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Biomedical subjects

John B Fiveash

Publications and source records attributed to John B Fiveash.

17 recordsLinked to original sources
PubMed2006

Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma.

PURPOSE: TM-601 binds to malignant brain tumor cells with high affinity and does not seem to bind to normal brain tissue. Preclinical studies suggest that iodine-131 (131I) -TM-601 may be an effective targeted therapy for the treatment of glioma. We evaluated the safety, biodistribution, and dosimetry of intracavitary-administered 131I-TM-601 in patients with recurrent glioma. PATIENTS AND METHODS: Eighteen adult patients (17 with glioblastoma multiforme and one with anaplastic astrocytoma) with histologically documented recurrent glioma and a Karnofsky performance status of > or = 60% who were eligible for cytoreductive craniotomy were enrolled. An intracavitary catheter with subcutaneous reservoir was placed in the tumor cavity during surgery. Two weeks after surgery, patients received a single dose of 131I-TM-601 from one of three dosing panels (0.25, 0.50, or 1.0 mg of TM-601), each labeled with 10 mCi of 131I. RESULTS: Intracavitary administration was well tolerated, with no dose-limiting toxicities observed. 131I-TM-601 bound to the tumor periphery and demonstrated long-term retention at the tumor with minimal uptake in any other organ system. Nonbound peptide was eliminated from the body within 24 to 48 hours. Only minor adverse events were reported during the 22 days after administration. At day 180, four patients had radiographic stable disease, and one had a partial response. Two of these patients further improved and were without evidence of disease for more than 30 months. CONCLUSION: A single dose of 10 mCi 131I-TM-601 was well tolerated for 0.25 to 1.0 mg TM-601 and may have an antitumoral effect. Dosimetry and biodistribution from this first trial suggest that phase II studies of 131I-TM-601 are indicated.

Adult↗
PubMed2006

Preoperative radiation therapy with selective dose escalation to the margin at risk for retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcomas (RPSs) are rare tumors with poor survival rates due to difficult resectability and high local and distant recurrence rates. Preoperative radiation therapy appears to have dosimetric advantages to utilize the tumor as a tissue expander to limit exposure of small bowel to higher radiation doses. METHODS: Between June 1999 and December 2003, 16 consecutive patients with biopsy-proven RPS were treated with preoperative radiation with selective dose escalation. This included 45 grays (Gy) in 25 fractions to the entire tumor plus margin and a boost dose of 57.5 Gy to the volume predicted as high risk for positive surgical margins. Treatment toxicity and local control were evaluated prospectively as primary endpoints. The secondary goal was the theoretical calculation of future dose escalation and feasibility. Each patient underwent laparotomy. Tumor response was judged using computed tomography (CT) scan and by necrosis on final pathology. Theoretical treatment plans evaluated the potential for additional radiation dose escalation. RESULTS: All patients completed the radiation protocol. The most common acute side effects were nausea/vomiting, which affected 4 patients (25%), with only 1 patient requiring inpatient intravenous hydration. There was no severe late postoperative morbidity or mortality. Twelve tumors (75%) decreased in maximum dimension, with a median decrease of 9.4%. Fourteen of 16 patients (88%) underwent complete macroscopic resection. With a median follow-up of 28 months (range, 7-52 months), there were only 2 local recurrences. The actuarial 2-year local control rate was 80%. Theoretical treatment plans suggest that significant dose escalation (up to 80 Gy) may be possible. CONCLUSIONS: Preoperative radiation therapy with selective dose escalation to the margin at risk is tolerable and allows higher radiation dose to the volume judged to be at greatest risk for local tumor recurrence.

Adult↗
PubMed2006

Phase I trial of erlotinib with radiation therapy in patients with glioblastoma multiforme: results of North Central Cancer Treatment Group protocol N0177.

