Reirradiation of painful bone metastases in nonresponders or patients with recurrent pain after initial response is performed in up to 42% of patients initially treated with radiotherapy. Literature ...on the effect of reirradiation for pain control in those patients is scarce. In this systematic review and meta-analysis, we quantify the effectiveness of reirradiation for achieving pain control in patients with painful bone metastases.
A free text search was performed to identify eligible studies using the MEDLINE, EMBASE, and the Cochrane Collaboration library electronic databases. After study selection and quality assessment, a pooled estimate was calculated for overall pain response for reirradiation of metastatic bone pain.
Our literature search identified 707 titles, of which 10 articles were selected for systematic review and seven entered the meta-analysis. Overall study quality was mediocre. Of the 2,694 patients initially treated for metastatic bone pain, 527 (20%) patients underwent reirradiation. Overall, a pain response after reirradiation was achieved in 58% of patients (pooled overall response rate 0.58, 95% confidence interval = 0.49-0.67). There was a substantial between-study heterogeneity (I² = 63.3%, p = 0.01) because of clinical and methodological differences between studies.
Reirradiation of painful bone metastases is effective in terms of pain relief for a small majority of patients; approximately 40% of patients do not benefit from reirradiation. Although the validity of results is limited, this meta-analysis provides a comprehensive overview and the most quantitative estimate of reirradiation effectiveness to date.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
In this randomized trial, women with extremely dense breast tissue were invited to undergo MRI screening or received only mammography during a 2-year screening period. There was a 50% lower rate of ...interval cancers among the women invited for MRI screening. Among those who underwent MRI-directed biopsies, 26% had breast cancer.
Purpose
This meta-analysis was designed to evaluate the utility of preoperative axillary ultrasound combined with US-guided lymph node biopsy if indicated (AUS ± biopsy), in terms of staging the ...axilla and preventing two-step axillary surgery in the form of sentinel node biopsy (SNB) followed by completion axillary lymph node (ALN) dissection.
Methods
We systematically searched electronic databases for studies that addressed preoperative assessment of ALN status by AUS ± biopsy. A pooled estimate was calculated for the false-negative rate (FNR) of AUS ± biopsy (defined as the proportion of women with a negative AUS ± biopsy result subsequently proven to have a positive axilla) and sensitivity (defined as the proportion of women with a positive AUS ± biopsy result among all women with a tumor positive axilla).
Results
The pooled FNR was 25 % (95 % confidence interval CI = 24–27) and the pooled sensitivity was 50 % (95 % CI = 43–57). There was substantial heterogeneity across studies for both FNR (
I
2
= 69.42) and sensitivity (
I
2
= 93.25), which was not explained by between-study differences in biopsy technique, mean/median tumor size, biopsy indication, or study design. Sensitivity was increased in studies with a high prevalence of ALN metastases.
