Role of diffusion tensor magnetic resonance tractography in predicting the extent of resection in glioma surgery

Diffusion tensor imaging (DTI) tractography enables the in vivo visualization of the course of white matter tracts inside or around a tumor, and it provides the surgeon with important information in resection planning. This study is aimed at assessing the ability of preoperative DTI tractography in predicting the extent of the resection achievable in surgical removal of gliomas. Patients with low-grade gliomas (LGGs; 46) and high-grade gliomas (HGGs; 27) were studied using a 3T scanner according to a protocol including a morphological study (T2, fluid-attenuated inversion-recovery, T1 sequences) and DTI acquisitions (b = 1000 s/mm(2), 32 gradient directions). Preoperative tractography was performed off-line on the basis of a streamline algorithm, by reconstructing the inferior fronto-occipital (IFO), the superior longitudinal fascicle (SLF), and the corticospinal tract (CST). For each patient, the relationship between each bundle reconstructed and the lesion was analyzed. Initial and residual tumor volumes were measured on preoperative and postoperative 3D fluid-attenuated inversion-recovery images for LGGs and postcontrast T1-weighted scans for HGGs. The presence of intact fascicles was predictive of a better surgical outcome, because these cases showed a higher probability of total resection than did subtotal and partial resection. The presence of infiltrated or displaced CST or infiltrated IFO was predictive of a lower probability of total resection, especially for tumors with preoperative volume <100 cm(3). DTI tractography can thus be considered to be a promising tool for estimating preoperatively the degree of radicality to be reached by surgical resection. This information will aid clinicians in identifying patients who will mostly benefit from surgery.     

Acquisition-weighted chemical shift imaging improves SLOOP quantification of human cardiac phosphorus metabolites

PurposePhosphorous metabolite ratios in human myocardium were determined by a combination of acquisition weighted CSI and a SLOOP evaluation and the results were compared to corresponding SLOOP experiments using standard CSI.Materials and Methods10 healthy subjects were examined at 1.5 T using both standard CSI and acquisition weighted CSI. Both experiments were performed with a similar acquisition time and the same spatial resolution. The PCr/ATP ratio was determined and the localization properties of both experiments were compared.ResultsThe PCr/ATP ratio of 2.2 ± 0.4 found for the experiment using acquisition weighted CSI was almost identical to the value of 2.0 ± 0.4 for standard CSI. The sensitivity and the localization properties improved in all subjects using SLOOP evaluation of the acquisition weighted sampling in comparison to the standard CSI acquisition with an average of 3% and 18%, respectively.ConclusionThe employment of acquisition weighting allows for a further improvement of the ³¹P SLOOP spectroscopy of the human heart.     

Study of the Reduced Field-of-View Diffusion-Weighted Imaging of the Breast

BackgroundThis study aimed to compare the imaging quality, apparent diffusion coefficient (ADC) values, and application values between reduced field-of-view diffusion-weighted imaging (rFOV DWI) and single-shot echo-planar–imaging diffusion-weighted imaging (SS-EPI DWI) of breast tissue.Patients and MethodsFor 87 cases (75 with normal breast tissue, 12 with mammary cancer), breasts were scanned with SS-EPI DWI and rFOV DWI (b values, 800 s/mm²). Image quality and ADC values of breast tissue images were compared between SS-EPI DWI and rFOV DWI.ResultsThe average image quality score for the 87 cases was 4.73 in rFOV DWI and 3.62 in SS-EPI DWI. The difference was statistically significant (P < .01). The resolution of rFOV DWI was 2.25 mm × 1.23 mm, which was higher than the resolution of SS-EPI DWI (2.25 mm × 2.25 mm). The mean ADC value of 75 cases with normal breast tissue was 1.696 × 10^-3 mm²/s by rFOV DWI and 1.832 × 10^-3 mm²/s by SS-EPI DWI, and the difference was statistically significant (P < .01). The mean ADC value for the 12 cases with breast cancer was 1.065 × 10^-3 mm²/s by rFOV DWI and 1.192 × 10^-3 mm²/s by SS-EPI DWI, which was a statistically significant difference (P < .05).ConclusionrFOV DWI presented images with higher resolution and less distortion than SS-EPI DWI, and this difference may be helpful in disease diagnosis.     

