Pub Date : 2024-02-01Epub Date: 2024-01-05DOI: 10.1007/s10585-023-10258-y
Sachin G Nair, Sonu Benny, Wesley M Jose, Aneesh T P
The prevailing treatment stratagem in cancer therapy still challenges the dilemma of a probable metastatic spread following an initial diagnosis. Including an anti-metastatic agent demands a significant focus to overrule the incidence of treatment failures. Adrenergic stimulation underlying the metastatic spread paved the way for beta blockers as a breakthrough in repurposing as an anti-metastatic agent. However, the current treatment approach fails to fully harness the versatile potential of the drug in inhibiting probable metastasis. The beta blockers were seen to show a myriad of grip over the pro-metastatic and prognostic parameters of the patient. Novel interventions in immune therapy, onco-hypertension, surgery-induced stress, induction of apoptosis and angiogenesis inhibition have been used as evidence to interpret our objective of discussing the potential adjuvant role of the drug in the existing anti-cancer regimens. Adding weight to the relative incidence of onco-hypertension as an unavoidable side effect from chemotherapy, the slot for an anti-hypertensive agent is necessitated, and we try to suggest beta-blockers to fill this position. However, pointing out the paucity in the clinical study, we aim to review the current status of beta blockers under this interest to state how the drug should be included as a drug of choice in every patient undergoing cancer treatment.
{"title":"Beta-blocker adjunct therapy as a prospective anti-metastatic with cardio-oncologic regulation.","authors":"Sachin G Nair, Sonu Benny, Wesley M Jose, Aneesh T P","doi":"10.1007/s10585-023-10258-y","DOIUrl":"10.1007/s10585-023-10258-y","url":null,"abstract":"<p><p>The prevailing treatment stratagem in cancer therapy still challenges the dilemma of a probable metastatic spread following an initial diagnosis. Including an anti-metastatic agent demands a significant focus to overrule the incidence of treatment failures. Adrenergic stimulation underlying the metastatic spread paved the way for beta blockers as a breakthrough in repurposing as an anti-metastatic agent. However, the current treatment approach fails to fully harness the versatile potential of the drug in inhibiting probable metastasis. The beta blockers were seen to show a myriad of grip over the pro-metastatic and prognostic parameters of the patient. Novel interventions in immune therapy, onco-hypertension, surgery-induced stress, induction of apoptosis and angiogenesis inhibition have been used as evidence to interpret our objective of discussing the potential adjuvant role of the drug in the existing anti-cancer regimens. Adding weight to the relative incidence of onco-hypertension as an unavoidable side effect from chemotherapy, the slot for an anti-hypertensive agent is necessitated, and we try to suggest beta-blockers to fill this position. However, pointing out the paucity in the clinical study, we aim to review the current status of beta blockers under this interest to state how the drug should be included as a drug of choice in every patient undergoing cancer treatment.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-10-17DOI: 10.1007/s10585-023-10238-2
Kainat Zahra, Hanzala Ahmed Farooqi
{"title":"Cutting-edge innovations in breast cancer diagnosis- the potential of HDMI biomarkers.","authors":"Kainat Zahra, Hanzala Ahmed Farooqi","doi":"10.1007/s10585-023-10238-2","DOIUrl":"10.1007/s10585-023-10238-2","url":null,"abstract":"","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-12-23DOI: 10.1007/s10585-023-10251-5
Margarida Varela Dos Santos, Arild Holth, Katharina Bischof, Ben Davidson
The objective of this study was to analyze the expression and prognostic role of the tight junction protein occludin in high-grade serous carcinoma (HGSC). Occludin protein expression by immunohistochemistry was analyzed in 602 HGSC (417 effusions, 185 surgical specimens). Expression in mesothelioma (n = 87; 45 effusions, 42 surgical specimens) was studied for comparative purposes. Occludin protein expression was found in 587/602 (98%) HGSC vs. 40/87 (46%) mesotheliomas and was predominantly limited to < 5% of cells in the latter (p < 0.001). Occludin was additionally overexpressed in HGSC effusions compared to surgical specimens (p < 0.001) and was overexpressed in post-chemotherapy effusions compared to chemo-naive effusions tapped at diagnosis (p = 0.015). Occludin expression in HGSC surgical specimens was associated with poor chemoresponse (p < 0.001) and primary resistance (p = 0.001). Expression in effusions and surgical specimens was unrelated to survival (p > 0.05). In conclusion, occludin expression is higher in HGSC compared to mesothelioma, and this protein is overexpressed in HGSC effusions, possibly reflecting changes in adhesion related to anchorage-independent growth in this microenvironment. Overexpression in post-chemotherapy compared to chemo-naïve effusions suggest a role in disease progression. Occludin expression in surgical specimens may be related to chemoresistance.
