Functional Magnetic Resonance Imaging in Cervical Cancer Diagnosis and Treatment.

Cervical Cancer is the fourth most common cancer in women worldwide. Treatment with chemoradiotherapy followed by brachytherapy achieves high local control, but recurrence with metastatic disease impacts survival. This highlights the need for predictive and prognostic biomarkers identifying populations at risk of poorer treatment response and survival. Magnetic resonance imaging (MRI) is routinely used in cervical cancer and is a potential source for biomarkers. Functional MRI (fMRI) can characterise tumour beyond anatomical MRI, which is limited to the assessment of morphology. This review summarises fMRI techniques used in cervical cancer and examines the role of fMRI parameters as predictive or prognostic biomarkers. Different techniques characterise different tumour factors, which helps to explain the variation in patient outcomes. These can impact simultaneously on outcomes, making biomarker identification challenging. Most studies are small, focussing on single MRI techniques, which raises the need to investigate combined fMRI approaches for a more holistic characterisation of tumour.

POD-Kalman filtering for improving noninvasive 3D temperature monitoring in MR-guided hyperthermia.

BACKGROUND: During resonance frequency (RF) hyperthermia treatment, the temperature of the tumor tissue is elevated to the range of 39-44°C. Accurate temperature monitoring is essential to guide treatments and ensure precise heat delivery and treatment quality. Magnetic resonance (MR) thermometry is currently the only clinical method to measure temperature noninvasively in a volume during treatment. However, several studies have shown that this approach is not always sufficiently accurate for thermal dosimetry in areas with motion, such as the pelvic region. Model-based temperature estimation is a promising approach to correct and supplement 3D online temperature estimation in regions where MR thermometry is unreliable or cannot be measured. However, complete 3D temperature modeling of the pelvic region is too complex for online usage. PURPOSE: This study aimed to evaluate the use of proper orthogonal decomposition (POD) model reduction combined with Kalman filtering to improve temperature estimation using MR thermometry. Furthermore, we assessed the benefit of this method using data from hyperthermia treatment where there were limited and unreliable MR thermometry measurements. METHODS: The performance of POD-Kalman filtering was evaluated in several heating experiments and for data from patients treated for locally advanced cervical cancer. For each method, we evaluated the mean absolute error (MAE) concerning the temperature measurements acquired by the thermal probes, and we assessed the reproducibility and consistency using the standard deviation of error (SDE). Furthermore, three patient groups were defined according to susceptibility artifacts caused by the level of intestinal gas motion to assess if the POD-Kalman filtering could compensate for missing and unreliable MR thermometry measurements. RESULTS: First, we showed that this method is beneficial and reproducible in phantom experiments. Second, we demonstrated that the combined method improved the match between temperature prediction and temperature acquired by intraluminal thermometry for patients treated for locally advanced cervical cancer. Considering all patients, the POD-Kalman filter improved MAE by 43% (filtered MR thermometry = 1.29°C, POD-Kalman filtered temperature = 0.74°C). Moreover, the SDE was improved by 47% (filtered MR thermometry = 1.16°C, POD-Kalman filtered temperature = 0.61°C). Specifically, the POD-Kalman filter reduced the MAE by approximately 60% in patients whose MR thermometry was unreliable because of the great amount of susceptibilities caused by the high level of intestinal gas motion. CONCLUSIONS: We showed that the POD-Kalman filter significantly improved the accuracy of temperature monitoring compared to MR thermometry in heating experiments and hyperthermia treatments. The results demonstrated that POD-Kalman filtering can improve thermal dosimetry during RF hyperthermia treatment, especially when MR thermometry is inaccurate.

Ultrasound guidance for cervical implantation.

