Reirradiated Patients Research Articles

Results of a pooled analysis of IOERT containing multimodality treatment for locally recurrent rectal cancer: Results of 565 patients of two major treatment centres

ObjectiveAim of this study is analysing the pooled results of Intra-Operative Electron beam Radiotherapy (IOERT) containing multimodality treatment of locally recurrent rectal cancer (LRRC) of two major treatment centres. Methods and materialsFive hundred sixty five patients with LRRC who underwent multimodality-treatment up to 2010 were studied. The preferred treatment was preoperative chemo-radiotherapy, surgery and IOERT. In uni- and multivariate analyses risk factors for local re-recurrence, distant metastasis free survival, relapse free survival, cancer-specific survival and overall survival were studied. ResultsTwo hundred fifty one patients (44%) underwent a radical (R0) resection. In patients who had no preoperative treatment the R0 resection rate was 26%, and this was 43% and 50% for patients who respectively received preoperative re-(chemo)-irradiation or full-course radiotherapy (p < 0.0001). After uni- and multivariate analysis it was found that all oncologic parameters were influenced by preoperative treatment and radicality of the resection. Patients who were re-irradiated had a similar outcome compared to patients, who were radiotherapy naive and could undergo full-course treatment, except the chance of local re-recurrence was higher for re-irradiated patients. Waiting-time between preoperative radiotherapy and IOERT was inversely correlated with the chance of local re-recurrence, and positively correlated with the chance of a R0 resection. ConclusionsR0 resection is the most important factor influencing oncologic parameters in treatment of LRRC. Preoperative (chemo)-radiotherapy increases the chance of achieving radical resections and improves oncologic outcomes. Short waiting-times between preoperative treatment and IOERT improves the effectiveness of IOERT to reduce the chance of a local re-recurrence.

Reirradiation for second primary or recurrent cancers of the head and neck: Dosimetric and outcome analysis.

The purpose of this study was to examine outcomes, toxicity, and dosimetric characteristics of patients treated with reirradiation for head and neck cancers. Fifty patients underwent ≥2 courses of radiation therapy (RT) postoperatively or definitively with or without chemotherapy. Composite dose volume histograms (DVHs) for selected anatomic structures were correlated with grade ≥3 late toxicity. Median initial and retreatment radiation dose was 64 and 60 Gy, respectively. Median overall survival (OS), progression-free survival (PFS), and 1-year PFS rates were 18 months, 11 months, and 45%, respectively, with 13 months median follow-up. Thirty-four percent of patients experienced grade ≥3 late toxicity with 1 death from carotid blowout. The DVH corresponding to the carotid blowout fell above the third quartile compared with other patients. Our analysis is the first to systematically evaluate the dose to the carotid artery using composite dosimetry in head and neck reirradiation patients, and demonstrates a promising technique for evaluating the dose to other normal tissue structures. © 2015 Wiley Periodicals, Inc. Head Neck 38: E961-E969, 2016.

Re-resection for recurrent high-grade glioma in the setting of re-irradiation: more is not always better.

The optimal treatment for patients with recurrent high grade glioma (HGG) remains controversial. Available therapies include surgery, re-irradiation, alternating electric fields or systemic therapy. Here we investigate whether re-resection will improve survival in patients receiving repeat radiotherapy for tumor recurrence. 231 consecutive patients with recurrent HGG treated with re-irradiation between 1994 and 2012 were analyzed. 105 patients underwent re-resection. Re-irradiation was delivered using daily fractions of 3.5Gy to a median total dose of 35Gy. Survival was then analyzed comparing patients with and without re-resection. Overall survival (OS) and survival from the first recurrence are reported. Univariate and cox-proportional hazard modeling was performed in a step-wise multivariate analysis using known prognostic factors. The median follow-up time from initial diagnosis was 25.7months. The median OS from initial diagnosis of the entire group was 22.5months. There was no significant difference in median overall survival between patients who received re-resection versus no re-resection, 23 versus 21.9months respectively (p=0.6). Additionally, there was no difference in median survival from the time of first recurrence 10.5months without re-resection versus 11.1months with re-resection (p=0.09). After adjusting for known prognostic variables, only age remained significant. Re-irradiation is an effective salvage therapy for patients with localized, progressive high grade glioma, achieving a median survival of 10-11months from re-irradiation. Our data reveals no significant improvement in survival with the addition of re-resection to re-irradiated patients with HGG.