{"title":"Occludin is overexpressed in tubo-ovarian high-grade serous carcinoma compared to mesothelioma and is a marker of tumor progression and chemoresistance.","authors":"Margarida Varela Dos Santos, Arild Holth, Katharina Bischof, Ben Davidson","doi":"10.1007/s10585-023-10251-5","DOIUrl":"10.1007/s10585-023-10251-5","url":null,"abstract":"<p><p>The objective of this study was to analyze the expression and prognostic role of the tight junction protein occludin in high-grade serous carcinoma (HGSC). Occludin protein expression by immunohistochemistry was analyzed in 602 HGSC (417 effusions, 185 surgical specimens). Expression in mesothelioma (n = 87; 45 effusions, 42 surgical specimens) was studied for comparative purposes. Occludin protein expression was found in 587/602 (98%) HGSC vs. 40/87 (46%) mesotheliomas and was predominantly limited to < 5% of cells in the latter (p < 0.001). Occludin was additionally overexpressed in HGSC effusions compared to surgical specimens (p < 0.001) and was overexpressed in post-chemotherapy effusions compared to chemo-naive effusions tapped at diagnosis (p = 0.015). Occludin expression in HGSC surgical specimens was associated with poor chemoresponse (p < 0.001) and primary resistance (p = 0.001). Expression in effusions and surgical specimens was unrelated to survival (p > 0.05). In conclusion, occludin expression is higher in HGSC compared to mesothelioma, and this protein is overexpressed in HGSC effusions, possibly reflecting changes in adhesion related to anchorage-independent growth in this microenvironment. Overexpression in post-chemotherapy compared to chemo-naïve effusions suggest a role in disease progression. Occludin expression in surgical specimens may be related to chemoresistance.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-11-09DOI: 10.1007/s10585-023-10240-8
Rajiv Dharnipragada, Kathryn Dusenbery, Yoichi Watanabe, Clara Ferreira, Clark C Chen
Purpose: Stereotactic radiosurgery (SRS) to the resection cavity is essential in the treatment of brain metastasis (BM) amenable to surgical resection. The two most common platforms for SRS delivery include Gamma Knife (GK) and LINAC. Here we collated the available peer-reviewed literature and performed a meta-analysis on clinical outcomes after GK or LINAC resection cavity SRS.
Methods: Following PRISMA Guidelines, a search on PUBMED and MEDLINE was performed to include all studies evaluating each post-operative SRS modality. Local control, overall survival, radiation necrosis, and leptomeningeal disease were evaluated from the available data. A proportional meta-analysis was performed via R using the metafor package to pool the outcomes of studies and a moderator effect to assess the significance between groups.
Results: We identified 21 GK studies (n = 2009) and 28 LINAC studies (n = 2219). The radiosurgery doses employed were comparable between GK and LINAC studies. The pooled estimate of 1-year local control, 1-year overall survival, and risk of leptomeningeal disease were statistically comparable between GK and LINAC (81.7 v 85.8%; 61.4 v 62.7%; 10.6 v 12.5%, respectively). However, the risk of radiation necrosis (RN) was higher for LINAC resection cavity SRS (5.4% vs. 10%, p = 0.036). The volume of the resection cavity was a significant modifying factor for RN in both modalities (p = 0.007) with a 0.5% and 0.7% increase in RN risk with every 1 cm3 increase in tumor volume for GK and LINAC, respectively.
