Radiation therapy (RT) has been successfully used in the treatment of breast cancer (BC) for over a century. While historically thought to be immunosuppressive, new data have shown that RT can work ...together with the immune system to eliminate cancer. It can cause immunogenic cell death and facilitate tumor neoantigen presentation and cross-priming of tumor-specific T-lymphocytes, turning irradiated tumor into an in-situ vaccine. Unfortunately, due to various immune escape mechanism put in place by the tumor, RT alone rarely results in a systemic response of metastatic disease sites (known as the abscopal effect). Immunotherapy, a series of agents designed to stimulate the immune system in order to generate tumor-specific immune response, is showing promise in treatment of various cancers, including BC, and can be an ideal complement to RT in stimulating a systemic immune response to reject the tumor cells. This review discusses the mechanisms in which RT can trigger an immune response for tumor rejection, and provide emerging preclinical and clinical data of combination immunoradiotherapy, and its potential in treating BC.
Detection of brain metastases is a paramount task in cancer management due both to the number of high-risk patients and the difficulty of achieving consistent detection. In this study, we aim to ...improve the accuracy of automated brain metastasis (BM) detection methods using a novel asymmetric UNet (asym-UNet) architecture. An end-to-end asymmetric 3D-UNet architecture, with two down-sampling arms and one up-sampling arm, was constructed to capture the imaging features. The two down-sampling arms were trained using two different kernels (3 × 3 × 3 and 1 × 1 × 3, respectively) with the kernel (1 × 1 × 3) dominating the learning. As a comparison, vanilla single 3D UNets were trained with different kernels and evaluated using the same datasets. Voxel-based Dice similarity coefficient (DSCv), sensitivity (Sv), precision (Pv), BM-based sensitivity (SBM), and false detection rate (FBM) were used to evaluate model performance. Contrast-enhanced T1 MR images from 195 patients with a total of 1034 BMs were solicited from our institutional stereotactic radiosurgery database. The patient cohort was split into training (160 patients, 809 lesions), validation (20 patients, 136 lesions), and testing (15 patients, 89 lesions) datasets. The lesions in the testing dataset were further divided into two subgroups based on the diameters (small S = 1-10 mm, large L = 11-26 mm). In the testing dataset, there were 72 and 17 BMs in the S and L sub-groups, respectively. Among all trained networks, asym-UNet achieved the highest DSCv of 0.84 and lowest FBM of 0.24. Although vanilla 3D-UNet with a single 1 × 1 × 3 kernel achieved the highest sensitivities for the S group, it resulted in the lowest precision and highest false detection rate. Asym-UNet was shown to balance sensitivity and false detection rate as well as keep the segmentation accuracy high. The novel asym-UNet segmentation network showed overall competitive segmentation performance and more pronounced improvement in hard-to-detect small BMs comparing to the vanilla single 3D UNet.
Purpose
Meningiomas are the most common primary brain tumors in adults with management varying widely based on World Health Organization (WHO) grade. However, there are limited datasets available for ...researchers to develop and validate radiomic models. The purpose of our manuscript is to report on the first dataset of meningiomas in The Cancer Imaging Archive (TCIA).
Acquisition and validation methods
The dataset consists of pre‐operative MRIs from 96 patients with meningiomas who underwent resection from 2010–2019 and include axial T1post and T2‐FLAIR sequences—55 grade 1 and 41 grade 2. Meningioma grade was confirmed based on the 2016 WHO Bluebook classification guideline by two neuropathologists and one neuropathology fellow. The hyperintense T1post tumor and hyperintense T2‐FLAIR regions were manually contoured on both sequences and resampled to an isotropic resolution of 1 × 1 × 1 mm3. The entire dataset was reviewed by a certified medical physicist.
Data format and usage notes
The data was imported into TCIA for storage and can be accessed at https://doi.org/10.7937/0TKV‐1A36. The total size of the dataset is 8.8GB, with 47 519 individual Digital Imaging and Communications in Medicine (DICOM) files consisting of 384 image series, and 192 structures.
