Changes In Tumor Volume Research Articles

Tumor volume regression of rectal cancer in daily MRI during preoperative chemoradiotherapy with capecitabine.

123 Background: Although cone beam computed tomography (CBCT) has been available for over a decade, the pattern of tumor volume change in rectal dancer during preoperative concurrent chemoradiotherapy (CCRT) has been under the veil due to poor soft tissue contrast of registration CBCT. This study was conducted to investigate daily rectal tumor volume change using registration magnetic resonance imaging (MRI). Methods: Patients diagnosed with cT3-4 and/or cN+ rectal adenocarcinoma undergoing preoperative CCRT with capecitabine on the pelvis up to 50 Gy in 25 daily fractions from November 2018 to June 2019 were consecutively included. Rectal tumor volume was uniformly measured by single physician (YKK) in daily 0.35T MRI obtained with ViewRay MRIdian Linac (ViewRay Inc., Oakwood, USA). The mean +/- standard deviation (SD) of daily tumor volume (cc), difference of tumor volume between first fraction and daily fraction (daily tumor volume – baseline tumor volume at first fraction), and tumor volume reduction rate (%, (daily tumor volume – baseline tumor volume at first fraction)/baseline tumor volume at first fraction x 100) were calculated. Statistical significance of differences were tested using the Wilcoxon’s signed rank test and paired t-test. Results: Thirteen patients were included. Median age was 65 and majority of the patients were male (92.3%). Most tumors were T3 (76.9%) and N1-2 (92.3%). Tumors were located median 6 cm (range: 2.4 – 9) above anal verge. Median follow-up was 27.3 months (range: 11.7 – 30.6) and 2 patients had recurred at the time of analysis (1 local and 1 distant). Tumor volume steadily regressed with daily administration of CCRT (mean 2.06 +/-1.73 cc; Figure 1). Significant tumor volume reduction compared to baseline was observed from fourth fraction (mean -12.37 +/- 16.72 cc; P < 0.0005). The difference of tumor volume between baseline and the last fraction was mean -49.33 +/- 68.13 cc ( P < 0.0002). The tumor volume reduction rate was significantly increased since fourth fraction (mean - 17.2 +/- 11.78 %; P < 0.0002). The tumor volume reduction rate at the last fraction was - 70.62 +/- 14.01 % ( P < 0.0001). Conclusions: For the first time, this study demonstrated daily tumor volume regression in preoperative rectal CCRT with capecitabine using daily MRI. Steady pattern of tumor regression may be explained in part by daily administration of capecitabine. Based on the hypothesis-generating observation, this study may warrant initiation of further investigations such as analysis and comparison with daily tumor volume regression with CCRT using leucovorin and 5-FU.

Application of Intravoxel Incoherent Motion Diffusion-Weighted Imaging in Predicting and Monitoring Early Efficacy of Anti-Angiogenic Therapy in the C6 Glioma Rat Model.

ObjectiveTo investigate the feasibility of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in evaluating early effects of anti-angiogenic therapy in the C6 glioma rat model.MethodsTwenty-six rats of the C6 glioma model were randomly divided into a treatment group (received bevacizumab) and a control group (physiological saline). IVIM-DWI was performed on days 0, 1, 3, 5, and 7 after anti-angiogenic therapy and tumor growth and IVIM-DWI parameters were dynamically observed. Hematoxylin and eosin, CD34 microvessel density (MVD), proliferation of cell nuclear antigen (PCNA), and Hif-α staining were performed on day 7. One-way ANOVA was used to compare intra-group differences and an independent-samples t-test was used to compare inter-group differences of MRI parameters. Correlations between IVIM-DWI parameters, tumor size, and pathological results were analyzed.ResultsThe relative change in tumor volume (ΔVolume) in the two groups differed significantly on days 5 and 7 (p = 0.038 and p < 0.001). The perfusion-related parameters D*- and f-values decreased in the treatment group and demonstrated significant differences compared with the control group on days 3, 5, and 7 (p = 0.033, p < 0.001, and p < 0.001, respectively). The diffusion-related parameters ADC and D-values increased in the treatment group and were found to be significantly differently different from the control group on days 5 and 7 (both p < 0.001). The initial D-value showed a negative correlation with ΔVolume (γ = −0.744, p < 0.001), whereas the initial D*-value and relative change of D-value had a positive correlation with ΔVolume (γ = 0.718, p < 0.001 and γ = 0.800, p < 0.001, respectively). MVD was strongly positively correlated with D*-value (r = 0.886, p = 0.019), PCNA was negatively correlated with ADC- and D-values (r = −0.848, p = 0.033; and r = −0.928 p = 0.008, respectively), and Hif-1α was strongly negatively correlated with D*-value (r = −0.879, p = 0.010).ConclusionIVIM-DWI was sensitive and accurate in predicting and monitoring the effects of early anti-angiogenesis therapy in a C6 glioma rat model.

