Combined PET-CT and MRI for response evaluation in patients with squamous cell anal carcinoma treated with curative-intent chemoradiotherapy.

OBJECTIVES: To assess the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for response assessment post curative-intent chemoradiotherapy (CRT) in anal squamous cell carcinoma (ASCC). METHODS: Consecutive ASCC patients treated with curative-intent CRT at a single centre between January 2018 and April 2020 were retrospectively identified. Clinical meta-data including progression-free survival (PFS) and overall survival (OS) outcomes were collated. Three radiologists evaluated PET-CT and MRI using qualitative response assessment criteria and agreed in consensus. Two-proportion z test was used to compare diagnostic performance metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy). Kaplan-Meier analysis (Mantel-Cox log-rank) was performed. RESULTS: MRI (accuracy 76%, PPV 44.8%, NPV 95.7%) and PET-CT (accuracy 69.3%, PPV 36.7%, NPV 91.1%) performance metrics were similar; when combined, there were statistically significant improvements (accuracy 94.7%, PPV 78.9%, NPV 100%). Kaplan-Meier analysis demonstrated significant differences in PFS between responders and non-responders at PET-CT (p = 0.007), MRI (p = 0.005), and consensus evaluation (p < 0.001). Cox regression analysis of PFS demonstrated a lower hazard ratio (HR) and narrower 95% confidence intervals for consensus findings (HR = 0.093, p < 0.001). Seventy-five patients, of which 52 (69.3%) were females, with median follow-up of 17.8 months (range 5-32.6) were included. Fifteen of the 75 (20%) had persistent anorectal and/or nodal disease after CRT. Three patients died, median time to death 6.2 months (range 5-18.3). CONCLUSION: Combined PET-CT and MRI response assessment post-CRT better predicts subsequent outcome than either modality alone. This could have valuable clinical benefits by guiding personalised risk-adapted patient follow-up. KEY POINTS: • MRI and PET-CT performance metrics for assessing response following chemoradiotherapy (CRT) in patients with anal squamous cell carcinoma (ASCC) were similar. • Combined MRI and PET-CT treatment response assessment 3 months after CRT in patients with ASCC was demonstrated to be superior to either modality alone. • A combined MRI and PET-CT assessment 3 months after CRT in patients with ASCC has the potential to improve accuracy and guide optimal patient management with a greater ability to predict outcome than either modality alone.

The benefit of MR-only radiotherapy treatment planning for anal and rectal cancers: A planning study.

INTRODUCTION: Limited evidence exists showing the benefit of magnetic resonance (MR)-only radiotherapy treatment planning for anal and rectal cancers. This study aims to assess the impact of MR-only planning on target volumes (TVs) and treatment plan doses to organs at risks (OARs) for anal and rectal cancers versus a computed tomography (CT)-only pathway. MATERIALS AND METHODS: Forty-six patients (29 rectum and 17 anus) undergoing preoperative or radical external beam radiotherapy received CT and T2 MR simulation. TV and OARs were delineated on CT and MR, and volumetric arc therapy treatment plans were optimized independently (53.2 Gy/28 fractions for anus, 45 Gy/25 fractions for rectum). Further treatment plans assessed gross tumor volume (GTV) dose escalation. Differences in TV volumes and OAR doses, in terms of Vx Gy (organ volume (%) receiving x dose (Gy)), were assessed. RESULTS: MR GTV and primary planning TV (PTV) volumes systematically reduced by 13 cc and 98 cc (anus) and 44 cc and 109 cc (rectum) respectively compared to CT volumes. Statistically significant OAR dose reductions versus CT were found for bladder and uterus (rectum) and bladder, penile bulb, and genitalia (anus). With GTV boosting, statistically significant dose reductions were found for sigmoid, small bowel, vagina, and penile bulb (rectum) and vagina (anus). CONCLUSION: Our findings provide evidence that the introduction of MR (whether through MR-only or CT-MR pathways) to radiotherapy treatment planning for anal and rectal cancers has the potential to improve treatments. MR-related OAR dose reductions may translate into less treatment-related toxicity for patients or greater ability to dose escalate.

Patient position verification in magnetic-resonance imaging only radiotherapy of anal and rectal cancers.