Volumetric modulated arc therapy versus 3D conformal radiotherapy for selected childhood neoplasms

AbstractAimThe comparative study of the plan quality between volumetric modulated arc therapy (VMAT) and 3D conformal therapy (3DCRT) for the treatment of selected representative childhood neoplasms was performed.Materials and methodsDuring the year 2013, 44 children with neoplasms were irradiated using VMAT. The 3DCRT plans were created retrospectively and compared with the VMAT plans for four tumour locations. The conformity parameters, dose volume histograms for target volume and organs at risk, number of monitor units and time used to deliver the single fraction were evaluated and compared for each plan. Additionally, for patients with brain tumour the comparison of different arcs configuration was made.ResultsVMAT modality presented the superiority over older conformal methods with regard to the improvement in the dose conformity and normal tissue sparing. The noncoplanar arcs arrangement was beneficial in the decrease of high-dose volume and the protection of the organs at risk located oppositely to the target volume.FindingsVMAT could be preferred technique for treating childhood neoplasms, especially when the complex-shaped target volume is localised close to the critical structures. The noncoplanar arcs arrangement could be the method of choice in the reirradiated patients and in these with laterally located brain tumours.

PT-01 * THE IMPACT OF INITIAL RADIATION IN INFANTS AND THE RE-IRRADIATION OF RECURRENT DISEASE ON THE SURVIVAL OF EPENDYMOMA PATIENTS AT THE HOSPITAL FOR SICK CHILDREN, TORONTO

BACKGROUND: Two significant changes in the management of ependymoma have taken place since 1990 at The Hospital for Sick Children, Toronto; the up-front irradiation of infants and the re-irradiation of recurrent disease. This study retrospectively reviews the impact of these changes on survival. METHODS: A retrospective case note analysis of children treated for ependymoma between 1990 and 2014 was undertaken. Survival was determined using the Kaplan Meier method. RESULTS: 76 ependymoma patients were identified with a median age of 4.58 years (0.42-17.6) including 31 infants < 3 years old (median age 1.51 years (0.42-2.97)). 45 (59.2%) were male and 31 (40.8%) were female. The majority (56 (73.7%)) were grade III histology and most (56 (73.7%)) were located within the posterior fossa. The median progression free survival (PFS) and overall survival (OS) was 41 months (95% CI 20.4-61.7) and 116 months (95% CI 63.5-169.4) respectively. 5 year PFS and OS were 43.3% and 59.3% respectively. 21 infants received up-front radiation and 10 received chemotherapy only. 5 year PFS and OS were significantly higher in irradiated compared to non-irradiated infants (PFS: 52.9% versus 0% (p = 0.000002), OS: 74.6% versus 30.0% (p = 0.004)). 38 patients recurred of which 26 were previously irradiated.19 patients received re-irradiation on recurrence whereas 7 did not. 5 year OS was significantly higher in the re-irradiated patients at 71.8% compared to 0% in the non re-irradiated patients (p = 0.00007). Both management strategies were consistently implemented from 2004. Patients treated pre (n = 34) and post (n = 42) 2004 showed a significant improvement in 5 year PFS from 33.4% to 53.3% (p = 0.037) and OS from 51.2% to 79.2% (p = 0.02). CONCLUSIONS: Both radiation of infants as the initial management of ependymoma and re-irradiation of recurrent ependymoma significantly improve survival. Implementing these treatment strategies has resulted in significant improvement in progression free and overall survival for ependymoma patients.

Reirradiation of recurrent medulloblastoma: does clinical benefit outweigh risk for toxicity?