Conclusions: Our meta-analysis suggests that GK and LINAC SRS of resection cavity achieve comparable 1-year local control and survival. However, resection cavity treated with GK SRS was associated with lowered RN risk relative to those treated with LINAC SRS.
{"title":"Comparison of Gamma Knife (GK) and Linear Accelerator (LINAC) radiosurgery of brain metastasis resection cavity: a systematic review and proportional meta-analysis.","authors":"Rajiv Dharnipragada, Kathryn Dusenbery, Yoichi Watanabe, Clara Ferreira, Clark C Chen","doi":"10.1007/s10585-023-10240-8","DOIUrl":"10.1007/s10585-023-10240-8","url":null,"abstract":"<p><strong>Purpose: </strong>Stereotactic radiosurgery (SRS) to the resection cavity is essential in the treatment of brain metastasis (BM) amenable to surgical resection. The two most common platforms for SRS delivery include Gamma Knife (GK) and LINAC. Here we collated the available peer-reviewed literature and performed a meta-analysis on clinical outcomes after GK or LINAC resection cavity SRS.</p><p><strong>Methods: </strong>Following PRISMA Guidelines, a search on PUBMED and MEDLINE was performed to include all studies evaluating each post-operative SRS modality. Local control, overall survival, radiation necrosis, and leptomeningeal disease were evaluated from the available data. A proportional meta-analysis was performed via R using the metafor package to pool the outcomes of studies and a moderator effect to assess the significance between groups.</p><p><strong>Results: </strong>We identified 21 GK studies (n = 2009) and 28 LINAC studies (n = 2219). The radiosurgery doses employed were comparable between GK and LINAC studies. The pooled estimate of 1-year local control, 1-year overall survival, and risk of leptomeningeal disease were statistically comparable between GK and LINAC (81.7 v 85.8%; 61.4 v 62.7%; 10.6 v 12.5%, respectively). However, the risk of radiation necrosis (RN) was higher for LINAC resection cavity SRS (5.4% vs. 10%, p = 0.036). The volume of the resection cavity was a significant modifying factor for RN in both modalities (p = 0.007) with a 0.5% and 0.7% increase in RN risk with every 1 cm<sup>3</sup> increase in tumor volume for GK and LINAC, respectively.</p><p><strong>Conclusions: </strong>Our meta-analysis suggests that GK and LINAC SRS of resection cavity achieve comparable 1-year local control and survival. However, resection cavity treated with GK SRS was associated with lowered RN risk relative to those treated with LINAC SRS.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-12-20DOI: 10.1007/s10585-023-10245-3
Sébastien Benzekry, Pirmin Schlicke, Alice Mogenet, Laurent Greillier, Pascale Tomasini, Eléonore Simon
Intracranial progression after curative treatment of early-stage non-small cell lung cancer (NSCLC) occurs from 10 to 50% and is difficult to manage, given the heterogeneity of clinical presentations and the variability of treatments available. The objective of this study was to develop a mechanistic model of intracranial progression to predict survival following a first brain metastasis (BM) event occurring at a time [Formula: see text]. Data included early-stage NSCLC patients treated with a curative intent who had a BM as the first and single relapse site (N = 31). We propose a mechanistic mathematical model able to derive computational markers from primary tumor and BM data at [Formula: see text] and estimate the amount and sizes of (visible and invisible) BMs, as well as their future behavior. These two key computational markers are [Formula: see text], the proliferation rate of a single tumor cell; and [Formula: see text], the per day, per cell, probability to metastasize. The predictive value of these individual computational biomarkers was evaluated. The model was able to correctly describe the number and size of metastases at [Formula: see text] for 20 patients. Parameters [Formula: see text] and [Formula: see text] were significantly associated with overall survival (OS) (HR 1.65 (1.07-2.53) p = 0.0029 and HR 1.95 (1.31-2.91) p = 0.0109, respectively). Adding the computational markers to the clinical ones significantly improved the predictive value of OS (c-index increased from 0.585 (95% CI 0.569-0.602) to 0.713 (95% CI 0.700-0.726), p < 0.0001). We demonstrated that our model was applicable to brain oligoprogressive patients in NSCLC and that the resulting computational markers had predictive potential. This may help lung cancer physicians to guide and personalize the management of NSCLC patients with intracranial oligoprogression.