Conclusions
Preoperative axillary ultrasound-guided biopsy is a useful step in the process of axillary staging. Approximately 50 % of women with axillary involvement can be identified preoperatively. Still, one in four women with an ultrasound-guided biopsy-“proven” negative axilla has a positive SNB.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary Background The efficacy of radioembolisation for the treatment of liver tumours depends on the selective distribution of radioactive microspheres to tumorous tissue. The distribution of ...holmium-166 (166 Ho) poly(L-lactic acid) microspheres can be visualised in vivo by both single-photon-emission CT (SPECT) and MRI. In this phase 1 clinical trial, we aimed to assess the safety and the maximum tolerated radiation dose (MTRD) of166 Ho-radioembolisation in patients with liver metastases. Methods Between Nov 30, 2009, and Sept 19, 2011, patients with unresectable, chemorefractory liver metastases were enrolled in the Holmium Embolization Particles for Arterial Radiotherapy (HEPAR) trial. Patients were treated with intra-arterial166 Ho-radioembolisation in cohorts of three patients, with escalating aimed whole-liver absorbed doses of 20, 40, 60, and 80 Gy. Cohorts were extended to a maximum of six patients if dose-limiting toxicity occurred. Patients were assigned a dose in the order of study entry, with dose escalation until dose-limiting toxicity was encountered in at least two patients of a dose cohort. Clinical or laboratory toxicities were scored according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0. The primary endpoint was the MTRD. Analyses were per protocol. This study is registered with ClinicalTrials.gov , number NCT01031784. Findings 15 patients underwent166 Ho-radioembolisation at doses of 20 Gy (n=6), 40 Gy (n=3), 60 Gy (n=3), and 80 Gy (n=3). Mean estimated whole-liver absorbed doses were 18 Gy (SD 2) for the 20 Gy cohort, 35 Gy (SD 1) for the 40 Gy cohort, 58 Gy (SD 3) for the 60 Gy cohort, and 73 Gy (SD 4) for the 80 Gy cohort. The 20 Gy cohort was extended to six patients because of the occurrence of dose-limiting toxicity in one patient (pulmonary embolism). In the 80 Gy cohort, dose-limiting toxicity occurred in two patients: grade 4 thrombocytopenia, grade 3 leucopenia, and grade 3 hypoalbuminaemia in one patient, and grade 3 abdominal pain in another patient. The MTRD was identified as 60 Gy. The most frequently encountered laboratory toxicities (including grade 1) were lymphocytopenia, hypoalbuminaemia, raised alkaline phosphatase, raised aspartate aminotransferase, and raised gamma-glutamyltransferase, which were all noted in 12 of 15 patients. Stable disease or partial response regarding target lesions was achieved in 14 of 15 patients (93%, 95% CI 70–99) at 6 weeks and nine of 14 patients (64%, 95% CI 39–84) at 12 weeks after radioembolisation. Compared with baseline, the average global health status and quality of life scale score at 6 weeks after treatment had decreased by 13 points (p=0·053) and by 14 points at 12 weeks (p=0·048). In all patients, technetium-99m (99m Tc)-macro-aggregated albumin SPECT,166 Ho scout dose SPECT, and166 Ho treatment dose SPECT showed similar patterns of the presence or absence of extrahepatic deposition of activity. Interpretation166 Ho-radioembolisation is feasible and safe for the treatment of patients with unresectable and chemorefractory liver metastases and enables image-guided treatment. Clinical166 Ho-radioembolisation should be done with an aimed whole-liver absorbed dose of 60 Gy. Funding Dutch Cancer Society, Dutch Technology Foundation STW.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
After yttrium-90 ((90)Y) microsphere radioembolization (RE), evaluation of extrahepatic activity and liver dosimetry is typically performed on (90)Y Bremsstrahlung SPECT images. Since these images ...demonstrate a low quantitative accuracy, (90)Y PET has been suggested as an alternative. The aim of this study is to quantitatively compare SPECT and state-of-the-art PET on the ability to detect small accumulations of (90)Y and on the accuracy of liver dosimetry.
SPECT/CT and PET/CT phantom data were acquired using several acquisition and reconstruction protocols, including resolution recovery and Time-Of-Flight (TOF) PET. Image contrast and noise were compared using a torso-shaped phantom containing six hot spheres of various sizes. The ability to detect extra- and intrahepatic accumulations of activity was tested by quantitative evaluation of the visibility and unique detectability of the phantom hot spheres. Image-based dose estimates of the phantom were compared to the true dose. For clinical illustration, the SPECT and PET-based estimated liver dose distributions of five RE patients were compared. At equal noise level, PET showed higher contrast recovery coefficients than SPECT. The highest contrast recovery coefficients were obtained with TOF PET reconstruction including resolution recovery. All six spheres were consistently visible on SPECT and PET images, but PET was able to uniquely detect smaller spheres than SPECT. TOF PET-based estimates of the dose in the phantom spheres were more accurate than SPECT-based dose estimates, with underestimations ranging from 45% (10-mm sphere) to 11% (37-mm sphere) for PET, and 75% to 58% for SPECT, respectively. The differences between TOF PET and SPECT dose-estimates were supported by the patient data.