Patients with recurrent medulloblastoma (MB) have a dismal prognosis. There has been a reluctance to use radiation in the salvage therapy regimens for these patients because of concerns about toxicity and unknown efficacy. Comparing survival outcomes and toxicities in relapsed patients treated with and without radiation may help to define its role. A retrospective review was conducted that included 38 patients with recurrent MB treated with similar risk-adapted therapy at initial diagnosis; reirradiation was a component of salvage therapy in 14. Overall survival (OS) and toxicity were evaluated according to the use of radiation, prior risk stratification, and other factors. For relapsed standard-risk patients, the use of additional irradiation resulted in a statistically significant improvement in OS from initial diagnosis (P = .036), with 5- and 10-year OS rates of 55% ± 14% and 33% ± 16% versus 46% ± 14% and 0% for reirradiated patients versus others, respectively. Similar improvement was observed in high-risk patients (P = .003). There was an association between the use of additional irradiation and an increased rate of necrosis as determined by neuroimaging (P = .0468). The use of irradiation as a component of salvage therapy for relapsed MB may prolong survival. The benefit appears to be greatest for relapsed standard-risk patients.

Re-irradiation and bevacizumab in recurrent high-grade glioma: an effective treatment option

Re-irradiation has been shown to be a meaningful option for recurrent high-grade glioma (HGG) patients. Furthermore, bevacizumab exerts certain activity in combination with chemotherapy/as monotherapy and was safely tested in combination with radiotherapy in several previous studies. To our knowledge, this is the largest cohort of patients treated with both re-irradiation and bevacizumab to date. After receiving standard radiotherapy (with or without TMZ) patients with recurrent HGG were treated with bevacizumab (10mg/kg intravenously at d1 and d15) during re-irradiation. Median prescribed radiation dose during re-treatment was 36Gy, conventionally fractionated. Datasets of 71 re-irradiated patients were retrospectively analyzed. Patients either received bevacizumab (N=57) or not (N=14; other substances (N=4) and sole radiation (N=10)). In patients receiving bevacizumab, both post-recurrence survival (PRS) (median 8.6 vs. 5.7months; p=0.003, log-rank test) and post-recurrence progression-free survival (PR-PFS, 5.6 vs. 2.5months; p=0.005, log-rank test; PFS-6 42.1% for the bevacizumab group) were significantly increased which was confirmed by multivariate analysis. KPS, re-surgery, MGMT methylation status, sex, WHO grade, tumor volume and age were no significant predictors for neither PR-PFS nor PRS (univariate analysis). Re-irradiation with bevacizumab remains a feasible and highly effective treatment schedule. Studies on further salvage strategies and timing of sequential treatment options versus observation are warranted.

Vaginal tolerance of CT based image-guided high-dose rate interstitial brachytherapy for gynecological malignancies