早期非小细胞肺癌(NSCLC)治愈性治疗后的颅内进展发生率为 10%至 50%,鉴于临床表现的异质性和现有治疗方法的差异性,这种进展很难控制。本研究的目的是建立一个颅内进展的机理模型,以预测首次发生脑转移(BM)事件后的生存期[公式:见正文]。数据包括以治愈为目的接受治疗的早期 NSCLC 患者,他们的首次和单一复发部位均为脑转移灶(N = 31)。我们提出了一个机理数学模型,能够从原发肿瘤和骨髓瘤数据中得出计算标记物[公式:见正文],并估算(可见和不可见)骨髓瘤的数量和大小及其未来行为。这两个关键的计算标记是:[公式:见正文],单个肿瘤细胞的增殖率;[公式:见正文],每个细胞每天发生转移的概率。对这些计算生物标志物的预测价值进行了评估。该模型能够正确描述 20 名患者在[公式:见正文]时的转移数量和大小。公式:见正文]和[公式:见正文]参数与总生存期(OS)显著相关(分别为 HR 1.65 (1.07-2.53) p = 0.0029 和 HR 1.95 (1.31-2.91) p = 0.0109)。在临床标记物中加入计算标记物可明显提高 OS 的预测价值(c 指数从 0.585(95% CI 0.569-0.602)提高到 0.713(95% CI 0.700-0.726),p = 0.0029)。
{"title":"Computational markers for personalized prediction of outcomes in non-small cell lung cancer patients with brain metastases.","authors":"Sébastien Benzekry, Pirmin Schlicke, Alice Mogenet, Laurent Greillier, Pascale Tomasini, Eléonore Simon","doi":"10.1007/s10585-023-10245-3","DOIUrl":"10.1007/s10585-023-10245-3","url":null,"abstract":"<p><p>Intracranial progression after curative treatment of early-stage non-small cell lung cancer (NSCLC) occurs from 10 to 50% and is difficult to manage, given the heterogeneity of clinical presentations and the variability of treatments available. The objective of this study was to develop a mechanistic model of intracranial progression to predict survival following a first brain metastasis (BM) event occurring at a time [Formula: see text]. Data included early-stage NSCLC patients treated with a curative intent who had a BM as the first and single relapse site (N = 31). We propose a mechanistic mathematical model able to derive computational markers from primary tumor and BM data at [Formula: see text] and estimate the amount and sizes of (visible and invisible) BMs, as well as their future behavior. These two key computational markers are [Formula: see text], the proliferation rate of a single tumor cell; and [Formula: see text], the per day, per cell, probability to metastasize. The predictive value of these individual computational biomarkers was evaluated. The model was able to correctly describe the number and size of metastases at [Formula: see text] for 20 patients. Parameters [Formula: see text] and [Formula: see text] were significantly associated with overall survival (OS) (HR 1.65 (1.07-2.53) p = 0.0029 and HR 1.95 (1.31-2.91) p = 0.0109, respectively). Adding the computational markers to the clinical ones significantly improved the predictive value of OS (c-index increased from 0.585 (95% CI 0.569-0.602) to 0.713 (95% CI 0.700-0.726), p < 0.0001). We demonstrated that our model was applicable to brain oligoprogressive patients in NSCLC and that the resulting computational markers had predictive potential. This may help lung cancer physicians to guide and personalize the management of NSCLC patients with intracranial oligoprogression.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138799467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2024-01-04DOI: 10.1007/s10585-023-10259-x
Christina Schnoz, Katrin Schmid, Guacimara Ortega Sanchez, Sabina Schacher-Kaufmann, Michel Adamina, Georgios Peros, Dieter Erdin, Peter Karl Bode
Lymph node status is one of the most important prognostic factors in colorectal cancer, and accurate pathological nodal staging and detection of lymph node metastases is crucial for determination of post-operative management. Current guidelines, including the TNM staging system and European Society for Medical Oncology (ESMO) guidelines, recommend examination of at least 12 lymph nodes. However, identification of an adequate number of lymph nodes can be challenging, especially in the setting of neoadjuvant treatment, which may reduce nodal size. In this study, we investigated 384 colorectal cancer resections that were processed at our department of pathology between January 2012 and December 2022, in which the number of detected lymph nodes was less than 12 subsequent to conventional preparation of mesocolic fat tissue. By means of acetone compression, lymph node harvest increased significantly (p < 0.0001), and the intended number of ≥ 12 lymph nodes was achieved in 98% of resection specimens. The number of nodal positive cases increased significantly from n = 95 (24.7%) before versus n = 131 (34.1%) after acetone compression due to additionally identified lymph node metastases (p < 0.001). In 36 patients (9.4%) initially considered as nodal negative, acetone compression led to a staging adjustment to a nodal positive category and thereby drove a recommendation to offer post-operative therapy. In conclusion, acetone compression is a reliable and useful method implementable in routine surgical pathology for the retrieval of lymph nodes in colorectal cancer specimen, allowing for an adequate lymph node sampling and an increase in nodal staging reliability.
