthermore, the accuracy by which the linear Poisson model predicts the probability of obliteration and how the haemorrhage history, location and volume of the AVM influence its radiosensitivity are investigated. The study patient material consists of 85 patients who received radiation for AVM therapy. Radiation-induced AVM obliterations were assessed on the basis of post-irradiation angiographies and other radiological findings. For each patient the dose delivered to the clinical target volume and the clinical treatment outcome were available. These data were used in a maximum likelihood analysis to calculate the best estimates of the parameters of the linear Poisson model. The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was studied. AVM radiosensitivity was assumed to be the same for all the patients. The radiobiological model used was proved suitable for predicting the treatment outcome pattern of the studied patient material. The radiobiological parameters of the model were calculated for different AVM locations, bleeding histories and AVM sizes. The range of parameter variability had considerable effect on the dose-response curve of AVM. The correlation between the dosimetric data and their corresponding clinical effect could be accurately modelled using the linear Poisson model. The derived response parameters can be introduced into the clinical routine with the calculated accuracy assuming the same methodology in target definition and delineation. The known volume dependence of AVM radiosensitivity was confirmed. Moreover, a trend relating AVM location with its radiosensitivity was observed.