BackgroundPurpose of this study was to identify predictors of vaginal ulcer after CT based three-dimensional image-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for gynecologic malignancies.MethodsRecords were reviewed for 44 female (14 with primary disease and 30 with recurrence) with gynecological malignancies treated with HDR-ISBT with or without external beam radiation therapy. The HDR-ISBT applicator insertion was performed with image guidance by trans-rectal ultrasound and CT.ResultsThe median clinical target volume was 35.5 ml (2.4-142.1 ml) and the median delivered dose in equivalent dose in 2 Gy fractions (EQD2) for target volume D90 was 67.7 Gy (48.8-94.2 Gy, doses of external-beam radiation therapy and brachytherapy were combined). For re-irradiation patients, median EQD2 of D2cc for rectum and bladder, D0.5cc, D1cc, D2cc, D4cc, D6cc and D8cc for vaginal wall was 91.1 Gy, 100.9 Gy, 260.3 Gy, 212.3 Gy, 170.1 Gy, 117.1 Gy, 105.2 Gy, and 94.7 Gy, respectively. For those without prior radiation therapy, median EQD2 of D2cc for rectum and bladder, D0.5cc, D1cc, D2cc, D4cc, D6cc and D8cc for vaginal wall was 56.3 Gy, 54.3 Gy, 147.4 Gy, 126.2 Gy, 108.0 Gy, 103.5 Gy, 94.7 Gy, and 80.7 Gy, respectively. Among five patients with vaginal ulcer, three had prior pelvic radiation therapy in their initial treatment and three consequently suffered from fistula formation. On univariate analysis, re-irradiation and vaginal wall D2cc in EQD2 was the clinical predictors of vaginal ulcer (p = 0.035 and p = 0.025, respectively). The ROC analysis revealed that vaginal wall D2cc is the best predictor of vaginal ulcer. The 2-year incidence rates of vaginal ulcer in the patients with vaginal wall D2cc in EQD2 equal to or less than 145 Gy and over 145 Gy were 3.7% and 23.5%, respectively, with a statistically significant difference (p = 0.026).ConclusionsRe-irradiation and vaginal D2cc is a significant predictor of vaginal ulcer after HDR-ISBT for gynecologic malignancies. Three-dimensional image-guided treatment planning should be performed to ensure adequate target coverage while minimizing vaginal D2cc in order to avoid vagina ulcer.

Role of radiation therapy in the conservative management of sarcoma within an irradiated field

To report on clinical outcome and toxicity profile after combined treatment that included radiation therapy (RT) in patients with localized sarcoma within an irradiated field. Individual clinical data from all consecutive patients diagnosed and treated for a localized SIF between January 2000 and October 2011 at the Institut Claudius Regaud, Toulouse, France, were retrospectively reviewed. Outcomes of patients with SIF who underwent adjuvant or definitive radiotherapy were compared with patients who did not receive further RT. Of the 27 patients eligible for this study: surgery alone (S), surgery followed by RT (S + RT) or definitive RT (RT) was performed in 16, 8 and 2 cases respectively. The rate of unresectable, gross or microscopically positive margin disease among the 10 re-irradiated patients was significantly higher than the non re-irradiated group (90% vs. 12% p < 0.001). After a median follow-up of 3.8 years, there was a trend toward longer survival and better local control in the subgroup of patients who received adjuvant or definitive RT compared to the rest of the cohort with an acceptable toxicity profile. The 4-year relapse free survival rates of patients treated with and without RT were 53% and 27% respectively (p = 0.09). SIF complete surgical resection is often difficult to achieve, enhancing the risk of relapse. RT should be discussed in case of unresectable tumor or after suboptimal surgery as part of intensified local management that has a curative intent.

Efficacy of Reirradiation for Patients With Recurrent High-grade Glioma

Efficacy of Reirradiation for Patients With Recurrent High-grade Glioma

Second course of proton beam therapy for recurrent uveal melanoma

AbstractPurpose To evaluate the outcomes of patients with recurrent uveal melanoma, treated by a second course of fractionated proton beam therapy (PBT) or by enucleationMethods Tumor recurrence was documented in 54 patients treated with PBT for uveal melanoma. Of these patients, 26 received a second course of PBT and 22 underwent enucleation. The mean patient age was 60,4 years (range, 27–85 years). Among patients with recurrence, the mean followup time was 5,8 years (range, 6 months–16,4 years). The mean visual acuity was 4,5/10 initially. All patients received 60 cobalt Gray equivalent for both courses. 24 recurrences occurred at the margin. The tumor regrowth was within the irradiated area in 17 patients (global recurrence), through the sclera in 4 patients (extra sclera extension), and completely outside the irradiated area in 9 patients.Results The 5‐year cumulative rate of local recurrence after the second treatment was 7,69 % (2 patients among 26 reirradiation). There had 5 enucleations (19,3%) among 26 reirradiations. A third of reirradiated patients maintained useful vision after a second course of PBT : 39% had 20/200 vision or better after the second treatment. The Kaplan‐Meier overall survival rate is better with Proton Beam Therapy (PBT) VS Enucleation ( p&lt;0,02)Conclusion A second course of PBRT for recurrent uveal melanoma was associated with a relatively good probability of local control and a low enucleation rate. This retrospective analysis suggests that survival in reirradiated patients is not compromised by administration of a second course of PBT for recurrent uveal melanoma.