PURPOSE: To evaluate the toxicity and maximum tolerated dose (MTD) of erlotinib plus radiation therapy (RT) in patients with glioblastoma multiforme (GBM) in a multicenter phase I trial. METHODS AND MATERIALS: Patients were stratified on the basis of the use of enzyme-inducing anticonvulsants (EIACs). After resection or biopsy, patients were treated with erlotinib for 1 week before concurrent erlotinib and 6 weeks (60 Gy) of RT and maintained on erlotinib until progression. The erlotinib dose was escalated in cohorts of 3 starting at 100 mg/day. RESULTS: Twenty patients were enrolled and 19 were evaluable for the MTD and efficacy endpoints. Of these patients, 14 were males and 5 were females, with a median age of 54 years. Seven had undergone biopsy only, 5 had subtotal resections, and 7 had gross total resections. The highest dose level was 150 mg/day erlotinib for patients not on EIACs (Group 1) and 200 mg/day for patients on EIACs (Group 2). MTD was not reached in either group. In Group 1 at 100 mg (n=6) and at 150 mg (n=4), only 1 dose-limiting toxicity (DLT) occurred (stomatitis at 100 mg). No DLTs have occurred in Group 2 at 100 mg (n=3), 150 mg (n=3), and 200 mg (n=3). With a median follow-up of 52 weeks, progression was documented in 16 patients and 13 deaths occurred. Median time to progression was 26 weeks, and median survival was 55 weeks. CONCLUSION: Toxicity is acceptable at the current doses of erlotinib plus RT. The study was modified to include concurrent and adjuvant temozolomide, and accrual is in progress.

Adult↗
PubMed2006

Dosimetric and radiobiological impact of dose fractionation on respiratory motion induced IMRT delivery errors: a volumetric dose measurement study.

Respiratory motion can introduce substantial dose errors during IMRT delivery. These errors are difficult to predict because of the nonsynchronous interplay between radiation beams and tissues. The present study investigates the impact of dose fractionation on respiratory motion induced dosimetric errors during IMRT delivery and their radiobiological implications by using measured 3D dose. We focused on IMRT delivery with dynamic multileaf collimation (DMLC-IMRT). IMRT plans using several beam arrangements were optimized for and delivered to a polystyrene phantom containing a simulated target and critical organs. The phantom was set in linear sinusoidal motion at a frequency of 15 cycles/min (0.25 Hz). The amplitude of the motion was +/- 0.75 cm in the longitudinal direction and +/- 0.25 cm in the lateral direction. Absolute doses were measured with a 0.125 cc ionization chamber while dose distributions were measured with transverse films spaced 6 mm apart. Measurements were performed for varying number of fractions with motion, with respiratory-gated motion, and without motion. A tumor control probability (TCP) model for an inhomogeneously irradiated tumor was used to calculate and compare TCPs for the measurements and the treatment plans. Equivalent uniform doses (EUD) were also computed. For individual fields, point measurements using an ionization chamber showed substantial dose deviations (-11.7% to 47.8%) for the moving phantom as compared to the stationary phantom. However, much smaller deviations (-1.7% to 3.5%) were observed for the composite dose of all fields. The dose distributions and DVHs of stationary and gated deliveries were in good agreement with those of treatment plans, while those of the nongated moving phantom showed substantial differences. Compared to the stationary phantom, the largest differences observed for the minimum and maximum target doses were -18.8% and +19.7%, respectively. Due to their random nature, these dose errors tended to average out over fractionated treatments. The results of five-fraction measurements showed significantly improved agreement between the moving and stationary phantom. The changes in TCP were less than 4.3% for a single fraction, and less than 2.3% for two or more fractions. Variation of average EUD per fraction was small (< 3.1 cGy for a fraction size of 200 cGy), even when the DVHs were noticeably different from that of the stationary tumor. In conclusion, IMRT treatment of sites affected by respiratory motion can introduce significant dose errors in individual field doses; however, these errors tend to cancel out between fields and average out over dose fractionation. 3D dose distributions, DVHs, TCPs, and EUDs for stationary and moving cases showed good agreement after two or more fractions, suggesting that tumors affected by respiration motion may be treated using IMRT without significant dosimetric and biological consequences.

Artifacts↗
PubMed2006

Radiation therapy for retroperitoneal sarcoma.

Retroperitoneal soft-tissue sarcoma is an uncommon cancer of mesodermal origin, which is difficult to treat owing to its location and proximity to vital structures. Complete gross resection, often involving en bloc resection, is the standard of care as it represents the only treatment that improves overall survival. Unlike extremity sarcoma, retroperitoneal soft-tissue sarcoma tumor mortality is from local recurrence. Radiation therapy is the only adjuvant treatment that has improved local control in several institutional series. However, there remains no definitive prospective, randomized trial that establishes the role of adjuvant radiation versus no radiation. Owing to significant radiation morbidity with adjacent organs, especially the small bowel, there exists no consensus on radiation timing, delivery method or dosing. Recent and current protocols use preoperative external-beam radiation with or without a method of focal boost dosing. Methods of boost dosing include brachytherapy, intraoperative radiation therapy and intensity-modulated radiation therapy. Further studies are needed to definitively include radiation therapy in the standard treatment of retroperitoneal soft-tissue sarcoma and to find the optimal balance between acceptable radiation toxicity and effective local control in treatment protocols.

