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Nature Reviews. Clinical Oncology Aug 2023Immunotherapy has revolutionized the clinical management of many malignancies but is infrequently associated with durable objective responses when used as a standalone... (Review)
Review
Immunotherapy has revolutionized the clinical management of many malignancies but is infrequently associated with durable objective responses when used as a standalone treatment approach, calling for the development of combinatorial regimens with superior efficacy and acceptable toxicity. Radiotherapy, the most commonly used oncological treatment, has attracted considerable attention as a combination partner for immunotherapy owing to its well-known and predictable safety profile, widespread clinical availability, and potential for immunostimulatory effects. However, numerous randomized clinical trials investigating radiotherapy-immunotherapy combinations have failed to demonstrate a therapeutic benefit compared with either modality alone. Such a lack of interaction might reflect suboptimal study design, choice of end points and/or administration of radiotherapy according to standard schedules and target volumes. Indeed, radiotherapy has empirically evolved towards radiation doses and fields that enable maximal cancer cell killing with manageable toxicity to healthy tissues, without much consideration of potential radiation-induced immunostimulatory effects. Herein, we propose the concept that successful radiotherapy-immunotherapy combinations might require modifications of standard radiotherapy regimens and target volumes to optimally sustain immune fitness and enhance the antitumour immune response in support of meaningful clinical benefits.
Topics: Humans; Combined Modality Therapy; Radiation Oncology; Neoplasms; Immunotherapy; Immunization; Radiotherapy
PubMed: 37280366
DOI: 10.1038/s41571-023-00782-x -
Abdominal Radiology (New York) Sep 2023The Society of Abdominal Radiology's Colorectal and Anal Cancer Disease-Focused Panel (DFP) first published a rectal cancer lexicon paper in 2019. Since that time, the... (Review)
Review
The Society of Abdominal Radiology's Colorectal and Anal Cancer Disease-Focused Panel (DFP) first published a rectal cancer lexicon paper in 2019. Since that time, the DFP has published revised initial staging and restaging reporting templates, and a new SAR user guide to accompany the rectal MRI synoptic report (primary staging). This lexicon update summarizes interval developments, while conforming to the original lexicon 2019 format. Emphasis is placed on primary staging, treatment response, anatomic terminology, nodal staging, and the utility of specific sequences in the MRI protocol. A discussion of primary tumor staging reviews updates on tumor morphology and its clinical significance, T1 and T3 subclassifications and their clinical implications, T4a and T4b imaging findings/definitions, terminology updates on the use of MRF over CRM, and the conundrum of the external sphincter. A parallel section on treatment response reviews the clinical significance of near-complete response and introduces the lexicon of "regrowth" versus "recurrence". A review of relevant anatomy incorporates updated definitions and expert consensus of anatomic landmarks, including the NCCN's new definition of rectal upper margin and sigmoid take-off. A detailed review of nodal staging is also included, with attention to tumor location relative to the dentate line and locoregional lymph node designation, a new suggested size threshold for lateral lymph nodes and their indications for use, and imaging criteria used to differentiate tumor deposits from lymph nodes. Finally, new treatment terminologies such as organ preservation, TNT, TAMIS and watch-and-wait management are introduced. This 2023 version aims to serve as a concise set of up-to-date recommendations for radiologists, and discusses terminology, classification systems, MRI and clinical staging, and the evolving concepts in diagnosis and treatment of rectal cancer.
Topics: Humans; Rectal Neoplasms; Anus Neoplasms; Rectum; Neoplasm Staging; Magnetic Resonance Imaging; Radiology
PubMed: 37145311
DOI: 10.1007/s00261-023-03893-2 -
Cell Reports. Medicine Aug 2023The tumor microenvironment (TME) plays a critical role in disease progression and is a key determinant of therapeutic response in cancer patients. Here, we propose a...
The tumor microenvironment (TME) plays a critical role in disease progression and is a key determinant of therapeutic response in cancer patients. Here, we propose a noninvasive approach to predict the TME status from radiological images by combining radiomics and deep learning analyses. Using multi-institution cohorts of 2,686 patients with gastric cancer, we show that the radiological model accurately predicted the TME status and is an independent prognostic factor beyond clinicopathologic variables. The model further predicts the benefit from adjuvant chemotherapy for patients with localized disease. In patients treated with checkpoint blockade immunotherapy, the model predicts clinical response and further improves predictive accuracy when combined with existing biomarkers. Our approach enables noninvasive assessment of the TME, which opens the door for longitudinal monitoring and tracking response to cancer therapy. Given the routine use of radiologic imaging in oncology, our approach can be extended to many other solid tumor types.