Diffusion tensor imaging: possible implications for radiotherapy treatment planning of patients with high-grade glioma

AimsRadiotherapy treatment planning for high-grade gliomas (HGG) is hampered by the inability to image peri-tumoural white-matter infiltration. Diffusion tensor imaging (DTI) is an imaging technique that seems to show white-matter abnormalities resulting from tumour infiltration that cannot be visualised by conventional computed tomography or magnetic resonance imaging (MRI). We propose a new term, the image-based high-risk volume (IHV) for such abnormalities, which are distinct from the gross-tumour volume (GTV). For IHV based on DTI, we use the term IHV_DTI. This study assesses the value of DTI for the individualisation of radiotherapy treatment planning for patients with HGG.MethodsSeven patients with biopsy-proven HGG were included in a theoretical planning exercise, comparing standard planning techniques with individualised plans based on DTI. Standard plans were generated using a 2.5 cm clinical target volume (CTV) margin added to the GTV. For DTI-based plans, the CTV was generated by adding a 1 cm margin to the IHV_DTI. Estimates of normal tissue complication probability (NTCP) were calculated and used to estimate the level of dose escalation that could be achieved using the DTI-based plans.ResultsThe use of DTI resulted in non-uniform margins being added to the GTV to encompass areas at high risk of tumour involvement, but, in six out of seven cases, the IHV_DTI was encapsulated by the standard CTV margin. In all cases, DTI could be used to reduce the size of the planning-target volume (PTV) (mean 35%, range 18–46%), resulting in escalated doses (mean 67 Gy, range 64–74 Gy), with NTCP levels that matched the conventional treatment plans.ConclusionDTI can be used to individualise radiotherapy target volumes, and reduction in the CTV permits modest dose escalation without an increase in NTCP. DTI may also be helpful in stratifying patients according to the degree of white-matter infiltration.     

Convolutional Neural Network Detection of Axillary Lymph Node Metastasis Using Standard Clinical Breast MRI

BackgroundAxillary lymph node status is important for breast cancer staging and treatment planning as the majority of breast cancer metastasis spreads through the axillary lymph nodes. There is currently no reliable noninvasive imaging method to detect nodal metastasis associated with breast cancer.Materials and MethodsMagnetic resonance imaging (MRI) data were those from the peak contrast dynamic image from 1.5 Tesla MRI scanners at the pre-neoadjuvant chemotherapy stage. Data consisted of 66 abnormal nodes from 38 patients and 193 normal nodes from 61 patients. Abnormal nodes were those determined by expert radiologist based on ¹⁸Fluorodeoxyglucose positron emission tomography images. Normal nodes were those with negative diagnosis of breast cancer. The convolutional neural network consisted of 5 convolutional layers with filters from 16 to 128. Receiver operating characteristic analysis was performed to evaluate prediction performance. For comparison, an expert radiologist also scored the same nodes as normal or abnormal.ResultsThe convolutional neural network model yielded a specificity of 79.3% ± 5.1%, sensitivity of 92.1% ± 2.9%, positive predictive value of 76.9% ± 4.0%, negative predictive value of 93.3% ± 1.9%, accuracy of 84.8% ± 2.4%, and receiver operating characteristic area under the curve of 0.91 ± 0.02 for the validation data set. These results compared favorably with scoring by radiologists (accuracy of 78%).ConclusionThe results are encouraging and suggest that this approach may prove useful for classifying lymph node status on MRI in clinical settings in patients with breast cancer, although additional studies are needed before routine clinical use can be realized. This approach has the potential to ultimately be a noninvasive alternative to lymph node biopsy.     

