Lung cancer incidence and mortality rates are increasing worldwide, posing a significant public health challenge and an immense burden to affected families. Lung cancer encompasses distinct subtypes, namely, non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). In clinical investigations, researchers have observed that neuroendocrine tumors can be classified into four types: typical carcinoid, atypical carcinoid, small-cell carcinoma, and large-cell neuroendocrine carcinoma based on their unique features. However, there exist combined forms of neuroendocrine cancer. This study focuses specifically on combined pulmonary carcinomas with a neuroendocrine component. In this comprehensive review article, the authors provide an overview of combined lung cancers and present two pathological images to visually depict these distinctive subtypes.
{"title":"Advances in combined neuroendocrine carcinoma of lung cancer","authors":"Zesen Han, Fujun Yang, Fang Wang, Huayu Zheng, Xiujian Chen, Hongyu Meng, Fenglei Li","doi":"10.3389/pore.2024.1611693","DOIUrl":"https://doi.org/10.3389/pore.2024.1611693","url":null,"abstract":"Lung cancer incidence and mortality rates are increasing worldwide, posing a significant public health challenge and an immense burden to affected families. Lung cancer encompasses distinct subtypes, namely, non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). In clinical investigations, researchers have observed that neuroendocrine tumors can be classified into four types: typical carcinoid, atypical carcinoid, small-cell carcinoma, and large-cell neuroendocrine carcinoma based on their unique features. However, there exist combined forms of neuroendocrine cancer. This study focuses specifically on combined pulmonary carcinomas with a neuroendocrine component. In this comprehensive review article, the authors provide an overview of combined lung cancers and present two pathological images to visually depict these distinctive subtypes.","PeriodicalId":20037,"journal":{"name":"Pathology and Oncology Research","volume":"15 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140981754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-14DOI: 10.3389/pore.2024.1611768
Gréta Antal, Anna Zsigmond, Á. Till, Eniko Orsi, Ildiko Szanto, Gergely Büki, László Kereskai, Zsuzsanna Herbert, K. Hadzsiev, Judit Bene
Background: Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental anomalies are present in approximately 30%–70% of patients with Gardner syndrome and can be discovered during routine dental examinations. However, sometimes the diagnosis is challenging due to the high clinical variability and incomplete clinical picture. Herein, we report a family with various dental and bone anomalies, in which the definitive diagnosis was established with the help of a comprehensive genetic analysis based on state-of-the-art next-generation sequencing technology.Case presentation: A 17-year-old female index patient presented with dental (caries, impacted, retained and anteriorly located teeth) and atypical bone anomalies not resembling Gardner syndrome. She was first referred to our Genetic Counselling Unit at the age of 11 due to an atypical bone abnormality identified by a panoramic X-ray. Tooth 3.6 was surgically removed and the histopathology report revealed a Paget’s disease-like bone metabolic disorder with mixed osteoblastic and osteoclastic activity of the mandible. A small lumbar subcutaneous tumor was discovered by physical examination. Ultrasound examination of the tumor raised the possibility of a soft tissue propagation of chondromatosis. Her sister, 2 years younger at the age of 14, had some benign tumors (multiple exostoses, odontomas, epidermoid cysts) and impacted teeth. Their mother had also skeletal symptoms. Her lower teeth did not develop, the 9th-10th ribs were fused, and she complained of intermittent jaw pain. A cranial CT scan showed fibrous dysplasia on the cranial bones. Whole exome sequencing identified a heterozygous pathogenic nonsense mutation (c.4700C>G; p.Ser1567*) in the APC gene in the index patient’s DNA. Targeted sequencing revealed the same variant in the DNA of the other affected family members (the sister and the mother).Conclusion: Early diagnosis of this rare, genetically determined syndrome is very important, because of the potentially high malignant transformation of intestinal polyps. Dentists should be familiar with the typical maxillofacial features of this disorder, to be able to refer patients to genetic counseling. Dental anomalies often precede the intestinal polyposis and facilitate the early diagnosis, thereby increasing the patients’ chances of survival. Genetic analysis may be necessary in patients with atypical phenotypic signs.
