Filip Claus

Interobserver Delineation Variation Using CT versus Combined CT + MRI in Intensity–Modulated Radiotherapy for Prostate Cancer

Purpose:To quantify interobserver variation of prostate and seminal vesicle delineations using CT only versus CT + MRI in consensus reading with a radiologist.Material and Methods:The prostate and seminal vesicles of 13 patients treated with intensity–modulated radiotherapy for prostatic adenocarcinoma were retrospectively delineated by three radiation oncologists on CT only and on CT + MRI in consensus reading with a radiologist. The volumes and margin positions were calculated and intermodality and interobserver variations were assessed for the clinical target volume (CTV), seminal vesicles, prostate and three prostatic subdivisions (apical, middle and basal third).Results:Using CT + MRI as compared to CT alone, the mean CTV, prostate and seminal vesicle volumes significantly decreased by 6.54%, 5.21% and 10.47%, respectively. More importantly, their standard deviations significantly decreased by 63.06%, 62.65% and 44.83%, respectively. The highest level of variation was found at the prostatic apex, followed by the prostatic base and seminal vesicles.Conclusion: Addition of MRI to CT in consensus reading with a radiologist results in a moderate decrease of the CTV, but an important decrease of the interobserver delineation variation, especially at the prostatic apex.Ziel:Quantifizierung der Interobserver–Variation bei der Abgrenzung von Prostata und Samenblasen im CT im Vergleich zur Kombination CT und MRT nach einer Konsensusbefundung mit einem Radiologen.Material und Methodik: Die Prostata und die Samenblasen von 13 Patienten, die für eine intensitätsmodulierte Strahlentherapie wegen Adenokarzinoms der Prostata vorgesehen waren, wurden retrospektiv im CT und mit der Kombination CT und MRT durch drei Strahlentherapeuten nach einer Konsensusbefundung mit einem Radiologen abgegrenzt. Volumen und Randpositionen wurden berechnet und die Intermodalitäts- bzw. Interobservervariationen für das klinische Zielvolumen (CTV), die Samenblasen, die Prostata und drei Prostatasegmente (apikales, mittleres und basales Drittel) beurteilt.Ergebnisse:Mit der Kombination von CT und MRT verringerte sich im Vergleich zur alleinigen CT der Mittelwert für das CTV, Prostata– und Samenblasenvolumen signifikant um 6,54%, 5,21% und 10,47%. Von größerer Bedeutung war die signifikante Abnahme der Standardabweichungen um 63,06%, 62,65% und 44,83%. Die höchste Variation wurde im Apex der Prostata festgestellt, gefolgt von der Basis der Prostata und den Samenblasen.Schlussfolgerung:Die Kombination von CT und MRT nach Konsensus mit einem Radiologen resultiert in einer bedeutenden Abnahme der Interobservervariation bei der anatomischen Abgrenzung, insbesondere im Bereich des Apex der Prostata, und zusätzlich in einer moderaten Verringerung des CTV.

Value of Diffusion-Weighted Magnetic Resonance Imaging for Prediction and Early Assessment of Response to Neoadjuvant Radiochemotherapy in Rectal Cancer: Preliminary Results

PURPOSE To evaluate diffusion-weighted magnetic resonance imaging (DWI) for response prediction before and response assessment during and early after preoperative radiochemotherapy (RCT) for locally advanced rectal cancer (LARC). METHODS AND MATERIALS Twenty patients receiving RCT for LARC underwent MRI including DWI before RCT, after 10-15 fractions and 1 to 2 weeks before surgery. Tumor volume and apparent diffusion coefficient (ADC; b-values: 0-1000 s/mm(2)) were determined at all time points. Pretreatment tumor ADC and volume, tumor ADC change (∆ADC), and volume change (∆V) between pretreatment and follow-up examinations were compared with histopathologic findings after total mesorectal excision (pathologic complete response [pCR] vs. no pCR, ypT0-2 vs. ypT3-4, T-downstaging or not). The discriminatory capability of pretreatment tumor ADC and volume, ∆ADC, and ∆V for the detection of pCR was compared with receiver operating characteristics analysis. RESULTS Pretreatment ADC was significantly lower in patients with pCR compared with patients without (in mm(2)/s: 0.94 ± 0.12 × 10(-3) vs. 1.19 ± 0.22 × 10(-3), p = 0.003), yielding a sensitivity of 100% and specificity of 86% for detection of pCR. The volume reduction during and after RCT was significantly higher in patients with pCR compared with patients without (in %: ΔV(during): -62 ± 16 vs. -33 ± 16, respectively, p = 0.015; and ΔV(post): -86 ± 12 vs. -60 ± 21, p = 0.012), yielding a sensitivity of 83% and specificity of 71% for the ΔV(during) and, respectively, 83% and 86% for the ΔV(post). The ∆ADC during (ΔADC(during)) and after RCT (ΔADC(post)) showed a significantly higher value in patients with pCR compared with patients without (in %: ΔADC(during): 72 ± 14 vs. 16 ± 12, p = 0.0006; and ΔADC(post): 88 ± 35 vs. 26 ± 19, p = 0.0011), yielding a sensitivity and specificity of 100% for the ΔADC(during) and, respectively, 100% and 93% for the ΔADC(post). CONCLUSIONS These initial findings indicate that DWI, using pretreatment ADC, ΔADC(during), and ΔADC(post) may be useful for prediction and early assessment of pathologic response to preoperative RCT of LARC, with higher accuracy than volumetric measurements.