BACKGROUND AND PURPOSE: Magnetic resonance (MR)-only treatment pathways require either the MR-simulation or synthetic-computed tomography (sCT) as an alternative reference image for cone beam computed tomography (CBCT) patient position verification. This study assessed whether using T2 MR or sCT as CBCT reference images introduces systematic registration errors as compared to CT for anal and rectal cancers. MATERIALS AND METHODS: A total of 32 patients (18 rectum,14 anus) received pre-treatment CT- and T2 MR- simulation. Routine treatment CBCTs were acquired. sCTs were generated using a validated research model. The local clinical registration protocol, using a grey-scale registration algorithm, was performed for 216 CBCTs using CT, MR and sCT as the reference image. Linear mixed effects modelling identified systematic differences between modalities. RESULTS: Systematic translation and rotation differences to CT for MR were -0.3 to + 0.3 mm and -0.1 to 0.4° for anal cancers and -0.4 to 0.0 mm and 0.0 to 0.1° for rectal cancers, and for sCT were -0.4 to + 0.8 mm, -0.1 to 0.2° for anal cancers and -0.6 to + 0.2 mm, -0.1 to + 0.1° for rectal cancers. CONCLUSIONS: T2 MR or sCT can successfully be used as reference images for anal and rectal cancer CBCT position verification with systematic differences to CT <±1 mm and <±0.5°. Clinical enabling of alternative modalities as reference images by vendors is required to reduce challenges associated with their use.

Orosensory Perception of Fat/Sweet Stimuli and Appetite-Regulating Peptides before and after Sleeve Gastrectomy or Gastric Bypass in Adult Women with Obesity.

The aim of this study was to explore the impact of bariatric surgery on fat and sweet taste perceptions and to determine the possible correlations with gut appetite-regulating peptides and subjective food sensations. Women suffering from severe obesity (BMI > 35 kg/m2) were studied 2 weeks before and 6 months after a vertical sleeve gastrectomy (VSG, n = 32) or a Roux-en-Y gastric bypass (RYGB, n = 12). Linoleic acid (LA) and sucrose perception thresholds were determined using the three-alternative forced-choice procedure, gut hormones were assayed before and after a test meal and subjective changes in oral food sensations were self-reported using a standardized questionnaire. Despite a global positive effect of both surgeries on the reported gustatory sensations, a change in the taste sensitivity was only found after RYGB for LA. However, the fat and sweet taste perceptions were not homogenous between patients who underwent the same surgery procedure, suggesting the existence of two subgroups: patients with and without taste improvement. These gustatory changes were not correlated to the surgery-mediated modifications of the main gut appetite-regulating hormones. Collectively these data highlight the complexity of relationships between bariatric surgery and taste sensitivity and suggest that VSG and RYGB might impact the fatty taste perception differently.

Multicentre, deep learning, synthetic-CT generation for ano-rectal MR-only radiotherapy treatment planning.

BACKGROUND AND PURPOSE: Comprehensive dosimetric analysis is required prior to the clinical implementation of pelvic MR-only sites, other than prostate, due to the limited number of site specific synthetic-CT (sCT) dosimetric assessments in the literature. This study aims to provide a comprehensive assessment of a deep learning-based, conditional generative adversarial network (cGAN) model for a large ano-rectal cancer cohort. The following challenges were investigated; T2-SPACE MR sequences, patient data from multiple centres and the impact of sex and cancer site on sCT quality. METHOD: RT treatment position CT and T2-SPACE MR scans, from two centres, were collected for 90 ano-rectal patients. A cGAN model trained using a focal loss function, was trained and tested on 46 and 44 CT-MR ano-rectal datasets, paired using deformable registration, respectively. VMAT plans were created on CT and recalculated on sCT. Dose differences and gamma indices assessed sCT dosimetric accuracy. A linear mixed effect (LME) model assessed the impact of centre, sex and cancer site. RESULTS: A mean PTV D95% dose difference of 0.1% (range: -0.5% to 0.7%) was found between CT and sCT. All gamma index (1%/1 mm threshold) measurements were >99.0%. The LME model found the impact of modality, cancer site, sex and centre was clinically insignificant (effect ranges: -0.4% and 0.3%). The mean dose difference for all OAR constraints was 0.1%. CONCLUSION: Focal loss cGAN models using T2-SPACE MR sequences from multiple centres can produce generalisable, dosimetrically accurate sCTs for ano-rectal cancers.

Melt inclusion vapour bubbles: the hidden reservoir for major and volatile elements.