{"title":"Case report: Initial atypical skeletal symptoms and dental anomalies as first signs of Gardner syndrome: the importance of genetic analysis in the early diagnosis","authors":"Gréta Antal, Anna Zsigmond, Á. Till, Eniko Orsi, Ildiko Szanto, Gergely Büki, László Kereskai, Zsuzsanna Herbert, K. Hadzsiev, Judit Bene","doi":"10.3389/pore.2024.1611768","DOIUrl":"https://doi.org/10.3389/pore.2024.1611768","url":null,"abstract":"Background: Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental anomalies are present in approximately 30%–70% of patients with Gardner syndrome and can be discovered during routine dental examinations. However, sometimes the diagnosis is challenging due to the high clinical variability and incomplete clinical picture. Herein, we report a family with various dental and bone anomalies, in which the definitive diagnosis was established with the help of a comprehensive genetic analysis based on state-of-the-art next-generation sequencing technology.Case presentation: A 17-year-old female index patient presented with dental (caries, impacted, retained and anteriorly located teeth) and atypical bone anomalies not resembling Gardner syndrome. She was first referred to our Genetic Counselling Unit at the age of 11 due to an atypical bone abnormality identified by a panoramic X-ray. Tooth 3.6 was surgically removed and the histopathology report revealed a Paget’s disease-like bone metabolic disorder with mixed osteoblastic and osteoclastic activity of the mandible. A small lumbar subcutaneous tumor was discovered by physical examination. Ultrasound examination of the tumor raised the possibility of a soft tissue propagation of chondromatosis. Her sister, 2 years younger at the age of 14, had some benign tumors (multiple exostoses, odontomas, epidermoid cysts) and impacted teeth. Their mother had also skeletal symptoms. Her lower teeth did not develop, the 9th-10th ribs were fused, and she complained of intermittent jaw pain. A cranial CT scan showed fibrous dysplasia on the cranial bones. Whole exome sequencing identified a heterozygous pathogenic nonsense mutation (c.4700C>G; p.Ser1567*) in the APC gene in the index patient’s DNA. Targeted sequencing revealed the same variant in the DNA of the other affected family members (the sister and the mother).Conclusion: Early diagnosis of this rare, genetically determined syndrome is very important, because of the potentially high malignant transformation of intestinal polyps. Dentists should be familiar with the typical maxillofacial features of this disorder, to be able to refer patients to genetic counseling. Dental anomalies often precede the intestinal polyposis and facilitate the early diagnosis, thereby increasing the patients’ chances of survival. Genetic analysis may be necessary in patients with atypical phenotypic signs.","PeriodicalId":20037,"journal":{"name":"Pathology and Oncology Research","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140981953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.3389/pore.2024.1611635
A. Kerpel-Fronius, K. Bogos
Lung cancer, the leading cause of malignancy-related deaths worldwide, demands proactive measures to mitigate its impact. Low-dose computer tomography (LDCT) has emerged as a promising tool for secondary prevention through lung cancer screening (LCS). The HUNCHEST study, inspired by the success of international trials, including the National Lung Cancer Screening Trial and the Dutch NELSON study, embarked on the first LDCT-based LCS program in Hungary. The initiative assessed the screening efficiency, incorporating lung function tests and exploring the interplay between lung cancer and chronic obstructive pulmonary disease (COPD). Building upon this foundation, an implementation trial involving 18 Hungarian centers supported by the Ministry of Human Capacities demonstrated the feasibility of LCS within a multicentric framework. These centers, equipped with radiology capabilities, collaborated with multidisciplinary oncology teams, ensuring optimal patient pathways. However, a critical challenge remained the patient recruitment. To address this, the HUNCHEST 3 project, initiated in 2023, seeks to engage general practitioners (GPs) to reach out to eligible patients within a municipality collective of 60 thousand inhabitants. The project’s ultimate success is contingent upon the willingness of eligible individuals to undergo LDCT scans. In conclusion, the HUNCHEST program represents a crucial step in advancing lung cancer screening in Hungary. With a focus on efficiency, multidisciplinary collaboration, and innovative patient recruitment strategies, it endeavors to contribute to the reduction of lung cancer mortality and serve as a blueprint for potential nationwide LCS programs.