An implementation strategy for IMRT of ethmoid sinus cancer with bilateral sparing of the optic pathways.

PURPOSE To develop a protocol for the irradiation of ethmoid sinus cancer, with the aim of sparing binocular vision; of developing a strategy of intensity-modulated radiation therapy (IMRT) planning that produces dose distributions that (1) are consistent with the protocol prescriptions and (2) are deliverable by static segmental IMRT techniques within a 15-minute time slot; of fine tuning the implementation strategy to a class solution approach that is sufficiently automated and efficient, allowing routine clinical application; of reporting on the early clinical implementation involving 11 patients between February 1999 and July 2000. patients and methods: Eleven consecutive T1-4N0M0 ethmoid sinus cancer patients were enrolled in the study. For Patients 1-8, a first protocol was implemented, defining a planning target volume prescription dose of 60 to 66 Gy in 30-33 fractions and a maximum dose (Dmax) of 50 Gy to optic pathway structures and spinal cord and limit of 60 Gy to brainstem. For Patients 9-11, an adapted (now considered mature) protocol was implemented, defining a (planning target volume) prescription dose of 70 Gy in 35 fractions and a Dmax to optic pathway structures and brainstem of 60 Gy and to spinal cord of 50 Gy. RESULTS The class solution-directed strategy developed during this study reduced the protocol translation process from a few days to about 2 hours of planner time. The mature class solution involved the use of 7 beam incidences (20-37 segments), which could be delivered within a 15-minute time slot. Acute side effects were limited and mild. None of the patients developed dry eye syndrome or other visual disturbances. The follow-up period is too short for detection of retinopathy or optic nerve and chiasm toxicity. CONCLUSION Conventional radiotherapy of ethmoid sinus tumors is associated with serious morbidity, including blindness. We hypothesize that IMRT has the potential to save binocular vision. The dose to the optic pathway structures can be reduced selectively by IMRT. Further enrollment of patients and longer follow-up will show whether the level of reduction tested by the clinical protocol is sufficient to save binocular vision. An adaptive strategy of IMRT planning was too inefficient for routine clinical practice. A class solution-directed strategy improved efficiency by eliminating human trial and error during the IMRT planning process.

Postoperative intensity-modulated radiotherapy in sinonasal carcinoma - Clinical results in 39 patients

Carcinoma of the paranasal sinuses is rare. Standard therapeutic modalities consist of surgery and radiotherapy (RT). Because of the often advanced stage and the vicinity of optic structures, RT‐induced ocular toxicity is a feared side effect of conventional RT. Intensity‐modulated radiotherapy (IMRT) is a relatively new technique, which is implemented with the hypothesis that, compared with conventional RT, it would result in a lower rate of ocular toxicity for an equal local control (LC).

