Median Planning Target Volume Research Articles

Comparison of conventional and three-dimensional conformal CT planning techniques for preoperative chemoradiotherapy for locally advanced rectal cancer

We assessed the impact of three-dimensional (3D) conformal planning vs conventional planning of preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) on small bowel and bladder sparing and in optimising coverage of tumour target volume. Conformal and conventional plans were created for 50 consecutive patients. The conformal plan delineated a gross tumour volume (GTV), a clinical target volume (CTV) 1 to cover potential subclinical disease spread, a CTV2 to outline the mesorectum and lymph node areas at risk, and a planning target volume (PTV) to cover set-up error and organ movement. The conventional plan was created using digitally reconstructed radiographs (DRRs). Patients were treated with a dose of 45 Gy in 25 fractions with concurrent chemotherapy over 5 weeks. Dose-volume histograms (DVHs) were created and compared for GTV, PTV, small bowel and bladder. The GTV was covered by the conventional plan in all patients. Significant differences were shown for median PTV coverage with conformal planning compared with conventional planning: 99.2% vs 94.2% (range 95.9-100% vs 75.5-100%); p<0.05. The median volume of irradiated small bowel was significantly lower for CT plans at all DVH levels. Median bladder doses did not differ significantly. 3D conformal CT planning is superior to conventional planning in terms of coverage of the tumour volume. It significantly reduces the volume of small bowel irradiated with no decrease in the rate of R0 resection compared with published data, and at the present time should be considered as the standard of care for rectal cancer planning.

Quantitative assessment of inter-observer variability in target volume delineation on stereotactic radiotherapy treatment for pituitary adenoma and meningioma near optic tract

BackgroundTo assess inter-observer variability in delineating target volume and organs at risk in benign tumor adjacent to optic tract as a quality assurance exercise.MethodsWe quantitatively analyzed 21 plans made by 11 clinicians in seven CyberKnife centers. The clinicians were provided with a raw data set (pituitary adenoma and meningioma) including clinical information, and were asked to delineate the lesions and create a treatment plan. Their contouring and plans (10 adenoma and 11 meningioma plans), were then compared. In addition, we estimated the influence of differences in contouring by superimposing the respective contours onto a default plan.ResultsThe median planning target volume (PTV) and the ratio of the largest to the smallest contoured volume were 9.22 cm3 (range, 7.17 - 14.3 cm3) and 1.99 for pituitary adenoma, and 6.86 cm3 (range 6.05 - 14.6 cm3) and 2.41 for meningioma. PTV volume was 10.1 ± 1.74 cm3 for group 1 with a margin of 1 -2 mm around the CTV (n = 3) and 9.28 ± 1.8 cm3(p = 0.51) for group 2 with no margin (n = 7) in pituitary adenoma. In meningioma, group 1 showed larger PTV volume (10.1 ± 3.26 cm3) than group 2 (6.91 ± 0.7 cm3, p = 0.03). All submitted plan keep the irradiated dose to optic tract within the range of 50 Gy (equivalent total doses in 2 Gy fractionation). However, contours superimposed onto the dose distribution of the default plan indicated that an excessive dose 23.64 Gy (up to 268% of the default plan) in pituitary adenoma and 24.84 Gy (131% of the default plan) in meningioma to the optic nerve in the contours from different contouring.ConclusionQuality assurance revealed inter-observer variability in contour delineation and their influences on planning for pituitary adenoma and meningioma near optic tract.

Preclinical Assessment of Volumetric Modulated Arc Therapy for Total Marrow Irradiation

A preclinical investigation was undertaken to explore a treatment technique for total marrow irradiation using RapidArc, a volumetric modulated arc technique. Computed tomography datasets of 5 patients were included. Plans with eight overlapping coaxial arcs were optimized for 6-MV photon beams. Dose prescription was 12 Gy in 2 Gy per fraction, normalized so that 100% isodose covered 85% of the planning target volume (PTV). The PTV consisted of the whole skeleton (including ribs and sternum), from the top of the skull to the medium distal third of the femurs. Planning objectives for organs at risk (OARs) were constrained to a median dose <6 to 7 Gy. OARs included brain, eyes, oral cavity, parotids, thyroid, lungs, heart, kidneys, liver, spleen, stomach, abdominal cavity, bladder, rectum, and genitals. Pretreatment quality assurance consisted of portal dosimetry comparisons, scoring the delivery to calculation agreement with the gamma agreement index. The median total body volume in the study was 57 liters (range, 49-81 liters), for an average diameter of 47 cm (range, 46-53 cm) and a total length ranging from 95 to 112 cm. The median PTV volume was 6.8 liters (range, 5.8-10.8 liters). The mean dose to PTV was 109% (range, 107-112%). The global mean of median dose to all OARs was 4.9 Gy (range, 4.5-5.1 Gy over the 5 patients). The individual mean of median doses per organ ranged from 2.3 Gy (oral cavity) to 7.3 Gy (bowels cavity). Preclinical quality assurance resulted in a mean gamma agreement index of 94.3 ± 5.1%. The delivery time measured from quality assurance runs was 13 minutes. Sparing of normal tissues with adequate coverage of skeletal bones was shown to be feasible with RapidArc. Pretreatment quality assurance measurements confirmed the technical agreement between expected and actually delivered dose distributions, suggesting the possibility of incorporating this technique in the treatment options for patients.