Survival Benefit for Pediatric Patients With Recurrent Ependymoma Treated With Reirradiation

The outcome of recurrent ependymoma in children is dismal. Reirradiation has been proposed as an effective modality for ependymoma at relapse. However, the toxicity and outcome benefits of this approach have not been well established. We conducted a retrospective population-based study of all patients with recurrent ependymoma treated between 1986 and 2010 in our institution. Demographic, treatment, and outcome data were analyzed for the entire cohort. Of 113 patients with intracranial ependymoma, 47 patients relapsed. At the time of relapse, 29 patients were treated with surgical resection and/or chemotherapy, and 18 patients received full-dose (≥ 54 Gy focal and/or craniospinal) reirradiation with or without surgery at recurrence. Reirradiation was tolerated well with no severe acute complications noticed. Three-year overall survival was 7% ± 6% and 81% ± 12% for nonreirradiated and reirradiated patients, respectively (p < 0.0001). Time to second progression after reirradiation was significantly longer than time to first progression. This surprising phenomenon was associated with improved progression-free survival for tumors with evidence of DNA damage (n = 15; p = 0.002). At a mean follow-up of 3.73 years, only 2/18 patients had endocrine dysfunction, and 1 patient required special education support. However, a decline in intellectual function from pre- to postreirradiation assessment was observed. Reirradiation is an effective treatment that may change the natural history of recurrent ependymoma in children. However, this change may be associated with increased neurocognitive toxicity. Additional follow-up is needed to determine the risk of late recurrence, secondary radiation-induced tumors, and long-term functional outcome of these patients.

Reirradiation in head and neck cancers

Salvage surgery is the mainstay of treatment for recurrences or secondary primary tumors in areas that were irradiated earlier. However, locoregional recurrence remains the main cause of death after surgery. Adjuvant reirradiation dramatically reduces locoregional recurrences but the risk-benefit ratio seems to be advantageous mostly for residual microscopic disease. In contrast, the rate of distant metastasis among reirradiated patients indicates that the local treatment alone is not sufficient. Full-dose exclusive chemo-reirradiation (over 60 Gy) can cure a subset of patients when surgery is not feasible. However, reirradiation is associated with a significant rate of severe toxicity and should, therefore, be compared with chemotherapy in randomized trials. Accrual may be difficult because of selection biases such as tumor volume, small volumes (largest axis less than 3-4 cm) being more likely to be irradiated. In addition, patients in poor general condition with severe comorbidities, organ dysfunction, or incomplete healing after salvage surgery, are unlikely to benefit from reirradiation. Noteworthy volumes to be reirradiated must be established between the head and neck surgeon and the radiation oncologist: the definition of the clinical target volume should be taken into account, the natural history of recurrent tumors, especially with regard to extension modalities, and the absence of strict correlation between imaging and histological real extension. This is even more critical with the advent of new irradiation techniques. Chemotherapy associations and new radiosensitizing agents are also under investigation. Comparison between reirradiation modalities is difficult because most trials are phase 2 mono-institutional trials. As selection of patients is a key issue, only phase 3 multiinstitutional trials can provide definitive results.