Frequency of Immune Cell Subtypes in Peripheral Blood Correlates With Outcome for Patients With Metastatic Breast Cancer Treated With High-Dose Chemotherapy

BackgroundThe frequency of circulating leukocytes has been shown to be a prognostic factor in patients being treated for different types of cancer. In breast cancer, tumor-infiltrating leukocytes may predict patient outcome, but few studies have investigated such associations for circulating leukocytes.Patients and MethodsMultiparametric flow cytometry was used to examine the immunophenotypes of circulating peripheral blood mononuclear cells for 88 patients with metastatic breast cancer, which was then correlated to breast cancer–specific survival. Patients had been treated either with high-dose cyclophosphamide-containing regimens (group 1, n = 51 patients) or high-dose paclitaxel-containing regimens (group 2, n = 37 patients).ResultsThe frequency of peripheral blood CD14⁺ monocytes indicated prognosis for patients in group 1 (but not group 2), while higher levels of CD11c⁺ dendritic cells indicated a better prognosis for patients in group 2 (but not group 1). The frequency of a number of different CD4⁺ or CD8⁺ T cell subtypes also predicted prognosis for patients in group 2. For example, patients in group 2 with a higher frequency of circulating CD4⁺ or CD8⁺ naive T cells (CD45RA⁺CD95−CD27⁺CD28⁺) showed a poorer prognosis. In contrast, T cells were not associated with prognosis for patients in group 1.ConclusionCirculating leukocytes can predict clinical outcome for patients with breast cancer. Prediction of clinical outcome in this cohort of metastatic breast cancer patients was specific to the type of chemotherapy, and this finding is likely to apply to other therapies.     

The Effect of Adjuvant Treatment in Small Node-negative HER2-positive Breast Cancer: Which Subgroup Will Benefit?

BackgroundWe conducted this study to evaluate whether patients with T1a/b, node-negative (N⁻), human epidermal growth factor receptor 2-positive (HER2⁺) breast cancers benefited from adjuvant therapy, and explored better treatment strategies for these patients.Patients and MethodsPatients with T1a/b, N⁻, HER2⁺ breast cancers during 2000 through 2004 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The Gray test was used to evaluate breast cancer-specific death (BCSD) and non-BCSD. To identify patients more suitable for chemotherapy, subgroup analyses were conducted according to tumor size and estrogen receptor (ER) status, and plots of hazard rate of death (HRD) were drawn to present the changes of BCSD.ResultsA total of 2940 patients with T1a/b, N⁻, HER2⁺ breast cancers were included; more patients in the T1b group received chemotherapy compared with the T1a group (65.18% vs. 29.30%; P < .001). Patients receiving chemotherapy did not benefit from it (5-year incidences of BCSD: 1.00% in the non-chemotherapy group vs. 1.18% in the chemotherapy group; P = .853). Compared with those in the T1a group, patients in the T1b group had similar prognosis (P = .532), whereas ER status was significantly associated with survival (P = .048). HRD had a peak in years 2 to 5, which was more obvious in the ER⁻ group.ConclusionChemotherapy, which is mainly decided by tumor size, fails to render survival benefits for patients with T1a/b, N⁻, HER2⁺ breast cancers. ER status, rather than tumor size, is important for clinicians to make adjuvant treatment decisions. The peak of BCSD occurs 2 to 5 years after diagnosis, and an at least 5-year follow-up is recommended for these patients.     