Ultrasound can provide real-time imagery without the risk of radiation exposure, and it is widely available at a relatively low cost. It can provide updated three-dimensional information that can improve the physician's spatial awareness during a brachytherapy procedure for cervical cancer. There is mounting evidence demonstrating the numerous benefits of ultrasound-guided brachytherapy in the published literature. This evidence supports its routine use to improve the safety and the effectiveness of cervical brachytherapy. In this report we will review various methods in which ultrasound imaging has been used during cervical brachytherapy. We also include a description of our own institutional approach to ultrasound-guided cervical implementation that has been in use for all cervical brachytherapy procedures over the past two decades.

Deep learning-based auto-segmentation of clinical target volumes for radiotherapy treatment of cervical cancer.

OBJECTIVES: Because radiotherapy is indispensible for treating cervical cancer, it is critical to accurately and efficiently delineate the radiation targets. We evaluated a deep learning (DL)-based auto-segmentation algorithm for automatic contouring of clinical target volumes (CTVs) in cervical cancers. METHODS: Computed tomography (CT) datasets from 535 cervical cancers treated with definitive or postoperative radiotherapy were collected. A DL tool based on VB-Net was developed to delineate CTVs of the pelvic lymph drainage area (dCTV1) and parametrial area (dCTV2) in the definitive radiotherapy group. The training/validation/test number is 157/20/23. CTV of the pelvic lymph drainage area (pCTV1) was delineated in the postoperative radiotherapy group. The training/validation/test number is 272/30/33. Dice similarity coefficient (DSC), mean surface distance (MSD), and Hausdorff distance (HD) were used to evaluate the contouring accuracy. Contouring times were recorded for efficiency comparison. RESULTS: The mean DSC, MSD, and HD values for our DL-based tool were 0.88/1.32 mm/21.60 mm for dCTV1, 0.70/2.42 mm/22.44 mm for dCTV2, and 0.86/1.15 mm/20.78 mm for pCTV1. Only minor modifications were needed for 63.5% of auto-segmentations to meet the clinical requirements. The contouring accuracy of the DL-based tool was comparable to that of senior radiation oncologists and was superior to that of junior/intermediate radiation oncologists. Additionally, DL assistance improved the performance of junior radiation oncologists for dCTV2 and pCTV1 contouring (mean DSC increases: 0.20 for dCTV2, 0.03 for pCTV1; mean contouring time decrease: 9.8 min for dCTV2, 28.9 min for pCTV1). CONCLUSIONS: DL-based auto-segmentation improves CTV contouring accuracy, reduces contouring time, and improves clinical efficiency for treating cervical cancer.

Indocyanine Green-Based Theranostic Nanoplatform for NIR Fluorescence Image-Guided Chemo/Photothermal Therapy of Cervical Cancer.

PURPOSE: Indocyanine green (ICG) is a favorable fluorescence nanoprobe for its strong NIR-I fluorescence emission and good photothermal capabilities. However, the stability and tumor targeting ability of ICG is poor, which limits its further applications. To further improve the photothermal and therapeutic efficiency of ICG, bovine serum albumin (BSA) was utilized to encapsulate the ICG and the chemotherapeutic drug doxorubicin (DOX) was loaded to form the BSA@ICG-DOX theranostic nanoplatform. METHODS: In this study, ICG-loaded BSA nanoparticles (NPs) and the BSA@ICG-DOX NPs were fabricated using reprecipitation methods. Next, the tumour inhibition ability and biocompatibility of the NPs were evaluated. A subcutaneous xenografted nude mice model was established and imaging guided synergetic therapy was performed with the assistance of BSA@ICG-DOX NPs under 808 nm laser irradiation. RESULTS: The BSA@ICG NPs exhibited strong NIR-I fluorescence emission, excellent photothermal properties, biocompatibility, and tumor targeting ability. To further improve the therapeutic efficiency, the chemotherapeutic drug doxorubicin (DOX) was loaded into the BSA@ICG NPs to form the BSA@ICG-DOX theranostic nanoplatform. The BSA@ICG-DOX NPs were spherical with an average size of ~194.7 nm. The NPs had high encapsulation efficiency (DOX: 19.96% and ICG: 60.57%), and drug loading content (DOX: 0.95% and ICG: 3.03%). Next, excellent NIR-I fluorescence and low toxicity of the BSA@ICG-DOX NPs were verified. Targeted NIR-I fluorescence images were obtained after intravenous injection of the NPs into the subcutaneous cervical tumors of the mice. CONCLUSION: To improve the anti-tumor efficiency of the ICG@BSA NPs, the chemotherapeutic drug DOX was loaded into the BSA@ICG NPs. The NIR excitation/emission and targeted BSA@ICG-DOX NPs enables high-performance diagnosis and chemo/photothermal therapy of subcutaneous cervical tumors, providing a promising approach for further biomedical applications.