Topics: Humans; Stomach Neoplasms; Deep Learning; Tumor Microenvironment; Immunotherapy; Chemotherapy, Adjuvant
PubMed: 37557177
DOI: 10.1016/j.xcrm.2023.101146 -
Annals of Oncology : Official Journal... Mar 2024Current evaluation of treatment response in solid tumors depends on dynamic changes in tumor diameters as measured by imaging. However, these changes can only be... (Review)
Review
Current evaluation of treatment response in solid tumors depends on dynamic changes in tumor diameters as measured by imaging. However, these changes can only be detected when there are enough macroscopic changes in tumor volume, which limits the usability of radiological response criteria in evaluating earlier stages of disease response and necessitates much time to lapse for gross changes to be notable. One promising approach is to incorporate dynamic changes in circulating tumor DNA (ctDNA), which occur early in the course of therapy and can predict tumor responses weeks before gross size changes manifest. However, several issues need to be addressed before recommending the implementation of ctDNA response criteria in daily clinical practice such as clinical, biological, and regulatory challenges and, most importantly, the need to standardize/harmonize detection methods and ways to define ctDNA response and/or progression for precision oncology. Herein, we review the use of liquid biopsy (LB) to evaluate response in solid tumors and propose a plan toward standardization of LB-RECIST.
Topics: Humans; Neoplasms; Response Evaluation Criteria in Solid Tumors; Precision Medicine; Liquid Biopsy; Circulating Tumor DNA; Biomarkers, Tumor
PubMed: 38145866
DOI: 10.1016/j.annonc.2023.12.007 -
Biomaterials Science Sep 2023Matrix metalloproteinases (MMP) are enzymes that degrade the extracellular matrix and regulate essential normal cell behaviors. Inhibition of these enzymes has been a... (Review)
Review
Matrix metalloproteinases (MMP) are enzymes that degrade the extracellular matrix and regulate essential normal cell behaviors. Inhibition of these enzymes has been a strategy for anti-cancer therapy since the 1990s, but with limited success. A new type of MMP-targeting strategy exploits the innate selective hydrolytic activity and consequent catalytic signal amplification of the proteinases, rather than inhibiting it. Using nanomaterials, the enzymatic chemical reaction can trigger the temporal and spatial activation of the anti-cancer effects, amplify the associated response, and cause mechanical damage or report on cancer cells. We analyzed nearly 60 literature studies that incorporate chemical design strategies that lead to spatial, temporal, and mechanical control of the anti-cancer effect through four modes of action: nanomaterial shrinkage, induced aggregation, formation of cytotoxic nanofibers, and activation by de-PEGylation. From the literature analysis, we derived chemical design guidelines to control and enhance MMP activation of nanomaterials of various chemical compositions (peptide, lipid, polymer, inorganic). Finally, the review includes a guide on how multiple characteristics of the nanomaterial, such as substrate modification, supramolecular structure, and electrostatic charge should be collectively considered for the targeted MMP to result in optimal kinetics of enzyme action on the nanomaterial, which allow access to amplification and additional levels of spatial, temporal, and mechanical control of the response. Although this review focuses on the design strategies of MMP-responsive nanomaterials in cancer applications, these guidelines are expected to be generalizable to systems that target MMP for treatment or detection of cancer and other diseases, as well as other enzyme-responsive nanomaterials.
Topics: Humans; Nanostructures; Neoplasms; Peptides; Antineoplastic Agents; Hydrolysis
PubMed: 37623747
DOI: 10.1039/d3bm00840a -
Journal of Clinical Oncology : Official... Sep 2023The molecular classification of endometrial cancer (EC) has proven to have prognostic value and is predictive of response to adjuvant chemotherapy. Here, we investigate...
PURPOSE
The molecular classification of endometrial cancer (EC) has proven to have prognostic value and is predictive of response to adjuvant chemotherapy. Here, we investigate its predictive value for response to external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) in early-stage endometrioid EC (EEC).
METHODS
Data of the randomized PORTEC-1 trial (n = 714) comparing pelvic EBRT with no adjuvant therapy in early-stage intermediate-risk EC and the PORTEC-2 trial (n = 427) comparing VBT with EBRT in early-stage high-intermediate-risk EC were used. Locoregional (including vaginal and pelvic) recurrence-free survival was compared between treatment groups across the four molecular classes using Kaplan-Meier's methodology and log-rank tests.