Conformal Radiotherapy in the Treatment of Advanced Juvenile Nasopharyngeal Angiofibroma With Intracranial Extension: An Institutional Experience

To describe the results of conformal radiotherapy in advanced juvenile nasopharyngeal angiofibroma in a tertiary care institution. Retrospective chart review was conducted for 8 patients treated with conformal radiotherapy between 2006 and 2009. The median follow-up was 17 months. All patients had Stage IIIB disease with intracranial extension. Radiotherapy was considered as treatment because patients were deemed inoperable owing to extensive intracranial/intraorbital extension or proximity to optic nerve. All but 1 patient were treated with intensity-modulated radiotherapy using seven coplanar fields. Median (range) dose prescribed was 39.6 (30-46) Gy. Actuarial analysis of local control and descriptive analysis of toxicity profile was conducted. Despite the large and complex target volume (median planning target volume, 292 cm(3)), intensity-modulated radiotherapy achieved conformal dose distributions (median van't Reit index, 0.66). Significant sparing of the surrounding organs at risk was obtained. No significant Grade 3/4 toxicities were experienced during or after treatment. Actual local control at 2 years was 87.5%. One patient died 1 month after radiotherapy secondary to massive epistaxis. The remaining 7 patients had progressive resolution of disease and were symptom-free at last follow-up. Persistent rhinitis was the only significant toxicity, seen in 1 patient. Conformal radiotherapy results in good local control with minimal acute and late side effects in juvenile nasopharyngeal angiofibromas, even in the presence of advanced disease.

Stereotactic Irradiation of the Postoperative Resection Cavity for Brain Metastasis: A Frameless Linear Accelerator-Based Case Series and Review of the Technique

Whole-brain radiation therapy (WBRT) is the standard of care after resection of a brain metastasis. However, concern regarding possible neurocognitive effects and the lack of survival benefit with this approach has led to the use of stereotactic radiosurgery (SRS) to the resection cavity in place of WBRT. We report our initial experience using an image-guided linear accelerator-based frameless stereotactic system and review the technical issues in applying this technique. We retrospectively reviewed the setup accuracy, treatment outcome, and patterns of failure of the first 18 consecutive cases treated at Brigham and Women's Hospital. The target volume was the resection cavity without a margin excluding the surgical track. The median number of brain metastases per patient was 1 (range, 1-3). The median planning target volume was 3.49 mL. The median prescribed dose was 18 Gy (range, 15-18 Gy) with normalization ranging from 68% to 85%. In all cases, 99% of the planning target volume was covered by the prescribed dose. The median conformity index was 1.6 (range, 1.41-1.92). The SRS was delivered with submillimeter accuracy. At a median follow-up of 12.7 months, local control was achieved in 16/18 cavities treated. True local recurrence occurred in 2 patients. No marginal failures occurred. Distant recurrence occurred in 6/17 patients. Median time to any failure was 7.4 months. No Grade 3 or higher toxicity was recorded. A long interval between initial cancer diagnosis and the development of brain metastasis was the only factor that trended toward a significant association with the absence of recurrence (local or distant) (log-rank p = 0.097). Frameless stereotactic irradiation of the resection cavity after surgery for a brain metastasis is a safe and accurate technique that offers durable local control and defers the use of WBRT in select patients. This technique should be tested in larger prospective studies.