Near-infrared emissive polymer-coated IR-820 nanoparticles assisted photothermal therapy for cervical cancer cells.

Photothermal therapy (PTT) has attracted wide attention due to its noninvasiveness and its thermal ablation ability. As photothermal agents are crucial factor in PTT, those with the characteristics of biocompatibility, non-toxicity and high photothermal stability have attracted great interest. In this work, new indocyanine green (IR-820) was utilized as a photothermal agent and near-infrared (NIR) fluorescence imaging nanoprobe. To improve the biocompatibility, poly(styrene-co-maleic anhydride) (PSMA) was utilized to encapsulate the IR-820 molecules to form novel IR-820@PSMA nanoparticles (NPs). Then, the optical and thermal properties of IR-820@PSMA NPs were studied in detail. The IR-820@PSMA NPs showed excellent photothermal stability and biocompatibility. The cellular uptaking ability of the IR-820@PSMA NPs was further confirmed in HeLa cells by the NIR fluorescent confocal microscopic imaging technique. The IR-820@PSMA NPs assisted PTT of living HeLa cells was conducted under 793 nm laser excitation, and a high PTT efficiency of 73.3% was obtained.

Benefits of positron emission tomography scans for the evaluation of radiotherapy.

The assessment of tumour response during and after radiotherapy determines the subsequent management of patients (adaptation of treatment plan, monitoring, adjuvant treatment, rescue treatment or palliative care). In addition to its role in extension assessment and therapeutic planning, positron emission tomography combined with computed tomography provides useful functional information for the evaluation of tumour response. The objective of this article is to review published data on positron emission tomography combined with computed tomography as a tool for evaluating external radiotherapy for cancers. Data on positron emission tomography combined with computed tomography scans acquired at different times (during, after initial and after definitive [chemo-]radiotherapy, during post-treatment follow-up) in solid tumours (lung, head and neck, cervix, oesophagus, prostate and rectum) were collected and analysed. Recent recommendations of the National Comprehensive Cancer Network are also reported. Positron emission tomography combined with computed tomography with (18F)-labelled fluorodeoxyglucose has a well-established role in clinical routine after chemoradiotherapy for locally advanced head and neck cancers, particularly to limit the number of neck lymph node dissection. This imaging modality also has a place for the evaluation of initial chemoradiotherapy of oesophageal cancer, including the detection of distant metastases, and for the post-therapeutic evaluation of cervical cancer. Several radiotracers for positron emission tomography combined with computed tomography, such as choline, are also recommended for patients with prostate cancer with biochemical failure. (18F)-fluorodeoxyglucose positron emission tomography combined with computed tomography is optional in many other circumstances and its clinical benefits, possibly in combination with MRI, to assess response to radiotherapy remain a very active area of research.

Multifunctional theranostic nanosystems enabling photothermal-chemo combination therapy of triple-stimuli-responsive drug release with magnetic resonance imaging.