Dynamic contrast-enhanced magnetic resonance imaging for evaluating early response to radiosurgery in patients with vestibular schwannoma.

This study aimed to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to evaluate early treatment response in vestibular schwannoma (VS) patients after radiosurgery. Twenty-four VS patients who underwent gamma knife radiosurgery were prospectively followed up for at least four years. DCE-MRI sequences, in addition to standard MRI protocol, were obtained prior to radiosurgery, at 3 and 6months. Conventionally, treatment responses based on tumor volume changes were classified as regression or stable (RS), transient tumor enlargement (TTE), and continuous tumor enlargement (CTE). DCE-MRI parameters, such as Ktrans, Kep and Ve, were compared according to follow-up periods and between groups. The diagnostic performance was tested using receiver operating characteristic (ROC) curves. Changes in tumor volume were as follows at the last 48 months of follow-up: RS in 11 patients (45.8%), TTE in 10 patients (41.7%), and CTE in three patients (12.5%). The median time required to distinguish TTE from CTE using conventional MRI was 12months (range 9-18). The Ktrans and Ve were significantly decreased in patients with RS and TTE at 3 and 6months, but did not differ significantly in patients with CTE. There were no significant differences in Ktrans and Ve between patients with RS and TTE at 3 and 6months. Both Ktrans and Ve demonstrated high diagnostic performance in evaluating early treatment response to radiosurgery in patients with VS. DCE-MRI may aid in the monitoring and early prediction of treatment response in patients with VS following radiosurgery.

Regression Analysis of Rectal Cancer and Possible Application of Artificial Intelligence (AI) Utilization in Radiotherapy

Artificial Intelligence (AI) has been widely employed in the medical field in recent years in such areas as image segmentation, medical image registration, and computer-aided detection. This study explores one application of using AI in adaptive radiation therapy treatment planning by predicting the tumor volume reduction rate (TVRR). Cone beam computed tomography (CBCT) scans of twenty rectal cancer patients were collected to observe the change in tumor volume over the course of a standard five-week radiotherapy treatment. In addition to treatment volume, patient data including patient age, gender, weight, number of treatment fractions, and dose per fraction were also collected. Application of a stepwise regression model showed that age, dose per fraction and weight were the best predictors for tumor volume reduction rate.

Efficacy of First- & Second-Line Treatment in an In Vivo Model of Poorly Differentiated Neuroendocrine Carcinoma of the Pancreas

Introduction: Poorly differentiated neuroendocrine carcinoma of the pancreas (PD-NEC) is a rare but deadly pancreatic tumor type with limited systemic treatment options. The absence of a preclinical animal model of PD-NEC has made translational research for this rare tumor type difficult. The aim of this study was to develop a novel patient-derived xenograft (PDX) of PD-NEC and assess the efficacy of currently proposed first- and second-line therapeutics in this fatal subtype of pancreatic cancer. Methods: With appropriate consent and approval, patient tissue was obtained from surgical resection and implanted into the flanks of NOD/SCID mice. Mouse tumors were verified as PD-NEC by a Mayo Clinic pathologist. Mice were randomized into 4 groups and treated for 3 weeks: 1) vehicle, 2) cisplatin + irinotecan, 3) capecitabine + temozolomide, and 4) everolimus. Treatment efficacy was measured by change in tumor volume as compared to vehicle. Toxicity was assessed by change in mouse weight during treatment. Results: Figure 1 demonstrates tumor volume fold change over time for each treatment arm. Capecitabine + temozolomide arm demonstrated a 47% decrease in tumor volume fold change versus vehicle (p=0.0001) while cisplatin + irinotecan arrested tumor growth with an average fold change of 1.02 versus vehicle (p=0.019). Figure 2 demonstrates the change in mouse weight throughout the course of the treatment study. Conclusions: PD-NEC is a rare but lethal pancreas cancer. To our knowledge, this is the first report of treatment efficacy of both first-line and second-line combinatorial therapeutics in a validated animal model of PD-NEC.