Hypofractionated stereotactic radiotherapy for acoustic neuromas: safety and effectiveness over 8 years of experience

Little information is available about long-term outcomes of hypofractionated stereotactic radiotherapy (hypo-FSRT) for acoustic neuromas. In this study, the safety and effectiveness of hypo-FSRT for unilateral acoustic neuroma were reviewed over 8 years of experience at our institution. Between May 1998 and October 2006, 27 patients were consecutively treated by linear accelerator-based hypo-FSRT. Two patients were excluded from this study because they were lost to follow-up within 12months. The median follow-up period for the rest was 59(range 24-133) months. Two types of treatment schedules were adopted. Thirteen patients received 30-39Gy, given in 10-13 fractions (regimen A), whereas after July 2003, 12 patients received 20-24Gy, given in 5-6 fractions at the tumor periphery (regimen B). These treatments were scheduled to be delivered in three fractions per week (Monday, Wednesday, Friday). The median planning target volume was 2.0, with 1.7ml (range 0.7-10.6) in regimen A and 5.2ml (range 0.9-9.3) in regimen B. In the pretreatment audiogram, seven patients (two in regimen A and five in regimen B) had serviceable hearing (Gardner-Robertson Class I-II). Local control rates were 100% with regimen A and 92% with regimen B. Serviceable hearing was preserved in four of five patients in regimen B but no patients in regimen A at the last follow-up. No permanent facial or trigeminal nerve morbidity was observed following treatment, and no salvage surgery was needed. Hypo-FSRT for acoustic neuromas achieved a high local control rate with minimal facial and trigeminal nerve morbidity.

CyberKnife Stereotactic Radiotherapy as Monotherapy for Low- to Intermediate-Stage Prostate Cancer: Early Experience, Feasibility, and Tolerance

The CyberKnife (CK), a linear accelerator mounted on a robotic device, enables excellent dose conformation to the target and minimizes dose to surrounding normal tissue. It is a very suitable device for performing hypofractionated stereotactic body radiotherapy as monotherapy for low- to intermediate-risk prostate cancer patients. We report our early experience using this technique. Between June 2008 and June 2009, 10 patients underwent CK monotherapy as treatment for their prostate cancer (stage <or=T2b, Gleason score (GS) <or=7, initial PSA <or=15 microg/L). The prescribed dose was 38 Gy in four daily fractions of 9.5 Gy. The International Prostate Symptom Score and Radiation Therapy Oncology Group symptom scale were prospectively administered before and at 0.5, 1, 2, 3, 6, and 12 months. Median age of the patients was 71 years (range, 66-76). Three patients had stage T2a and 7a T1c disease, one patient had GS of 7, and all others had GS of 6. Median follow-up was 5.1 months. Median initial PSA was 8.3 ng/mL (range, 1.3-13.6 ng/mL). Median planning target volume delineated on computed tomography after matching with the magnetic resonance imaging scan was 107 cc (range, 42-158 cc). The median V100 of the prostate was 95.8% (range, 94.8-97.2). The D95 of the prostate was 38.3 Gy (range, 38.1-38.8 Gy). The constraints for the bladder, rectum, and urethra were well met. The International Prostate Symptom Scores after 3 months were stable compared with the pretreatment scores. Urinary and bowel Radiation Therapy Oncology Group symptoms were mild and within the expected levels. This regimen of stereotactic CK monotherapy for low- to intermediate-risk prostate cancer with excellent dose coverage of the prostate was well tolerated. Data collection is ongoing for further assessment of toxicity and PSA response.

Comparison of positron emission tomography (PET) and computed tomography (CT) for better target volume definition in radiation therapy planning

In cancer patients, positron emission tomography/ computed tomography (PET/CT) fused images present less variability in target contouring, respect to use only CT images, respectively. However, the gold standard has not yet been clearly established between radiation oncologists with regard to PET images and the methodology of contouring targets with confidence using PET/CT fused images. The aim of this study was to determine whether integrated PET/CT fused images provide advantages in virtual simulation compared with morphological contouring only with CT. Thirty cancer patients were evaluated in an adapted PET/CT hybrid in radiotherapy (RT) setup position, with 20 of them being suitable for RT: 17 were suitable for curative intent, which was the group of interest in this study. All image series were sent to the RT work station (WS) where CT and PET series were automatically fused by Digital Imaging and Communications in Medicine (DICOM) in each case. PET series were threshold and were subjected to source-to-background contrast algorithms to fi nally redefine the original tumour description. Three different radiotherapy plans (RTP) for each patient were compared after targets were contoured: [1] planning over metabolic (PET) contoured targets, [2] planning over only morphologic (CT) targets, and [3] planning over targets obtained for treatment based on fused PET/CT images. PET/CT findings altered initial-stage planning in four patients (23.5%) because they had been undergoing chemotherapy. Gross target volume (GTV) and planning target volume (PTV) based only on PET showed more homogeneity to obtain mean doses (p = 0.025) with respect to those based on PET/CT, respectively. However, no percentage differences were observed in median PTV doses between the planning methods, although there was higher variability in PET/CT planning. Morphological (CT) and PET/ CT target volumes were more voluminous than metabolic (PET) volumes. On the other hand, 20% of metabolic (PET) PTV were out of those defined by PET/CT. Thoracic RT plans based on PET preserved better bilateral lung [percentage volume of lung irradiated with a dose of 20 Gy (V20); significance, R(2) = 0.559, p = 0.006]. For our physicians, PET/CT fused images allowed better contouring of primary tumours in 40% of head and neck cancers and 34% of thoracic cancers. PET/CT provides useful information for virtual simulation therapy. Image treatment and planning in an RT workstation is mandatory.

