Spinal cord constraints in the era of high-precision radiotherapy : Retrospective analysis of 62 spinal/paraspinal lesions with possible infringements of spinal cord constraints within a minimal volume.

OBJECTIVE: Current constraints aim to minimize the risk of radiation myelitis by the use of restrictive maximal spinal cord doses, commonly 50 Gy. However, several studies suggested that a dose-volume effect could exist. Based on these observations, we evaluated patients receiving potentially excessive doses to the spinal cord within minimal volumes. PATIENTS AND METHODS: Patients receiving radiotherapy between June 2010 and May 2015 using the NovalisTM (Varian, Palo Alto, CA, USA; Brainlab, Heimstetten, Germany) radiosurgery system were retrospectively analyzed. A total of 56 patients with 62 treated lesions that had been prescribed radiation doses close to the spinal cord potentially higher than the common 50 Gy 2­Gy equivalent-dose (EQD2) constraint were selected for further analysis. Of these patients, 26 with 31 lesions had no history of previous irradiation, while 30 patients with 31 lesions had been previously irradiated within the treatment field. RESULTS: According to different dose evaluation approaches (spinal canal, spinal cord contour), 16 and 10 out of 31 primary irradiated lesions infringed constraints. For the 16 lesions violating spinal canal doses, the maximum doses ranged from 50.5 to 61.9 Gy EQD2. Reirradiated lesions had an average and median cumulative dose of 70.5 and 69 Gy, respectively. Dose drop-off was steep in both groups. Median overall survival was 17 months. No radiation myelitis or radiomorphological alterations were observed during follow-up. CONCLUSION: This study adds to the increasing body of evidence indicating that excessive spinal cord doses within a minimal volume, especially in a reirradiation setting with topographically distinct high-point doses, may be given to patients after careful evaluation of treatment- and tumor-associated risks.

Dosimetric implications of inter- and intrafractional prostate positioning errors during tomotherapy : Comparison of gold marker-based registrations with native MVCT.

INTRODUCTION: For high-dose radiation therapy (RT) of prostate cancer, image-guided (IGRT) and intensity-modulated RT (IMRT) approaches are standard. Less is known regarding comparisons of different IGRT techniques and the resulting residual errors, as well as regarding their influences on dose distributions. PATIENTS AND METHODS: A total of 58 patients who received tomotherapy-based RT up to 84 Gy for high-risk prostate cancer underwent IGRT based either on daily megavoltage CT (MVCT) alone (n = 43) or the additional use of gold markers (n = 15) under routine conditions. Planned Adaptive (Accuray Inc., Madison, WI, USA) software was used for elaborated offline analysis to quantify residual interfractional prostate positioning errors, along with systematic and random errors and the resulting safety margins after both IGRT approaches. Dosimetric parameters for clinical target volume (CTV) coverage and exposition of organs at risk (OAR) were also analyzed and compared. Interfractional as well as intrafractional displacements were determined. RESULTS: Particularly in the vertical direction, residual interfractional positioning errors were reduced using the gold marker-based approach, but dosimetric differences were moderate and the clinical relevance relatively small. Intrafractional prostate motion proved to be quite high, with displacements of 1-3 mm; however, these did not result in additional dosimetric impairments. CONCLUSION: Residual interfractional positioning errors were reduced using gold marker-based IGRT; however, this resulted in only slightly different final dose distributions. Therefore, daily MVCT-based IGRT without markers might be a valid alternative.

Permanent interstitial low-dose-rate brachytherapy for patients with low risk prostate cancer: An interim analysis of 312 cases.