Quantitative Changes in Skin Composition Parameters after Radiation Therapy According to Surgery Types Among Patients with Breast Cancer: A Prospective Study

BackgroundIn the current study, we sought to evaluate and compare the objective changes in biophysical parameters and patient-reported outcomes following radiation therapy (RT) in patients with breast cancer who underwent breast-conserving surgery (BCS) or modified radical mastectomy (MRM).Materials and methodsPatients older than 18 years, with stage I to III breast cancer, who were expected to receive RT were recruited between August 2015 and March 2019. Skin hydration, sebum content, pigmentation, and elasticity of the irradiated and unirradiated breast or chest wall were assessed using a noninvasive bioengineering device. Assessments were performed before the initiation of RT (T0); after the 5th (T1), 15th (T2), and 25th (T3) fractions; and 1 (T4) and 3 months (T5) after the completion of RT. Patient-reported outcomes were also evaluated using Radiation Dermatitis Assessment for Breast Cancer 11.ResultsHydration and sebum levels on the irradiated breast decreased during RT and had not returned to baseline at T5. Erythema on the irradiated breast increased two-fold between T0 and T3, and melanin levels were significantly higher than those at baseline and those of the contralateral unirradiated breast until T5 (106.0 vs. 115.8, P = .03). More than half of the patients continued to report skin color changes, dryness, and pain after RT. The erythema in the irradiated site at T1 was significantly higher in the MRM group than in the BCS group (P for interaction = .04), while there were no significant differences in the changes of the other parameters.ConclusionRT-induced changes in hydration, sebum, and melanin, and the majority of patient-reported pain, color changes, and dryness, even 3 months after the completion of treatment. There were no remarkable differences in the measurable skin parameters according to the surgery type, with the exception of erythema, which was higher in the MRM group 1 week after the start of RT.     

弥散张量成像在脑肿瘤中的应用

目的 探讨脑肿瘤弥散张量成像(DTI)的特点及其在脑肿瘤中的诊断和鉴别诊断价值.方法 对39例经病理证实的脑肿瘤患者(脑膜瘤10例,胶质瘤17例,转移瘤12例),采用PhilipsAchieva 1.5 T磁共振行常规MRI和DTI,在工作站上重建部分各向异性(FA)图、表观弥散系数(ADC)图和三维白质纤维束图,选择...     

Characterization of inflammatory changes in the breast cancer associated adipose tissue and comparison to the unaffected contralateral breast

BackgroundAdipose tissue has emerged as an important window into cancer pathophysiology, revealing potential targets for novel therapeutic interventions. The goal of this study was to compare the breast adipose tissue (BrAT) immune milieu surrounding breast carcinoma and contralateral unaffected breast tissue obtained from the same patient.Materials and methodsPatients undergoing bilateral mastectomy for unilateral breast cancer were enrolled for bilateral BrAT collection at the time of operation. After BrAT was processed, adipocyte and stromal vascular fraction (SVF) gene expression was quantified by PCR. SVF cells were also processed for flow cytometric immune cell characterization.ResultsTwelve patients underwent bilateral mastectomy for unilateral ductal carcinoma. BrAT adipocyte CXCL2 gene expression trended higher in the tumor-affected breast as compared to the unaffected breast. Macrophage MCP-1 and PPARγ gene expression also tended to be higher in the tumor-affected breasts. T cell gene expression of FOXP3 (p = 0.0370) were significantly greater in tumor-affected breasts than unaffected breasts. Affected BrAT contained higher numbers of Th2 CD4⁺ cells (p = 0.0165) and eosinophils (p = 0.0095) while trending towards increased macrophage and lower Th1 CD4⁺ cells infiltration than tumor-affected BrAT.ConclusionThis preliminary study aimed to identify the immunologic environment present within BrAT and is the first to directly compare this in individual patients’ tumor-associated and unaffected BrAT. These findings suggest that cancer-affected BrAT had increased levels of T cell specific FOXP3 and higher levels of anti-inflammatory/regulatory cells compared to the contralateral BrAT.     