In this study we quantitatively demonstrated that the image quality of state-of-the-art PET is superior over Bremsstrahlung SPECT for the assessment of the (90)Y microsphere distribution after radioembolization.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
To compare the diagnostic value of conventional, bilateral diffusion‐weighted imaging (DWI) and high‐resolution targeted DWI of known breast lesions.
Materials and Methods
Twenty‐one ...consecutive patients with known breast cancer or suspicious breast lesions were scanned with the conventional bilateral DWI technique, a high‐resolution, reduced field of view (rFOV) DWI technique, and dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) (3.0 T). We compared bilateral DWI and rFOV DWI quantitatively by measuring the lesions' apparent diffusion coefficient (ADC) values. For qualitative comparison, three dedicated breast radiologists scored image quality and performed lesion interpretation.
Results
In a phantom, ADC values were in good agreement with the reference values. Twenty‐one patients (30 lesions: 14 invasive carcinomas, 10 benign lesions of which 5 cysts, 3 high‐risk, and 3 in situ carcinomas) were included. Cysts and high‐risk lesions were excluded from the quantitative analysis. Quantitatively, both bilateral and rFOV DWI measured lower ADC values in invasive tumors than other lesions. In vivo, rFOV DWI gave lower ADC values than bilateral DWI (1.11 × 10‐3 mm2/s vs. 1.24 × 10‐3 mm2/s, P = 0.002). Regions of interest (ROIs) were comparable in size between the two techniques (2.90 vs. 2.13 cm2, P = 0.721). Qualitatively, all three radiologists scored sharpness of rFOV DWI images as significantly higher than bilateral DWI (P ≤ 0.002). Receiver operating characteristic (ROC) curve analysis showed a higher area under the curve (AUC) in BI‐RADS classification for rFOV DWI compared to bilateral DWI (0.71 to 0.93 vs. 0.61 to 0.76, respectively).
Conclusion
Tumor morphology can be assessed in more detail with high‐resolution DWI (rFOV) than with standard bilateral DWI by providing significantly sharper images. J. MAGN. RESON. IMAGING 2015. J. MAGN. RESON. IMAGING 2015;42:1656–1665.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objectives
To assess the safety and feasibility of MRI-guided high-intensity focused ultrasound (MR-HIFU) ablation in breast cancer patients using a dedicated breast platform.
Methods
Patients with ...early-stage invasive breast cancer underwent partial tumour ablation prior to surgical resection. MR-HIFU ablation was performed using proton resonance frequency shift MR thermometry and an MR-HIFU system specifically designed for breast tumour ablation. The presence and extent of tumour necrosis was assessed by histopathological analysis of the surgical specimen. Pearson correlation coefficients were calculated to assess the relationship between sonication parameters, temperature increase and size of tumour necrosis at histopathology.
Results
Ten female patients underwent MR-HIFU treatment. No skin redness or burns were observed in any of the patients. No correlation was found between the applied energy and the temperature increase. In six patients, tumour necrosis was observed with a maximum diameter of 3–11 mm. In these patients, the number of targeted locations was equal to the number of areas with tumour necrosis. A good correlation was found between the applied energy and the size of tumour necrosis at histopathology (Pearson = 0.76, p = 0.002).
Conclusions
Our results show that MR-HIFU ablation with the dedicated breast system is safe and results in histopathologically proven tumour necrosis.
Key Points
•
MR-HIFU ablation with the dedicated breast system is safe and feasible
•
In none of the patients was skin redness or burns observed
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No correlation was found between the applied energy and the temperature increase
•
The correlation between applied energy and size of tumour necrosis was good
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Background
Chemotherapy treatment induces parenchymal changes that potentially affect imaging of CRLM. The purpose of this meta-analysis was to provide values of diagnostic performance of magnetic ...resonance imaging (MRI), computed tomography (CT), fluorodeoxyglucose positron emission tomography (FDG-PET), and FDG-PET/CT for preoperative detection of colorectal liver metastases (CRLM) in patients treated with neoadjuvant chemotherapy.