Determining the optimum tumor control probability model in radiotherapy of glioblastoma multiforme using magnetic resonance imaging data pre- and post- radiation therapy

Background:Glioblastoma multiforme (GBM) is the most common and malignant brain tumor. The current standard of care is surgery followed by radiation therapy (RT). Radiotherapy treatment plan evaluation relies on radiobiological models for accurate estimation of tumor control probability (TCP). This study aimed to assess the impact of obtained magnetic resonance imaging (MRI) data before and 12 weeks after RT to achieve the optimum TCP model to improve dose prescriptions in radiation therapy of GBM.Materials and Methods::In this quasi-experimental study, MR images and its relevant data from 30 patients consisting of 9 females and 21 males (mean age of 46.3 ± 15.8 years) diagnosed with GBM, whose referred for radiotherapy were selected. The data of age, gender, tumor size, volume, and signal intensity using analysis of MRI data pre- and postradiotherapy were used for calculating TCP. TCP was calculated from three common radiobiological models including Poisson, linear quadratic, and equivalent uniform dose. The impact of some radiobiological parameters on final TCP in all patients planned with three-dimensional conformal radiation therapy was obtained.Results:A statistically significant difference was found among TCP in Poisson model compared to the other two models (P < 0.001). Changes in tumor volume and size after treatment were statistically significant (P < 0.05). Different combinations of radiobiological parameters (α/β and SF2 in all models) observed were meaningful (P < 0.05).Conclusion:The results showed that among TCP radiobiological models, the optimum is the Poisson. The results also identified the importance of TCP radiobiological models in order to improve radiotherapy dose prescriptions.

Biologically effective dose correlates with linear tumor volume changes after upfront single-fraction stereotactic radiosurgery for vestibular schwannomas

Biologically effective dose correlates with linear tumor volume changes after upfront single-fraction stereotactic radiosurgery for vestibular schwannomas

The Neurosurgical Challenge of Primary Central Nervous System Lymphoma Diagnosis: A Multimodal Intraoperative Imaging Approach to Overcome Frameless Neuronavigated Biopsy Sampling Errors

Background: Intracranial lymphoma remains a challenging differential diagnosis in daily neurosurgical practice. We analyzed our early experience with a surgical series of frameless neuronavigated biopsies in Primary CNS Lymphomas (PCNSLs), highlighting the importance of using an intraoperative combined imaging protocol (5-ALA fluorescence, i-CT and 11C-MET-PET) to overcome potential targeting errors secondary to tumor volume reduction after corticosteroid therapy. Materials and methods: All patients treated for PCNLSs at our center in a 24-month period (1/1/2019 to 31/12/2020) were analyzed. Our cohort included 6 patients (4 males), with a median age of 67 years (59–82). A total of 45 samples were evaluated for correlation between intraoperative fluorescence and pathological findings. 39 samples biopsy were evaluated. Results: 54% samples showed a clear diagnosis of PCNSL. 64% of samples had a lava like fluorescence. i-CT scan showed tumor volume changes, in comparison to preoperative MRI, in all cases and helped in planning correct trajectories on updated imaging; after biopsy i-CT confirmed sampling accuracy and excluded procedural complications in all cases. Conclusions: We believe that the use of a multimodal intraoperative imaging approach overcomes the demonstrated PCNSL morphological changes caused by corticosteroid therapy and gives a reliable tissue diagnosis by frameless biopsy.

Pattern of F-18 FDG Uptake in Colon Cancer after Bacterial Cancer Therapy Using Engineered Salmonella Typhimurium: A Preliminary In Vivo Study.