{"title":"HUNCHEST projects—advancing low-dose CT lung cancer screening in Hungary","authors":"A. Kerpel-Fronius, K. Bogos","doi":"10.3389/pore.2024.1611635","DOIUrl":"https://doi.org/10.3389/pore.2024.1611635","url":null,"abstract":"Lung cancer, the leading cause of malignancy-related deaths worldwide, demands proactive measures to mitigate its impact. Low-dose computer tomography (LDCT) has emerged as a promising tool for secondary prevention through lung cancer screening (LCS). The HUNCHEST study, inspired by the success of international trials, including the National Lung Cancer Screening Trial and the Dutch NELSON study, embarked on the first LDCT-based LCS program in Hungary. The initiative assessed the screening efficiency, incorporating lung function tests and exploring the interplay between lung cancer and chronic obstructive pulmonary disease (COPD). Building upon this foundation, an implementation trial involving 18 Hungarian centers supported by the Ministry of Human Capacities demonstrated the feasibility of LCS within a multicentric framework. These centers, equipped with radiology capabilities, collaborated with multidisciplinary oncology teams, ensuring optimal patient pathways. However, a critical challenge remained the patient recruitment. To address this, the HUNCHEST 3 project, initiated in 2023, seeks to engage general practitioners (GPs) to reach out to eligible patients within a municipality collective of 60 thousand inhabitants. The project’s ultimate success is contingent upon the willingness of eligible individuals to undergo LDCT scans. In conclusion, the HUNCHEST program represents a crucial step in advancing lung cancer screening in Hungary. With a focus on efficiency, multidisciplinary collaboration, and innovative patient recruitment strategies, it endeavors to contribute to the reduction of lung cancer mortality and serve as a blueprint for potential nationwide LCS programs.","PeriodicalId":20037,"journal":{"name":"Pathology and Oncology Research","volume":" 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140996878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-22DOI: 10.3389/pore.2024.1611743
Gabriella Mihalekné Fűr, Kolos Nemes, Éva Magó, Alexandra Á. Benő, Petronella Topolcsányi, Judit Moldvay, L. Pongor
Small cell lung cancer (SCLC) is a highly aggressive type of cancer frequently diagnosed with metastatic spread, rendering it surgically unresectable for the majority of patients. Although initial responses to platinum-based therapies are often observed, SCLC invariably relapses within months, frequently developing drug-resistance ultimately contributing to short overall survival rates. Recently, SCLC research aimed to elucidate the dynamic changes in the genetic and epigenetic landscape. These have revealed distinct subtypes of SCLC, each characterized by unique molecular signatures. The recent understanding of the molecular heterogeneity of SCLC has opened up potential avenues for precision medicine, enabling the development of targeted therapeutic strategies. In this review, we delve into the applied models and computational approaches that have been instrumental in the identification of promising drug candidates. We also explore the emerging molecular diagnostic tools that hold the potential to transform clinical practice and patient care.
{"title":"Applied models and molecular characteristics of small cell lung cancer","authors":"Gabriella Mihalekné Fűr, Kolos Nemes, Éva Magó, Alexandra Á. Benő, Petronella Topolcsányi, Judit Moldvay, L. Pongor","doi":"10.3389/pore.2024.1611743","DOIUrl":"https://doi.org/10.3389/pore.2024.1611743","url":null,"abstract":"Small cell lung cancer (SCLC) is a highly aggressive type of cancer frequently diagnosed with metastatic spread, rendering it surgically unresectable for the majority of patients. Although initial responses to platinum-based therapies are often observed, SCLC invariably relapses within months, frequently developing drug-resistance ultimately contributing to short overall survival rates. Recently, SCLC research aimed to elucidate the dynamic changes in the genetic and epigenetic landscape. These have revealed distinct subtypes of SCLC, each characterized by unique molecular signatures. The recent understanding of the molecular heterogeneity of SCLC has opened up potential avenues for precision medicine, enabling the development of targeted therapeutic strategies. In this review, we delve into the applied models and computational approaches that have been instrumental in the identification of promising drug candidates. We also explore the emerging molecular diagnostic tools that hold the potential to transform clinical practice and patient care.","PeriodicalId":20037,"journal":{"name":"Pathology and Oncology Research","volume":"52 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140672559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-19DOI: 10.3389/pore.2024.1611593
I. Krencz, D. Sztankovics, A. Sebestyén, J. Pápay, T. Dankó, D. Moldvai, Elmar Lutz, Andras Khoor