Reirradiation of metastatic spinal cord compression: Definitive results of two randomized trials

PurposeIncidence, outcome and prognostic factors of metastatic spinal cord compression (MSCC) patients reirradiated for in-field recurrence were analyzed. Radiation therapists’ attitude in reirradiate spinal cord relapses, doses adopted and incidence of myelopathy were also examined. Materials and methodsData deriving from 579 evaluable patients entered two randomized trials on radiotherapy (RT) for MSCC were revised. ResultsTwenty-four (4.15%) patients had an in-field recurrence and 12 (50%) were reirradiated. At the time of analysis all reirradiated patients had died. Median time from first and second RT was 5months (range, 2–31). Six patients received an 8Gy single-dose, 2 patients 5×3Gy and remaining four patients 2×8, 5×4, or a single dose of 7 and 4Gy, respectively. The median cumulative Biologically Effective Dose (BED) calculated was 114.5Gy2 (range, 80–120Gy2). Six of seven (85.7%) ambulant patients maintained walking ability, whereas none of five not ambulant patients recovered the function. Median duration of response was 4.5 months (range, 1–24). The effect of reirradiation on motor function was significantly associated with walking capacity before reirradiation. Myelopathy was never recorded. ConclusionsIn MSCC reirradiation was safe and effective. Patient walking capacity before reirradiation was the strongest prognostic factor for functional outcome. Reirradiation was given in about one-half of patients with in-field recurrence and different doses and fractionations were used, even though cumulative BED was in all cases ⩽120Gy2.

Mature results of a phase I trial of bortezomib, cisplatin, and radiotherapy for advanced or recurrent head and neck cancer.

5560 Background: Proteasome inhibitor bortezomib (VELCADE) has radiosensitzing properties and preclinical activity against head and neck cancer (HNC). A phase I trial of bortezomib, cisplatin, and radiotherapy (XRT) for advanced or recurrent HNC was conducted. Methods: Eligible patients had locoregionally advanced or recurrent HNC, with disease states for which no standard chemo-XRT regimen exists (e.g. reirradiation or salivary gland cancer). Patients had performance status 0 or 1, good hematologic and renal reserve, and no pre-existing grade >2 peripheral neuropathy. XRT was given once daily for at least 2 weeks. Cisplatin was given once weekly at 30 mg/m2/wk. Bortezomib was given on days 1, 4, 8, and 11 of a 21-day cycle, starting day 1 of XRT. The initial starting dose of bortezomib was 0.7 mg/m2, with planned escalation levels of 1.0 mg/m2 and 1.3 mg/m2. Dose escalation was performed after patients at the previous dose level were assessed > 30 days to rule out any dose limiting toxicity (DLTs), defined as grade 4-5 toxicity or grade 3 toxicity attributable to bortezomib that required hospitalization. Results: 27 patients with previously untreated local-regionally advanced (10 patients) or recurrent/previously irradiated (17 patients) HNC were enrolled. All patients completed XRT as planned (median 60.8 Gy); the median number of doses of bortezomib received was 7. There were no grade 5 toxicities. There were no DLTs in 7 patients enrolled in dose level I (0.7 mg/m2), and one DLT of grade 4 neutropenia in 10 patients enrolled in dose level II (1.0 mg/m2; re-irradiation). In dose level III (1.3 mg/m2), 2 DLT's occurred in 10 patients (asymptomatic grade 4 thrombocytopenia, both re-irradiation). grade 3 toxicities were common at all dose levels (17 of 27 evaluable patients), with most attributable to XRT/cisplatin (e.g. mucositis) and not considered DLTs. There was no clinically significant peripheral neuropathy (grade >2). At a median 7.3 month follow-up, 8 patients (30%) are without progression. Conclusions: Bortezomib in combination with XRT and weekly cisplatin is feasible and active. MTD was reached at 1.3 mg/m2 for radiation-naive patients and 1.0 mg/m2for re-irradiation patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium

Uveal Melanoma Recurrence After Fractionated Proton Beam Therapy: Comparison of Survival in Patients Treated With Reirradiation or With Enucleation