Olivine-hosted melt inclusions (MIs) provide samples of magmatic liquids and their dissolved volatiles from deep within the plumbing system. Inevitable post-entrapment modifications can lead to significant compositional changes in the glass and/or any contained bubbles. Re-heating is a common technique to reverse MI crystallisation; however, its effect on volatile contents has been assumed to be minor. We test this assumption using crystallised and glassy basaltic MIs, combined with Raman spectroscopy and 3D imaging, to investigate the changes in fluid and solid phases in the bubbles before and after re-heating. Before re-heating, the bubble contains CO2 gas and anhydrite (CaSO4) crystallites. The rapid diffusion of major and volatile elements from the melt during re-heating creates new phases within the bubble: SO2, gypsum, Fe-sulphides. Vapour bubbles hosted in naturally glassy MIs similarly contain a plethora of solid phases (carbonates, sulphates, and sulphides) that account for up to 84% of the total MI sulphur, 80% of CO2, and 14% of FeO. In both re-heated and naturally glassy MIs, bubbles sequester major and volatile elements that are components of the total magmatic budget and represent a "loss" from the glass. Analyses of the glass alone significantly underestimates the original magma composition and storage parameters.

Low hydrogen contents in the cores of terrestrial planets.

Hydrogen has been thought to be an important light element in Earth's core due to possible siderophile behavior during core-mantle segregation. We reproduced planetary differentiation conditions using hydrogen contents of 450 to 1500 parts per million (ppm) in the silicate phase, pressures of 5 to 20 GPa, oxygen fugacity varying within IW-3.7 and IW-0.2 (0.2 to 3.7 log units lower than iron-wüstite buffer), and Fe alloys typical of planetary cores. We report hydrogen metal-silicate partition coefficients of ~2 × 10-1, up to two orders of magnitude lower than reported previously, and indicative of lithophile behavior. Our results imply H contents of ~60 ppm in the Earth and Martian cores. A simple water budget suggests that 90% of the water initially present in planetary building blocks was lost during planetary accretion. The retained water segregated preferentially into planetary mantles.

Dehydration of chlorite explains anomalously high electrical conductivity in the mantle wedges.

Mantle wedge regions in subduction zone settings show anomalously high electrical conductivity (~1 S/m) that has often been attributed to the presence of aqueous fluids released by slab dehydration. Laboratory-based measurements of the electrical conductivity of hydrous phases and aqueous fluids are significantly lower and cannot readily explain the geophysically observed anomalously high electrical conductivity. The released aqueous fluid also rehydrates the mantle wedge and stabilizes a suite of hydrous phases, including serpentine and chlorite. In this present study, we have measured the electrical conductivity of a natural chlorite at pressures and temperatures relevant for the subduction zone setting. In our experiment, we observe two distinct conductivity enhancements when chlorite is heated to temperatures beyond its thermodynamic stability field. The initial increase in electrical conductivity to ~3 × 10(-3) S/m can be attributed to chlorite dehydration and the release of aqueous fluids. This is followed by a unique, subsequent enhancement of electrical conductivity of up to 7 × 10(-1) S/m. This is related to the growth of an interconnected network of a highly conductive and chemically impure magnetite mineral phase. Thus, the dehydration of chlorite and associated processes are likely to be crucial in explaining the anomalously high electrical conductivity observed in mantle wedges. Chlorite dehydration in the mantle wedge provides an additional source of aqueous fluid above the slab and could also be responsible for the fixed depth (120 ± 40 km) of melting at the top of the subducting slab beneath the subduction-related volcanic arc front.

Cosmochemical fractionation by collisional erosion during the Earth's accretion.

Early in the Solar System's history, energetic collisions of differentiated bodies affected the final composition of the terrestrial planets through partial destruction. Enstatite chondrites (EC) are the best candidates to represent the primordial terrestrial precursors as they present the most similar isotopic compositions to Earth. Here we report that collisional erosion of >15% of the early Earth's mass can reconcile the remaining compositional differences between EC and the Earth. We base our demonstration on experimental melting of an EC composition at pressures between 1 bar and 25 GPa. At low pressures, the first silicate melts are highly enriched in incompatible elements Si, Al and Na, and depleted in Mg. Loss of proto-crusts through impacts raises the Earth's Mg/Si ratio to its present value. To match all major element compositions, our model implies preferential loss of volatile lithophile elements and re-condensation of refractory lithophile elements after the impacts.

Melting of subducted basalt at the core-mantle boundary.