Effects of chemotherapy on aging white matter microstructure: A longitudinal diffusion tensor imaging study

ObjectiveWe aimed to use diffusion tensor imaging (DTI) to detect alterations in white matter microstructure in older patients with breast cancer receiving chemotherapy.MethodsWe recruited women age ≥60 years with stage I–III breast cancer (chemotherapy [CT] group; n = 19) to undergo two study assessments: at baseline and within one month after chemotherapy. Each assessment consisted of a brain magnetic resonance imaging scan with DTI and neuropsychological (NP) testing using the National Institutes of Health (NIH) Toolbox Cognition Battery. An age- and sex-matched group of healthy controls (HC, n = 14) underwent the same assessments at matched intervals. Four DTI parameters (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], and radial diffusivity [RD]) were calculated and correlated with NP testing scores.ResultsFor CT group but not HCs, we detected statistically significant increases in MD and RD in the genu of the corpus callosum from time point 1 to time point 2 at p < 0.01, effect size:0.3655 and 0.3173, and 95% confidence interval: from 0.1490 to 0.5821, and from 0.1554 to 0.4792, for MD and RD respectively. AD values increased for the CT group and decreased for the HC group over time, resulting in significant between-group differences (p = 0.0056, effect size:1.0215, 95% confidence interval: from 0.2773 to 1.7657). There were no significant correlations between DTI parameters and NP scores (p > 0.05).ConclusionsWe identified alterations in white matter microstructures in older women with breast cancer undergoing chemotherapy. These findings may potentially serve as neuroimaging biomarkers for identifying cognitive impairment in older adults with cancer.     

A Phase II Study Evaluating the Safety and Efficacy of Sunitinib Malate in Combination With Weekly Paclitaxel Followed by Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF as Neoadjuvant Chemotherapy for Locally Advanced or Inflammatory Breast Cancer

IntroductionNeoadjuvant chemotherapy is standard treatment for locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). We hypothesized that adding sunitinib, a tyrosine kinase inhibitor with antitumor and antiangiogenic activity, to an anthracycline and taxane regimen would improve pathologic complete response (pCR) rates to a prespecified endpoint of 45% in patients with HER2-negative LABC or IBC.MethodsWe conducted a multicenter, phase II trial of neoadjuvant sunitinib with paclitaxel (S+T) followed by doxorubicin and cyclophosphamide plus G-CSF for patients with HER2-negative LABC or IBC. Patients received sunitinib 25 mg PO daily with paclitaxel 80 mg/m² IV weekly ×12 followed by doxorubicin 24 mg/m² IV weekly + cyclophosphamide 60 mg/m² PO daily with G-CSF support. Response was evaluated using pCR in the breast and the CPS + EG score (clinical-pathologic scoring + estrogen receptor [ER] and grade).ResultsSeventy patients enrolled, and 66 were evaluable for efficacy. Eighteen patients (27%) had pCR in the breast (10 had ER⁺ disease and 8 had triple-negative disease). When defining response as pCR and/or CPS + EG score ≤2, 31 (47%) were responders. In pateints with ER positive disease, 23 (64%) were responders. The most common toxicities were cytopenias and fatigue.ConclusionsNeoadjuvant S+T followed by AC+G-CSF was safe and tolerable in LABC and IBC. The study did not meet the prespecified endpoint for pCR; however, 47% were responders using pCR and/or CPS + EG score ≤2. ER positive patients had the highest response rate (64%). The addition of sunitinib to neoadjuvant chemotherapy may provide promising incremental benefit for patients with ER positive LABC.     

Évaluation monocentrique de la tolérance de l’association concomitante de trastuzumab et de radiothérapie