RESULTS
A total of 880 molecularly classified ECs, 484 from PORTEC-1 and 396 from PORTEC-2, were included. The majority were FIGO-2009 stage I EEC (97.2%). The median follow-up was 11.3 years. No locoregional recurrences were observed in EC with a pathogenic mutation of DNA polymerase-ε (mut EC). In mismatch repair-deficient (MMRd) EC, locoregional recurrence-free survival was similar after EBRT (94.2%), VBT (94.2%), and no adjuvant therapy (90.3%; = .74). In EC with a p53 abnormality (p53abn EC), EBRT (96.9%) had a substantial benefit over VBT (64.3%) and no adjuvant therapy (72.2%; = .048). In EC with no specific molecular profile (NSMP EC), both EBRT (98.3%) and VBT (96.2%) yielded better locoregional control than no adjuvant therapy (87.7%; < .0001).
CONCLUSION
The molecular classification of EC predicts response to radiotherapy in stage I EEC and may guide adjuvant treatment decisions. Omitting radiotherapy seems to be safe in mut EC. The benefit of radiotherapy seems to be limited in MMRd EC. EBRT yields a significantly better locoregional recurrence-free survival than VBT or no adjuvant therapy in p53abn EC. VBT is the treatment of choice for NSMP EC as it is as effective as EBRT and significantly better than no adjuvant therapy for locoregional tumor control.
Topics: Female; Humans; Radiation Oncology; Endometrial Neoplasms; Brachytherapy; Combined Modality Therapy
PubMed: 37487144
DOI: 10.1200/JCO.23.00062 -
Cancer Letters Jul 2023Radiotherapy (RT) is one of the key modalities for cancer treatment, and more than 70% of tumor patients will receive RT during the course of their disease. Particle... (Review)
Review
Radiotherapy (RT) is one of the key modalities for cancer treatment, and more than 70% of tumor patients will receive RT during the course of their disease. Particle radiotherapy, such as proton radiotherapy, carbon-ion radiotherapy (CIRT) and boron neutron capture therapy (BNCT), is currently available for the treatment of patients Immunotherapy combined with photon RT has been successfully used in the clinic. The effect of immunotherapy combined with particle RT is an area of interest. However, the molecular mechanisms underlying the effects of combined immunotherapy and particle RT remain largely unknown. In this review, we summarize the properties of different types of particle RT and the mechanisms underlying their radiobiological effects. Additionally, we compared the main molecular players in photon RT and particle RT and the mechanisms involved the RT-mediated immune response.
Topics: Humans; Radioimmunotherapy; Boron Neutron Capture Therapy; Neoplasms; Radiation Oncology; Radiobiology
PubMed: 37331583
DOI: 10.1016/j.canlet.2023.216268 -
Journal of the American College of... Oct 2023Despite rising popularity and performance, studies evaluating the use of large language models for clinical decision support are lacking. Here, we evaluate ChatGPT...
OBJECTIVE
Despite rising popularity and performance, studies evaluating the use of large language models for clinical decision support are lacking. Here, we evaluate ChatGPT (Generative Pre-trained Transformer)-3.5 and GPT-4's (OpenAI, San Francisco, California) capacity for clinical decision support in radiology via the identification of appropriate imaging services for two important clinical presentations: breast cancer screening and breast pain.
METHODS
We compared ChatGPT's responses to the ACR Appropriateness Criteria for breast pain and breast cancer screening. Our prompt formats included an open-ended (OE) and a select all that apply (SATA) format. Scoring criteria evaluated whether proposed imaging modalities were in accordance with ACR guidelines. Three replicate entries were conducted for each prompt, and the average of these was used to determine final scores.
RESULTS
Both ChatGPT-3.5 and ChatGPT-4 achieved an average OE score of 1.830 (out of 2) for breast cancer screening prompts. ChatGPT-3.5 achieved a SATA average percentage correct of 88.9%, compared with ChatGPT-4's average percentage correct of 98.4% for breast cancer screening prompts. For breast pain, ChatGPT-3.5 achieved an average OE score of 1.125 (out of 2) and a SATA average percentage correct of 58.3%, as compared with an average OE score of 1.666 (out of 2) and a SATA average percentage correct of 77.7%.
DISCUSSION
Our results demonstrate the eventual feasibility of using large language models like ChatGPT for radiologic decision making, with the potential to improve clinical workflow and responsible use of radiology services. More use cases and greater accuracy are necessary to evaluate and implement such tools.
Topics: Humans; Female; Mastodynia; Radiology; Breast Neoplasms; Decision Making
PubMed: 37356806
DOI: 10.1016/j.jacr.2023.05.003