The geological materials in Earth's lowermost mantle control the characteristics and interpretation of seismic ultra-low velocity zones at the base of the core-mantle boundary. Partial melting of the bulk lower mantle is often advocated as the cause, but this does not explain the nonubiquitous character of these regional seismic features. We explored the melting properties of mid-oceanic ridge basalt (MORB), which can reach the lowermost mantle after subduction of oceanic crust. At a pressure representative of the core-mantle boundary (135 gigapascals), the onset of melting occurs at ~3800 kelvin, which is ~350 kelvin below the mantle solidus. The SiO2-rich liquid generated either remains trapped in the MORB material or solidifies after reacting with the surrounding MgO-rich mantle, remixing subducted MORB with the lowermost mantle.

Impact of 18F-FDG PET/CT on target volume delineation in recurrent or residual gynaecologic carcinoma.

BACKGROUND: To evaluate the impact of 18F-FDG PET/CT on target volume delineation in gynaecological cancer. METHODS: F-FDG PET/CT based RT treatment planning was performed in 10 patients with locally recurrent (n = 5) or post-surgical residual gynaecological cancer (n = 5). The gross tumor volume (GTV) was defined by 4 experienced radiation oncologists first using contrast enhanced CT (GTVCT) and secondly using the fused 18F-FDG PET/CT datasets (GTVPET/CT). In addition, the GTV was delineated using the signal-to-background (SBR) ratio-based adaptive thresholding technique (GTVSBR). Overlap analysis were conducted to assess geographic mismatches between the GTVs delineated using the different techniques. Inter- and intra-observer variability were also assessed. RESULTS: The mean GTVCT (43.65 cm3) was larger than the mean GTVPET/CT (33.06 cm3), p = 0.02. In 6 patients, GTVPET/CT added substantial tumor extension outside the GTVCT even though 90.4% of the GTVPET/CT was included in the GTVCT and 30.2% of the GTVCT was found outside the GTVPET/CT. The inter- and intra-observer variability was not significantly reduced with the inclusion of 18F-FDG PET imaging (p = 0.23 and p = 0.18, respectively). The GTVSBR was smaller than GTVCT p ≤ 0.005 and GTVPET/CT p ≤ 0.005. CONCLUSIONS: The use of 18F-FDG PET/CT images for target volume delineation of recurrent or post-surgical residual gynaecological cancer alters the GTV in the majority of patients compared to standard CT-definition. The use of SBR-based auto-delineation showed significantly smaller GTVs. The use of PET/CT based target volume delineation may improve the accuracy of RT treatment planning in gynaecologic cancer.

Twice-weekly hypofractionated intensity-modulated radiotherapy for localized prostate cancer with low-risk nodal involvement: toxicity and outcome from a dose escalation pilot study.

PURPOSE: To evaluate the toxicity and preliminary outcome of patients with localized prostate cancer treated with twice-weekly hypofractionated intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between 2003 and 2006, 82 prostate cancer patients with a nodal involvement risk ≤20% (Roach index) have been treated to the prostate with or without seminal vesicles with 56 Gy (4 Gy/fraction twice weekly) and an overall treatment time of 6.5 weeks. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Radiation Therapy Oncology Group (RTOG) grading system. Median follow-up was 48 months (range, 9-67 months). RESULTS: All patients completed the treatment without interruptions. No patient presented with Grade ≥3 acute GU or GI toxicity. Of the patients, 4% presented with Grade 2 GU or GI persistent acute toxicity 6 weeks after treatment completion. The estimated 4-year probability of Grade ≥2 late GU and GI toxicity-free survival were 94.2% ± 2.9% and 96.1% ± 2.2%, respectively. One patient presented with Grade 3 GI and another patient with Grade 4 GU late toxicity, which were transitory in both cases. The 4-year actuarial biochemical relapse-free survival was 91.3% ± 5.9%, 76.4% ± 8.8%, and 77.5% ± 8.9% for low-, intermediate-, and high-risk groups, respectively. CONCLUSIONS: In patients with localized prostate cancer, acute and late toxicity were minimal after dose-escalation administering twice-weekly 4 Gy to a total dose of 56 Gy, with IMRT. Further prospective trials are warranted to further assess the best fractionation schemes for these patients.

Dose escalation study with two different hypofractionated intensity modulated radiotherapy techniques for localized prostate cancer: acute toxicity.