RICTOR gene, which encodes the scaffold protein of mTORC2, can be amplified in various tumor types, including squamous cell carcinoma (SCC) of the lung. RICTOR amplification can lead to hyperactivation of mTORC2 and may serve as a targetable genetic alteration, including in lung SCC patients with no PD-L1 expression who are not expected to benefit from immune checkpoint inhibitor therapy. This study aimed to compare RICTOR amplification detected by fluorescence in situ hybridization (FISH) with Rictor and PD-L1 protein expression detected by immunohistochemistry (IHC) in SCC of the lung. The study was complemented by analysis of the publicly available Lung Squamous Cell Carcinoma (TCGA, Firehose legacy) dataset. RICTOR amplification was observed in 20% of our cases and 16% of the lung SCC cases of the TCGA dataset. Rictor and PD-L1 expression was seen in 74% and 44% of the cases, respectively. Rictor IHC showed two staining patterns: membrane staining (16% of the cases) and cytoplasmic staining (58% of the cases). Rictor membrane staining predicted RICTOR amplification as detected by FISH with high specificity (95%) and sensitivity (70%). We did not find any correlation between RICTOR amplification and PD-L1 expression; RICTOR amplification was detected in 18% and 26% of PD-L1 positive and negative cases, respectively. The TCGA dataset analysis showed similar results; RICTOR copy number correlated with Rictor mRNA and protein expression but showed no association with PD-L1 mRNA and protein expression. In conclusion, the correlation between RICTOR amplification and Rictor membrane staining suggests that the latter can potentially be used as a surrogate marker to identify lung SCC cases with RICTOR amplification. Since a significant proportion of PD-L1 negative SCC cases harbor RICTOR amplification, analyzing PD-L1 negative tumors by RICTOR FISH or Rictor IHC can help select patients who may benefit from mTORC2 inhibitor therapy.
{"title":"RICTOR amplification is associated with Rictor membrane staining and does not correlate with PD-L1 expression in lung squamous cell carcinoma","authors":"I. Krencz, D. Sztankovics, A. Sebestyén, J. Pápay, T. Dankó, D. Moldvai, Elmar Lutz, Andras Khoor","doi":"10.3389/pore.2024.1611593","DOIUrl":"https://doi.org/10.3389/pore.2024.1611593","url":null,"abstract":"RICTOR gene, which encodes the scaffold protein of mTORC2, can be amplified in various tumor types, including squamous cell carcinoma (SCC) of the lung. RICTOR amplification can lead to hyperactivation of mTORC2 and may serve as a targetable genetic alteration, including in lung SCC patients with no PD-L1 expression who are not expected to benefit from immune checkpoint inhibitor therapy. This study aimed to compare RICTOR amplification detected by fluorescence in situ hybridization (FISH) with Rictor and PD-L1 protein expression detected by immunohistochemistry (IHC) in SCC of the lung. The study was complemented by analysis of the publicly available Lung Squamous Cell Carcinoma (TCGA, Firehose legacy) dataset. RICTOR amplification was observed in 20% of our cases and 16% of the lung SCC cases of the TCGA dataset. Rictor and PD-L1 expression was seen in 74% and 44% of the cases, respectively. Rictor IHC showed two staining patterns: membrane staining (16% of the cases) and cytoplasmic staining (58% of the cases). Rictor membrane staining predicted RICTOR amplification as detected by FISH with high specificity (95%) and sensitivity (70%). We did not find any correlation between RICTOR amplification and PD-L1 expression; RICTOR amplification was detected in 18% and 26% of PD-L1 positive and negative cases, respectively. The TCGA dataset analysis showed similar results; RICTOR copy number correlated with Rictor mRNA and protein expression but showed no association with PD-L1 mRNA and protein expression. In conclusion, the correlation between RICTOR amplification and Rictor membrane staining suggests that the latter can potentially be used as a surrogate marker to identify lung SCC cases with RICTOR amplification. Since a significant proportion of PD-L1 negative SCC cases harbor RICTOR amplification, analyzing PD-L1 negative tumors by RICTOR FISH or Rictor IHC can help select patients who may benefit from mTORC2 inhibitor therapy.","PeriodicalId":20037,"journal":{"name":"Pathology and Oncology Research","volume":" 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140684423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-19DOI: 10.3389/pore.2024.1611716
Zsuzsanna Orosz, Árpád Kovács
Locally advanced non-small lung cancer encompasses a diverse range of tumors. In the last few years, the treatment of stage III unresectable non-small lung cancer has evolved significantly. The PACIFIC trial opened a new therapeutic era in the treatment of locally advanced NSCLC, establishing durvalumab consolidation therapy as the new standard of care worldwide. A careful evaluation of this type of lung cancer and a discussion of the management of these patients within a multidisciplinary team represents a crucial step in defining the best treatment strategy for each patient. For unresectable stage III NSCLC, definitive concurrent chemoradiotherapy (CCRT) was historically recommended as a treatment with a 5-year survival rate ranging from 20% to 30%. The PACIFIC study conducted in 2017 compared the use of chemoradiotherapy and maintenance therapy with the anti-PD-L1 monoclonal antibody durvalumab to a placebo in patients with locally advanced NSCLC who had not experienced disease progression. The study was prospective, randomized, and phase III. The administration of this medication in patients with locally advanced non-small cell lung cancer (NSCLC) has demonstrated a notable improvement in overall survival. Multiple clinical trials are currently exploring various immune checkpoint inhibition regimens to enhance the treatment efficacy in patients with stage III cancer. Our goal is to offer an up-to-date summary of the planned clinical trials for treatment options, focusing on the significant obstacles and prospects in the post-PACIFIC era.
