Peter Nowak

Stereotactic body radiation therapy for primary and metastatic liver tumors: A single institution phase i-ii study

The feasibility, toxicity and tumor response of stereotactic body radiation therapy (SBRT) for treatment of primary and metastastic liver tumors was investigated. From October 2002 until June 2006, 25 patients not suitable for other local treatments were entered in the study. In total 45 lesions were treated, 34 metastases and 11 hepatocellular carcinoma (HCC). Median follow-up was 12.9 months (range 0.5–31). Median lesion size was 3.2 cm (range 0.5–7.2) and median volume 22.2 cm3 (range 1.1–322). Patients with metastases, HCC without cirrhosis, and HCCu200a<u200a4 cm with cirrhosis were mostly treated with 3×12.5 Gy. Patients with HCC ≥4cm and cirrhosis received 5×5 Gy or 3×10 Gy. The prescription isodose was 65%. Acute toxicity was scored following the Common Toxicity Criteria and late toxicity with the SOMA/LENT classification. Local failures were observed in two HCC and two metastases. Local control rates at 1 and 2 years for the whole group were 94% and 82%. Acute toxicity grade ≥3 was seen in four patients; one HCC patient with Child B developed a liver failure together with an infection and died (grade 5), two metastases patients presented elevation of gamma glutamyl transferase (grade 3) and another asthenia (grade 3). Late toxicity was observed in one metastases patient who developed a portal hypertension syndrome with melena (grade 3). SBRT was feasible, with acceptable toxicity and encouraging local control. Optimal dose-fractionation schemes for HCC with cirrhosis have to be found. Extreme caution should be used for patients with Child B because of a high toxicity risk.

Radiosurgery for brain metastases: Relationship of dose and pattern of enhancement to local control

PURPOSEnThis study aimed to analyze dose, initial pattern of enhancement, and other factors associated with freedom from progression (FFP) of brain metastases after radiosurgery (RS).nnnMETHODS AND MATERIALSnAll brain metastases treated with gamma-knife RS at the University of California, San Francisco, from 1991 to 1994 were reviewed. Evaluable lesions were those with follow-up magnetic resonance or computed tomographic imaging. Actuarial FFP was calculated using the Kaplan-Meier method, measuring FFP from the date of RS to the first imaging study showing tumor progression. Controlled lesions were censored at the time of the last imaging study. Multivariate analyses were performed using a stepwise Cox proportional hazards model.nnnRESULTSnOf 261 lesions treated in 119 patients, 219 lesions in 100 patients were evaluable. Major histologies included adenocarcinoma (86 lesions), melanoma (77), renal cell carcinoma (21), and carcinoma not otherwise specified (17). The median prescribed RS dose was 18.5 Gy (range, 10-22) and the median tumor volume was 1.3 ml (range, 0.02-30.9). The initial pattern of contrast enhancement was homogeneous in 68% of lesions, heterogeneous in 12%, and ring-enhancing in 19%. The actuarial FFP was 82% at 6 months and 77% at 1 year for all lesions, and 93 and 90%, respectively, for 145 lesions receiving > or = 18 Gy. Multivariate analysis showed that longer FFP was significantly associated with higher prescribed RS dose, a homogeneous pattern of contrast enhancement, and a longer interval between primary diagnosis and RS. Adjusted for these factors, adenocarcinomas had longer FFP than melanomas. No significant differences in FFP were noted among lesions undergoing RS for recurrence after prior radiotherapy (119 lesions), RS alone as initial treatment (45), or RS boost (55).nnnCONCLUSIONnA minimum prescribed radiosurgical dose > or = 18 Gy yields excellent local control of brain metastases. The influence of pattern of enhancement on local control, a new finding in this retrospective analysis, needs to be confirmed.