To assess acute gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with a sequential dose escalation hypofractionated intensity-modulated radiotherapy (IMRT) study using two different delivery methods. Since 2003, 88 and 48 patients were sequentially treated to 56 Gy and to 60 Gy (4 Gy/fraction twice weekly), respectively. IMRT with 6 MV beams was delivered with five fields in Geneva and with nine in Barcelona. Acute GI and GU side effects were scored weekly during treatment and 6 weeks after treatment completion using the Radiation Therapy Oncology Group (RTOG) toxicity scale. Clinical, technical, and dosimetric parameters were analyzed in order to assess for a potential correlation with toxicity. Grade 1-2, GU and GI toxicities during and 6 weeks after treatment completion were 64%, and 24%, and 35% and 12%, respectively. Only one Grade 4 GU toxicity, consisting of transitory urinary obstruction, was observed. Patients treated to 60 Gy in Geneva presented a higher rate of Grade 1-2 GU toxicity (p = 0.01), while patients treated to both 56 and 60 Gy in Barcelona presented a higher Grade 1-2 GI toxicity (p = 0.02). A lower rate of rectal toxicity was observed in the subgroup of 22 patients treated with a rectal balloon (p = 0.02). The use of androgen deprivation therapy was associated with a higher rate of Grade 1-2 GU toxicity after the end of the treatment (p = 0.02). Dose escalation with either 14 _ 4 Gy or 15 _ 4 Gy delivered with two different IMRT techniques is feasible and is associated with a tolerable acute toxicity.

Whole brain radiotherapy with a conformational external beam radiation boost for lung cancer patients with 1-3 brain metastasis: a multi institutional study.

BACKGROUND: To determine the outcome of patients with brain metastasis (BM) from lung cancer treated with an external beam radiotherapy boost (RTB) after whole brain radiotherapy (WBRT). METHODS: A total of 53 BM patients with lung cancer were treated sequentially with WBRT and RTB between 1996 and 2008 according to our institutional protocol. Mean age was 58.8 years. The median KPS was 90. Median recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) grouping were 2 and 2.5, respectively. Surgery was performed on 38 (71%) patients. The median number of BM was 1 (range, 1-3). Median WBRT and RTB combined dose was 39 Gy (range, 37.5-54). Median follow-up was 12.0 months. RESULTS: During the period of follow-up, 37 (70%) patients died. The median overall survival (OS) was 14.5 months. Only 13 patients failed in the brain. The majority of patients (n = 29) failed distantly. The 1-year OS, -local control, extracranial failure rates were 61.2%, 75.2% and 60.8%, respectively. On univariate analysis, improved OS was found to be significantly associated with total dose (< or = 39 Gy vs. > 39 Gy; p < 0.01), age < 65 (p < 0.01), absence of extracranial metastasis (p < 0.01), GPA > or = 2.5 (p = 0.01), KPS > or = 90 (p = 0.01), and RPA < 2 (p = 0.04). On multivariate analysis, total dose (p < 0.01) and the absence of extracranial metastasis (p = 0.03) retained statistical significance. CONCLUSIONS: The majority of lung cancer patients treated with WBRT and RTB progressed extracranially. There might be a subgroup of younger patients with good performance status and no extracranial disease who may benefit from dose escalation after WBRT to the metastatic site.

Unilateral radiotherapy for tonsil cancer: potential dose distribution optimization with a simple two-field intensity-modulated radiation therapy beam arrangement.

BACKGROUND AND PURPOSE: To evaluate the feasibility and dosimetric optimization potential of a unilateral two-field intensity-modulated radiotherapy (IMRT) technique in the curative treatment of lateralized tonsil cancer. MATERIALS AND METHODS: Six patients with lateralized tonsillar carcinoma were treated unilaterally with a two-field IMRT technique (oblique-anterior and oblique-posterior fields, with or without collimator and couch rotation). Alternative IMRT plans using seven non-opposed coplanar fields were compared with the two-field plans for each patient. RESULTS: Planning target volume (PTV) coverage was excellent with the two-field technique, using a relatively low number of monitor units (MU) (median, 441; range, 309-550). Dose constraints were respected for all organs at risk (OAR). Mean doses to contralateral parotid and submandibular glands were 3.9 and 17.7 Gy, respectively. Seven-field IMRT provided similar PTV coverage, with statistically significant better dose homogeneity and conformality. However, the mean delivered dose to the contralateral parotid (3.9 vs. 9.0 Gy, p=0.001) as well as the mean number of MU (437 vs. 814, p=0.002) and consequently machine time were lower with two-field IMRT. CONCLUSIONS: Unilateral two-field IMRT is a simple and feasible technique providing excellent tumor coverage and optimal OAR sparing while reducing the number of MU and treatment time.

Recurrence pattern after [(18)F]fluoroethyltyrosine-positron emission tomography-guided radiotherapy for high-grade glioma: a prospective study.