Leaf position optimization for step-and-shoot IMRT

PURPOSE To describe the theoretical basis, the algorithm, and implementation of a tool that optimizes segment shapes and weights for step-and-shoot intensity-modulated radiation therapy delivered by multileaf collimators. METHODS AND MATERIALS The tool, called SOWAT (Segment Outline and Weight Adapting Tool) is applied to a set of segments, segment weights, and corresponding dose distribution, computed by an external dose computation engine. SOWAT evaluates the effects of changing the position of each collimating leaf of each segment on an objective function, as follows. Changing a leaf position causes a change in the segment-specific dose matrix, which is calculated by a fast dose computation algorithm. A weighted sum of all segment-specific dose matrices provides the dose distribution and allows computation of the value of the objective function. Only leaf position changes that comply with the multileaf collimator constraints are evaluated. Leaf position changes that tend to decrease the value of the objective function are retained. After several possible positions have been evaluated for all collimating leaves of all segments, an external dose engine recomputes the dose distribution, based on the adapted leaf positions and weights. The plan is evaluated. If the plan is accepted, a segment sequencer is used to make the prescription files for the treatment machine. Otherwise, the user can restart SOWAT using the new set of segments, segment weights, and corresponding dose distribution. The implementation was illustrated using two example cases. The first example is a T1N0M0 supraglottic cancer case that was distributed as a multicenter planning exercise by investigators from Rotterdam, The Netherlands. The exercise involved a two-phase plan. Phase 1 involved the delivery of 46 Gy to a concave-shaped planning target volume (PTV) consisting of the primary tumor volume and the elective lymph nodal regions II-IV on both sides of the neck. Phase 2 involved a boost of 24 Gy to the primary tumor region only. SOWAT was applied to the Phase 1 plan. Parotid sparing was a planning goal. The second implementation example is an ethmoid sinus cancer case, planned with the intent of bilateral visus sparing. The median PTV prescription dose was 70 Gy with a maximum dose constraint to the optic pathway structures of 60 Gy. RESULTS The initial set of segments, segment weights, and corresponding dose distribution were obtained, respectively, by an anatomy-based segmentation tool, a segment weight optimization tool, and a differential scatter-air ratio dose computation algorithm as external dose engine. For the supraglottic case, this resulted in a plan that proved to be comparable to the plans obtained at the other institutes by forward or inverse planning techniques. After using SOWAT, the minimum PTV dose and PTV dose homogeneity increased; the maximum dose to the spinal cord decreased from 38 Gy to 32 Gy. The left parotid mean dose decreased from 22 Gy to 19 Gy and the right parotid mean dose from 20 to 18 Gy. For the ethmoid sinus case, the target homogeneity increased by leaf position optimization, together with a better sparing of the optical tracts. CONCLUSIONS By using SOWAT, the plans improved with respect to all plan evaluation end points. Compliance with the multileaf collimator constraints is guaranteed. The treatment delivery time remains almost unchanged, because no additional segments are created.

Intrarenal Resistive Index after Renal Transplantation

BACKGROUND The intrarenal resistive index is routinely measured in many renal-transplantation centers for assessment of renal-allograft status, although the value of the resistive index remains unclear. METHODS In a single-center, prospective study involving 321 renal-allograft recipients, we measured the resistive index at baseline, at the time of protocol-specified renal-allograft biopsies (3, 12, and 24 months after transplantation), and at the time of biopsies performed because of graft dysfunction. A total of 1124 renal-allograft resistive-index measurements were included in the analysis. All patients were followed for at least 4.5 years after transplantation. RESULTS Allograft recipients with a resistive index of at least 0.80 had higher mortality than those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 5.20 [95% confidence interval {CI}, 2.14 to 12.64; P<0.001]; 3.46 [95% CI, 1.39 to 8.56; P=0.007]; and 4.12 [95% CI, 1.26 to 13.45; P=0.02], respectively). The need for dialysis did not differ significantly between patients with a resistive index of at least 0.80 and those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 1.95 [95% CI, 0.39 to 9.82; P=0.42]; 0.44 [95% CI, 0.05 to 3.72; P=0.45]; and 1.34 [95% CI, 0.20 to 8.82; P=0.76], respectively). At protocol-specified biopsy time points, the resistive index was not associated with renal-allograft histologic features. Older recipient age was the strongest determinant of a higher resistive index (P<0.001). At the time of biopsies performed because of graft dysfunction, antibody-mediated rejection or acute tubular necrosis, as compared with normal biopsy results, was associated with a higher resistive index (0.87 ± 0.12 vs. 0.78 ± 0.14 [P=0.05], and 0.86 ± 0.09 vs. 0.78 ± 0.14 [P=0.007], respectively). CONCLUSIONS The resistive index, routinely measured at predefined time points after transplantation, reflects characteristics of the recipient but not those of the graft. (ClinicalTrials.gov number, NCT01879124 .).