An initial report of cyberknife radiosurgery for primary hepatic carcinoma

To study the efficacy and toxicity of cyberknife radiosurgery for primary hepatic carcinoma. From September 2006 to March 2008, 17 patients with clinical stage I-III primary hepatic carcinoma were treated with cyberknife at Tianjin Cancer Hospital. 12 patients received previous treatment of surgery, or interventional therapy or radiofrequency therapy before the cyberknife radiosurgery. Totally 23 lesions in the liver were treatment. The median planning target volume (PTV) was 75 ml (13 - 351 ml). Fiducials were placed in or adjacent to the tumor one week before the CT scan simulation. The median total prescription dose was 45 Gy (range: 39 - 52 Gy) at 3-8 fractions and the median prescription isodose lines was of 78.0% (range: 75.0% - 81.0%. The follow-up time was 3-30 months (median: 14 months). All patients finished the treatment and slightly fatigue was the most common complain. There were 12 patients alive and 5 patients died. All the lesions in liver treated by the cyberknife radiosurgery achieved local control. The cyberknife radiosurgery for primary hepatic carcinoma showed a high rate of local control and minimal toxicity. Long time follow-up is necessary to evaluate the survival data and late toxicity.

Proton Beam Radiotherapy Versus Three-Dimensional Conformal Stereotactic Body Radiotherapy in Primary Peripheral, Early-Stage Non–Small-Cell Lung Carcinoma: A Comparative Dosimetric Analysis

Proton radiotherapy (PT) and stereotactic body radiotherapy (SBRT) have the capacity to optimize the therapeutic ratio. We analyzed the dosimetric differences between PT and SBRT in treating primary peripheral early-stage non-small-cell lung cancer. Eight patients were simulated, planned, and treated with SBRT according to accepted techniques. SBRT treatments were retrospectively planned using heterogeneity corrections. PT treatment plans were generated using single-, two-, and three-field passively scattered and actively scanned proton beams. Calculated dose characteristics were compared. Comparable planning target volume (PTV) median minimum and maximum doses were observed between PT and SBRT plans. Higher median maximum doses 2 cm from the PTV were observed for PT, but higher median PTV doses were observed for SBRT. The total lung mean and V5 doses were significantly lower with actively scanned PT. The lung V13 and V20 were comparable. The dose to normal tissues was lower with PT except to skin and ribs. Although the maximum doses to skin and ribs were similar or higher with PT, the median doses to these structures were higher with SBRT. Passively scattered plans, compared with actively scanned plans, typically demonstrated higher doses to the PTV, lung, and organs at risk. Single-, two-, or three-field passively or actively scanned proton therapy delivered comparable PTV dose with generally less dose to normal tissues in these hypothetic treatments. Actively scanned beam plans typically had more favorable dose characteristics to the target, lung, and other soft tissues compared with the passively scanned plans. The clinical significance of these findings remains to be determined.

Radioprotective Effect of Moderate Wine Consumption in Patients With Breast Carcinoma

Given the high cost and side effects of radioprotective agents such as amifostine, attention has been focused on potentially equally effective but less expensive and toxic natural substances. We evaluated the potential radioprotective effects of wine in preventing skin toxicity in patients with breast cancer. Before treatment, the medical history and habits of patients were assessed and the information recorded in their clinical folders. Patients were divided into three groups based on the dose/fractionation scheme used: control group, 60.4 Gy (standard technique); Modulated Accelerated Radiotherapy in Adjuvant treatment of breast cancer (MARA)-1 protocol group, 44 Gy (concomitant boost to tumoral bed); and MARA-2 protocol group, 60 Gy (concomitant boost to tumoral bed). The impact of the following variables on acute skin toxicity was evaluated by chart review: radiotherapy protocol, planning target volume (PTV), comorbidity (e.g., hypertension and diabetes), hemoglobin level before therapy, adjuvant hormone therapy, adjuvant chemotherapy, cigarette smoking, and drinking habits. The study population consisted of 348 patients. More severe skin toxicity was significantly associated with the radiotherapy protocol (p < 0.001) and median PTV (p = 0.005). In addition, the incidence of acute toxicity of Grade 2 or greater was higher in patients without alcohol intake (38.4% vs. 22.3%, p = 0.021). The daily amount of alcohol intake also influenced the incidence of skin toxicity, with an incidence of 38.4% in patients with no wine intake, 31.8% in patients drinking half a glass per day, 13.6% in patients drinking one glass per day, and 35.0% in patients drinking two glasses per day. Multivariate analysis showed that wine intake, PTV, and radiotherapy protocol were all significantly correlated with acute toxicity. Our results indicate that wine may have a radioprotective effect; however, prospective studies are needed to confirm this beneficial effect of wine and its components.