Potential applications
Grade 1 and 2 meningiomas have different treatment paradigms and are often treated based on radiologic diagnosis alone. Therefore, predicting grade prior to treatment is essential in clinical decision‐making. This dataset will allow researchers to create models to auto‐differentiate grade 1 and 2 meningiomas as well as evaluate for other pathologic features including mitotic index, brain invasion, and atypical features. Limitations of this study are the small sample size and inclusion of only two MRI sequences. However, there are no meningioma datasets on TCIA and limited datasets elsewhere although meningiomas are the most common intracranial tumor in adults.
Colorectal cancer (CRC) is associated with alterations of the fecal and tissue-associated microbiome. Preclinical models support a pathogenic role of the microbiome in CRC, including in promoting ...metastasis and modulating antitumor immune responses. To investigate whether the microbiome is associated with lymph node metastasis and T cell infiltration in human CRC, we performed 16S rRNA gene sequencing of feces, tumor core, tumor surface, and healthy adjacent tissue collected from 34 CRC patients undergoing surgery (28 fecal samples and 39 tissue samples). Tissue microbiome profiles-including increased
-were significantly associated with mesenteric lymph node (MLN) involvement. Fecal microbes were also associated with MLN involvement and accurately classified CRC patients into those with or without MLN involvement. Tumor T cell infiltration was assessed by immunohistochemical staining of CD3 and CD8 in tumor tissue sections. Tumor core microbiota, including members of the
and
genera, were significantly associated with tumor T cell infiltration. Abundance of specific fecal microbes including a member of the
genus predicted high vs. low total and cytotoxic T cell infiltration in random forests classifiers. These findings support a link between the microbiome and antitumor immune responses that may influence prognosis of locally advanced CRC.
The Grade of meningioma has significant implications for selecting treatment regimens ranging from observation to surgical resection with adjuvant radiation. For most patients, meningiomas are ...diagnosed radiologically, and Grade is not determined unless a surgical procedure is performed. The goal of this study is to train a novel auto-classification network to determine Grade I and II meningiomas using T1-contrast enhancing (T1-CE) and T2-Fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. Ninety-six consecutive treatment naïve patients with pre-operative T1-CE and T2-FLAIR MR images and subsequent pathologically diagnosed intracranial meningiomas were evaluated. Delineation of meningiomas was completed on both MR images. A novel asymmetric 3D convolutional neural network (CNN) architecture was constructed with two encoding paths based on T1-CE and T2-FLAIR. Each path used the same 3 × 3 × 3 kernel with different filters to weigh the spatial features of each sequence separately. Final model performance was assessed by tenfold cross-validation. Of the 96 patients, 55 (57%) were pathologically classified as Grade I and 41 (43%) as Grade II meningiomas. Optimization of our model led to a filter weighting of 18:2 between the T1-CE and T2-FLAIR MR image paths. 86 (90%) patients were classified correctly, and 10 (10%) were misclassified based on their pre-operative MRs with a model sensitivity of 0.85 and specificity of 0.93. Among the misclassified, 4 were Grade I, and 6 were Grade II. The model is robust to tumor locations and sizes. A novel asymmetric CNN with two differently weighted encoding paths was developed for successful automated meningioma grade classification. Our model outperforms CNN using a single path for single or multimodal MR-based classification.
In this phase I dose-escalation trial, we assess the maximum tolerated dose (MTD) of Bermekimab in combination with Nanoliposomal Irinotecan (Nal-Iri) and 5-Fluorouracil/Folinic Acid (5-FU/FA). ...Secondarily, we investigate effects on weight, lean body mass, quality-of-life, the gut microbiome composition, inflammatory biomarkers, progression-free survival, and overall survival. This was a single-arm, open-label adaptive Bayesian dose-escalation study of Bermekimab combined with Nal-Iri and 5FU/FA in patients with advanced or locally advanced PDAC who failed gemcitabine-based chemotherapy. 22 patients enrolled between 2017 and 2019. 3 of 21 patients experienced dose-limiting toxicities attributable to the chemotherapy backbone. 58% (10/17) of patients exhibited weight stability. Physical performance status was preserved among all subjects. Patients reported improvements in quality-of-life metrics via QLQ-PAN26 questioner (-3.6, p = 0.18) and functional well-being (1.78, p = 0.02). Subjects exhibited a decrease in inflammatory cytokines, notably, vascular endothelial growth factor (-0.86, p = 0.017) with Bermekimab. Bermekimab treatment was associated with an increased abundance of gut health-promoting bacterial genera Akkermansia, with 3.82 Log2-fold change from baseline. In sum, Bermekimab is safe to be used in conjunction with Nal-Iri and 5-FU/FA chemotherapy. This benign toxicological profile warrants further Phase I/II investigation of Bermekimab in combinatorial strategies, and the impact of anti-IL-1α antibodies on the gut microbiome.Clinical trials registration: NCT03207724 05/07/2017.