Purpose Bacterial cancer therapy (BCT) research using engineered Salmonella typhimurium has increased in recent years. 2-Deoxy-2[18F] fluoro-D-glucose positron emission tomography (FDG PET) is widely used in cancer patients to detect cancer, monitor treatment responses, and predict prognoses. The aim of this pilot study was to investigate FDG uptake patterns in a mouse tumor model after BCT. Procedures. BCT was performed via the intravenous injection of attenuated S. typhimurium (SLΔppGpp/lux) into female mice bearing a tumor (derived from CT26 murine colon cancer cells) in the right thigh. 18F-FDG PET images acquired before BCT and at different time points after BCT. In vivo bioluminescence imaging confirmed bacterial presence in the tumor. The tumor volume, standardized uptake value (SUV) of FDG (SUVmax and SUVmean), early SUV reduction%, and normalized tumor volume change were analyzed. Results Early after BCT (1 or 2 days post-injection (dpi)), FDG tumor uptake decreased in 10 out of 11 mice and then increased at later stages. FDG uptake before BCT was correlated with normalized tumor volume change after BCT. Early FDG reduction% after BCT was correlated with normalized volume change after BCT. Conclusions Early after BCT, FDG tumor uptake decreased and then increased at later stages. The higher the FDG tumor uptake before BCT, the better the BCT response. FDG uptake patterns were related to tumor volume change after BCT. Therefore, FDG uptake was a good candidate for evaluating BCT.

Effect of applicator removal from target volume for cervical cancer patients treated with Venezia high-dose-rate brachytherapy applicator.

PurposeThe volume of Venezia applicator with vaginal caps can be relatively large compared to target volumes. This study investigated the dosimetric and radiobiological effects of applicator volume removal for cervical cancer patients treated with Venezia (VZ) and tandem and split-ring (TSR) applicators used in the clinic.Material and methodsA total of 40 patients (101 plans) with stage IIA-IIIC cervical cancer were retrospectively reviewed. Thirty patients were treated with VZ and ten patients were treated with TSR. Applicators were contoured on planning CTs where target contours were involved. Applicator contours were subtracted from the target contours. External beam radiation therapy (EBRT) and brachytherapy doses were calculated in biologically equivalent doses in 2 Gy fractions (EQD2) and combined using full parameter addition for dose-volume histogram (DVH) parameters of composited dose. D90%, D50%, V100%, V150%, V200%, and tumor control probability (TCP) were evaluated and compared for targets after applicator exclusion.ResultsThe average volume changes in gross tumor volume (GTV), high-risk clinical target volume (HR-CTV), and intermediate-risk clinical target volume (IR-CTV) after VZ applicator exclusion were 1.4 ±1.5 cm3, 15.7 ±6.6 cm3, and 33.8 ±15.1 cm3, respectively. VZ exclusion resulted in significant changes (p < 0.05) in small volume parameters (D50%) and high-dose parameters (V150% and V200%) for HR-CTV and IR-CTV. Dosimetric impact of TSR exclusion on targets was not significant. There was no significant change in TCP after applicator exclusion.ConclusionsVenezia applicator with vaginal caps has significant impact on small volume and high-dose DVH parameters of the target. Applicator contour exclusion is recommended for dosimetric evaluation when Venezia applicator is used.

The Effect of Black Cohosh on Ki67 expression and Tumor Volume: A Pilot Study of Ductal Carcinoma in Situ Patients.

Black cohosh (BC) (Cimicifuga racemosa) may prevent and treat breast cancer through anti-proliferative, pro-apoptotic, anti-estrogenic, and anti-inflammatory effects. This study sought to evaluate the effect of BC on tumor cellular proliferation, measured by Ki67 expression, in a pre-operative window trial of ductal carcinoma in situ (DCIS) patients. Patients were treated pre-operatively for 2 to 6 weeks with BC extract. Eligible subjects were those who had DCIS on core biopsy. Ki67 was measured using automated quantitative immunofluorescence (AQUA) pre/post-operatively. Ki67, tumor volume, and hormone changes were assessed with 2-sided Wilcoxon signed-rank tests, α = .05. Thirty-one patients were treated for an average of 24.5 days (median 25; range 15-36). Ki67 decreased non-significantly (n = 26; P = .20; median pre-treatment 1280, post-treatment 859; range pre-treatment 175-7438, post-treatment 162-3370). Tumor volume, estradiol, and FSH did not change significantly. No grade 3 or 4 adverse events were reported. BC use showed no significant impact on cellular proliferation, tumor volume, or invasive disease upgrade rates in DCIS patients. It was well-tolerated, with no observed significant toxicities. Further study is needed to elucidate BC's role in breast cancer treatment and prevention.ClinicalTrials.gov Identifier: NCT01628536https://clinicaltrials.gov/ct2/show/NCT01628536.