{"title":"Acetone compression improves lymph node yield and metastasis detection in colorectal cancer.","authors":"Christina Schnoz, Katrin Schmid, Guacimara Ortega Sanchez, Sabina Schacher-Kaufmann, Michel Adamina, Georgios Peros, Dieter Erdin, Peter Karl Bode","doi":"10.1007/s10585-023-10259-x","DOIUrl":"10.1007/s10585-023-10259-x","url":null,"abstract":"<p><p>Lymph node status is one of the most important prognostic factors in colorectal cancer, and accurate pathological nodal staging and detection of lymph node metastases is crucial for determination of post-operative management. Current guidelines, including the TNM staging system and European Society for Medical Oncology (ESMO) guidelines, recommend examination of at least 12 lymph nodes. However, identification of an adequate number of lymph nodes can be challenging, especially in the setting of neoadjuvant treatment, which may reduce nodal size. In this study, we investigated 384 colorectal cancer resections that were processed at our department of pathology between January 2012 and December 2022, in which the number of detected lymph nodes was less than 12 subsequent to conventional preparation of mesocolic fat tissue. By means of acetone compression, lymph node harvest increased significantly (p < 0.0001), and the intended number of ≥ 12 lymph nodes was achieved in 98% of resection specimens. The number of nodal positive cases increased significantly from n = 95 (24.7%) before versus n = 131 (34.1%) after acetone compression due to additionally identified lymph node metastases (p < 0.001). In 36 patients (9.4%) initially considered as nodal negative, acetone compression led to a staging adjustment to a nodal positive category and thereby drove a recommendation to offer post-operative therapy. In conclusion, acetone compression is a reliable and useful method implementable in routine surgical pathology for the retrieval of lymph nodes in colorectal cancer specimen, allowing for an adequate lymph node sampling and an increase in nodal staging reliability.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-13DOI: 10.1007/s10585-023-10252-4
Jamie Magrill, Dan Moldoveanu, Jiayao Gu, Mathieu Lajoie, Ian R Watson
Melanoma is a highly immunogenic malignancy with an elevated mutational burden, diffuse lymphocytic infiltration, and one of the highest response rates to immune checkpoint inhibitors (ICIs). However, over half of all late-stage patients treated with ICIs will either not respond or develop progressive disease. Spatial imaging technologies are being increasingly used to study the melanoma tumor microenvironment (TME). The goal of such studies is to understand the complex interplay between the stroma, melanoma cells, and immune cell-types as well as their association with treatment response. Investigators seeking a better understanding of the role of cell location within the TME and the importance of spatial expression of biomarkers are increasingly turning to highly multiplexed imaging approaches to more accurately measure immune infiltration as well as to quantify receptor-ligand interactions (such as PD-1 and PD-L1) and cell-cell contacts. CyTOF-IMC (Cytometry by Time of Flight - Imaging Mass Cytometry) has enabled high-dimensional profiling of melanomas, allowing researchers to identify complex cellular subpopulations and immune cell interactions with unprecedented resolution. Other spatial imaging technologies, such as multiplexed immunofluorescence and spatial transcriptomics, have revealed distinct patterns of immune cell infiltration, highlighting the importance of spatial relationships, and their impact in modulating immunotherapy responses. Overall, spatial imaging technologies are just beginning to transform our understanding of melanoma biology, providing new avenues for biomarker discovery and therapeutic development. These technologies hold great promise for advancing personalized medicine to improve patient outcomes in melanoma and other solid malignancies.