PURPOSE: The biochemical relapse-free survival (bRFS) rate after treatment with permanent iodine-125 seed implantation (PSI) or combined seeds and external beam radiotherapy (COMB) for clinical stage T1-T2 localized prostate cancer is a clinically relevant endpoint. The goal of this work was to evaluate the influence of relevant patient- and treatment-related factors. MATERIALS AND METHODS: The study population comprised 312 consecutive patients treated with permanent seed implantation. All patients were evaluable for analysis of overall survival (OS) and disease-specific survival (DSS), 230 for bRFS, of which 192 were in the PSI group and 38 in the COMB group. The prescribed minimum peripheral dose was 145 Gy for PSI, for COMB 110 Gy implant and external beam radiotherapy of 45 Gy. The median follow-up time was 33 months (range 8-66 months). bRFS was defined as a serum prostate-specific antigen (PSA) level ≤ 0.2 ng/ml at last follow-up. RESULTS: Overall, the actuarial bRFS at 50 months was 88.4 %. The 50-month bRFS rate for PSI and COMB was 90.9 %, and 77.2 %, respectively. In the univariate analysis, age in the categories ≤ 63 and > 63 years (p < 0.00), PSA nadir (≤ 0.5 ng/ml and > 0.5 ng\ml) and PSA bounce (yes/no) were the significant predicting factors for bRFS. None of the other patient and treatment variables (treatment modality, stage, PSA, Gleason score, risk group, number of risk factors, D90 and various other dose parameters) were found to be a statistically significant predictor of 50-month bRFS. CONCLUSION: The biochemical failure rates were low in this study. As a proof of principle, our large monocenteric analysis shows that low-dose-rate brachytherapy is an effective and safe procedure for patients with early stage prostate cancer.

Image-guided intensity-modulated radiotherapy for patients with locally advanced gastric cancer: a clinical feasibility study.

BACKGROUND: The aim of this study was to determine the medical and technical feasibility of intensity-modulated radiotherapy (IMRT) in high-risk nonmetastatic gastric cancer stage II and III after primary gastrectomy and D2 lymphadenectomy. METHODS AND MATERIALS: A prospective nonrandomized phase II trial was performed on 25 consecutive patients with gastric cancer with high risk (T3-4, N1-3, G2-3, R0-1). The dose delivered was 45 Gy (1.80 Gy per fraction) in IMRT technique. Concurrent 5-fluorouracil-based chemotherapy at 225 mg/m(2) was administered as a continuous intravenous infusion. Primary endpoints were acute gastrointestinal toxicity (CTC 4.0) and technical feasibility of IMRT in regard to dose planning and radiation delivery. RESULTS: Early acute events were defined as clinical and chemical adverse effects of IMRT and concurrent chemotherapy during treatment. By definition, 90 days after the end of IMRT has been evaluated as acute-phase toxicity. No patient had grade 4 or higher acute adverse events. Clinical grade 3 toxicity occurred in two patients (8%) with diarrhea and in one case (4%) with nausea. Hematological changes with grade 3 occurred in three cases (12%) with hemoglobin decrease, in five cases (25%) as leukopenia, and in one case (4%) with thrombocytopenia. The mean dose for liver was 16 Gy and the percentage volume exceeding 30 Gy (V30) was 21%. Mean dose for right and left kidney was 9 and 13 Gy, respectively, and V20 was 9% and 13%, respectively. Heart received a median dose of 15 Gy and V40 was 17%. The mean dose to the bowel was 11 Gy and V40 was 6%. Spinal cord had at maximum 33 Gy in median. Specifics of dose distribution, including the coverage, for the target region were as follows: minimum was 33 Gy, maximum 48.6 Gy, and mean dose 44.6 Gy. The prescribed dose (45 Gy) covered 99% and 95% of planning target volume (OTV) in 66% and 92% of cases, respectively. Median PTV was 15.77 ml (range, 805-3,604 ml). CONCLUSIONS: The data support the practical feasibility of IMRT in adjuvant treatment in high-risk gastric cancer in the postoperative setting as a proof of principle. Acute toxicity has been tolerable.

Residual translational and rotational errors after kV X-ray image-guided correction of prostate location using implanted fiducials.

PURPOSE: To evaluate the residual errors and required safety margins after stereoscopic kilovoltage (kV) X-ray target localization of the prostate in image-guided radiotherapy (IGRT) using internal fiducials. PATIENTS AND METHODS: Radiopaque fiducial markers (FMs) have been inserted into the prostate in a cohort of 33 patients. The ExacTrac/Novalis Body™ X-ray 6d image acquisition system (BrainLAB AG, Feldkirchen, Germany) was used. Corrections were performed in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) direction. Rotational errors around LR (x-axis), AP (y) and SI (z) have been recorded for the first series of nine patients, and since 2007 for the subsequent 24 patients in addition corrected in each fraction by using the Robotic Tilt Module™ and Varian Exact Couch™. After positioning, a second set of X-ray images was acquired for verification purposes. Residual errors were registered and again corrected. RESULTS: Standard deviations (SD) of residual translational random errors in LR, AP, and SI coordinates were 1.3, 1.7, and 2.2 mm. Residual random rotation errors were found for lateral (around x, tilt), vertical (around y, table), and longitudinal (around z, roll) and of 3.2°, 1.8°, and 1.5°. Planning target volume (PTV)-clinical target volume (CTV) margins were calculated in LR, AP, and SI direction to 2.3, 3.0, and 3.7 mm. After a second repositioning, the margins could be reduced to 1.8, 2.1, and 1.8 mm. CONCLUSION: On the basis of the residual setup error measurements, the margin required after one to two online X-ray corrections for the patients enrolled in this study would be at minimum 2 mm. The contribution of intrafractional motion to residual random errors has to be evaluated.