Enhancing Intersystem Crossing by Intermolecular Dimer-Stacking of Cyanine as Photosensitizer for Cancer Therapy

Enhancing Intersystem Crossing by Intermolecular Dimer-Stacking of Cyanine as Photosensitizer for Cancer Therapy

Early PSA Change after [177Lu]PSMA-617 Radioligand Therapy as a Predicator of Biochemical Response and Overall Survival.

Simple SummaryRadioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) is a promising therapeutic option for metastatic castration-resistant prostate cancers (mCRPC), as its clinical relevance has recently been confirmed in the phase III VISION-trial. As prostate-specific antigen (PSA) plays an important role in the response evaluation of this therapy, and the aim of this study was to prospectively assess the prognostic value of early PSA measurements. We found PSA changes as early as four weeks after the first administration of PSMA-RLT to be predictive of both long-term biochemical and PET imaging response, as well as overall survival. We then evaluated relevant predictive thresholds in PSA change at that time point, as the early detection of long-term (non-)response to PSMA-RLT can be of great benefit in the clinical management of terminally ill mCRPC-patients.Purpose: Radioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCPRP). This study assessed the prognostic value of early PSA measurements during PSMA-RLT. Methods: 27 patients with mCRPC scheduled for PSMA-RLT were prospectively enrolled for a serial short-interval PSA-assessment. Change in PSA (∆%PSA) during two treatment cycles was correlated with biochemical response (BR) and change in tumor volume on PET (TV) after 16 weeks (w16), as well as overall survival (OS). PCWG3 criteria and the recently recommended threshold of ∆%PSA ≤ −30% were assessed for their predictive value. Results: ∆%PSA first correlated with BR, TV and OS after 4 weeks (c1w4). At c1w4, ∆%PSA ≤ −30% was associated with the biochemical response at w16 (p = 0.003) and a longer median OS (p = 0.025), whereas the PCWG3-derived threshold of ∆%PSA ≤ −50% showed no such correlation. In contrast, ∆%PSA ≥ 25% at c1w4 was associated with biochemical progression at w16 (p = 0.003) and a shorter median OS (p < 0.001). Conclusion: PSA changes as early as four weeks after PSMA-RLT allow a significant prediction of later biochemical and PET-based imaging response, as well as OS. At this early time point, a more lenient threshold for a PSA decrease of at least 30% appears better-suited for the prediction of a positive biochemical response and longer OS. In contrast, the PCWG3-derived threshold for PSA increase (+25%) reliably anticipates biochemical progression and shorter OS.

Imaging response assessment for predicting outcomes after bioselection chemotherapy in larynx cancer: A secondary analysis of two prospective trials

Background and purposeBioselection with induction chemotherapy in larynx cancer is associated with excellent larynx preservation and disease-specific survival but requires visual inspection of the primary tumor. We retrospectively compare clinical and imaging response in bioselected patients to develop predictive models of surgeon-assessed response (SR), laryngectomy-free survival (LFS), and overall survival (OS) in bioselected patients. Materials and methodsIn a secondary analysis of patients on two single-institution bioselection trials, model building used a regularized regression model (elastic-net) and applied nested cross-validation. Logistic regression-based model was used to predict SR and Cox proportional hazard-based models were used to predict LFS and OS. ResultsIn 115 patients with a median age of 57 years, most patients had supraglottic tumors (73.0%) and T3/T4 disease (94.8%). Definitive treatment was chemoradiation in 76.5% and laryngectomy in 23.5%. Change in primary tumor (OR = 5.78, p < 0.001) and N-classification (OR = 1.64, p = 0.003) predicted SR (AUC 0.847). Change in tumor volume (HR = 0.58, p < 0.001) predicted LFS (c-index 0.724). N-classification (HR = 1.48, p = 0.04) and pre-chemotherapy tumor volume (HR = 1.30, p = 0.174) predicted OS (c-index 0.552). ConclusionsImaging offers a non-invasive opportunity to evaluate response to induction chemotherapy, complementary to surgeon assessment. Further evaluation of approaches to bioselection that optimize generalizability of this paradigm are needed, and clinical trials utilizing imaging to predict outcomes including LFS are warranted.

