Pub Date : 2024-03-11DOI: 10.1007/s10585-024-10276-4
Takae Okuno, Takeshi Isobe, Yukari Tsubata
Lung cancer is a type of cancer that can metastasize to the lungs, brain, bones, liver, adrenal glands, and other organs; however, the occurrence of brain metastases is the most common event. Symptoms of brain metastasis include motor dysfunction, mental dysfunction, seizures, headaches, nausea, and vomiting, and significantly reduce the quality of life of cancer patients. Brain metastases are a poor prognostic factor, and controlling them is extremely important for prolonging prognosis and improving the quality of life. Currently, local surgery and radiotherapy are recommended for their treatment. However, recently, cancer treatments using molecular-targeted drugs and immune checkpoint inhibitors have been introduced, which may also be effective against brain metastases. Therefore, it is necessary to determine whether local or systemic therapy is optimal for each case. In this review, we focus on recent findings regarding drug therapy in treating brain metastases from advanced non-small cell lung cancer.
{"title":"Current pharmacologic treatment of brain metastasis in non-small cell lung cancer","authors":"Takae Okuno, Takeshi Isobe, Yukari Tsubata","doi":"10.1007/s10585-024-10276-4","DOIUrl":"https://doi.org/10.1007/s10585-024-10276-4","url":null,"abstract":"<p>Lung cancer is a type of cancer that can metastasize to the lungs, brain, bones, liver, adrenal glands, and other organs; however, the occurrence of brain metastases is the most common event. Symptoms of brain metastasis include motor dysfunction, mental dysfunction, seizures, headaches, nausea, and vomiting, and significantly reduce the quality of life of cancer patients. Brain metastases are a poor prognostic factor, and controlling them is extremely important for prolonging prognosis and improving the quality of life. Currently, local surgery and radiotherapy are recommended for their treatment. However, recently, cancer treatments using molecular-targeted drugs and immune checkpoint inhibitors have been introduced, which may also be effective against brain metastases. Therefore, it is necessary to determine whether local or systemic therapy is optimal for each case. In this review, we focus on recent findings regarding drug therapy in treating brain metastases from advanced non-small cell lung cancer.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097468","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 : 2024-02-17DOI: 10.1007/s10585-024-10278-2
Negar Pourjamal, Narjes Yazdi, Aleksi Halme, Vadim Le Joncour, Pirjo Laakkonen, Pipsa Saharinen, Heikki Joensuu, Mark Barok
Human epidermal growth factor 2 (HER2)-positive breast cancer with lung metastases resistant to targeted agents is a common therapeutic challenge. Absence of preclinical lung metastasis models that are resistant to multiple anti-HER2 targeted drugs hampers the development of novel therapies. We established a novel HER2-positive breast cancer cell line (L-JIMT-1) with a high propensity to form lung metastases from the parenteral JIMT-1 cell line by injecting JIMT-1 cells into immunodeficient SCID mice. Lung metastases developed in all mice injected with L-JIMT-1 cells, and more rapidly and in greater numbers compared with the parental JIMT-1 cells. L-JIMT-1 cells expressed more epidermal growth factor receptor and HER2 than JIMT-1 cells. L-JIMT-1 cells were resistant to all five tyrosine kinase inhibitors tested in vitro (afatinib, erlotinib, lapatinib, sapitinib, and tucatinib). When we compared JIMT-1 and L-JIMT-1 sensitivity to three HER2-targeting antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and disitamab vedotin (DV) in vitro, JIMT-1 cells were resistant T-DXd, partially sensitive to T-DM1, and sensitive to DV, while L-JIMT-1 cells were resistant to both T-DM1 and T-DXd, but moderately sensitive to DV. In a mouse model, all three ADCs inhibited the growth of L-JIMT-1 lung metastases compared to a vehicle, but DV and T-DXd more strongly than T-DM1, and DV treatment led to the smallest tumor burden. The L-JIMT breast cancer lung metastasis model developed may be useful in the evaluation of anti-cancer agents for multiresistant HER2-positive advanced breast cancer.