{"title":"Mapping the single cell spatial immune landscapes of the melanoma microenvironment","authors":"Jamie Magrill, Dan Moldoveanu, Jiayao Gu, Mathieu Lajoie, Ian R Watson","doi":"10.1007/s10585-023-10252-4","DOIUrl":"https://doi.org/10.1007/s10585-023-10252-4","url":null,"abstract":"<p>Melanoma is a highly immunogenic malignancy with an elevated mutational burden, diffuse lymphocytic infiltration, and one of the highest response rates to immune checkpoint inhibitors (ICIs). However, over half of all late-stage patients treated with ICIs will either not respond or develop progressive disease. Spatial imaging technologies are being increasingly used to study the melanoma tumor microenvironment (TME). The goal of such studies is to understand the complex interplay between the stroma, melanoma cells, and immune cell-types as well as their association with treatment response. Investigators seeking a better understanding of the role of cell location within the TME and the importance of spatial expression of biomarkers are increasingly turning to highly multiplexed imaging approaches to more accurately measure immune infiltration as well as to quantify receptor-ligand interactions (such as PD-1 and PD-L1) and cell-cell contacts. CyTOF-IMC (Cytometry by Time of Flight - Imaging Mass Cytometry) has enabled high-dimensional profiling of melanomas, allowing researchers to identify complex cellular subpopulations and immune cell interactions with unprecedented resolution. Other spatial imaging technologies, such as multiplexed immunofluorescence and spatial transcriptomics, have revealed distinct patterns of immune cell infiltration, highlighting the importance of spatial relationships, and their impact in modulating immunotherapy responses. Overall, spatial imaging technologies are just beginning to transform our understanding of melanoma biology, providing new avenues for biomarker discovery and therapeutic development. These technologies hold great promise for advancing personalized medicine to improve patient outcomes in melanoma and other solid malignancies.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139458922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-13DOI: 10.1007/s10585-023-10262-2
Theresa L Schwartz
Axillary management in patients with breast cancer is in a constant state of evolution. To provide appropriate treatment recommendations, we must understand the historical implications and the current indications for nodal staging as well as the clinical implications of nodal metastases. As we move away from maximal axillary surgical intervention that was previously the mainstay of breast cancer management, future research efforts will focus on targeted therapies based on tumor biology and identifying oncologically safe methods to de-escalate our management strategies.