To retrospectively compare survival in recurrent uveal melanoma, between patients treated by enucleation or by a second course of fractionated proton beam therapy (PBT). Tumor recurrence was documented in 73 patients treated with PBT for uveal melanoma. Of the patients, 31 received a second course of PBT and 42 underwent enucleation. The mean patient age was 56 and 61 years for those undergoing enucleation and those undergoing reirradiation, respectively. Both primary and recurrent tumors were larger in patients undergoing enucleation. Tumor location and the presence or absence of ciliary body involvement did not differ significantly between the groups. The median follow-up after enucleation and after re-treatment was 79 and 59 months, respectively. Cumulative rates of outcomes and differences in rates between the reirradiated and enucleation groups were calculated by the Cox proportional hazards model and the log-rank test, respectively. The median survival duration in the enucleated and reirradiated groups was 42 and 90 months, respectively. The median time free of metastases was 38 months in enucleated patients and 97 months in reirradiated patients. At 5 years after enucleation and after reirradiation, the probability of overall survival was 36% and 63%, respectively (p=0.040, log-rank test); the probability of freedom from metastases was 31% and 66%, respectively (p=0.028, log-rank test). These differences persisted after adjustment for recurrent tumor largest diameter and volume at the time of reirradiation or enucleation. This retrospective analysis suggests that survival in reirradiated patients is not compromised by administration of a second course of PBT for recurrent uveal melanoma.

Phase I Study of Bevacizumab Added to Fluorouracil- and Hydroxyurea-Based Concomitant Chemoradiotherapy for Poor-Prognosis Head and Neck Cancer

We conducted a phase I dose escalation study to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of bevacizumab, when added to the standard FHX (fluorouracil [FU], hydroxyurea [HU], radiation) chemoradiotherapy platform in poor-prognosis head and neck cancer (HNC) patients. Patients with recurrent, previously radiated or poor-prognosis, treatment-naive HNC were eligible. Treatment was repeated every 14 days for seven cycles: Bevacizumab was escalated 2.5 to 10 mg/kg, FU 600 to 800 mg/m(2) (120 hours continuous infusion), and hydroxyurea from 500 to 1,000 mg (twice daily for 5 days), starting day 1. At the MTD, the cohort was expanded. Forty-three patients were treated. DLT was reached at level 3 (bevacizumab 5 mg/kg, FU 800 mg/m(2), HU 1,000 mg) with two grade 3 transaminase elevations and one grade 4 neutropenia, attributed to the combination of chemotherapy with bevacizumab. For level 4, chemotherapy doses were reduced (FU 600 mg/(2), HU 500 mg), and bevacizumab escalation continued to 10 mg/kg. Treatment of six assessable patients resulted in one venous thrombosis; this dose level was expanded to 26 patients. Late complications included five patients with fistula formation (11.6%) and four with ulceration/tissue necrosis (9.3%). Serious toxicities (hemorrhage/thrombosis/death) were comparable to prior reirradiation reports. Median overall survival for reirradiated patients with recurrent, nonmetastatic disease was 10.3 months [95% CI, 5.6 to 13.5]; 2-year cumulative incidence of death resulting from disease was 51.7% (95% CI, 31.7 to 68.5). Bevacizumab can be integrated with FHX chemoradiotherapy at a dose of 10 mg/m(2) every 2 weeks with decreased chemotherapy doses because of neutropenia. The regimen shows antitumor activity. Observed fistula formation/tissue necrosis may be bevacizumab related, and further investigation should proceed with careful monitoring.

Preliminary Report of Pulsed Dose Rate Brachytherapy in Head-and-Neck Cancer

To assess the feasibility and acute/delayed toxicity of pulsed-dose-rate brachytherapy (PDR BT) in head-and-neck tumors. 45 head and neck cancer patients underwent interstitial or contact PDR BT at a dose of 10.2-70 Gy (median, 70 Gy) and 0.6 or 1.0 Gy/pulse/h. 42 patients were administered BT as part of their curative treatment; 32 of them had sole BT. Three reirradiated patients with recurrent tumor had palliative BT. PDR BT was well tolerated. Intense bleeding was the only complication associated with catheter removal from the tongue and bucca. 44 patients who completed BT experienced acute mucositis. Grade 3 toxicity of skin and oral mucosa occurred in three (6.8%) and six patients (13.6%), respectively. At a median follow-up of 22 months (range, 2-67 months), late serious toxicity (grade 4, for soft tissue and bone) was seen in seven patients (15.9%). Among the parameters analyzed, only dental care performed before BT had a significant impact on mucosal side effects. Acute severe mucositis was observed in 23% of patients without dental care compared to 0% of those with dental care (p=0.044). Late severe mucositis occurred in 17.7% and 26.9% of the respective patients (p=0.035), overall in 23%. The larger the volume encompassed by the reference isodose, the more late (p=0.004) mucosal reactions were observed. PDR BT continued over a few days is a feasible and safe approach in head-and-neck tumors; however, it is accompanied by some toxicity. Dental care should precede isotope application.