Clinical Trials as Topic↗
PubMed2005

Simultaneous optimization of sequential IMRT plans.

Radiotherapy often comprises two phases, in which irradiation of a volume at risk for microscopic disease is followed by a sequential dose escalation to a smaller volume either at a higher risk for microscopic disease or containing only gross disease. This technique is difficult to implement with intensity modulated radiotherapy, as the tolerance doses of critical structures must be respected over the sum of the two plans. Techniques that include an integrated boost have been proposed to address this problem. However, clinical experience with such techniques is limited, and many clinicians are uncomfortable prescribing nonconventional fractionation schemes. To solve this problem, we developed an optimization technique that simultaneously generates sequential initial and boost IMRT plans. We have developed an optimization tool that uses a commercial treatment planning system (TPS) and a high level programming language for technical computing. The tool uses the TPS to calculate the dose deposition coefficients (DDCs) for optimization. The DDCs were imported into external software and the treatment ports duplicated to create the boost plan. The initial, boost, and tolerance doses were specified and used to construct cost functions. The initial and boost plans were optimized simultaneously using a gradient search technique. Following optimization, the fluence maps were exported to the TPS for dose calculation. Seven patients treated using sequential techniques were selected from our clinical database. The initial and boost plans used to treat these patients were developed independently of each other by dividing the tolerance doses proportionally between the initial and boost plans and then iteratively optimizing the plans until a summation that met the treatment goals was obtained. We used the simultaneous optimization technique to generate plans that met the original planning goals. The coverage of the initial and boost target volumes in the simultaneously optimized plans was equivalent to the independently optimized plans actually used for treatment. Tolerance doses of the critical structures were respected for the plan sum; however, the dose to critical structures for the individual initial and boost plans was different between the simultaneously optimized and the independently optimized plans. In conclusion, we have demonstrated a method for optimization of initial and boost plans that treat volume reductions using the same dose per fraction. The method is efficient, as it avoids the iterative approach necessitated by currently available TPSs, and is generalizable to more than two treatment phases. Comparison with clinical plans developed independently suggests that current manual techniques for planning sequential treatments may be suboptimal.

Algorithms↗
PubMed2004

IMRT dose escalation for positive para-aortic lymph nodes in patients with locally advanced cervical cancer while reducing dose to bone marrow and other organs at risk.

PURPOSE: To evaluate the feasibility of dose-escalated para-aortic lymph node (PALN) intensity modulated radiation therapy (IMRT) in reducing the dose to bone marrow, bowel, spinal cord, and kidneys, compared with conventional radiation techniques of PALNs in patients with locally advanced cervical cancer and PALN metastases. METHODS AND MATERIALS: Computed tomography scans and MRI studies of 5 cervical cancer patients with PALN involvement were transferred to an IMRT treatment planning workstation (Eclipse/Helios) for image fusion and definition of target volumes and critical structures. The positive PALNs identified on fused computed tomography-magnetic resonance images were defined as the gross target volume (GTV), and the PALN region was defined as the planning target volume. There were 2 distinct treatment regions: the PALN region superior to the isocenter and the whole-pelvis region inferior to the isocenter. Three treatment planning techniques were compared: AP/PA (both regions), 4-field box (both regions), and PALN-IMRT with 4-field box to the whole-pelvis field. With IMRT, the radiation dose to the GTV was escalated from the conventional 45 Gy to 60 Gy (2.4 Gy/fraction), whereas the planning target volume and whole-pelvis region received 45 Gy. The treatment planning isocenter was placed at the L4-L5 vertebral body interspace, and this allowed the two treatment regions to be abutted using independent jaws. RESULTS: This study has demonstrated the feasibility of escalating the dose delivered to grossly positive PALNs to 60 Gy (2.4 Gy/fraction) with a 95.6% median GTV coverage, concomitantly with conventional treatment of the whole-pelvis region. PALN-IMRT significantly reduced V(40) bone marrow compared to the AP/PA and 4-field box techniques with a median of 21.3%, 98%, and 49.7%, respectively. The PALN-IMRT and 4-field box techniques showed a reduction in V(45) bowel over the AP/PA technique, but a level of statistical significance was not reached. The spinal cord received a significantly higher maximum dose when PALNs were treated with AP/PA fields. Alternatively, the use of the 4-field box technique yielded a significant increase in V(22) kidney on both sides. The placement of the treatment planning isocenter at the L4-L5 interspace allowed the PALN-IMRT and whole-pelvis regions to be treated with a relatively uniform dose at the abutment region. CONCLUSION: In this dosimetric analysis, we demonstrated that dose-escalated PALN-IMRT with conventional whole-pelvis radiotherapy is feasible with significant sparing of critical normal structures compared to PALN conventional radiation techniques.