Berberine enhances gemcitabine‑induced cytotoxicity in bladder cancer by downregulating Rad51 expression through inactivating the PI3K/Akt pathway.

Although gemcitabine (GEM) has been used to treat bladder cancer (BC) for a number of years, severe adverse events or drug resistance frequently develops. A series of drugs have been proved to sensitize patients to GEM and reduce the side effects. The aim of the present study was to evaluate the potential effects of berberine (BER) on GEM‑induced cytotoxicity in BC and to explore the possible underlying mechanisms. T24 and 5637 human BC cell lines were treated with GEM and/or BER before cell proliferation, apoptosis and migration were studied. Oncomine databases and Gene Expression Profiling Interactive Analysis (GEPIA) were used to retrieve RAD51 recombinase (Rad51) mRNA expression. Overexpression plasmid or specific Rad51 small interfering RNA were used to examine the role of Rad51 in drug‑treated BC cells. BC model mice were administered with GEM and/or BER before changes in tumor volume, size and Ki67 expression were assessed. BER enhanced GEM‑induced cytotoxicity, apoptosis and inhibition of migration, whilst attenuating the GEM‑induced upregulation of phosphorylated Akt and Rad51 expression. According to Oncomine and GEPIA analyses, Rad51 was found to be significantly upregulated in BC tissues compared with that in normal tissues, where there was a weak positive correlation between Rad51 and Akt1 expression. Knockdown of Rad51 enhanced GEM‑induced cytotoxicity, whilst overexpression of Rad51 reversed the suppressed cell viability induced by BER and GEM. Inactivation of the PI3K/Akt pathway by LY294002 or BER enhanced GEM‑induced cytotoxicity and downregulated Rad51 expression, whilst overexpression of constitutively active Akt restored Rad51 expression and cell viability that was previously decreased by BER and GEM. BER additively inhibited tumor growth and Ki67 expression when combined with GEM invivo. These results suggest that BER can enhance GEM‑induced cytotoxicity in BC by downregulating Rad51 expression through inactivating the PI3K/Akt pathway, which may represent a novel therapeutic target for BC treatment.

O-P05 Gemcitabine and paclitaxel loaded microbubbles for the treatment of pancreatic cancer

Abstract Background Ultrasound targeted microbubble destruction (UTMD) has emerged as an effective strategy for the delivery of drug payloads to solid tumours. However, loading a single microbubble (MB) formulation with two drug payloads is challenging and often involves several manipulations post-MB preparation to enable attachment of drug payloads which can be cumbersome and generally results in low / inconsistent drug loading. Here we report a one-step synthesis of a gemcitabine-functionalised phospholipid and its subsequent incorporation into a stable MB formulation co-loaded with paclitaxel (PTX). The efficacy of the MB conjugate was determined in a Panc-1 spheroid model and ectopic BxPC-3 tumour model of pancreatic cancer. Methods Gemcitabine-modified phospholipid (Lipid-Gem MB) was prepared from 1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC) though a transphosphatidylation reaction using gemcitabine (Gem) as the acceptor alcohol. Lipid-Gem MB and Lipid-Gem-PTX MB were prepared from Lipid-Gem MB and/or PTX using a standard thin-film hydration technique followed by sonication in the presence of PFB gas. In vitro efficacy of Lipid-Gem MB and Lipid-Gem-PTX MB were determined in Panc-1 spheroids using an MTT assay. The in vivo effectiveness was determined in BxPC-3 tumour bearing mice following IV administration of either Lipid-Gem MB or Lipid-Gem-PTX MB plus ultrasound (US). Free Gem, free Gem + PTX and untreated mice were used for comparative purposes. Results Spheroids treated with Lipid-Gem MB +US or Lipid-Gem-PTX MB +US were significantly reduced relative to spheroids treated with US alone (p = 0.033 and p = 0.0031 respectively) or with the respective MB formulation alone (i.e. no US) (p = 0.0336 and p = 0.0037 respectively). Furthermore, cell viability for spheroids treated with Lipid-Gem-PTX MB +US was significantly reduced compared with spheroids treated with Lipid-Gem MB +US (p = 0.0077) (Figure a). Mice treated with Lipid-Gem MB +US or Lipid-Gem-PTX MB +US showed an average change in tumour volume of + 7 ± 7% and -10 ± 10 % respectively compared with +45 ±10% and +30 ± 10% for free gem and free gem + PTX respectively (Figure b). Conclusions A Gem-modified lipid was succesfully synthesised using a single step reaction and was subsequently incorporated into MBs containging PTX, eliminating the need for cumbersome drug conjgation methods. UTMD mediated treatment of Panc-1 spheroids and BxPC-3 tumours demonstrated the efficacy and tolerability of the formulations. Given that all components of this formulation are already clinicaly apporved, UTMD using Lipid-Gem-PTX MB offers a promising alternative to existing treatments