Intensity-Modulated Radiotherapy for Complex-Shaped Meningioma of the Skull Base: Long-Term Experience of a Single Institution

We analyzed our long-term experience with intensity-modulated radiotherapy (IMRT) in patients with complex-shaped meningioma of the skull base. Between January 1998 and December 2004, 94 patients with complex-shaped meningioma were treated using IMRT at our institution. Tumor distribution was: World Health Organization (WHO) Grade 1 in 54.3%, WHO Grade 2 in 9.6%, and WHO Grade 3 in 4.2%. In 31.9% of patients, the clinical and radiologic characteristics of the tumor were consistent with the diagnosis of meningioma. Twenty-six patients received radiotherapy as primary treatment and 14 patients postoperative for residual disease. Fifty-four patients were treated after local recurrence. Median target volume was 81.4 mL, median total dose was 57.6 Gy given in 32 fractions. Median follow-up was 4.4 years. Overall local control was 93.6%. Sixty-nine patients had stable disease based on computed tomography/magnetic resonance imaging (MRI), whereas 19 had a tumor volume reduction after IMRT. Six patients showed local tumor progression on MRI 22.3 months' median after IMRT. Three patients died from non-treatment-related conditions after IMRT. In 39.8% of the patients, preexisting neurologic deficits improved. Worsening of preexisting neurologic symptoms was seen in 4 patients and 2 patients developed new clinical symptoms from local tumor progression. Transient side effects such as headache were seen in 7 patients. Treatment-induced loss of vision was seen in 1 of 53 reirradiated patients with a Grade 3 meningioma 9 months after retreatment with IMRT. These data demonstrate that IMRT is an effective and safe treatment modality for long-term local control of complex-shaped and otherwise difficult to treat meningioma.

487 ORAL The VEGF-R tyrosine kinase inhibitor ZD6474 enhanced the anti-tumoural effects of temozolomide in the intracerebral BT4C rat glioma model

Incidence, outcome and prognostic factors of metastatic spinal cord compression (MSCC) patients reirradiated for in-field recurrence were analyzed. Radiation therapists’ attitude in reirradiate spinal cord relapses, doses adopted and incidence of myelopathy were also examined.Data deriving from 579 evaluable patients entered two randomized trials on radiotherapy (RT) for MSCC were revised.Twenty-four (4.15%) patients had an in-field recurrence and 12 (50%) were reirradiated. At the time of analysis all reirradiated patients had died. Median time from first and second RT was 5 months (range, 2–31). Six patients received an 8 Gy single-dose, 2 patients 5 × 3 Gy and remaining four patients 2 × 8, 5 × 4, or a single dose of 7 and 4 Gy, respectively. The median cumulative Biologically Effective Dose (BED) calculated was 114.5 Gy2 (range, 80–120 Gy2). Six of seven (85.7%) ambulant patients maintained walking ability, whereas none of five not ambulant patients recovered the function. Median duration of response was 4.5 months (range, 1–24). The effect of reirradiation on motor function was significantly associated with walking capacity before reirradiation. Myelopathy was never recorded.In MSCC reirradiation was safe and effective. Patient walking capacity before reirradiation was the strongest prognostic factor for functional outcome. Reirradiation was given in about one-half of patients with in-field recurrence and different doses and fractionations were used, even though cumulative BED was in all cases ⩽120 Gy2.