局部晚期非小肺癌包括多种肿瘤。在过去几年中，III 期不可切除非小肺癌的治疗发生了显著变化。PACIFIC试验开创了局部晚期NSCLC治疗的新纪元，将durvalumab巩固治疗确立为全球新的治疗标准。在多学科团队中仔细评估这类肺癌并讨论如何治疗这些患者，是为每位患者确定最佳治疗策略的关键一步。对于无法切除的 III 期 NSCLC，历史上曾推荐采用明确的同期化放疗（CCRT）作为治疗手段，其 5 年生存率在 20% 至 30% 之间。2017年开展的PACIFIC研究比较了未出现疾病进展的局部晚期NSCLC患者使用化放疗和抗PD-L1单克隆抗体durvalumab维持治疗与安慰剂的效果。该研究为前瞻性、随机、III 期研究。对局部晚期非小细胞肺癌（NSCLC）患者使用这种药物后，总生存期明显改善。目前，多项临床试验正在探索各种免疫检查点抑制方案，以提高 III 期癌症患者的治疗效果。我们的目标是对治疗方案计划中的临床试验进行最新总结，重点关注 "后太平洋倡议 "时代的重大障碍和前景。
{"title":"The role of chemoradiotherapy and immunotherapy in stage III NSCLC","authors":"Zsuzsanna Orosz, Árpád Kovács","doi":"10.3389/pore.2024.1611716","DOIUrl":"https://doi.org/10.3389/pore.2024.1611716","url":null,"abstract":"Locally advanced non-small lung cancer encompasses a diverse range of tumors. In the last few years, the treatment of stage III unresectable non-small lung cancer has evolved significantly. The PACIFIC trial opened a new therapeutic era in the treatment of locally advanced NSCLC, establishing durvalumab consolidation therapy as the new standard of care worldwide. A careful evaluation of this type of lung cancer and a discussion of the management of these patients within a multidisciplinary team represents a crucial step in defining the best treatment strategy for each patient. For unresectable stage III NSCLC, definitive concurrent chemoradiotherapy (CCRT) was historically recommended as a treatment with a 5-year survival rate ranging from 20% to 30%. The PACIFIC study conducted in 2017 compared the use of chemoradiotherapy and maintenance therapy with the anti-PD-L1 monoclonal antibody durvalumab to a placebo in patients with locally advanced NSCLC who had not experienced disease progression. The study was prospective, randomized, and phase III. The administration of this medication in patients with locally advanced non-small cell lung cancer (NSCLC) has demonstrated a notable improvement in overall survival. Multiple clinical trials are currently exploring various immune checkpoint inhibition regimens to enhance the treatment efficacy in patients with stage III cancer. Our goal is to offer an up-to-date summary of the planned clinical trials for treatment options, focusing on the significant obstacles and prospects in the post-PACIFIC era.","PeriodicalId":20037,"journal":{"name":"Pathology and Oncology Research","volume":" 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140684530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-17DOI: 10.3389/pore.2024.1611744
G. Kaval, Merve Gülbiz Dağoğlu Kartal, S. Azamat, Eda Cingoz, Gokhan Ertas, Şule Karaman, Basak Kurtuldu, Metin Keskin, Neslihan Berker, Senem Karabulut, E. Oral, Nergiz Dagoglu Sakin
Studies examining prediction of complete response (CR) in locally advanced rectum cancer (LARC) from pre/post chemoradiotherapy (CRT) magnetic resonance imaging (MRI) are performed mostly with segmentations of the tumor, whereas only in two studies segmentation included tumor and mesorectum. Additionally, pelvic extramesorectal region, which is included in the clinical target volume (CTV) of radiotherapy, may contain information. Therefore, we aimed to compare predictive rates of radiomics analysis with features extracted from segmentations of tumor, tumor+mesorectum, and CTV.Ninety-three LARC patients who underwent CRT in our institution between 2012 and 2019 were retrospectively scanned. Patients were divided into CR and non-CR groups. Tumor, tumor+mesorectum and CTV were segmented on T2 preCRT MRI images. Extracted features were compared for best area under the