Theranostic nanosystems are emerging as a promising approach for controlled drug delivery, diagnosis and multimodal therapeutics. Herein, a multifunctional theranostic nanoplatform is reported for photothermal-chemo combination therapy functioned with magnetic and thermal imaging. Hyaluronic acid (HA) coated Fe3O4@polydopamine nanoparticles equipped with redox-sensitive disulfide linkers have been subsequently deposited with an anticancer drug, doxorubicin (DOX) (termed as FPCH-DOX NPs). These nanocomposites possess an average diameter of 120 nm, a saturation magnetization of 28.5 emu g-1, DOX loading capacity of 7.13% and a transverse relaxation rate of 171.76 mM-1 s-1. The drug release could be triggered by pH, glutathione (GSH) concentration and light irradiation. Prussian blue staining and confocal microscopy demonstrate that these nanoplatforms have improved biocompatibility and cellular uptake in CD44-positive HeLa cell lines rather than in CD44-negative NIH 3T3 normal cell lines. In vitro evaluations demonstrate that the combination therapy of FPCH-DOX NPs lowers the cell viability to 16.2%, less than that of individual chemotherapy (55.3%) or PTT (52.1%). In vivo MRI indicates that the tumor accumulation of FPCH-DOX NPs provides enhanced MRI contrast, and in vivo thermal imaging verified their localized photothermal conversion effect in tumor tissues. Importantly, FPCH-DOX NPs present remarkable anti-tumor efficacy by photothermal-chemo combination therapy. H&E and Ki67 staining tests show obvious necrosis and weak cell proliferation at the region of the tumor. Thus, FPCH-DOX NPs are promising multifunctional nanoplatforms for highly effective cancer theranostics.

Multi-functional FITC-silica@gold nanoparticles conjugated with guar gum succinate, folic acid and doxorubicin for CT/fluorescence dual imaging and combined chemo/PTT of cancer.

A novel type of multi-functional fluorescein isothiocyanate (FITC)-silica (SiO2)@gold (Au) core-shell nanoparticles covered with folic acid (FA)-conjugated guar gum succinate (GGS) and doxorubicin (DOX) (FITC-SiO2@Au-DOX-GGS-FA NPs) was prepared for imaging and therapy of cancer. The physicochemical properties of these NPs were analyzed with 1H NMR, TEM and DLS. The FITC-SiO2@Au-DOX-GGS-FA NPs exhibited the fluorescence and X-ray attenuation properties due to the presence of FITC-SiO2@Au hybrid nanostructure. Due to acid-cleavable hydrazone bond between the DOX and NPs, the quantity of DOX delivered from the FITC-SiO2@Au-DOX-GGS-FA NPs was increased at pH 5.6 than that at pH 7.4. Besides, the multi-functional NPs presented the improved cellular uptake by HeLa cells via FA-receptor-mediated endocytosis due to the existence of FA. The developed NPs also presented the improved cytotoxicity towards the HeLa cells due to its tumor-targetability and DOX/photothermal effect. These results suggested that the FITC-SiO2@Au-DOX-GGS-FA NPs could be ideal for computed tomography (CT)/fluorescence dual imaging and combined chemo/photothermal therapy (PTT) of cancer.

Primary Preclinical and Clinical Evaluation of 68Ga-DOTA-TMVP1 as a Novel VEGFR-3 PET Imaging Radiotracer in Gynecological Cancer.