PurposeProspective monocentric study of the skin and heart tolerance of a concurrent administration of trastuzumab (T) and radiotherapy (RT) for breast cancer (BC).Patients and methodsFrom February 2004 to January 2007, 57 patients (pts), were treated by a concomitant administration of T and normo-fractionated RT of either whole breast (± boost) or chest. The perfusion of T started either with or after chemotherapy (CT). Left ventricular ejection fractions (LEVF), assessed at baseline, before start of RT, after completion of RT and then every four to six months with either echocardiography or multiple gated acquisition scanning, were considered normal if greater or equal to 50% or stated so by the cardiologist. Inclusion criteria included a normal LVEF at baseline. Skin toxicity was evaluated using CTCAEV3. Median age was 49 years (25–80). CT with anthracycline was administered in 84% (total dose 300 mg/m²). All but one patient (treated weekly) received T every three weeks (8 mg/kg followed by 6 mg/kg) for a median duration of 12 months (6–33). The internal mammary chain was irradiated in 88% of cases. Median follow-up for LVEF assessment was 13 months (2–33).ResultsLVEF at pre-RT were normal in 54 pts (100%, three Missing Data [MD]), at post-RT in 56 pts (98%, no MD) and at last follow-up in 53 pts (95%, one MD). There were two grade 0, 44 grade I and 11 grade II skin reactions. For the 27 patients with a skin toxicity assessment after six months, late skin toxicity was grade 0 in 22 pts, grade 1 in four, grade 2 in one.ConclusionProvided that the technique is adapted, the acute skin and heart toxicities of the concomitant administration of T-RT appeared satisfactory. More patients and longer follow-up are still mandatory.     

Common breast cancer risk alleles and risk assessment: a study on 35 441 individuals from the Danish general population

BackgroundWe hypothesized that common breast cancer risk alleles are associated with incidences of breast cancer and other cancers in the general population, and identify low risk women among those invited for screening mammography.Participants and methodsAbout 35 441 individuals from the Danish general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0–2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer.ResultsBreast cancer incidence in the 19 010 women was increased across allele sum quintiles (log-rank trend test; P = 1×10 ^− 12), but not incidence of other cancers (P = 0.41). Age- and study-adjusted hazard ratio for the fifth versus the first allele sum quintile was 1.82 (95% confidence interval; 1.53–2.18). Corresponding hazard ratios per allele were 1.04 (1.03–1.05) and 1.05 (1.02–1.08) for breast cancer incidence and mortality, similar across risk factors. In 50-year-old women, the starting age for screening mammography in Denmark, the average 5-year breast cancer risk was 1.5%, overall and 1.1%, 1.4%, 1.6%, 1.7%, 2.1%, for the first through fifth quintile, respectively. Based on age, nulliparity, familial history, and allele sum, 25% of women aged 50–69 years, and 94% of women aged 40–49 years, had absolute 5-year breast cancer risks ≤ 1.5%. Using polygenic risk score led to similar results.ConclusionCommon breast cancer risk alleles are associated with incidence and mortality of breast cancer in the general population, but not with other cancers. After including breast cancer allele sum in risk assessment, 25% of women currently being offered screening mammography had an absolute 5-year risk below the cutoff of average risk for a 50-year-old woman.     

Volumetric 23Na Single and Triple-Quantum Imaging at 7T: 3D-CRISTINA

PurposeTo measure multi-quantum coherence (MQC) ²³Na signals for noninvasive cell physiological information in the whole-brain, the 2D-CRISTINA method was extended to 3D. This experimental study investigated the use and results of a new sequence, 3D-CRISTINA, on a phantom and healthy volunteers.MethodsThe 3D Cartesian single and triple-quantum imaging of ²³Na (3D-CRISTINA) was developed and implemented at 7T, favoring a non-selective volume excitation for increased signal-to-noise ratio (SNR) and lower energy deployment than its 2D counterpart. Two independent phase cycles were used in analogy to the 2D method. A comparison of 6-steps cycles and 12-steps cycles was performed.We used a phantom composed of different sodium and agarose concentrations, 50 mM to 150 mM Na+, and 0–5% agarose for sequence validation. Four healthy volunteers were scanned at 7T for whole brain MQC imaging. The sequence 3D-CRISTINA was developed and tested at 7T.ResultsAt 7T, the 3D-CRISTINA acquisition allowed to reduce the TR to 230 ms from the previous 390 ms for 2D, resulting in a total acquisition time of 53 min for a 3D volume of 4 × 4 × 8 mm resolution. The phase cycle evaluation showed that the 7T acquisition time could be reduced by 4-fold with moderate single and triple-quantum signals SNR loss. The healthy volunteers demonstrated clinical feasibility at 7T and showed a difference in the MQC signals ratio of White Matter (WM) and Grey Matter (GM).ConclusionVolumetric CRISTINA multi-quantum imaging allowed whole-brain coverage. The non-selective excitation enabled a faster scan due to a decrease in energy deposition which enabled a lower repetition time. Thus, it should be the preferred choice for future in vivo multi-quantum applications compared to the 2D method. A more extensive study is warranted to explore WM and GM MQC differences.     