Congenital diaphragmatic hernia

Infants with congenital diaphragmatic hernia (CDH) have significant mortality and long-term morbidity. Only 60–70% survive and usually those in high-volume centres. The current Task Force, therefore, has convened experts to evaluate the current literature and make recommendations on both the antenatal and post-natal management of CDH. The incidence of CDH varies from 1.7 to 5.7 per 10,000 live-born infants depending on the study population. Antenatal ultrasound scanning is routine and increasingly complemented by the use of magnetic resonance imaging. For isolated CDH, antenatal interventions should be considered, but the techniques need vigorous evaluation. After birth, management protocols are often used and have improved outcome in nonrandomised studies, but immediate intubation at birth and gentle ventilation are important. Pulmonary hypertension is common and its optimal management is crucial as its severity predicts the outcome. Usually, surgery is delayed to allow optimal medical stabilisation. The role of minimal invasive post-natal surgery remains to be further defined. There are differences in opinion about whether extracorporeal membrane oxygenation improves outcome. Survivors of CDH can have a high incidence of comorbidities; thus, multidisciplinary follow-up is recommended. Multicentre international trials are necessary to optimise the antenatal and post-natal management of CDH patients.

Short term toxicity profile for 32 sinonasal cancer patients treated with IMRT. Can we avoid dry eye syndrome

Intensity modulated radiation therapy (IMRT) was given for 32 patients with M0 sinonasal cancer, with a median follow-up of 15 months. Acute toxicity was mucositis grades 1-2 in 28 patients and grade 3 in four patients. No corneal injury was observed, except in one patient where it was present before the start of IMRT. Conjunctivitis and dry eye symptoms were mild (no grade 3-4 toxicity) and no evolution to dry eye syndrome was observed. We conclude that high dose conformality of IMRT results in mild acute toxicity and that IMRT allows avoiding dry eye syndrome by its ability to create concave dose distributions which avoid the main lacrimal glands. Follow-up it too short to evaluate local control, optic nerve or retinal toxicity.

Postoperative radiotherapy for adenocarcinoma of the ethmoid sinuses: treatment results for 47 patients

PURPOSE Ethmoid sinus cancer is a rare malignancy. Treatment results are mostly reported together with other sinonasal tumors, grouping a wide range of different histologies and treatment approaches. This study reports on the treatment outcome of 47 patients diagnosed with adenocarcinoma of the ethmoid sinuses and treated with surgery and high-dose postoperative radiation therapy. METHODS AND MATERIALS Between September 1985 and October 2001, 51 patients with adenocarcinoma of the ethmoid sinuses were referred to the Ghent University Hospital. Four patients were treated with low-dose palliative radiation because of very extended inoperable disease or distant metastasis at the time of diagnosis. They were not included in this analysis. The other 47 patients, all staged as N0M0, were treated with surgery and postoperative high-dose radiation therapy. The median follow-up was 32 months. The T-stages were T1 for 2, T2 for 17, T3 for 11, and T4 for 17 patients. All 47 patients were staged as N0M0. RESULTS The 3-year, 5-year, and 7-year overall survival are respectively 71%, 60%, and 38%. The 3-year and 5-year disease-free survival are respectively 62% and 36%. The 3-year and 5-year disease-free survival for T1-T2 stages are respectively 87% and 55%, for T3 stages 57% and 28%, and for T4 stages 41% and 25%. The locoregional tumor control was 70% and 59% at respectively 3 and 5 years. Patients presenting with intracranial tumor invasion at the time of diagnosis relapsed within 7 months after the end of radiotherapy. Radiation-induced severe dry eye syndrome and optic neuropathy was observed in respectively 7 and 2 of the 47 cases. CONCLUSION Postoperative radiotherapy for adenocarcinoma of the ethmoid sinuses is associated with good local control rates. Crucial for a favorable prognosis is the absence of intracranial invasion. The rarity of these tumors makes it difficult to evaluate new therapeutic advances.

The correlation between lung volume and liver herniation measurements by fetal MRI in isolated congenital diaphragmatic hernia: a systematic review and meta‐analysis of observational studies

We conducted a meta‐analysis to assess the correlation of lung volume and liver position measured by magnetic resonance imaging (MRI) with survival until discharge in fetuses with isolated congenital diaphragmatic hernia (CDH).