Introduction
There is evidence that the combination of ipilimumab and stereotactic radiosurgery (SRS) for brain metastases improves outcomes. We investigated clinical outcomes, radiation toxicity, ...and impact of ipilimumab timing in patients treated with SRS for melanoma brain metastases.
Methods
We retrospectively identified 91 patients treated with SRS at our institution for melanoma brain metastases from 2006 to 2015. Concurrent ipilimumab administration was defined as within ± 4 weeks of SRS procedure. Acute and late toxicities were graded with CTCAE v4.03. Overall survival (OS), local failure, distant brain failure, and failure-free survival were analyzed with the Kaplan–Meier method. OS was analyzed with Cox regression.
Results
Twenty-three patients received ipilimumab concurrent with SRS, 28 patients non-concurrently, and 40 patients did not receive ipilimumab. The median age was 62 years and 91% had KPS ≥ 80. The median follow-up time was 7.4 months. Patients who received ipilimumab had a median OS of 15.1 months compared to 7.8 months in patients who did not (p = 0.02). In multivariate analysis, ipilimumab (p = 0.02) and diagnosis-specific graded prognostic assessment (p = 0.02) were associated with OS. There were no differences in intracranial control by ipilimumab administration or timing. The incidence of radiation necrosis was 5%, with most events occurring in patients who received ipilimumab.
Conclusions
Patients who received ipilimumab had improved OS even after adjusting for prognostic factors. Ipilimumab did not appear to increase risk for acute toxicity. The majority of radiation necrosis events, however, occurred in patients who received ipilimumab. Our results support the continued use of SRS and ipilimumab as clinically appropriate.
Micro-Abstract The overall and breast cancer-specific survival of women aged 20 to 40 years with stage I-II breast cancer treated with breast-conserving therapy or mastectomy from 1998 to 2003 were ...compared using the national Surveillance, Epidemiology, and End Results database. Overall, 3249 underwent lumpectomy plus radiation and 2627 underwent mastectomy alone. When compared by stage, no statistically significant difference was found in the outcomes between the 2 treatment groups.
There is evidence that detection and treatment of oligometastases (≤5 lesions) may improve survival in breast cancer patients. However, there are no current national guidelines for screening of ...early, asymptomatic metastases. This study examined the patterns and timing of recurrence with respect to survival in node-positive breast cancer (NPBC) patients at higher risk for developing metastases.
A single-institution retrospective review of NPBC patients treated with trimodality therapy was performed to collect patient and disease characteristics, recurrence location, method of detection, and survival outcome. Univariate and multivariate analyses were done to identify factors associated with recurrence.
Ninety-four NPBC patients treated at a safety-net hospital between 2008 and 2019 were identified. Twenty-one developed recurrence and were divided into oligometastatic (OM) (n=10) or diffusely metastatic (DM) (n=11) subgroups. Median recurrence-free survival in OM and DM was 18 and 36 months, respectively. Median overall survival (OS) for OM was not reached. Median OS for DM was 57 months. Four patients with OM progressed to diffuse disease in a median period of 17 months; median survival thereafter was 57 months. All patients with recurrence had distant metastases on initial detection, with the most common site being bone (14). Recurrence was most frequently detected by computed tomography (CT) (13), with the majority of disease located within the thorax region.
All NPBC patients had distant metastasis at time of recurrence. Patients with OM had shorter interval to recurrence yet longer OS compared with DM. This study highlights improved surveillance imaging for timely detection of OM breast cancer that may yet be amenable to aggressive local salvage therapy to prevent progression to diffuse disease.
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