High-definition fiber tractography for the evaluation of perilesional white matter tracts in high-grade glioma surgery

Conventional white matter (WM) imaging approaches, such as diffusion tensor imaging (DTI), have been used to preoperatively identify the location of affected WM tracts in patients with intracranial tumors in order to maximize the extent of resection and potentially reduce postoperative morbidity. DTI, however, has limitations that include its inability to resolve multiple crossing fibers and its susceptibility to partial volume effects. Therefore, recent focus has shifted to more advanced WM imaging techniques such as high-definition fiber tractography (HDFT). In this paper, we illustrate the application of HDFT, which in our preliminary experience has enabled accurate depiction of perilesional tracts in a 3-dimensional manner in multiple anatomical compartments including edematous zones around high-grade gliomas. This has facilitated accurate surgical planning. This is illustrated by using case examples of patients with glioblastoma multiforme. We also discuss future directions in the role of these techniques in surgery for gliomas.     

18FDG PET-CT for diagnosis of distant metastases in breast cancer patients. A meta-analysis

BackgroundWe performed a meta-analysis to evaluate the value of ¹⁸FDG PET-CT for diagnosis of distant metastases in breast cancer patients.MethodsStudies about PET-CT were systematically searched in the MEDLINE and EMBASE databases. We calculated sensitivities, specificities, likelihood ratios, and constructed summary receiver operating characteristic curves for PET-CT. We also compared the performance of PET-CT with that of conventional imaging by analyzing studies that had also used conventional imaging on the same patients.ResultsAcross 8 PET-CT studies (748 patients), sensitivity and specificity of PET-CT were 0.96 (95% confidence interval [CI] = 0.90–0.98) and 0.95 (95% CI = 0.92–0.97). Across 6 comparative studies (664 patients), sensitivity and specificity of PET-CT were 0.97 (95% CI = 0.84–0.99) and 0.95 (95% CI = 0.93–0.97), and of conventional imaging were 0.56 (95% CI = 0.38–0.74) and 0.91 (95% CI = 0.78–0.97), respectively.ConclusionsCompared with conventional imaging, ¹⁸FDG PET-CT has higher sensitivity for diagnosis of distant metastases in breast cancer patients.     

Magnetic resonance analysis of malignant transformation in recurrent glioma

BackgroundPatients with low-grade glioma (LGG) have a relatively long survival, and a balance is often struck between treating the tumor and impacting quality of life. While lesions may remain stable for many years, they may also undergo malignant transformation (MT) at the time of recurrence and require more aggressive intervention. Here we report on a state-of-the-art multiparametric MRI study of patients with recurrent LGG.MethodsOne hundred and eleven patients previously diagnosed with LGG were scanned at either 1.5 T or 3 T MR at the time of recurrence. Volumetric and intensity parameters were estimated from anatomic, diffusion, perfusion, and metabolic MR data. Direct comparisons of histopathological markers from image-guided tissue samples with metrics derived from the corresponding locations on the in vivo images were made. A bioinformatics approach was applied to visualize and interpret these results, which included imaging heatmaps and network analysis. Multivariate linear-regression modeling was utilized for predicting transformation.ResultsMany advanced imaging parameters were found to be significantly different for patients with tumors that had undergone MT versus those that had not. Imaging metrics calculated at the tissue sample locations highlighted the distinct biological significance of the imaging and the heterogeneity present in recurrent LGG, while multivariate modeling yielded a 76.04% accuracy in predicting MT.ConclusionsThe acquisition and quantitative analysis of such multiparametric MR data may ultimately allow for improved clinical assessment and treatment stratification for patients with recurrent LGG.     