Rotterdam and Brussels CT-based neck nodal delineation compared with the surgical levels as defined by the American Academy of Otolaryngology–Head and Neck Surgery

PURPOSE/OBJECTIVEnRotterdam and Brussels have independently published guidelines for the definition and delineation of CT-based neck nodal Levels I-VI. This paper first reports on the adequacy of contouring of the Rotterdam delineation protocol. Rotterdam and Brussels differed slightly in translating the original surgical level definitions as proposed by the 2002 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) to CT guidelines. To adapt to the surgical level definitions to come to a unifying concept, adjustments of both CT-based classifications are proposed.nnnMETHODS AND MATERIALSnThe clinical neck nodal target volumes of patients irradiated in Rotterdam by three-dimensional conformal radiotherapy (3D-CRT) between December 1998 and March 2001 were reviewed. Thirty-four patients with N0 and 27 patients with N+ disease with primary tumors located in the oral cavity (n = 1) oropharynx (n = 24), hypopharynx (n = 7), and larynx (n = 29) were evaluated. Seven patients underwent unilateral (3 N0 patients, 4 N+ patients) and 54 underwent bilateral (31 N0 patients, 23 N+ patients) irradiation of the neck. In 11 N+ patients, 3D-CRT of the neck was followed by unilateral neck dissection. The dose to the primary and nonresected N+ necks was 70 Gy and to the N0 neck was 46 Gy. Neck levels were analyzed for adequacy of contouring, dose distribution, and patterns of relapse. The mean dose and the percentage of the volume receiving a minimum of 95% (V95) or >107% (V107) of the prescribed dose was computed.nnnRESULTSnIn 4 patients treated with bilateral 3D-CRT, contouring was not in concordance with the guidelines of the protocol. The V95 and V107 in the 81 adequately contoured N0 necks (63 irradiated N0 necks from 33 N0 patients, 18 irradiated N0 necks from 24 N+ patients) was 95.6% and 6.3%, respectively. For the 26 N+ necks (15 N+ necks from 13 N+ RT-only patients, 11 N+ necks from 11 preoperatively irradiated patients), the V95 and V107 was 94.6% and 6.7%, respectively. With a median follow-up of 29 months, in 4 (8.6%) of 46 patients treated by 3D-CRT only, regional relapse was found. An actuarial regional and locoregional relapse-free survival and disease-free survival rate at 3 years of 90%, 78%, and 68%, respectively, was observed. All regional relapses were observed in the N0 necks of patients with supraglottic laryngeal carcinoma. Taking the surgical 2002 AAO-HNS classification as a reference, adjustments are proposed for the Rotterdam and Brussels delineation protocols to arrive at a unified CT-based neck nodal classification.nnnCONCLUSIONnAdequate dose coverage for the Rotterdam CT-based contours of the neck nodal levels was found. In the RT-only patients, only four failures were observed: one regional and three locoregional relapses. As a next step in optimizing the current Rotterdam and Brussels CT-based delineation protocols, adaptations are proposed to resolve the discrepancies compared with the 2002 AAO-HNS surgical classification.

Clinical validation of atlas-based auto-segmentation of multiple target volumes and normal tissue (swallowing/mastication) structures in the head and neck.

PURPOSEnTo validate and clinically evaluate autocontouring using atlas-based autosegmentation (ABAS) of computed tomography images.nnnMETHODS AND MATERIALSnThe data from 10 head-and-neck patients were selected as input for ABAS, and neck levels I-V and 20 organs at risk were manually contoured according to published guidelines. The total contouring times were recorded. Two different ABAS strategies, multiple and single subject, were evaluated, and the similarity of the autocontours with the atlas contours was assessed using Dice coefficients and the mean distances, using the leave-one-out method. For 12 clinically treated patients, 5 experienced observers edited the autosegmented contours. The editing times were recorded. The Dice coefficients and mean distances were calculated among the clinically used contours, autocontours, and edited autocontours. Finally, an expert panel scored all autocontours and the edited autocontours regarding their adequacy relative to the published atlas.nnnRESULTSnThe time to autosegment all the structures using ABAS was 7 min/patient. No significant differences were observed in the autosegmentation accuracy for stage N0 and N+ patients. The multisubject atlas performed best, with a Dice coefficient and mean distance of 0.74 and 2 mm, 0.67 and 3 mm, 0.71 and 2 mm, 0.50 and 2 mm, and 0.78 and 2 mm for the salivary glands, neck levels, chewing muscles, swallowing muscles, and spinal cord-brainstem, respectively. The mean Dice coefficient and mean distance of the autocontours vs. the clinical contours was 0.8 and 2.4 mm for the neck levels and salivary glands, respectively. For the autocontours vs. the edited autocontours, the mean Dice coefficient and mean distance was 0.9 and 1.6 mm, respectively. The expert panel scored 100% of the autocontours as a minor deviation, editable or better. The expert panel scored 88% of the edited contours as good compared with 83% of the clinical contours. The total editing time was 66 min.nnnCONCLUSIONnMultiple-subject ABAS of computed tomography images proved to be a useful novel tool in the rapid delineation of target and normal tissues. Although editing of the autocontours is inevitable, a substantial time reduction was achieved using editing, instead of manual contouring (180 vs. 66 min).