Fractionated Stereotactic Radiotherapy in the Treatment of Pituitary Macroadenomas

The use of fractionated stereotactic radiotherapy (FSRT) has evolved with technical advances in noninvasive immobilization, radiation delivery, and image guidance. The application of FSRT to pituitary tumours is aimed at reducing toxicity through improved dose conformality and reduced treatment margins. The aim of the present paper is to report our own experience and to review the published data on FSRT for pituitary macroadenomas. Between September 2000 and October 2005, 13 patients with pituitary macroadenoma underwent FSRT at our institution. In 12 patients, radiotherapy treatment followed surgical resection (transsphenoidal resection in 8, frontal craniotomy in 3, and multiple transsphenoidal resections followed by craniotomy in 1). In 4 patients, the tumours were functional (2 adrenocorticotropic hormone-secreting, 1 prolactinoma, and 1 growth hormone-secreting); the tumours in the remaining patients were clinically non-secretory. Before radiation, 3 patients had panhypopituitarism, and 6 patients had visual field defects. All patients were treated with FSRT using non-coplanar micro-multileaf collimation portals. A median dose of 50.4 Gy (range: 45-60 Gy) was prescribed to the 76.9%-95.2% isodose surface and delivered in 1.8-Gy fractions. The median planning target volume (gross tumour plus 3 mm) was 33.5 cm3 (range: 3.2-75 cm3). After a median follow-up of 24 months (range: 6-60 months), local control was 100%. One patient achieved clinical complete response. Treatment was well tolerated acutely for all patients. Neither radiation-induced optic neuropathy nor any radiation-related endocrine dysfunction was observed in our patients. In accordance with published series, we found FSRT to be safe and effective in the management of large pituitary macroadenomas.

Additional PET/CT in week 5–6 of radiotherapy for patients with stage III non-small cell lung cancer as a means of dose escalation planning?

Background and purpose Loco-regional failure after radiotherapy with total doses of 60–70 Gy for non-small cell lung cancer (NSCLC) remains a major clinical problem. Escalation of radiation dose is often limited because of exceeding normal tissue constraints. The present study was designed to test the hypothesis that a reduction in disease volume during radiotherapy detected by FDG PET/CT would facilitate radiation dose escalation, whilst remaining within normal tissue constraints. Materials and methods Ten patients with localised inoperable NSCLC were prospectively enrolled. Each received standard 3D-conformally planned radiotherapy to a dose of 66 Gy in 33 fractions over 6.5 weeks. FDG PET/CT imaging in the treatment position was performed prior to treatment and repeated following 50 or 60 Gy. CT and PET-delineated gross tumour volumes were generated and a composite created. A margin of 15 mm was added in all planes to form the planning target volume (PTV). Treatment planning was performed to compare two dose escalation strategies: 78 Gy delivered to the initial PTV with treatment in two phases (shrinking field), i.e., 66 Gy to the initial PTV with a 12 Gy-boost to the PTV after 50/60 Gy. As an alternative planning approach the maximal dose without exceeding normal tissue constraints was evaluated for each patient (individualized dose prescription). Results There was a median PTV reduction after 50/60 Gy of 20%. Delivering 78 Gy to the initial PTV could have been achieved in 4/10 patients. Of the remaining 6, delivering 78 Gy to the initial PTV would have exceeded normal tissue constraints and no benefit was seen when delivered in two phases. The results from the individualized dose prescription indicated a higher median maximal dose when treatment would be given in two phases compared to one phase resulting in a modest increase of calculated tumour control probability. Conclusions Our data suggest that despite tumour shrinkage determined by subsequent FDG PET/CT during treatment the tested adaptive targeting strategy would result only in a modest improvement in the context of dose escalation. Further studies on the optimal use of FDG PET/CT and other approaches for dose escalation in loco-regionally advanced NSCLC are warranted.