The Effect of Image Guidance on Dose Distributions in Breast Boost Radiotherapy

AimsTo determine the effect of image-guided radiotherapy on the dose distributions in breast boost treatments.Materials and methodsComputed tomography images from a cohort of 60 patients treated within the IMPORT HIGH trial (CRUK/06/003) were used to create sequential and concomitant boost treatment plans (30 cases each). Two treatment plans were created for each case using tumour bed planning target volume (PTV) margins of 5 mm (achieved with image-guided radiotherapy) and 8 mm (required for bony anatomy verification). Dose data were collected for breast, lung and heart; differences with margin size were tested for statistical significance.ResultsA median decrease of 29 cm³ (range 11–193 cm³) of breast tissue receiving 95% of the prescribed dose was observed where image-guided radiotherapy margins were used. Decreases in doses to lungs, contralateral breast and heart were modest, but statistically significant (P < 0.01). Plan quality was compromised with the 8 mm PTV margin in one in eight sequential boost plans and one third of concomitant boost plans. Tumour bed PTV coverage was <95% (>91%) of the prescribed dose in 12 cases; in addition, the required partial breast median dose was exceeded in nine concomitant boost cases by 0.5–3.7 Gy.ConclusionsThe use of image guidance and, hence, a reduced tumour bed PTV margin, in breast boost radiotherapy resulted in a modest reduction in radiation dose to breast, lung and heart tissues. Reduced margins enabled by image guidance were necessary to discriminate between dose levels to multiple PTVs in the concomitant breast boost plans investigated.     

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer

BackgroundAbemaciclib is a selective cyclin-dependent kinase 4 and 6 inhibitor administered continuously for hormone receptor-positive (HR⁺), human epidermal growth factor receptor 2-negative (HER2^?) advanced breast cancer. Abemaciclib is associated with dose-dependent early-onset diarrhea. nextMONARCH evaluated abemaciclib monotherapy (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory metastatic breast cancer (MBC) after chemotherapy.Patients and MethodsnextMONARCH is an open-label, controlled, randomized, phase II study of women with endocrine-refractory HR⁺, HER2^? MBC previously treated with chemotherapy. Patients received abemaciclib 150 mg plus tamoxifen 20 mg (A+T), abemaciclib 150 mg every 12 hours (A-150), or abemaciclib 200 mg plus prophylactic loperamide (A-200). The primary objective was progression-free survival (PFS). PFS analyses tested superiority of A+T to A-200 and informal noninferiority of A-150 to A-200. The secondary objectives included the objective response rate (ORR), safety, and pharmacokinetics.ResultsThe median PFS was 9.1 months for A+T versus 7.4 months for A-200 (hazard ratio, 0.815; 95% confidence interval, 0.556-1.193; P = .293). The A-200 PFS was comparable to that with A-150 at 6.5 months (hazard ratio, 1.045; 95% confidence interval, 0.711-1.535; P = .811). The ORR was 34.6%, 24.1%, and 32.5% for A+T, A-150, and A-200, respectively. No new safety signals were identified. The incidence and severity of diarrhea (62.3%; grade 3, 7.8%) with A-200 was similar to that with A-150 (67.1%; grade 3, 3.8%). The pharmacokinetics were comparable to previous observations.ConclusionsThe addition of tamoxifen to abemaciclib did not significantly improve PFS or ORR compared with abemaciclib monotherapy but confirmed the single-agent activity of abemaciclib in heavily pretreated HR⁺, HER2^? MBC. Dose reductions and antidiarrheal medication generally managed diarrhea while maintaining efficacy.