Potential impact of (68)Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas.

PURPOSE: Since meningiomas show a high expression of somatostatin receptor subtype 2, PET with (68)Ga-DOTATOC was proposed as an additional imaging modality beside CT and MRI for planning radiotherapy. We investigated the input of (68)Ga-DOTATOC-PET/CT on the definition of the "gross tumour volume" (GTV) in meningiomas, in order to assess the potential value of this method. METHODS: Prior to radiotherapy, 42 patients with meningiomas (26 f, 16 m, mean age 55) underwent MRI and (68)Ga-DOTATOC-PET/CT examinations. HISTORY: operated n = 24, radiotherapy n = 1, operation and radiotherapy n = 8, no treatment n = 9. PET/CT and MRI data were co-registered using a BrainLAB workstation. For comparison, the GTV was defined first under consideration of CT and MRI data, then using PET data. RESULTS: 3/42 patients were excluded from the analysis (two with negative PET results, one with an extensive tumour, not precisely delineable by MRI or PET/CT). The average GTV(CT/MRI) was 22(+/-19)cm(3); GTV(PET) was 23(+/-20)cm(3). Additional GTV, obtained as a result of PET was 9(+/-10)cm(3) and was observed in patients with osseous infiltration. In some pre-treated patients there were intratumoural areas (as identified in CT/MRI) without SR-expression (7(+/-11)cm(3)). Common GTV as obtained by both CT/MRI and PET was 15(+/-14)cm(3). The mean bi-directional difference between the GTV(CT/MRI) and GTV(PET) accounted to 16(+/-15)cm(3) (93%, p < 0.001). In a subgroup of seven patients with multiple meningiomas, PET showed a total of 19 lesions; nine of them were not recognizable by CT or MRI. CONCLUSION: (68)Ga-DOTATOC-PET enables delineation of SR-positive meningiomas and delivers additional information to both CT and MRI regarding the planning of stereotactic radiotherapy. The acquisition on a PET/CT scanner helps to estimate the relation of PET findings to anatomical structures and is especially useful for detection of osseous infiltration. (68)Ga-DOTATOC-PET also allows detection of additional lesions in patients with multiple meningiomas.

Postimplantation analysis enables improvement of dose-volume histograms and reduction of toxicity for permanent seed implantation.

PURPOSE: To demonstrate how postimplantation analysis is useful for improving permanent seed implantation and reducing toxicity. PATIENTS AND METHODS: We evaluated 197 questionnaires completed by patients after permanent seed implantation (monotherapy between 1999 and 2003). For 70% of these patients, a computed tomography was available to perform postimplantation analysis. The index doses and volumes of the dose-volume histograms (DVHs) were determined and categorized with respect to the date of implantation. Differences in symptom scores relative to pretherapeutic status were analyzed with regard to follow-up times and DVH descriptors. Acute and subacute toxicities in a control group of 117 patients from an earlier study (June 1999 to September 2001) by Wust et al. (2004) were compared with a matched subgroup from this study equaling 110 patients treated between October 2001 and August 2003. RESULTS: Improved performance, identifying a characteristic time dependency of DVH parameters (after implantation) and toxicity scores, was demonstrated. Although coverage (volume covered by 100% of the prescription dose of the prostate) increased slightly, high-dose regions decreased with the growing experience of the users. Improvement in the DVH and a reduction of toxicities were found in the patient group implanted in the later period. A decline in symptoms with follow-up time counteracts this gain of experience and must be considered. Urinary and sexual discomfort was enhanced by dose heterogeneities (e.g., dose covering 10% of the prostate volume, volume covered by 200% of prescription dose). In contrast, rectal toxicities correlated with exposed rectal volumes, especially the rectal volume covered by 100% of the prescription dose. CONCLUSION: The typical side effects occurring after permanent seed implantation can be reduced by improving the dose distributions. An improvement in dose distributions and a reduction of toxicities were identified with elapsed time between 1999 and 2003.

Locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma.

BACKGROUND: The dismal overall survival (OS) prognosis of glioblastoma, even after trimodal therapy, can be attributed mainly to the frequent incidence of intracranial relapse (ICR), which tends to present as an in-field recurrence after a radiation dose of 60 Gray (Gy). In this study, molecular marker-based prognostic indices were used to compare the outcomes of radiation with a standard dose versus a moderate dose escalation. METHODS: This retrospective analysis included 156 patients treated between 2009 and 2016. All patients were medically fit for postoperative chemoradiotherapy. In the dose-escalation cohort a simultaneous integrated boost of up to 66 Gy (66 Gy RT) within small high-risk volumes was applied. All other patients received daily radiation to a total dose of 60 Gy or twice daily to a total dose of 59.2 Gy (60 Gy RT). RESULTS: A total of 133 patients received standard 60 Gy RT, while 23 received 66 Gy RT. Patients in the 66 Gy RT group were younger (p <  0.001), whereas concomitant temozolomide use was more frequent in the 60 Gy RT group (p <  0.001). Other intergroup differences in known prognostic factors were not observed. Notably, the median time to ICR was significantly prolonged in the 66 Gy RT arm versus the 60 Gy RT arm (12.2 versus 7.6 months, p = 0.011), and this translated to an improved OS (18.8 versus 15.3 months, p = 0.012). A multivariate analysis revealed a strong association of 66 Gy RT with a prolonged time to ICR (hazard ratio = 0.498, p = 0.01) and OS (hazard ratio = 0.451, p = 0.01). These differences remained significant after implementing molecular marker-based prognostic scores (ICR p = 0.008, OS p = 0.007) and propensity-scored matched pairing (ICR p = 0.099, OS p = 0.023). CONCLUSION: Radiation dose escalation was found to correlate with an improved time to ICR and OS in this cohort of glioblastoma patients. However, further prospective validation of these results is warranted.

A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas.

BACKGROUND: The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N) cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy. METHODS: Between 1987 and 1995 we treated 122 patients with unresectable (stage IV head and neck) cancer by two different protocols. The sequential protocol (SEQ; 1987-1992) started with two courses of neoadjuvant chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i.) of folinic acid [FA] and 5-fluorouracil [5-FU]), followed by a course of radiochemotherapy using conventional fractionation up to 70 Gy. The concomitant protocol (CON; since 1993) combined two courses of FA/5-FU c.i. plus mitomycin (MMC) concomitantly with a course of radiotherapy up to 30 Gy in conventional fractionation, followed by a hyperfractionated course up to 72 Gy. Results from the two groups were compared. RESULTS: Patient and tumor characteristics were balanced (SEQ = 70, CON = 52 pts.). Mean radiation dose achieved (65.3 Gy vs. 71.6 Gy, p = 0.00), response rates (67 vs. 90 % for primary, p = 0.02), and local control (LC; 17.6% vs. 41%, p = 0.03), were significantly lower in the SEQ group, revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08) and overall (14.7% vs. 23.7%, p = 0.11) survival rates after 5 years. Mucositis grades III and IV prevailed in the CON group (54% versus 44%). Late toxicity was similar in both groups. CONCLUSION: Concurrent chemotherapy seemed more effective in treating head and neck tumors than induction chemotherapy followed by chemoradiation, resulting in better local control and a trend towards improved survival.

Clinical and physical determinants for toxicity of 125-I seed prostate brachytherapy.