{"title":"Comparison of trastuzumab emtansine, trastuzumab deruxtecan, and disitamab vedotin in a multiresistant HER2-positive breast cancer lung metastasis model","authors":"Negar Pourjamal, Narjes Yazdi, Aleksi Halme, Vadim Le Joncour, Pirjo Laakkonen, Pipsa Saharinen, Heikki Joensuu, Mark Barok","doi":"10.1007/s10585-024-10278-2","DOIUrl":"https://doi.org/10.1007/s10585-024-10278-2","url":null,"abstract":"<p>Human epidermal growth factor 2 (HER2)-positive breast cancer with lung metastases resistant to targeted agents is a common therapeutic challenge. Absence of preclinical lung metastasis models that are resistant to multiple anti-HER2 targeted drugs hampers the development of novel therapies. We established a novel HER2-positive breast cancer cell line (L-JIMT-1) with a high propensity to form lung metastases from the parenteral JIMT-1 cell line by injecting JIMT-1 cells into immunodeficient SCID mice. Lung metastases developed in all mice injected with L-JIMT-1 cells, and more rapidly and in greater numbers compared with the parental JIMT-1 cells. L-JIMT-1 cells expressed more epidermal growth factor receptor and HER2 than JIMT-1 cells. L-JIMT-1 cells were resistant to all five tyrosine kinase inhibitors tested in vitro (afatinib, erlotinib, lapatinib, sapitinib, and tucatinib). When we compared JIMT-1 and L-JIMT-1 sensitivity to three HER2-targeting antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and disitamab vedotin (DV) in vitro, JIMT-1 cells were resistant T-DXd, partially sensitive to T-DM1, and sensitive to DV, while L-JIMT-1 cells were resistant to both T-DM1 and T-DXd, but moderately sensitive to DV. In a mouse model, all three ADCs inhibited the growth of L-JIMT-1 lung metastases compared to a vehicle, but DV and T-DXd more strongly than T-DM1, and DV treatment led to the smallest tumor burden. The L-JIMT breast cancer lung metastasis model developed may be useful in the evaluation of anti-cancer agents for multiresistant HER2-positive advanced breast cancer.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139753286","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 : 2024-02-05DOI: 10.1007/s10585-023-10261-3
Abstract
Lymph nodes (LNs) are principal orchestrators of the adaptive immune response, yet in the context of malignancy, they are typically the first sites of metastasis. When tumors spread to LNs, they alter the immune repertoire, ultimately reconditioning it in a manner that suppresses anti-tumor immunity and promotes further metastatic dissemination. Conversely, activation of anti-tumor immunity within LNs is essential for immunotherapy, suggesting clinical approaches to radiotherapy in LNs and lymphadenectomy may need to be reconsidered in the context of immune checkpoint blockade (ICB). Herein, we discuss our understanding of the immune remodeling that coincides with LN metastasis as well as recent clinical studies exploring neoadjuvant immunotherapy and the roles of LNs in treatment of solid organ malignancies.
{"title":"Interrogating the roles of lymph node metastasis in systemic immune surveillance","authors":"","doi":"10.1007/s10585-023-10261-3","DOIUrl":"https://doi.org/10.1007/s10585-023-10261-3","url":null,"abstract":"<h3>Abstract</h3> <p>Lymph nodes (LNs) are principal orchestrators of the adaptive immune response, yet in the context of malignancy, they are typically the first sites of metastasis. When tumors spread to LNs, they alter the immune repertoire, ultimately reconditioning it in a manner that suppresses anti-tumor immunity and promotes further metastatic dissemination. Conversely, activation of anti-tumor immunity within LNs is essential for immunotherapy, suggesting clinical approaches to radiotherapy in LNs and lymphadenectomy may need to be reconsidered in the context of immune checkpoint blockade (ICB). Herein, we discuss our understanding of the immune remodeling that coincides with LN metastasis as well as recent clinical studies exploring neoadjuvant immunotherapy and the roles of LNs in treatment of solid organ malignancies.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139689523","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: 2024-01-05DOI: 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":4.0,"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":4.0,"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}