PURPOSE: Tumor periphery and lymph nodes of tumor-induced lymphangiogenesis often abundantly express VEGFR-3. In our previous study, we identified a 5-amino acid peptide named TMVP1, which binds specifically to VEGFR-3. The objective of this study was to develop a novel 68Ga-labeled TMVP1 for VEGFR-3 PET imaging and to investigate its safety, biodistribution, and tumor-localizing efficacy in xenograft tumor models and a small cohort of patients with recurrent ovarian and cervical cancer. EXPERIMENTAL DESIGN: The DOTA-conjugated TMVP1 peptide was labeled with radionuclide 68Ga. SPR and saturation binding assays were used for the receptor-binding studies. Gynecologic xenograft tumors were employed for small-animal PET imaging and biodistribution of 68Ga-DOTA-TMVP1 in vivo. In the clinical study, 5 healthy volunteers and 8 patients with gynecologic cancer underwent whole-body PET/CT after being injected with 68Ga-DOTA-TMVP1. RESULTS: DOTA-TMVP1 was successfully labeled with 68Ga. LECs showed higher binding capacity with 68Ga-DOTA-TMVP1 than LEC(shVEGFR-3) and human umbilical vein endothelial cells. In mice with subcutaneous C33-A and SKOV-3 xenografts, the tracer was rapidly eliminated through the kidney to the bladder, and the small-animal PET/CT helped to clearly visualize the tumors. In patients with recurrent ovarian cancer and cervical cancer, tracer accumulation well above the background level was demonstrated in most identified sites of disease; especially with recurrent endodermal sinus tumors, the diagnostic value of 68Ga-DOTA-TMVP1 was comparable with that of 18F-FDG PET/CT. CONCLUSIONS: 68Ga-DOTA-TMVP1 is a potential PET tracer for imaging VEGFR-3 with favorable pharmacokinetics.

Ag@Fe3O4@C nanoparticles for multi-modal imaging-guided chemo-photothermal synergistic targeting for cancer therapy.

Novel multifunctional core-shell nanoparticles (NPs) have attracted widespread attention due to their easy-to-modify surface properties and abundant functional groups. This study introduces a facile approach to synthesize Ag@ iron oxide (Fe3O4) @C NPs, and modify with amino-poly (ethylene glycol) (PEG)-carboxyl and folate (FA) on the exposed carbon surface to produce high contrast for excellent stability, good biocompatibility, cancer cell targeting, and synergistic treatment. The multi-armed PEG at the edge of Ag@Fe3O4@C NPs provides the materials an excellent capacity for doxorubicin (DOX) loading. The carbon layer could be used as a photothermal reagent due to its excellent near-infrared (NIR) absorbance capacity, and Fe3O4 was used as a reagent for magnetic resonance (MR) imaging. In vivo combination therapy with this agent was administered in a mouse tumor model, and a remarkable synergistic antitumor effect that is superior to that obtained by monotherapy was achieved. Concerning these features together, these unique multifunctional Ag@Fe3O4@C-PEG-FA/DOX NPs could be regarded as an attractive nanoplatforms for chemo-photothermal synergistic tumor therapy with dual-modal fluorescence and MR imaging-guided targeting.

Intelligent protein-coated bismuth sulfide and manganese oxide nanocomposites obtained by biomineralization for multimodal imaging-guided enhanced tumor therapy.

Radiotherapy (RT) has been used clinically to overcome cancer in recent decades. However, the abnormal tumor microenvironment (TME), involving hypoxia, acidosis and a dense extracellular matrix, is found to be related to the resistance of tumors to RT. Herein, intelligent bovine serum albumin (BSA)-coated Bi2S3 and MnO2 (Bi2S3-MnO2) nanocomposites synthesized via biomineralization are capable of modulating the hypoxic TME effectively to enhance the efficacy of RT. After intravenous injection, the BSA-Bi2S3-MnO2 nanocomposites show efficient accumulation in tumors, where endogenous H2O2 can react with MnO2 to generate oxygen in situ, leading to increased tumor oxygenation to overcome the hypoxia-associated resistance to RT. Moreover, the photothermal effect induced by the BSA-Bi2S3-MnO2 nanocomposites further relieves hypoxia in the TME and, finally, synergistically improves the effects of RT. In this work, we present a simple strategy to fabricate intelligent therapeutic nanoparticles to improve therapeutic efficiency towards cervical cancer.

The effect of modulated electro-hyperthermia on local disease control in HIV-positive and -negative cervical cancer women in South Africa: Early results from a phase III randomised controlled trial.