BACKGROUND AND PURPOSE: To assess acute as well as long-term toxicity after permanent prostate seed implantation. To find predictive clinical or dosimetric factors for side effects in order to work out strategies for improvement. PATIENTS AND METHODS: A group of 174 patients with localised prostate cancer was treated with permanent seed implantation between 1999 and 2001, either alone (140 patients) or in combination with external radiotherapy (34 patients). For the majority (114/174, i.e. 66%) a CT was performed four weeks after implantation and analysed in the planning system VariSeed. In the postimplant analysis, dosimetric descriptors (doses, volumes) were determined for the prostate and rectum and compared with the intraoperative values. In addition, a questionnaire was sent to all patients to assess and quantify acute and chronic toxicity (urinary, rectal, sexual) and the impact on subjective acceptance and quality of life (return rate of questionnaires 83%). The derived score changes were correlated with clinical and dosimetric factors. RESULTS: In the mono-brachytherapy group 14% (16/140) required a bladder catheter, of them 8% (9/140) with a manifest urinary obstruction. Long-term rectal toxicity (<5%) and impairment of potency (<30%) are moderate and obviously below other treatment options. Urinary toxicity is dominant with an overall long-term dysuria up to 30% (at a mean observation interval of ten months), and a significant trend to decline with follow-up time. Conversely, the erectile function tends to deteriorate with follow-up time. Nevertheless, quality of life is not significantly reduced and acceptance is high. Our analysis suggests that the main factor for urinary toxicity and impaired erectile function is the dose load to larger portions of the prostate (D(50)>240 Gy), which appears to be attributed to unnecessarily high numbers of seeds (for a fixed activity per seed) and needles. The rectal toxicity is correlated with the high dose regions in the rectum (>/=145 Gy). Urinary toxicity is lower for combined-brachytherapy, while rectal toxicity and impairment of potency are slightly higher. CONCLUSIONS: Toxicity spectrum and quality of life after permanent seed implantation for early prostate cancer are acceptable for nearly all patients (98%). To further improve tolerance we should attempt to achieve a better dose homogeneity, i.e. by reducing D(50). Therefore, special attention should be given to D(50) during the real-time planning process. The necessity of more homogeneous dose distributions might imply a reduction of the activity per seed, e.g. from 0.7 mCi down to 0.6 mCi.

The impact of 18 F-FET PET-CT on target definition in image-guided stereotactic radiotherapy in patients with skull base lesions.

BACKGROUND: 18 F-fluoro-ethyl-tyrosine PET is gaining more indications in the field of oncology. We investigated the potentials of usage of FET-PET/CT in addition to MRI for definition of gross tumor volume (GTV) in stereotactic radiotherapy of lesions of skull base. METHODS: We included in a prospective setting 21 cases. An MRI was performed, completed by FET PET/CT. Different GTV's were defined based on respective imaging tools: 1. GTVMRI, 2. GTV MRI /CT, 3. GTV composit (1 + 2), and GTVPET = GTV Boost. Lesions could be visualised by MRI and FET-PET/CT in all patients. RESULTS: FET tracer enhancement was found in all cases. Skull base infiltration by these lesions was observed by MRI, CT (PET/CT) and FET-PET (PET/CT) in all patients. Totally, brain tissue infiltration was seen in 10 patients. While, in 7 (out 10) cases, MRI and CT (from PET/CT) were indicating brain infiltration, FET-PET could add additional information regarding infiltrative behaviour: in 3 (out 10) patients, infiltration of the brain was displayed merely in FET-PET. An enlargement of GTVMRI/CT due to the FET-PET driven information, which revealed GTVcomposite , was necessary in 7 cases,. This enlargement was significant by definition (> 10% of GTVMRI/CT). The mean PET-effect on GTV counted for 1 ± 4 cm3. The restricted boost fields were based mainly on the GTVPET volume. In mean, about 8.5 cm3 of GTVMRI/CT, which showed no FET uptake, were excluded from target volume. GTV boost driven by only-PET-activity, was in mean by 33% smaller than the initial large treatment field, GTV composite, for those cases received boost treatment. FET-PET lead to significant (>10%) changes in the initial treatment fields in 11/21 patients and showed additional tumour volume relevant for radiation planning in 6/21 cases, and led to a subsequent decrease of more than 10% of the initial volumes for the boost fields. CONCLUSION: The implementation of FET PET into the planning procedures showed a benefit in terms of accurate definition of skull base lesions as targets for Image-guided stereotactic Radiotherapy. This has to be investigated prospectively in larger cohorts.

Results for local control and functional outcome after linac-based image-guided stereotactic radiosurgery in 190 patients with vestibular schwannoma.