Aorta↗
PubMed2004

Adenoviral vector-mediated augmentation of epidermal growth factor receptor (EGFr) enhances the radiosensitization properties of anti-EGFr treatment in prostate cancer cells.

PURPOSE: To determine whether an adenoviral vector approach to the augmentation of epidermal growth factor receptor (EGFr) expression results in increased antiproliferative and radiosensitization properties of anti-EGFr antibody therapy in prostate cancer cells. METHODS AND MATERIALS: DU145 and LNCaP human prostate cancer cells were used to test the above question in vitro. An adenoviral vector was utilized to transduce cells with an EGFr transgene (AdEGFr). Immunoblots were performed to measure EGFr expression and EGFr tyrosine phosphorylation. Radiolabeled ligand studies were employed to test binding of epidermal growth factor to EGFr. Scatchard analyses allowed for quantification of the number of EGFrs. Standard immunohistochemistry was performed to assess EGFr expression. Cellular proliferation was assessed after various combinations of treatment. RESULTS: Studies of prostate carcinoma cells infected with AdEGFr demonstrated an increase in EGFr expression. This increase in expression correlated with increased function of EGFr. Specifically, increased EGFr expression also resulted in increased ligand binding, ligand-induced internalization of EGFr, and ligand-induced EGFr tyrosine kinase activity that could be blocked with pre-exposure to IMC-C225 (an anti-EGFr monoclonal antibody). Transduction of the LNCaP cells with AdEGFr did not increase the antiproliferative effects of IMC-C225, but did significantly increase IMC-C225-induced radiosensitization as determined by cell proliferation. CONCLUSIONS: Augmentation of EGFr expression, through an adenoviral vector approach in prostate carcinoma cells, resulted in cells that demonstrated greater IMC-C225-induced radiosensitization compared to cells that were not treated with AdEGFr.

Adenoviridae↗
PubMed2004

Anti-EGFR-mediated radiosensitization as a result of augmented EGFR expression.

PURPOSE: Elevated epidermal growth factor receptor (EGFR) expression has correlated with a poor prognosis after standard treatment of several malignancies. However, it is not clear whether the absolute level of EGFR expression affects the radiosensitizing properties of anti-EGFR treatments. A better understanding of this question would be helpful for the design of protocols that deliver these treatments. To explore this question, cells (LS174T) that did not display inherent anti-EGFR treatment-induced radiosensitization were selected for studies that could potentially enhance EGFR expression. MATERIALS AND METHODS: Human colon carcinoma cells (LS174T), which did not show radiosensitization by anti-EGFR treatments, were employed for these studies. (Also, these cells were not responsive to the antiproliferative effects of anti-EGFR treatment.) Using standard transfection techniques (eukaryotic expression vector) as well as an adenoviral construct to enhance EGFR expression, LS174T cells were transduced in a manner that resulted in enhanced expression of EGFR. Subsequently, standard proliferation studies were performed to test the radiosensitizing properties of anti-EGFR treatment (an anti-EGFR monoclonal antibody: IMC-C225). RESULTS: Studies were undertaken to stably transfect LS174T cells with EGFR. The stable transfectants, LS174T.EGFR cells, were responsive to the antiproliferative effects of anti-EGFR treatment, in contrast to the parent LS174T cells. Similar results were demonstrated when the cells were infected with AdEGFR. Additionally, the LS174T.EGFR cells were responsive to the radiosensitizing properties of anti-EGFR treatment (IMC-C225), whereas the parent cells were not. CONCLUSIONS: Although the level of EGFR expression is of prognostic significance in many tumor models, the response of cells to anti-EGFR treatment alone, or combinations of this treatment with radiation or chemotherapy, depends upon many factors that are not necessarily related to the inherent EGFR expression of the tumor cells. However, the studies reported herein, demonstrate that when LS174T cells were transduced to show increased EGFR expression, they became responsive to the radiosensitizing properties of anti-EGFR treatments.