Hypofractionation vs Conventional Radiation Therapy for Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Matched-Cohort Analysis

PURPOSEnDespite conventional radiation therapy, 54 Gy in single doses of 1.8 Gy (54/1.8 Gy) over 6 weeks, most children with diffuse intrinsic pontine glioma (DIPG) will die within 1 year after diagnosis. To reduce patient burden, we investigated the role of hypofractionation radiation therapy given over 3 to 4 weeks. A 1:1 matched-cohort analysis with conventional radiation therapy was performed to assess response and survival.nnnMETHODS AND MATERIALSnTwenty-seven children, aged 3 to 14, were treated according to 1 of 2 hypofractionation regimens over 3 to 4 weeks (39/3 Gy, n=16 or 44.8/2.8 Gy, n=11). All patients had symptoms for ≤3 months, ≥2 signs of the neurologic triad (cranial nerve deficit, ataxia, long tract signs), and characteristic features of DIPG on magnetic resonance imaging. Twenty-seven patients fulfilling the same diagnostic criteria and receiving at least 50/1.8 to 2.0 Gy were eligible for the matched-cohort analysis.nnnRESULTSnWith hypofractionation radiation therapy, the overall survival at 6, 9, and 12 months was 74%, 44%, and 22%, respectively. Progression-free survival at 3, 6, and 9 months was 77%, 43%, and 12%, respectively. Temporary discontinuation of steroids was observed in 21 of 27 (78%) patients. No significant difference in median overall survival (9.0 vs 9.4 months; P=.84) and time to progression (5.0 vs 7.6 months; P=.24) was observed between hypofractionation vs conventional radiation therapy, respectively.nnnCONCLUSIONSnFor patients with newly diagnosed DIPG, a hypofractionation regimen, given over 3 to 4 weeks, offers equal overall survival with less treatment burden compared with a conventional regimen of 6 weeks.

Treatment portals for elective radiotherapy of the neck: an inventory in The Netherlands

PURPOSEnTo assess the variation in and the three-dimensional dosimetric consequences of treatment portals for elective neck irradiation.nnnMATERIALS AND METHODSnRadiation oncologists (n = 16) from all major Head and Neck Co-operative Groups in The Netherlands (n = 11) were asked to delineate treatment portals on a lateral and an anterior simulation film in case of elective neck irradiation for a T3N0 tumour of the supraglottic larynx and a T2N0 tumour of the mobile tongue. In addition, they had to define their target, i.e. which parts of the neck nodal regions they would choose to irradiate electively for these particular tumour sites. Subsequently, treatment portals were compared and evaluated using CT-data and a 3-dimensional (3D) treatment planning system.nnnRESULTSnSignificant variations were found in the shapes and sizes of the applied treatment techniques and portals. Also, among radiation oncologists who elected to irradiate the same lymph node regions, a significant variation in the delineated treatment portals was observed. As a consequence, substantial variations in treated volumes and in calculated normal tissue complication probabilities (NTCPs) for the parotid- and submandibular glands were observed.nnnCONCLUSIONnFor the tumour sites studied there appears to be a lack of standardisation in the areas of the neck to be irradiated electively. The observed differences may have consequences for the ultimate failure rate and particularly with regard to the side effects, e.g. the degree of xerostomia. It is argued that in the near future a more precise three-dimensional definition on CT of the lymph node regions in the neck might allow for a better standardisation of the treatment portals and, in addition, for the development and application of conformal radiotherapy techniques for optimal sparing of the critical normal tissues (e.g. parotid- and submandibular glands) with maximum tumour control probability.