BACKGROUND: We assessed local control (LC) and functional outcome after linac-based stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). METHODS: Between 1998 and 2008, 190 patients with VS were treated with SRS. All patients had tumors <2 cm diameter. Patients received 13.5 Gy prescribed to the 80th isodose at the tumor margin. The primary endpoint was LC. Secondary endpoints were symptomatic control and morbidity. RESULTS: Median follow-up was 40 months. LC was achieved in 88% of patients. There were no acute reactions exceeding Grade I. Trigeminal nerve dysfunction was present in 21.6% (n = 41) prior to SRS. After treatment, 85% (n = 155) had no change, 4.4,% (n = 8) had a relief of symptoms, 10.4% (n = 19) had new symptoms. Facial nerve dysfunction was present in some patients prior to treatment, e.g. paresis (12.6%; n = 24) and dysgeusia (0.5%; n = 1). After treatment 1.1% (n = 2) reported improvement and 6.1% (n = 11) experienced new symptoms. Hearing problems before SRS were present in 69.5% of patients (n = 132). After treatment, 62.6% (n = 144) had no change, 10.4% (n = 19) experienced improvement and 26.9% (n = 49) became hearing impaired. CONCLUSION: This series of SRS for small VS provided similar LC rates to microsurgery; thus, it is effective as a non-invasive, image-guided procedure. The functional outcomes observed indicate the safety and effectiveness of linac-based SRS. Patients may now be informed of the clinical equivalence of SRS to microsurgery.

Anal carcinoma: surgery does not influence prognosis when performed prior to concurrent radiochemotherapy.

BACKGROUND: Concurrent radiochemotherapy (cRCT) is the standard-of-care for patients with locally advanced anal cancer. There is a subgroup of patients however, vastly with small tumors, which undergo local excision before combined modality treatment. It was suggested that local excision prior to cRCT might improve the local control in comparison with cRCT. We evaluated local excision in comparison to incisional biopsy in this setting. PATIENTS AND METHODS: Between 2000 and 2005, 84 patients were included in the study. In the majority of patients, only incisional biopsy (INC) was performed for the histopathological verification. Other patients underwent surgery prior to the RCT course as excisional biopsy (EXC). The chemotherapy consisted of 5-fluorouracil (800/1000 mg/m(2)/d, 4 consecutive days, w 1, five) and mitomycin C (2 times 10 mg/m(2)). Radiotherapy was prescribed 45 at Gy. RESULTS: All patients (T1-2) were available for analysis. 14% of patients had node-positive disease. For the entire series, at five years and eight years, the actuarial OAS rates were 71% and 54%, respectively; the DSS rates were 74% and 68%, respectively; and the DFS rates were 54% and 54%, respectively. The actuarial control rate achieved by the EXC group was 80% after five years, better than the one for the INC group at 64%. Univariate analysis showed that tumor stage T3-T4 (p=0.04), tumor size ≥6 cm (p<0.001), nodal stage N1-3 (p<0.00) and OTT >40 days (p=0.05) are significantly correlated with poorer local disease control. Local excision in comparison with INC did not prove to be significant for local disease control (p=0.45). No significance was found for pre-therapeutic prognostic factors age, gender, histological type and grading. Multivariate analysis showed that tumor size as continuous variable (p=0.02) and OTT (p=0.04) remained significant when adjusted for T-stage and nodal stage. CONCLUSION: According to this highly qualitative trial, surgical excision prior to cRCT, did not improve results. cRCT was confirmed as the standard-of-care.

Image-guided radiotherapy with implanted markers and kilovoltage imaging and 6-dimensional position corrections for intrafractional motion of the prostate.

BACKGROUND/AIM: To assess intrafractional prostate and patient movement using intra-prostatic fiducials and stereoscopic kilovoltage (kV) X-ray imaging in a 6-dimensional (6D) position correction protocol. To evaluate potential gains of intra-treatment repositioning with respect to treatment margins. PATIENTS AND METHODS: In intensity-modulated radiotherapy of prostate cancer patients were positioned according to internal fiducials in six dimensions by the use of ExacTrac/Novalis Body™ (ET/NB) System and a robotic couch. Intrafractional displacement of both, prostate and patient were analyzed in 427 treatment fractions of 13 patients. Systematic and random components were specified and used for intra-treatment margin calculation. The potential reduction of treatment margins, and intrafractional repositioning by use of the ET Snap Verification presumed, was simulated. RESULTS: The mean treatment duration was 14.2±2.6 min. Standard deviations (SDs) of the effective intrafractional target displacement in superior-inferior (SI) and anterior-posterior (AP) axes were 2.4 mm and 2.1 mm, respectively. Systematic errors for patient were 1.8 and 1.7 mm, and for prostate movement were 2.1 and 2.0 mm in SI and AP, respectively. The SDs of intrafractional rotation errors of the prostate around SI and left right (LR) were on average 2.2 and 3.6 degrees, respectively. Margins covering intrafractional motion were 4.5 and 4.3 mm in SI and AP without intrafractional correction and were estimated to 2.9 mm and 2.8 mm in SI and AP, respectively for simulated intra-treatment intervention. CONCLUSION: After positioning according to fiducials, intrafractional motion is significant for treatment margins. Despite correcting rotational deviations by couch angulation, the systematic error for the component of prostate motion was somewhat larger than that of patient displacement. Intrafractional correction could be useful in reducing treatment margins.