ICG-Loaded PEG-Modified Black Phosphorus Nanosheets for Fluorescence Imaging-Guided Breast Cancer Therapy.

Indocyanine green (ICG) has been used in various surgical navigation systems and plays an important role in intraoperative imaging diagnosis. However, the poor photostability and unsatisfactory tumor-targeting ability have limited its broad application prospects. In the decades, the construction of a nanodrug delivery system for tumor-targeting diagnosis and therapy has become a research hotspot. Black phosphorus nanosheets (BPNS), as a new kind of biodegradable nanomaterials, have the advantages of high loading capacity, good biocompatibility, tumor targeting, and photothermal effect over other two-dimensional (2D) reported nanomaterials. Herein, ICG-loaded poly(ethylene glycol) (PEG)-modified BPNS (ICG@BPNS-PEG) nanocomposites are constructed to improve the tumor-targeting capacity and guide photothermal therapy through real-time fluorescence imaging. In this study, ICG@BPNS-PEG nanocomposites with a suitable size (240 ± 28 nm) have been successfully constructed. The photostability of ICG@BPNS-PEG nanocomposites surpassed that of free ICG after four on–off cycles of near laser irradiation (NIR). Moreover, ICG@BPNS-PEG nanocomposites have enhanced photothermal conversion ability. The cellular uptake result through flow cytometry showed that ICG@BPNS-PEG nanocomposites could be swallowed easily owing to the suitable size and passive cellular uptake. In addition, the cytotoxicity evaluation of MCF-7, 4T1 breast cancer cells, and healthy RPE cells through the MTT assay demonstrated that ICG@BPNS-PEG nanocomposites have lower cytotoxicity and good cellular compatibility without irradiation. However, the cytotoxicity and live/dead staining proved that ICG@BPNS-PEG nanocomposites have satisfactory photothermal therapeutic effects when irradiated. In the 4T1-bearing mice model, the fluorescence imaging after intravenous injection of nanocomposites showed that ICG@BPNS-PEG nanocomposites have superior passive tumor targeting accumulation through the enhanced permeability and retention (EPR) effect compared with that of free ICG. Also, changes in tumor volume showed a remarkable tumor growth inhibition effect compared with other groups. Moreover, the results of hematoxylin–eosin (H&E) staining of major organs in 4T1-bearing mice also demonstrated that the nanocomposites have good biocompatibility. Therefore, the constructed ICG@BPNS-PEG nanocomposites have substantial potential in breast cancer therapy.

Scintigraphic Imaging of Neovascularization With 99mTc-3PRGD2 for Evaluating Early Response to Endostar Involved Therapies on Pancreatic Cancer Xenografts In Vivo.