{"title":"Axillary nodal staging in breast cancer: what have we learned?","authors":"Theresa L Schwartz","doi":"10.1007/s10585-023-10262-2","DOIUrl":"https://doi.org/10.1007/s10585-023-10262-2","url":null,"abstract":"<p>Axillary management in patients with breast cancer is in a constant state of evolution. To provide appropriate treatment recommendations, we must understand the historical implications and the current indications for nodal staging as well as the clinical implications of nodal metastases. As we move away from maximal axillary surgical intervention that was previously the mainstay of breast cancer management, future research efforts will focus on targeted therapies based on tumor biology and identifying oncologically safe methods to de-escalate our management strategies.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139465429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In parotid gland cancer (PGC), cervical lymph node metastasis (LNM) and intra-parotid LNM are known as significant indicators of poor prognosis. However, the topography of LNM in the affected parotid gland and the lymphatic progression of PGC has never been explored in detail. This was a retrospective analysis of data from 423 patients with previously untreated primary PGC (2005 to 2020), excluding patients with squamous cell carcinoma, lymphoma or metastatic disease in the parotid gland. The pattern of LNM was analyzed by neck sub-level and parotid sub-site. Using the conditional probability of neck level involvement, a probability diagram was plotted on several thresholds to visualize the sequential progression of LNM in PGC. The pattern of LNM progression was found to be similar between low- and high-grade pathology, but the incidence differed significantly (8.0% vs. 45.4%). Intra-parotid LNs and level IIa LNs were the most common sites (57.3% and 61.0%) of LNM in PGC, followed by level III (31.7%), Ib (25.6%), IV (22.0%), IIb (20.7%) and Va (20.7%) LNM. In intra-parotid LNs, the incidence of LNM in the deep parotid LNs was relatively low (9.4%); most intra-parotid LNMs were observed in the superficial parotid (90.6%) and peri-tumoral (in contact with the tumor) (31.3%) LNs. LNM to levels Ia, Vb and contra-lateral LNM occurred only in the very late stage. Our results provide detailed information about LNM progression in PGC at the sub-level and can help clinicians decide the treatment extent, including surgery or radiation.
众所周知,在腮腺癌(PGC)中,颈淋巴结转移(LNM)和腮腺内淋巴结转移是预后不良的重要指标。然而,有关受影响腮腺内淋巴结转移的地形图以及 PGC 的淋巴发展过程的研究却从未详细探讨过。这是一项回顾性分析,研究对象是423名既往未接受过治疗的原发性PGC患者(2005年至2020年),排除了腮腺鳞状细胞癌、淋巴瘤或转移性疾病患者。按颈部亚层和腮腺亚部位分析了LNM的模式。利用颈部受累的条件概率,在几个阈值上绘制了概率图,以直观显示PGC中LNM的顺序进展。结果发现,低级别和高级别病理的 LNM 进展模式相似,但发生率却有显著差异(8.0% 对 45.4%)。腮腺内LNM和IIa级LNM是PGC中最常见的LNM部位(57.3%和61.0%),其次是III级(31.7%)、Ib级(25.6%)、IV级(22.0%)、IIb级(20.7%)和Va级(20.7%)LNM。在腮腺内LNM中,腮腺深层LNM的发生率相对较低(9.4%);大多数腮腺内LNM发生在腮腺浅层(90.6%)和瘤周(与肿瘤接触)LN(31.3%)。Ⅰa、Ⅴb级和对侧LNM仅发生在晚期。我们的研究结果提供了 PGC 亚层 LNM 进展的详细信息,有助于临床医生决定治疗范围,包括手术或放射治疗。
{"title":"Topography and probability diagram of cervical and intra-parotid lymph node metastasis in parotid gland cancer","authors":"Nayeon Choi, Yung Jee Kang, Junhun Cho, Dongryul Oh, Jaewoo Jeong, Han-Sin Jeong","doi":"10.1007/s10585-023-10244-4","DOIUrl":"https://doi.org/10.1007/s10585-023-10244-4","url":null,"abstract":"<p>In parotid gland cancer (PGC), cervical lymph node metastasis (LNM) and intra-parotid LNM are known as significant indicators of poor prognosis. However, the topography of LNM in the affected parotid gland and the lymphatic progression of PGC has never been explored in detail. This was a retrospective analysis of data from 423 patients with previously untreated primary PGC (2005 to 2020), excluding patients with squamous cell carcinoma, lymphoma or metastatic disease in the parotid gland. The pattern of LNM was analyzed by neck sub-level and parotid sub-site. Using the conditional probability of neck level involvement, a probability diagram was plotted on several thresholds to visualize the sequential progression of LNM in PGC. The pattern of LNM progression was found to be similar between low- and high-grade pathology, but the incidence differed significantly (8.0% vs. 45.4%). Intra-parotid LNs