Adenoviridae↗
PubMed2004

Brain metastases.

Explore the source record for details and available documents.

Antineoplastic Agents↗
PubMed2004

Radionecrosis of the inferior occipital lobes with altitudinal visual field loss after gamma knife radiosurgery.

A patient had bilateral superior altitudinal visual field defects because of radionecrosis of the inferior occipital lobes after gamma knife radiosurgery for a recurrent atypical cerebellar meningioma. Although radionecrosis of the anterior visual pathway has been well-documented, this is the first report of visual field loss associated with occipital lobe radionecrosis. The treatment dose this patient received is within the range of predicted tolerable radiosurgical dosing, although this patient was at increased risk for radionecrosis secondary to previous external beam radiotherapy. By offering an effective, noninvasive treatment, radiosurgery has changed the management of intracranial lesions. Radiosurgery targets a discrete volume of tissue and relatively spares the surrounding normal tissue. Radiation injury, or radionecrosis, is the only significant complication of radiosurgery (). We present a case of bilateral occipital lobe radionecrosis after gamma knife surgery that resulted in bilateral superior altitudinal defects.

Brain Diseases↗
PubMed2004

Refining the staging evaluation of pineal region germinoma using neuroendoscopy and the presence of preoperative diabetes insipidus.

Treatment strategies for CNS germinoma are currently evolving. Current approaches include reducing the volume and dose of radiation by adding pre-irradiation chemotherapy. Very accurate staging is necessary with such an approach to prevent failures. Eight consecutive patients with pineal germinoma at one institution underwent endoscopic surgery for tumor biopsy, direct visualization of the third ventricular region, and third ventriculostomy for those with hydrocephalus. All patients were treated with 4 cycles of chemotherapy. Conformal field radiation therapy followed, with the dose to the tumor bed dependent on the response to chemotherapy. Patients who had MRI, endoscopic, or cerebrospinal fluid evidence of multicentric or disseminated disease also received craniospinal radiation. Six patients had diabetes insipidus (DI) at presentation. All 6 had tumor studding the floor of the third ventricle on endoscopic visualization, while only 4 of those patients had MRI evidence of disease in that region. All patients have completed therapy and are alive, with no evidence of disease at median follow-up of 31.5 months from diagnosis. Direct endoscopic visualization of the third ventricular region may be more sensitive than MRI for evaluating the presence of suprasellar disease and appears to add important information. This parameter should be added to the staging evaluation when feasible. In this series, the presence of DI was 100% predictive of suprasellar disease, even when the MRI was negative for involvement of that region. Patients should be evaluated for DI as part of the initial staging, and if it is present, the patients should be treated for suprasellar disease regardless of MRI findings.

Adolescent↗
PubMed2003

Bulb of penis as a marker for prostatic apex in external beam radiotherapy of prostate cancer.

PURPOSE: To investigate the relationship between the bulb of the penis and the peak of the urethrogram, and to compare this measurement with the ischial tuberosities (ITs) to peak distance. METHODS AND MATERIALS: Pelvic CT scans from 50 consecutive patients with localized prostate cancer were analyzed to identify the penile bulb. Each patient was required to undergo retrograde urethrography during CT-based treatment planning with 3-mm slices. The peak of the urethrogram was defined as the last CT slice in which the contrast dye in the urethra could be visualized. Measurements were taken from the slice containing the most superior aspect of the penile bulb to the last slice of the urethrogram peak. The superior aspect of the penile bulb was defined as the CT slice nearest the peak that contained a bulbous structure at the base of the penis. This distance was defined as the bulb-peak distance. Similarly, the IT-peak distance was recorded for comparison. RESULTS: The mean bulb-peak and IT-peak distances were calculated for 47 of 50 patients. The peak of the urethrogram was unable to be evaluated in 3 patients. The mean, median, and range bulb-peak distance was 2.4 mm (SD 1.8), 3 mm, and 0-6 mm, respectively. The mean, median, and range IT-peak distance was 20.1 mm (SD 6.6), 21 mm, and 6-33 mm, respectively. No patient had the bulb located above the apex of the urethrogram. CONCLUSION: The bulb of the penis is a relatively consistent soft-tissue landmark compared with the ITs and is located an average of 3 mm below the peak of the urethrogram. Therefore, the bulb of the penis is another landmark for the identification of the prostatic apex and is less invasive than retrograde urethrography.