Image-guided stereotactic radiosurgery for cranial lesions: large margins compensate for reduced image guidance frequency.

BACKGROUND: We investigated patient positioning during radiosurgery of cranial lesions, and calculated clinical target volume (CTV) to planning target volume (PTV) margins using a modified common margin recipe. We simulated CTV-to-PTV margins for reduced image guidance, and repositioning for the first table angle only. PATIENTS AND METHODS: Patients were immobilized with a thermoplastic mask. Positioning was verified and corrected using the ExacTrac/Novalis Body. Each patient was repositioned before each beam. A common margin recipe was adapted for estimation of CTV-to-PTV margins. Necessary margins were estimated to correct positioning for the initial table angle only in comparison. RESULTS: In total, 269 radiosurgery treatments with 967 different-angle setups (mean 3.6 different angles) were performed on 190 patients. Residual translational errors were (one standard deviation) 0.3 mm in left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions, with a mean three-dimensional vector of 0.5 mm. Margins for residual errors after correction were calculated in LR, SI, and AP directions as 0.8 mm. For simulated reduced frequency setup correction, we calculated CTV-to-PTV margins as 1.9, 1.9, and 1.6 mm, respectively. CONCLUSIONS: The ExacTrac/Novalis Body system allows for accurate positioning of the patient with a residual error comparable to invasive mask fixation. If verification is only performed after initial positioning, adaption of CTV-to-PTV margins should be considered.

Contribution of 68Ga-DOTATOC PET/CT to target volume delineation of skull base meningiomas treated with stereotactic radiation therapy.

PURPOSE: To investigate the potential impact of 68Ga-DOTATOC positron emission tomography (68Ga-DOTATOC-PET) in addition to magnetic resonance imaging (MRI) and computed tomography (CT) for retrospectively assessing the gross tumor volume (GTV) delineation of meningiomas of the skull base in patients treated with fractionated stereotactic radiation therapy (FSRT). METHODS AND MATERIALS: The study population consisted of 48 patients with 54 skull base meningiomas, previously treated with FSRT. After scans were coregistered, the GTVs were first delineated with MRI and CT data (GTVMRI/CT) and then by PET (GTVPET) data. The overlapping regions of both datasets resulted in the GTVcommon, which was enlarged to the GTVfinal by adding volumes defined by only one of the complementary modalities (GTVMRI/CT-added or GTVPET-added). We then evaluated the contribution of conventional imaging modalities (MRI, CT) and 68Ga-DOTATOC-PET to the GTVfinal, which was used for planning purposes. RESULTS: Forty-eight of the 54 skull base lesions in 45 patients showed increased 68Ga-DOTATOC uptake and were further analyzed. The mean GTVMRI/CT and GTVPET were approximately 21 cm3 and 25 cm3, with a common volume of approximately 15 cm3. PET contributed a mean additional GTV of approximately 1.5 cm3 to the common volume (16%±34% of the GTVcommon). Approximately 4.5 cm3 of the GTVMRI/CT was excluded from the contribution to the common volume. The resulting mean GTVfinal was significantly smaller than both the GTVMRI/CT and the GTVPET. Compared with the initial GTVMRI/CT, the addition of 68Ga-DOTATOC-PET resulted in more than 10% modification of the size of the GTVfinal in 32 (67%) meningiomas CONCLUSIONS: 68Ga-DOTATOC-PET/CT seems to improve the target volume delineation in skull base meningiomas, often leading to a reduction of GTV compared with results from conventional imaging (MRI and CT).

Appropriate patient instructions can reduce prostate motion.