Methods
A comprehensive search was performed for original articles published from inception to 2011 assessing diagnostic performance of MRI, CT, FDG-PET, or FDG-PET/CT for preoperative evaluation of CRLM following chemotherapy. Intraoperative findings and/or histology were used as reference standard. For each imaging modality we calculated pooled sensitivities for patients who received neoadjuvant chemotherapy as well as for chemonaive patients, defined as number of malignant lesions detected divided by number of malignant lesions as confirmed by the reference standard.
Results
A total of 11 papers, comprising 223 patients with 906 lesions, were included. Substantial variation in study design, patient characteristics, imaging features, and reference tests was observed. Pooled sensitivity estimates of MRI, CT, FDG-PET, and FDG-PET/CT were 85.7% (69.7–94.0%), 69.9% (65.6–73.9%), 54.5% (46.7–62.1%), and 51.7% (37.8–65.4%), respectively. In chemonaive patients, sensitivity rates were 80.5% (67.0–89.4%) for CT, 81.3% (64.1–91.4%) for FDG-PET, and 71.0% (64.3–76.9%) for FDG-PET/CT. Specificity could not be calculated because of non-reporting of “true negative lesions.”
Conclusion
In the neoadjuvant setting, MRI appears to be the most appropriate imaging modality for preoperative assessment of patients with CRLM. CT is the second-best diagnostic modality and should be used in the absence of MRI. Diagnostic accuracy of FDG-PET and PET-CT is strongly affected by chemotherapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Radioembolization (RE) is a relatively novel treatment modality for primary and secondary hepatic malignancies. Microspheres embedded with a β-emitting radioisotope are injected into the hepatic ...artery, resulting in microsphere deposition in the tumor arterioles and normal portal triads. Microsphere deposition in nontumorous parenchyma can result in radiation-induced liver injury, with lethal RE-induced liver disease (REILD) at the outer end of the spectrum. The primary aim of this study was to evaluate RE-related hepatotoxicity and present an overview of the currently applied definitions and clinically relevant characteristics of REILD. A systematic literature search on REILD was performed. Studies after the introduction of the term REILD (2008) were screened for definitions of REILD. Hepatotoxicity and applied definitions of REILD were compared. Liver biochemistry test abnormalities occur in up to 100% of patients after RE, mostly self-limiting. The incidence of symptomatic REILD varied between 0 and 31%, although in most reports, the incidence was 0–8%, with a lethal outcome in 0–5%. With the exception of bilirubin, the presentation of hepatotoxicity and REILD was similar for cirrhotic and noncirrhotic patients. No uniform definition of REILD was established in the current literature. Here, we propose a unifying definition and grading system for REILD. RE-related hepatotoxicity is a common phenomenon; symptomatic REILD, however, is rare. Currently, reporting of REILD is highly variable, precluding reliable comparison between studies, identification of risk factors, and treatment developments.
Purpose
Metabolic MRI is a noninvasive technique that can give new insights into understanding cancer metabolism and finding biomarkers to evaluate or monitor treatment plans. Using this technique, a ...previous study has shown an increase in pH during neoadjuvant chemotherapy (NAC) treatment, while recent observation in a different study showed a reduced amide proton transfer (APT) signal during NAC treatment (negative relation). These findings are counterintuitive, given the known intrinsic positive relation of APT signal to pH.
Methods
In this study we combined APT MRI and 31P‐MRSI measurements to unravel the relation between the APT signal and pH in breast cancer. Twenty‐two breast cancer patients were scanned with a 7 T MRI before and after the first cycle of NAC treatment. pH was determined by the chemical shift of inorganic phosphate (Pi).
Results
While APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo.
Conclusions
As differentiation of cancer stages was confirmed by observation of a linear correlation between cell proliferation marker PE/Pi (phosphoethanolamine over inorganic phosphate) and pH in the tumor, our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.
31P‐MRS and CEST‐MRI were acquired in 22 breast cancer patients with a 7 T MRI. While APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo. Our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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