Humans↗
PubMed2003

Dosimetric effect of respiration-gated beam on IMRT delivery.

Intensity modulated radiation therapy (IMRT) with a dynamic multileaf collimator (DMLC) requires synchronization of DMLC leaf motion with dose delivery. A delay in DMLC communication is known to cause leaf lag and lead to dosimetric errors. The errors may be exacerbated by gated operation. The purpose of this study was to investigate the effect of leaf lag on the accuracy of doses delivered in gated IMRT. We first determined the effective leaf delay time by measuring the dose in a stationary phantom delivered by wedge-shaped fields. The wedge fields were generated by a DMLC at various dose rates. The so determined delay varied from 88.3 to 90.5 ms. The dosimetric effect of this delay on gated IMRT was studied by delivering wedge-shaped and clinical IMRT fields to moving and stationary phantoms at dose rates ranging from 100 to 600 MU/min, with and without gating. Respiratory motion was simulated by a linear sinusoidal motion of the phantom. An ionization chamber and films were employed for absolute dose and 2-D dose distribution measurements. Discrepancies between gated and nongated delivery to the stationary phantom were observed in both absolute dose and 2-D dose distribution measurements. These discrepancies increased monotonically with dose rate and frequency of beam interruptions, and could reach 3.7% of the total dose delivered to a 0.6 cm3 ion chamber. Isodose lines could be shifted by as much as 3 mm. The results are consistent with the explanation that beam hold-offs in gated delivery allowed the lagging leaves to catch up with the delivered monitor units each time that the beam was interrupted. Low dose rates, slow leaf speeds and low frequencies of beam interruptions reduce the effect of this delay-and-catch-up cycle. For gated IMRT it is therefore important to find a good balance between the conflicting requirements of rapid dose delivery and delivery accuracy.

Dose-Response Relationship, Radiation↗
PubMed2003

Validation of target volume and position in respiratory gated CT planning and treatment.

The capability of a commercial respiratory gating system based on video tracking of reflective markers to reduce motion-induced CT planning and treatment errors was evaluated. Spherical plastic shells (2.8-82 cm3), simulating the gross target volume (GTV), were placed in a water-filled body phantom that was moved sinusoidally along the longitudinal axis of the CT scanner and the accelerator for +/- 1 cm at 15-30 cycle/min. During gated CT imaging, the x-ray exposure was initiated by the gating system shortly before the end of expiration (so that the imaging time would be centered at the end of expiration); it was terminated by the scanner after completion of each slice. In nongated CT images, the target appeared distorted and often broken up. GTVs volume errors ranged 16%-110% in axial scans, and 7%-36% in spiral scans. In gated CT images, the spheres appeared 3 and 5 mm longer than their actual diameters (volume errors 2%-16%), at the respective respiration rates of 15 and 20 cycles/min. At 30 cycles/min the target appeared 1 cm longer, and volume error ranged 25%-53%. During treatment, gating kept the beam on for a duration equal to the CT acquisition time of 1 s/slice. The difference in positional errors between gated CT and portal films was 1 mm, regardless the size of residual motion errors. Because of the potential of suboptimal placement of the gating window between CT imaging and treatment, an extra 1.5-2.5 mm safety margin can be added regardless of the size of residual motion error. For respiratory rates > or = 30 cycles/min, the effectiveness of gating is limited by large residual motion in the 1 s CT acquisition time.

Humans↗
PubMedDate not supplied

Role of radiation therapy and radiosurgery in glioblastoma multiforme.

Randomized trials have supported a role for radiation therapy in the initial management of Glioblastoma Multiforme (GBM) for over twenty-five years. Although technological advances in imaging and three-dimensional treatment planning have reduced the toxicity for patients and have allowed safe radiation dose escalation, unfortunately they have not produced a correspondingly dramatic improvement in overall survival. The dose of 60 Gy partial brain RT remains the standard of care for patients with newly diagnosed GBM. Recently completed randomized trials of brachytherapy and radiosurgery do not support these modalities in the initial management of GBM, but these and other focal RT techniques such as intensity modulated radiation therapy enable safe retreatment in selected patients. Future studies will need to explore radiation biologic response modification and radiosensitization through targeted therapies.

Brachytherapy↗