Efficacy and toxicity of limited field concurrent chemoradiotherapy (CRT) with capecitabine for locally advanced pancreatic cancer (LAPC)

15586 Background: Treatment outcome in LAPC remains poor. As treatment-related toxicity limits CRT dose-intensification, we evaluated the efficacy/toxicity of capecitabine based CRT in LAPC patients using limited field irradiation, excluding elective nodal areas. Methods: 25 consecutive LAPC patients eligible for CRT were treated at a single institute. Capecitabine was administered at 500–600 mg/m2/b.i.d continuously (including weekends) from day one to completion of radiotherapy (RT). RT was delivered conformally to a dose of 50.4Gy in 28 fractions over 5.5 weeks. The gross tumour volume consisting of the pancreatic tumour and any involved peri-pancreatic nodes was isometrically expanded by 0.5 cm to generate the clinical target volume (CTV). The planning target volume (PTV) comprised the CTV plus a 1cm margin AP/LR and a 1.5 - 2 cm margin SI. Patients were reviewed weekly to monitor weight and collect toxicity data. Time to disease progression and survival were calculated from diagnosis. Results: Median age of the 25 patients (17 M; 8 F) was 66 years (range 45- 74). Tumour was located in the pancreatic head in 23 patients (92%) and histology available in 17 patients (68%). The median (range) PTV volume was 378 (146–860) cc. 2 patients did not complete treatment due to disease progression and post-surgical complication. Treatment was well tolerated with nausea and fatigue being the most common toxicities. Only one patient developed any grade 3 toxicity (nausea). With a median follow up of 8.3 months, the median time to progression was 9.7 months, with 25% remaining progression-free at 1 year. All patients had progressed by 2 years. Isolated loco-regional relapse was observed in only one patient. At progression, six patients were suitable for palliative chemotherapy. The median overall survival for all patients was 11.6 months with 1 year survival of 38%. Median survival for the 6 patients who received palliative chemotherapy at disease progression was 17 months. Conclusion: Limited field CRT using capecitabine 500–600 mg/m2 twice daily in LAPC is very well tolerated, with similar efficacy to historical CRT regimens. Avoiding elective nodal irradiation may allow CRT dose-intensification and combination with other anti-cancer agents. No significant financial relationships to disclose.

Optimization of Stereotactic Radiotherapy Treatment Delivery Technique for Base-Of-Skull Meningiomas

This study compares static conformal field (CF), intensity modulated radiotherapy (IMRT), and dynamic arcs (DA) for the stereotactic radiotherapy of base-of-skull meningiomas. Twenty-one cases of base-of-skull meningioma (median planning target volume [PTV] = 21.3 cm 3) previously treated with stereotactic radiotherapy were replanned with each technique. The plans were compared for Radiation Therapy Oncology Group conformity index (CI) and homogeneity index (HI), and doses to normal structures at 6 dose values from 50.4 Gy to 5.6 Gy. The mean CI was 1.75 (CF), 1.75 (DA), and 1.66 (IMRT) ( p < 0.05 when comparing IMRT to either CF or DA plans). The CI (IMRT) was inversely proportional to the size of the PTV (Spearman's rho = −0.53, p = 0.01) and at PTV sizes above 25 cm 3, the CI (IMRT) was always superior to CI (DA) and CI (CF). At PTV sizes below 25 cm 3, there was no significant difference in CI between each technique. There was no significant difference in HI between plans. The total volume of normal tissue receiving 50.4, 44.8, and 5.6 Gy was significantly lower when comparing IMRT to CF and DA plans ( p < 0.05). There was significantly improved dose sparing for the brain stem and ipsilateral temporal lobe with IMRT but no significant difference for the optic chiasm or pituitary gland. These results demonstrate that stereotactic IMRT should be considered to treat base-of-skull meningiomas with a PTV larger than 25 cm 3, due to improved conformity and normal tissue sparing, in particular for the brain stem and ipsilateral temporal lobe.

A Phase I Dose-Escalation Study of Fractionated Stereotactic Radiosurgery in Combination With Gefitinib in Patients With Recurrent Malignant Gliomas

To determine the maximum tolerated dose (MTD) of fractionated stereotactic radiosurgery (SRS) with gefitinib in patients with recurrent malignant gliomas. A Phase I clinical trial was performed. Eligible patients had pathologically proved recurrent anaplastic astrocytoma or glioblastoma. Patients started gefitinib (250 mg/day) 7 days before SRS and continued for 1 year or until disease progression. SRS was delivered in three fractions over 3 days. The planning target volume (PTV) was the T1-weighted MRI postcontrast enhancing lesion+2 mm. The first cohort received an SRS dose of 18 Gy, and subsequent cohorts received higher doses up to the maximum dose of 36 Gy. Dose-limiting toxicity (DLT) was any Grade 3 toxicity. The MTD was exceeded if 2 of 6 patients in a cohort experienced DLT. Characteristics of the 15 patients enrolled were: 9 men, 6 women; median age, 47 years (range, 23-65 years); 11 glioblastoma, 4 AA; median prior RT dose, 60 Gy (range, 54-61.2 Gy); median interval since RT, 12 months (range, 3-57 months); median PTV, 41 cc (range, 12-151 cc). Median follow-up time was 7 months (range, 2-28 months). Median time on gefitinib was 5 months (range, 2-12 months). No patient experienced a DLT, and the SRS dose was escalated from 18 to 36 Gy. Grade 1-2 gefitinib-related dermatitis and diarrhea were common (10 and 7 patients, respectively). Fractionated SRS to a dose of 36 Gy in three fractions is well tolerated with gefitinib at daily dose of 250 mg. Further studies of SRS and novel molecular targeted agents are warranted in this challenging clinical setting.