BACKGROUND: The global burden of cervical cancer remains high with the highest morbidity and mortality rates reported in developing countries. Hyperthermia as a chemo- and radiosensitiser has shown to improve treatment outcomes. This is an analysis of the local control results at six months post-treatment of patients enrolled in an ongoing study investigating the effects of the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for the treatment of HIV-positive and -negative cervical cancer patients in a low-resource setting. METHODS: This ongoing Phase III randomised controlled trial, conducted at a state hospital in Johannesburg, South Africa, was registered with the appropriate ethics committee. After signing an informed consent, participants with FIGO stages IIB to IIIB squamous cell carcinoma of the cervix were randomised to receive chemoradiotherapy with/without mEHT using a secure online random-sampling tool (stratum: HIV status) accounting for age and stage. Reporting physicians were blind to treatment allocation. HIV-positive participants on antiretroviral treatment, or with a CD4 count >200cell/µL were included. mEHT was administered 2/weekly immediately before external beam radiation. The primary end point is local disease control (LDC) and secondary endpoints are toxicity; quality of life analysis; and two year survival. We report on six month LDC, including nodes visualised in the radiation field on 18F-FDG PET/CT (censored for six month survival), and six month local disease free survival (LDFS) (based on intention to treat). Trial status: Recruitment closed (ClinicalTrials.gov: NCT03332069). RESULTS: 271 participants were recruited between January 2014 and November 2017, of which 210 were randomised for trial and 202 were available for analysis at six months post-treatment (mEHT: n = 101; Control: n = 101). Six month LDFS was higher in the mEHT Group (n = 39[38.6%]), than in the Control Group (n = 20[19.8%]); p = 0.003). LDC was also higher in the mEHT Group (n = 40[45.5%]) than the Control Group (n = 20[24.1%]); (p = 0.003). CONCLUSION: Our results show that mEHT is effective as a chemo-radiosensitiser for cervical cancer, even in high risk a patients and resource-constrained settings.

Application of Deep Learning Algorithm in Cervical Cancer MRI Image Segmentation Based on Wireless Sensor.

With the development of medical technology in China, new difficulties are gradually emerging in traditional medicine. Cervical cancer MRI image segmentation technology based on wireless network is one of the most famous means. But the traditional technology is not strong enough for information processing and analysis. Manual data processing alone may lead to errors in data processing and so on. Therefore, this research was aimed at the MRI image segmentation technology of cervical cancer based on wireless network, using depth learning algorithm to calculate and analyze. Through this kind of wireless network and the computer algorithm form, the data processing ability can be improved and increase the data processing ability be increased.

Hydrothermal Galvanic-Replacement-Tethered Synthesis of Ir-Ag-IrO2 Nanoplates for Computed Tomography-Guided Multiwavelength Potent Thermodynamic Cancer Therapy.

Beyond the synthesis of typical nanocrystals, various breakthrough approaches have been developed to provide more useful structural features and functionalities. Among them, galvanic replacement, a structural transformation reaction accompanied by constituent element substitution, has been applied to various areas. However, the innovative improvement for galvanic replacement needs to be considered because of the limitation of applicable element pairs to maintain structural stability. To expand the boundary of galvanic-replacement-mediated synthesis, we have become interested in the Group 9 metallic element Ir, which is considered a fascinating element in the field of catalysis, but whose size and shape regulation has been conventionally regarded as difficult. To overcome the current limitations, we developed a hydrothermal galvanic-replacement-tethered synthetic route to prepare Ir-Ag-IrO2 nanoplates (IrNPs) with a transverse length of tens of nanometers and a rough surface morphology. A very interesting photoreactivity was observed from the prepared IrNPs, with Ag and IrO2 coexisting partially, which showed photothermal conversion and photocatalytic activity at different ratios against extinction wavelengths of 473, 660, and 808 nm. The present IrNP platform showed excellent photothermal conversion efficiency under near-infrared laser irradiation at 808 nm and also represented an effective cancer treatment in vitro and in vivo through a synergistic effect with reactive oxygen species (ROS) generation. In addition, computed tomography (CT) imaging contrast effects from Ir and IrO2 composition were also clearly observed.