BackgroundMolecular imaging targeting angiogenesis can specifically monitor the early therapeutic effect of antiangiogenesis therapy. We explore the predictive values of an integrin αvβ3-targeted tracer, 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2), for monitoring the efficacy of Endostar antiangiogenic therapy and chemotherapy in animal models.MethodsThe pancreatic cancer xenograft mice were randomly divided into four groups, with seven animals in each group and treated in different groups with 10 mg/kg/day of Endostar, 10 mg/kg/day of gemcitabine, 10 mg/kg/day of Endostar +10 mg/kg/day of gemcitabine at the same time, and the control group with 0.9% saline (0.1 ml/day). 99mTc-3PRGD2 scintigraphic imaging was carried out to monitor therapeutic effects. Microvessel density (MVD) was measured using immunohistochemical staining of the tumor tissues. The region of interest (ROI) of tumor (T) and contralateral corresponding site (NT) was delineated, and the ratio of radioactivity (T/NT) was calculated. Two-way repeated-measure analysis of variance (ANOVA) was used to assess differences between treatment groups.ResultsTumor growth was significantly lower in treatment groups than that in the control group (p < 0.05), and the differences were noted on day 28 posttreatment. The differences of 99mTc-3PRGD2 uptakes were observed between the control group and Endostar group (p = 0.033) and the combined treatment group (p < 0.01) on day 7 posttreatment and on day 14 posttreatment between the control group and gemcitabine group (p < 0.01). The accumulation of 99mTc-3PRGD2 was significantly correlated with MVD (r = 0.998, p = 0.002).ConclusionWith 99mTc-3PRGD2 scintigraphic imaging, the tumor response to antiangiogenic therapy, chemotherapy, and the combined treatment can be observed at an early stage of the treatments, much earlier than the tumor volume change. It provides new opportunities for developing individualized therapies and dose optimization.

Treatment of Plexiform Neurofibromas with MEK Inhibitors: First Results with a New Therapeutic Option.

Neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PN) are peripheral nerve sheath tumors that can significantly affect the quality of life. Until recently, surgery was the only treatment for these tumors. However, in most cases, surgery cannot achieve complete tumor removal and carries a high risk of postoperative deficits. Therefore, the recent approval of the MEK inhibitor selumetinib for the treatment of NF1-associated PN provides a long-awaited novel therapeutic option. Here, we report our experience with MEK inhibitor treatment in 12 pediatric NF1 patients with inoperable symptomatic PN. Eight patients received trametinib (median therapy duration 12.13 months and range 4-29 months), and four patients received selumetinib (median therapy duration 6.25 months and range 4-11 months). Volumetric magnetic resonance imaging (MRI) after 6 months of treatment was available for seven trametinib patients (median tumor volume reduction of 26.5% and range 11.3-55.7%) and two selumetinib patients (21.3% tumor volume reduction in one patient and +3% tumor volume change in the other one). All patients reported clinical benefits such as improved range of motion or reduced disfigurement. Therapy-related adverse events occurred in 58.3% of patients and mainly consisted of skin toxicity, paronychia, and gastrointestinal symptoms. Two patients discontinued trametinib treatment after 14 and 29 months when severe skin toxicity occurred and no further reduction of tumor size was observed. In one patient, discontinuation of therapy resulted in a 27.2% tumor volume increase as demonstrated on volumetric MRI 6 months later. Our data show that MEK inhibition is a novel therapeutic approach for inoperable PN with promising results and a manageable safety profile.

An imaging signature to predict outcome in metastatic colorectal cancer using routine computed tomography scans

Background & aimsQuantitative analysis of computed tomography (CT) scans of patients with metastatic colorectal cancer (mCRC) can identify imaging signatures that predict overall survival (OS). MethodsWe retrospectively analysed CT images from 1584 mCRC patients on two phase III trials evaluating FOLFOX ± panitumumab (n = 331, 350) and FOLFIRI ± aflibercept (n = 437, 466). In the training set (n = 720), an algorithm was trained to predict OS landmarked from month 2; the output was a signature value on a scale from 0 to 1 (most to least favourable predicted OS). In the validation set (n = 864), hazard ratios (HRs) evaluated the association of the signature with OS using RECIST1.1 as a benchmark of comparison. ResultsIn the training set, the selected signature combined three features – change in tumour volume, change in tumour spatial heterogeneity, and tumour volume – to predict OS. In the validation set, RECIST1.1 classified patients in three categories: response (n = 166, 19.2%), stable disease (n = 636, 73.6%), and progression (n = 62, 7.2%). The HR was 3.93 (2.79–5.54). Using the same distribution for the signature, the HR was 21.04 (14.88–30.58), showing an incremental prognostic separation. Stable disease by RECIST1.1 was reclassified by the signature along a continuum where patients belonging to the most and least favourable signature quartiles had a median OS of 40.73 (28.49 to NA) months (n = 94) and 7.03 (5.66–7.89) months (n = 166), respectively. ConclusionsA signature combining three imaging features provides early prognostic information that can improve treatment decisions for individual patients and clinical trial analyses.