and level IIa LNs were the most common sites (57.3% and 61.0%) of LNM in PGC, followed by level III (31.7%), Ib (25.6%), IV (22.0%), IIb (20.7%) and Va (20.7%) LNM. In intra-parotid LNs, the incidence of LNM in the deep parotid LNs was relatively low (9.4%); most intra-parotid LNMs were observed in the superficial parotid (90.6%) and peri-tumoral (in contact with the tumor) (31.3%) LNs. LNM to levels Ia, Vb and contra-lateral LNM occurred only in the very late stage. Our results provide detailed information about LNM progression in PGC at the sub-level and can help clinicians decide the treatment extent, including surgery or radiation.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138568500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-09DOI: 10.1007/s10585-023-10249-z
Meret Grube, Arno Dimmler, Anja Schmaus, Rafael Saup, Tabea Wagner, Boyan K. Garvalov, Jonathan P. Sleeman, Wilko Thiele
Ketogenic diets (KDs) can improve the well-being and quality of life of breast cancer patients. However, data on the effects of KDs on mammary tumors are inconclusive, and the influence of KDs on metastasis in general remains to be investigated. We therefore assessed the impact of a KD on growth and metastasis of triple negative murine 4T1 mammary tumors, and on the progression of luminal breast tumors in an autochthonous MMTV-PyMT mouse model. We found that KD did not influence the metastasis of 4T1 and MMTV-PyMT mammary tumors, but impaired 4T1 tumor cell proliferation in vivo, and also temporarily reduced 4T1 primary tumor growth. Notably, the ketogenic ratio (the mass of dietary fat in relation to the mass of dietary carbohydrates and protein) that is needed to induce robust ketosis was twice as high in mice as compared to humans. Surprisingly, only female but not male mice responded to KD with a sustained increase in blood β-hydroxybutyrate levels. Together, our data show that ketosis does not foster primary tumor growth and metastasis, suggesting that KDs can be safely applied in the context of luminal breast cancer, and may even be advantageous for patients with triple negative tumors. Furthermore, our data indicate that when performing experiments with KDs in mice, the ketogenic ratio needed to induce ketosis must be verified, and the sex of the mice should also be taken into account.
{"title":"Ketogenic diet does not promote triple-negative and luminal mammary tumor growth and metastasis in experimental mice","authors":"Meret Grube, Arno Dimmler, Anja Schmaus, Rafael Saup, Tabea Wagner, Boyan K. Garvalov, Jonathan P. Sleeman, Wilko Thiele","doi":"10.1007/s10585-023-10249-z","DOIUrl":"https://doi.org/10.1007/s10585-023-10249-z","url":null,"abstract":"<p>Ketogenic diets (KDs) can improve the well-being and quality of life of breast cancer patients. However, data on the effects of KDs on mammary tumors are inconclusive, and the influence of KDs on metastasis in general remains to be investigated. We therefore assessed the impact of a KD on growth and metastasis of triple negative murine 4T1 mammary tumors, and on the progression of luminal breast tumors in an autochthonous MMTV-PyMT mouse model. We found that KD did not influence the metastasis of 4T1 and MMTV-PyMT mammary tumors, but impaired 4T1 tumor cell proliferation in vivo, and also temporarily reduced 4T1 primary tumor growth. Notably, the ketogenic ratio (the mass of dietary fat in relation to the mass of dietary carbohydrates and protein) that is needed to induce robust ketosis was twice as high in mice as compared to humans. Surprisingly, only female but not male mice responded to KD with a sustained increase in blood β-hydroxybutyrate levels. Together, our data show that ketosis does not foster primary tumor growth and metastasis, suggesting that KDs can be safely applied in the context of luminal breast cancer, and may even be advantageous for patients with triple negative tumors. Furthermore, our data indicate that when performing experiments with KDs in mice, the ketogenic ratio needed to induce ketosis must be verified, and the sex of the mice should also be taken into account.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138562879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}