Image-Guided Intensity-Modulated Photon Radiotherapy Using Multifractionated Regimen to Paraspinal Chordomas and Rare Sarcomas

Image-guided intensity-modulated radiotherapy enables delivery of high-dose radiation to tumors close to the spinal cord. We report our experience with multifractionated regimens using image-guided intensity-modulated radiotherapy to treat gross paraspinal disease to doses beyond cord tolerance. We performed a retrospective review of 27 consecutive patients with partially resected or unresectable paraspinal tumors irradiated to >5,300 cGy in standard fractionation. The median follow-up was 17.4 months (range, 2.1-47.3). Eighteen sarcomas, seven chordomas, and two ependymomas were treated. The median dose to the planning target volume was 6,600 cGy (range, 5,396-7,080) in 180- or 200-cGy fractions. The median planning target volume was 164 cm3 (range, 29-1,116). Seven patients developed recurrence at the treatment site (26%), and 6 of these patients had high-grade tumors. Three patients with recurrence had metastatic disease at the time of radiotherapy. The 2-year local control rate was 65%, and the 2-year overall survival rate was 79%. Of the 5 patients who died, 4 had metastatic disease at death. Twenty-three patients (84%) reported either no pain or improved pain at the last follow-up visit. Sixteen patients discontinued narcotic use after treatment (62.5%). Twenty-three patients (89%) had a stable or improved American Spine Injury Association score at the last follow-up visit. No patient experienced radiation-induced myelopathy. The dose to paraspinal tumors has traditionally been limited to respect cord tolerance. With image-guided intensity-modulated radiotherapy, greater doses of radiation delivered in multiple fractions can be prescribed with excellent target coverage, effective palliation, and acceptable toxicity and local control.

D7-01: 4-dimensional respiration-gated radiotherapy for concurrent chemo-radiotherapy in lung cancer

4-dimensional respiration-gated radiotherapy for concurrent chemo-radiotherapy in lung cancer Senan, Suresh1 Spoelstra, Femke O.1 Phernambucq, Erik C.2 van Sornsen de Koste, John R.1 Cuijpers, Johan C.1 Smit, Egbert F.2 Slotman, Ben J.1 Lagerwaard, Frank J.1 1 Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands 2 Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands Background: Concurrent chemo-radiotherapy (CT-RT) is the treatment of choice in locally advanced lung cancer, but it is associated with increased esophageal and lung toxicity. Toxicity can be reduced using respiration-gated radiotherapy (RGRT) in which treatment is delivered during pre-selected phases of the respiratory cycle, thereby allowing for smaller target volumes. The feasibility of such interventions for motion management during thoracic CT-RT is unknown. We studied the compliance and toxicity of RGRT in this setting. Methods: Details of gated concurrent CT-RT were analyzed in 31 consecutive patients with a minimum follow-up of 3 months. They included 28 with locally-advanced non-small cell lung cancer (LANSCLC) and 3 with limited-stage SCLC. A subgroup of LA-NSCLC patients underwent induction CT-RT, followed by mediastinal re-staging and surgery in downstaged patients. Concurrent chemotherapy consisted of either 2-3 cycles of cisplatin-etoposide or weekly cycles of cisplatin-docetaxel. Involved-field radiotherapy was delivered to a target volume defined using a 4-dimensional (4D) CT scan, FDG-PET and biopsy-proven nodal disease. The Varian Real-time Position Management respiratory gating system (Varian Medical Systems) was used for 4DCT acquisition, and for treatment delivery. A dose of 45-60 Gy was delivered in once-daily fractions of 1.8-2.0 Gy on a Varian 2100 C/D linear accelerator. RGRT was performed using either (i) audio-coached, phase-based gating in which radiation delivery is limited to the endinspiratory phase or (ii) amplitude-based gating in which radiation is delivered within the breathing threshold levels observed during 4DCT imaging. Audio-coached, end-inspiratory gating was the procedure of choice when tumour motion exceeded 7.5 mm and/or when a significant increase in total lung volume was expected. All other patients were treated with amplitude-based gating. Results: Only 1 patient, who died of pulmonary haemorrhage during treatment, failed to complete the planned treatment. Ten patients who were downstaged underwent surgical resection. The median follow-up was 5 months. The median planning target volume (PTV) was 649.9 cc (range 274-1616). The percentage of lung volume receiving a threshold dose of 20 Gy (V20) ranged from 12.4 44.6%. The median oesophageal circumference receiving 46 Gy was 6.6 (range 0-13.5) cm. CTC grade 3 esophagitis was observed in 23% (7 pts), and 52% (16 pts.) developed grade 2 esophagitis. The mean weight loss was 2.9 kg (range 0.5-10) and 13 patients treated with preoperative CT-RT received a feeding tube, which was a prophylactic measure in 6 patients. CTC grades 2 and 3 radiation pneumonitis developed in 2 patients at 4 and 3 months, respectively, post-treatment. At the last follow-up, 23 patients were free from disease progression. Five patients had extrathoracic metastases, with 4 having exclusively distant metastasis. Loco-regional failure was observed in 3 patients, with two being out-of-field recurrences. Conclusion: RGRT is well tolerated in patients undergoing concurrent CT-RT for lung cancer. The treatment drop-out rate of 3% in this unselected cohort compares favourably with the rates of 16-19% reported in phase III trials in LA-NSCLC [Fournel 2005; Albain 2005]. Updated results at a median follow-up of 11 months will be available.