Magnetic resonance imaging after external beam radiotherapy and concurrent chemotherapy for locally advanced cervical cancer helps to identify patients at risk of recurrence.

OBJECTIVE: Tumor volume and regression after external beam radiotherapy have been shown to be accurate parameters to assess treatment response via magnetic resonance imaging (MRI). The aim of the study was to evaluate the prognostic value of tumor size reduction rate after external beam radiotherapy and chemotherapy prior to brachytherapy. METHODS: Patients with locally advanced cervical cancer treated at two French comprehensive cancer centers between 1998 and 2010 were included. Treatment was pelvic external beam radiotherapy with platinum based chemotherapy followed by brachytherapy. Records were reviewed for demographic, clinical, imaging, treatment, and follow-up data. Anonymized linked data were used to ascertain the association between pre-external and post-external beam radiotherapy MRI results, and survival data. RESULTS: 185 patients were included in the study. Median age at diagnosis was 45 years (range 26-72). 77 patients (41.6%) were International Federation of Gynecology and Obstetrics stage IB2-IIA disease and 108 patients (58.4%) were stage IIB-IVA. Median tumor size after external beam radiotherapy and chemotherapy was 2.0 cm (range 0.0-8.0) and median tumor size reduction rate was 62.4% (range 0.0-100.0%). Tumor size and tumor reduction rate at 45 Gy external beam radiotherapy MRI were significantly associated with local recurrence free survival (P<0.001), disease free survival, and overall survival (P<0.05). Tumor reduction rate ≥60% was significantly associated with a decreased risk of relapse and death (HR (95% CI) 0.21 (0.09 to 0.50), P=0.001 for local recurrence free survival; 0.48 (0.30 to 0.77) P=0.002 for disease free survival; and 0.51 (0.29 to 0.88), P=0.014 for overall survival). CONCLUSIONS: Tumor size reduction rate >60% between pre-therapeutic and post-therapeutic 45 Gy external beam radiotherapy with concurrent chemotherapy was associated with improved survival. Future studies may help to identify patients who may ultimately benefit from completion surgery, adjuvant chemotherapy, and closer follow-up.

Defining Characteristics of Nodal Disease on PET/CT Scans in Patients With HIV-Positive and -Negative Locally Advanced Cervical Cancer in South Africa.

Literature reports increased FDG nodal uptake in HIV-positive patients. Our aim is to identify differences in presentation and characteristics of FDG-avid lymph nodes between HIV-positive and HIV-negative locally advanced cervical cancer (LACC) patients in our clinical setting. We evaluated 250 pre-treatment 18F-FDG PET/CT imaging studies from women screened for a phase III randomised controlled trial investigating modulated electro-hyperthermia as a radiosensitiser (Ethics approval: M120477). The number of nodes; size; maximum standardised uptake value (SUVmax); symmetry; and relationship between nodal size and SUVmax uptake, were assessed by region and by HIV status. In total, 1314 nodes with a SUVmax ≥ 2.5 were visualised. Of 128(51%) HIV-positive participants, 82% were on antiretroviral therapy (ART) and 10 had a CD4 count <200 cells/µL. Overall pattern of presentation and nodal characteristics were similar between HIV-positive and -negative groups and the uniformity in presentation of the nodes draining the cervix strongly suggests these nodes may be attributed to malignancy rather than HIV infection. Novel findings: HIV infection is associated with: >four nodes visualised in the neck, symmetrical inguinal lymph nodes, increased rates of supraclavicular node visualisation; FDG-avid axillary nodes were more common, but not exclusive, in HIV-positive participants. 18F-FDG PET/CT is a reliable staging method for LACC in HIV-positive patients who are not in acute stages of HIV infection, have a CD4 count >200 cells/µL, and/or are on ART and there is a potential risk of underestimating metastatic spread by attributing increased nodal metabolic activity to HIV infection in these patients.