Clinical thermometry, using the 27 MHz multi-electrode current-source interstitial hyperthermia system in brain tumours

BACKGROUND AND PURPOSEnIn interstitial hyperthermia, temperature measurements are mainly performed inside heating applicators, and therefore, give the maximum temperatures of a rather heterogeneous temperature distribution. The problem of how to estimate lesion temperatures using the multi-electrode current-source interstitial hyperthermia (MECS-IHT) system in the brain was studied.nnnMATERIALS AND METHODSnTemperatures were measured within the electrodes and in an extra catheter at the edge of a 4 x 4 x 4.5 cm(3) glioblastoma multiforme resection cavity. From the temperature decays during a power-off period, information was obtained about local maximum and minimum tissue temperatures. The significance of these data was examined through model calculations.nnnRESULTSnMaximum tissue temperatures could be estimated roughly by switching off all electrodes for about 5 s. Model calculations showed that the minimum tissue temperatures near a certain afterloading catheter correspond well with the temperature of the applicator inside, about 1 min after this applicator was switched off.nnnCONCLUSIONSnAlthough the electrode temperatures read during heating are not suitable to assess the temperature distribution, it is feasible to heat the brain adequately using the MECS-IHT system with extra sensors outside the electrodes and/or application of decay methods.

A microcosting study of microsurgery, LINAC radiosurgery, and gamma knife radiosurgery in meningioma patients

The aim of the present study is to determine and compare initial treatment costs of microsurgery, linear accelerator (LINAC) radiosurgery, and gamma knife radiosurgery in meningioma patients. Additionally, the follow-up costs in the first year after initial treatment were assessed. Cost analyses were performed at two neurosurgical departments in The Netherlands from the healthcare providers’ perspective. A total of 59 patients were included, of whom 18 underwent microsurgery, 15 underwent LINAC radiosurgery, and 26 underwent gamma knife radiosurgery. A standardized microcosting methodology was employed to ensure that the identified cost differences would reflect only actual cost differences. Initial treatment costs, using equipment costs per fraction, were €12,288 for microsurgery, €1,547 for LINAC radiosurgery, and €2,412 for gamma knife radiosurgery. Higher initial treatment costs for microsurgery were predominantly due to inpatient stay (€5,321) and indirect costs (€4,350). LINAC and gamma knife radiosurgery were equally expensive when equipment was valued per treatment (€2,198 and €2,412, respectively). Follow-up costs were slightly, but not significantly, higher for microsurgery compared with LINAC and gamma knife radiosurgery. Even though initial treatment costs were over five times higher for microsurgery compared with both radiosurgical treatments, our study gives indications that the relative cost difference may decrease when follow-up costs occurring during the first year after initial treatment are incorporated. This reinforces the need to consider follow-up costs after initial treatment when examining the relative costs of alternative treatments.

Fractionated stereotactic radiotherapy for cavernous haemangioma of the orbital apex.

between the posterior corneal surface and iris surface on the horizontal line scan image) were obtained using pentacam software version 1.17. Table 1 shows the IOP values, number of glaucoma medications and AC parameters before and 3 months postoperatively. Compared with preoperatively, the IOP (p < 0.0001) and the number of glaucoma medications (p = 0.0234) significantly decreased 3 months postoperatively; the IOP did not increase in any eyes postoperatively. The ACD (p < 0.0001), ACV (p < 0.0001) and ACA (p < 0.0001) increased significantly 3 months postoperatively compared with preoperatively and did not decrease in any eyes postoperatively; the difference between preand postoperative values of the AC parameters was statistically significant again when the eyes underwent cataract surgery alone or the eyes underwent cataract surgery and simultaneous goniosynechialysis was analysed separately (data not shown). In this study, all AC parameters increased significantly postoperatively, with concomitant significant decreases in IOP and the number of glaucoma medications. The results suggested the effectiveness of treating PAC with small-incisional cataract surgery and ⁄or goniosynechialysis (Takanashi et al. 2005; Nonaka et al. 2006). To the best of our knowledge, this study reporting the AC parameters measured using the Pentacam before and after cataract extraction in eyes with PAC is unique in the literature. The AC parameters increased 1.8–1.9 times postoperatively, which seemed equivalent to the 1.7-times increase in UBM-measured ACD reported postoperatively in eyes with PAC (Nonaka et al. 2006) and were greater than the 1.2to 1.3-times increases in ACD, ACV and ACA reported using Pentacam postoperatively in eyes without PAC (Ucakhan et al. 2009). Pentacam is useful to evaluate the postoperative angle widening, AC deepening and the increased ACV in eyes with PAC.