Intensity-modulated radiation therapy for prostate cancer: Late morbidity and results on biochemical control

Purpose To report on late morbidity and biochemical relapse-free survival (bRFS) after intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods Between 1998 and 2005 133 patients were treated with IMRT for T(1-4) N0 M0 prostate cancer. The median follow-up time was 36 months. In a first cohort, patients received a median planning target volume (PTV) dose of 74 Gy with a hard constraint on maximum rectum dose of 72 Gy (74R72, n = 51). Later, median PTV and maximum rectum dose were increased to 76 and 74 Gy, respectively (76R74; n = 82). We defined low-risk ( n = 20), intermediate-risk ( n = 70) and high-risk ( n = 43) groups. Androgen deprivation was given to patients in the intermediate- and high-risk group. Late gastro-intestinal (GI) and genito-urinary (GU) morbidity and biochemical relapse, in accordance with the ASTRO consensus, were recorded. Results We observed grade 2 GI (17%) and GU (19%), grade 3 GI (1%) and GU (3%) late toxicities. Except for hematuria, the median duration of side-effects was 6 months. Biochemical relapse-free survival (bRFS) at 3 and 5 years was 88% and 83%, respectively, with a significantly better 3-year bRSF for the 76R74 than for the 74R72 group ( p = 0.01). Five-year bRFS for patients in the low-risk, intermediate-risk and high-risk group was 100%, 94% and 74%, respectively ( p < 0.01). Conclusion IMRT for localized or locally advanced prostate cancer combines low morbidity with excellent biochemical control.

Absence of toxicity with hypofractionated 3-dimensional radiation therapy for inoperable, early stage non-small cell lung cancer

PurposeHypofractionated radiotherapy may overcome repopulation in rapidly proliferating tumors such as lung cancer. It is more convenient for the patients and reduces health care costs. This study reports our results on patients with medically inoperable, early stage, non-small cell lung cancer (NSCLC) treated with hypofractionation.Materials and methodsStage T1-2N0 NSCLC patients were treated with hypofractionation alone, 52.5 Gy/15 fractions, in 3 weeks, with 3-dimensional conformal planning. T1-2N1 patients with the hilar lymphnode close to the primary tumor were also eligible for this treatment. We did not use any approach to reduce respiratory motion, but it was monitored in all patients. Elective nodal radiotherapy was not performed. Routine follow up included assessment for acute and late toxicity and radiological tumor response. Median follow up time was 29 months for the surviving patients.ResultsThirty-two patients with a median age of 76 years, T1 = 15 and T2 = 17, were treated. Median planning target volume (PTV) volume was 150cc and median V16 of both lungs was 13%. The most important finding of this study is that toxicity was minimal. Two patients had grade ≤ 2 acute pneumonitis and 3 had mild (grade 1) acute esophagitis. There was no late toxicity. Actuarial 1 and 2-year overall survival rates are 78% and 56%, cancer specific survival rates (CSS) are 90% and 74%, and local relapse free survival rates are 93% and 76% respectively.Conclusion3-D planning, involved field hypofractionation at a dose of 52.5 Gy in 15 daily fractions is safe, well tolerated and easy radiation treatment for medically inoperable lung cancer patients. It shortens by half the traditional treatment. Results compare favorably with previously published studies. Further studies are needed to compare similar technique with other treatments such as surgery and stereotactic radiotherapy.