BACKGROUND: Interfraction prostate motion must be compensated by increased safety margins. If filling status of rectum and bladder is constant, motion should be reduced. We attempted to reduce interfraction motion errors by proper patient instruction. METHOD: In 38 patients pairs of radio-opaque fiducial markers were implanted prior to definitive radiotherapy. Patients were positioned either according to skin marks or infrared body marker. We measured prostate displacement, i.e. pelvic bones versus intraprostatic marker position, via ExacTrac (two orthogonal radiographies) in 1252 fractions. Systematic and random setup and displacement errors were determined and safety margins estimated. RESULTS: In our study interfraction prostate displacement is < 1 mm in RL direction, and < 2 mm in AP and SI direction. Systematic errors are slightly below random errors (< 1.5 mm). Positioning according skin marks results in higher inaccuracies of ±1.5 - 2 mm in RL and ±2 - 2.5 mm in AP/SI direction. CONCLUSIONS: In case of appropriate patient instructions (constant organ filling) the positioning via bone fusion requires CTV-PTV margins of 2 mm in RL, 4 mm in AP, and 5 mm in SI direction. Studies without any description of patient instruction found much higher margins of > 1 cm in AP and SI direction.

Interfraction rotation of the prostate as evaluated by kilovoltage X-ray fiducial marker imaging in intensity-modulated radiotherapy of localized prostate cancer.

To quantify the daily rotation of the prostate during a radiotherapy course using stereoscopic kilovoltage (kV) x-ray imaging and intraprostatic fiducials for localization and positioning correction. From 2005 to 2009, radio-opaque fiducial markers were inserted into 38 patients via perineum into the prostate. The ExacTrac/Novalis Body X-ray 6-day image acquisition system (ET/NB; BrainLab AG, Feldkirchen, Germany) was used to determine and correct the target position. During the first period in 10 patients we recorded all rotation errors but used only Y (table) for correction. For the next 28 patients we used for correction all rotational coordinates, i.e., in addition Z (superior-inferior [SI] or roll) and X (left-right [LR] or tilt/pitch) according to the fiducial marker position by use of the Robotic Tilt Module and Varian Exact Couch. Rotation correction was applied above a threshold of 1° displacement. The systematic and random errors were specified. Overall, 993 software-assisted rotational corrections were performed. The interfraction rotation errors of the prostate as assessed from the radiodense surrogate markers around the three axes Y, Z, and X were on average 0.09, -0.52, and -0.01° with standard deviations of 2.01, 2.30, and 3.95°, respectively. The systematic uncertainty per patient for prostate rotation was estimated with 2.30, 1.56, and 4.13° and the mean random components with 1.81, 2.02, and 3.09°. The largest rotational errors occurred around the X-axis (pitch), but without preferring a certain orientation. Although the error around Z (roll) can be compensated on average by a transformation with 4 coordinates, a significant error around X remains and advocates the full correction with 6 coordinates. Rotational errors as assessed via daily stereoscopic online imaging are significant and dominate around X. Rotation possibly degrades the dosimetric coverage of the target volume and may require suitable strategies for correction.

Contribution of (18)F-Fluoro-ethyl-tyrosine Positron Emission Tomography to Target Volume Delineation in Stereotactic Radiotherapy of Malignant Cranial Base Tumours: First Clinical Experience.

Increased amino acid uptake has been demonstrated in intracerebral tumours and head and neck carcinomas of squamous cell origin. We investigated the potential impact of using (18)F-fluoro-ethyl-tyrosine ((18)F-FET)-PET/CT in addition to conventional imaging for gross tumour volume (GTV) delineation in stereotactic radiotherapy of skull base tumours. The study population consisted of 14 consecutive patients with cranial base tumours (10 with squamous cell histology, 4 others). All patients underwent a FET-PET/CT examination in addition to contrast-enhanced CT and 11 patients underwent MRI. All tumours and histologic types showed increased FET uptake. The GTV was defined by all voxels showing hyperintensity in MRI or CT (GTV(MRI/CT)) or enhancement in PET (GTV(PET)), forming a GTV(composite) that was used for the initial treatment fields. An additional volume of infiltrative growth outside the GTV(MRI/CT) of about 1.0 ± 2 cm(3) (5% of the conventional volume) was demonstrated by FET-PET only (GTV(PETplus)) with significant enlargement (>10% of GTV(MRI/CT)) in three patients. From existing data, we found correlation between cellular density and the standardized uptake value (SUV) of FET. We were able to substantially reduce the volume of escalated radiation dose (GTV(boost)) by 11 ± 2 cm(3) (24%) of the conventional volume.