Amphiphilic redox-sensitive NIR BODIPY nanoparticles for dual-mode imaging and photothermal therapy.

Theranostics, integrating tumor treatment and diagnosis concurrently, has become an emerging and meaningful strategy in cancer therapy. In this work, an amphiphilic redox-sensitive near-infrared (NIR) BODIPY dye, which could be formed into nanoparticles (PEG-SS-BDP NPs) by self-assembly, was synthesized and possessed good capability of photothermal therapy (PTT), near-infrared fluorescence (NIRF) imaging, photoacoustic (PA) imaging and drug loading. The stable nanoparticles could be dissociated to turn on NIRF due to the rift of embedded disulfide bonds by glutathione (GSH). The enhanced fluorescence in vitro could be observed via confocal laser scanning microscopy (CLSM) after adding GSH, confirming the redox-sensitivity of disulfide bonds. NIRF and PA imaging demonstrated active accumulation in tumor and good imaging effect. At last, PEG-SS-BDP NPs could significantly suppress tumor growth in vivo upon irradiation. The amphiphilic redox-sensitive BODIPY nanoparticles provide a promising design strategy to formulate multifunctional stimuli-responsive theranostic nanoplatforms.

Calcium Phosphate Cement Paste Injection as a Fiducial Marker of Cervical Cancer.

BACKGROUND/AIM: Calcium phosphate cement (CPC) is used to fill bone voids in dental, orthopedic, and craniofacial applications. This study evaluated CPC marker as an injectable non-metallic fiducial marker. MATERIALS AND METHODS: Six patients received 3-5 injections of CPC paste placed at a depth of 10 mm into tumors of the cervix before treatment planning CT (TPCT). Patients were treated with external-beam radiotherapy (EBRT) and high-dose rate brachytherapy (BT). We investigated marker visibility on cone-beam CT (CBCT), T2-weighted MRI, and interfraction of the marker motion for cervical cancer patients. RESULTS: Of a total of 22 visible CPC markers at TPCT, 17 CPC markers were visible on the first CBCT. Excluding one patient, all markers were visible on CBCT during EBRT. Of 16 visible CPC markers on CBCT, 13 CPC markers were visible on the magnetic resonance imaging (MRI) obtained before BT. For CPC marker centroid movement, the mean-of-means/systematic variation/random variation were 0.2/0.4/1.4, -1.6/5.1/4.1, and -3.4/2.1/2.8 mm for the left-right, dorsal-ventral, and cranial-caudal directions, respectively. CONCLUSION: This is the first report of a CPC marker injected into tumors of the cervix. It can be visualized on CBCT and MRI with reductions in marker loss and artifacts.

Shape-Transformable, Fusible Rodlike Swimming Liquid Metal Nanomachine.

The T-1000 liquid metal terminator, which can transform and self-repair, represents a dream for decades that robots can fundamentally change our daily life. Until now, some large-scale liquid metal machines have been developed. However, there is no report on nanoscaled liquid metal machines and their biomedical applications. We describe here a shape-transformable and fusible rodlike swimming liquid metal nanomachine, based on the biocompatible and transformable liquid metal gallium. These nanomachines were prepared by a pressure-filter-template technology, and the diameter and length could be controlled by adjusting the nanoporous templates, filter time, and pressure. The as-prepared liquid gallium nanomotors display a core-shell nanorod structure composed of a liquid gallium core and solid gallium oxide shell. Upon exposure to an ultrasound field, the generated acoustic radiation force in the levitation plane can propel them to move autonomously. The liquid metal nanomachine can actively seek cancer cells and transform from a rod to a droplet after drilling into cells owing to the removal of gallium oxide layers in the acidic endosomes. These transformed nanomachines could fuse together inside cells and photothermally kill cancer cells under illumination of near-infrared light. Such acoustically propelled shape-transformable rodlike liquid metal nanomachines have great potential for biomedical applications.