PURPOSE: To assess the failure pattern observed after (18)F fluoroethyltyrosine (FET) planning after chemo- and radiotherapy (RT) for high-grade glioma. METHODS: All patients underwent prospectively RT planning using morphological gross tumour volumes (GTVs) and biological tumour volumes (BTVs). The post-treatment recurrence tumour volumes (RTVs) of 10 patients were transferred on their CT planning. First, failure patterns were defined in terms of percentage of RTV located outside the GTV and BTV. Second, the location of the RTV with respect to the delivered dose distribution was assessed using the RTV's DVHs. Recurrences with >95% of their volume within 95% isodose line were considered as central recurrences. Finally, the relationship between survival and GTV/BTV mismatches was assessed. RESULTS: The median percentages of RTV outside the GTV and BTV were 41.8% (range, 10.5-92.4) and 62.8% (range, 34.2-81.1), respectively. The majority of recurrences (90%) were centrally located. Using a composite target volume planning formalism, the degree of GTV and BTV mismatch did not correlate with survivorship. CONCLUSIONS: The observed failure pattern after FET-PET planning and chemo-RT is primarily central. The target mismatch-survival data suggest that using FET-PET planning may counteract the possibility of BTV-related progression, which may have a detrimental effect on survival.

Overexpression of phosphorylated 4E-BP1 predicts for tumor recurrence and reduced survival in cervical carcinoma treated with postoperative radiotherapy.

PURPOSE: To examine the prognostic value of the 4E-BP1 activation state and related upstream/downstream signaling proteins on the clinical outcome of patients with intermediate- or high-risk early-stage cervical carcinoma treated with postoperative radiotherapy and to determine the optimal treatment of early-stage cervical carcinoma. METHODS AND MATERIALS: Immunohistochemical staining was performed on 64 formalin-fixed, paraffin-embedded cervical carcinoma surgical specimens for each protein of the panel (p4E-BP1, phosphorylated mitogen-activated protein kinase, pAkt, vascular endothelial growth factor, KDR, Bcl-2, TP53, receptor for activated C-kinase 1). The expression patterns were related to the clinical data. All patients received postoperative radiotherapy. Concurrent chemotherapy was added if high-risk features were present. The median follow-up was 40 months. RESULTS: Of the 64 patients, 13 received concomitant chemotherapy. p4E-BP1 overexpression in moderate/high-risk early-stage cervical carcinoma correlated significantly with disease-free survival (hazard ratio, 4.39; p = .009) and overall survival (hazard ratio, 4.88; p = .005). Vascular endothelial growth factor, and its receptor KDR, had positive immunoreactivity in all tumor samples. No correlation with clinical outcome was found for the remaining proteins evaluated. CONCLUSION: In this study, moderate/high-risk early-stage cervical carcinoma with low p4E-BP1 expression was highly curable with the current postoperative treatments. For tumors with p4E-BP1 overexpression, new investigational strategies are needed.

[(18)F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for high-grade glioma.

BACKGROUND: To compare morphological gross tumor volumes (GTVs), defined as pre- and postoperative gadolinium enhancement on T1-weighted magnetic resonance imaging to biological tumor volumes (BTVs), defined by the uptake of (18)F fluoroethyltyrosine (FET) for the radiotherapy planning of high-grade glioma, using a dedicated positron emission tomography (PET)-CT scanner equipped with three triangulation lasers for patient positioning. METHODS: Nineteen patients with malignant glioma were included into a prospective protocol using FET PET-CT for radiotherapy planning. To be eligible, patients had to present with residual disease after surgery. Planning was performed using the clinical target volume (CTV = GTV union or logical sum BTV) and planning target volume (PTV = CTV + 20 mm). First, the interrater reliability for BTV delineation was assessed among three observers. Second, the BTV and GTV were quantified and compared. Finally, the geometrical relationships between GTV and BTV were assessed. RESULTS: Interrater agreement for BTV delineation was excellent (intraclass correlation coefficient 0.9). Although, BTVs and GTVs were not significantly different (p = 0.9), CTVs (mean 57.8 +/- 30.4 cm(3)) were significantly larger than BTVs (mean 42.1 +/- 24.4 cm(3); p < 0.01) or GTVs (mean 38.7 +/- 25.7 cm(3); p < 0.01). In 13 (68%) and 6 (32%) of 19 patients, FET uptake extended >or= 10 and 20 mm from the margin of the gadolinium enhancement. CONCLUSION: Using FET, the interrater reliability had excellent agreement for BTV delineation. With FET PET-CT planning, the size and geometrical location of GTVs and BTVs differed in a majority of patients.