curve (AUC) of CR prediction with 15 machine-learning models.CR was observed in 25 patients (26.8%), of whom 13 had pathological, and 12 had clinical complete response. For tumor, tumor+mesorectum and CTV segmentations, the best AUC were 0.84, 0.81, 0.77 in the training set and 0.85, 0.83 and 0.72 in the test set, respectively; sensitivity and specificity for the test set were 76%, 90%, 76% and 71%, 67% and 62%, respectively.Although the highest AUC result is obtained from the tumor segmentation, the highest accuracy and sensitivity are detected with tumor+mesorectum segmentation and these findings align with previous studies, suggesting that the mesorectum contains valuable insights for CR. The lowest result is obtained with CTV segmentation. More studies with mesorectum and pelvic nodal regions included in segmentation are needed.
{"title":"Evaluating complete response prediction rates in locally advanced rectal cancer with different radiomics segmentation approaches","authors":"G. Kaval, Merve Gülbiz Dağoğlu Kartal, S. Azamat, Eda Cingoz, Gokhan Ertas, Şule Karaman, Basak Kurtuldu, Metin Keskin, Neslihan Berker, Senem Karabulut, E. Oral, Nergiz Dagoglu Sakin","doi":"10.3389/pore.2024.1611744","DOIUrl":"https://doi.org/10.3389/pore.2024.1611744","url":null,"abstract":"Studies examining prediction of complete response (CR) in locally advanced rectum cancer (LARC) from pre/post chemoradiotherapy (CRT) magnetic resonance imaging (MRI) are performed mostly with segmentations of the tumor, whereas only in two studies segmentation included tumor and mesorectum. Additionally, pelvic extramesorectal region, which is included in the clinical target volume (CTV) of radiotherapy, may contain information. Therefore, we aimed to compare predictive rates of radiomics analysis with features extracted from segmentations of tumor, tumor+mesorectum, and CTV.Ninety-three LARC patients who underwent CRT in our institution between 2012 and 2019 were retrospectively scanned. Patients were divided into CR and non-CR groups. Tumor, tumor+mesorectum and CTV were segmented on T2 preCRT MRI images. Extracted features were compared for best area under the curve (AUC) of CR prediction with 15 machine-learning models.CR was observed in 25 patients (26.8%), of whom 13 had pathological, and 12 had clinical complete response. For tumor, tumor+mesorectum and CTV segmentations, the best AUC were 0.84, 0.81, 0.77 in the training set and 0.85, 0.83 and 0.72 in the test set, respectively; sensitivity and specificity for the test set were 76%, 90%, 76% and 71%, 67% and 62%, respectively.Although the highest AUC result is obtained from the tumor segmentation, the highest accuracy and sensitivity are detected with tumor+mesorectum segmentation and these findings align with previous studies, suggesting that the mesorectum contains valuable insights for CR. The lowest result is obtained with CTV segmentation. More studies with mesorectum and pelvic nodal regions included in segmentation are needed.","PeriodicalId":20037,"journal":{"name":"Pathology and Oncology Research","volume":"11 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140693959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.3389/pore.2024.1611735
Dániel Deme, B. Tamaskovics, Nizar Jammoul, Sándor Kovács, Emmanuel Oladunjoye Kayode, James W. Grice, András Telekes
Introduction: The 21-gene analysis (OncotypeDX) is validated test for pT1-3, pN0-1 with hormone receptor (HR) positive and normal expression of human epidermal growth factor receptor-2 (HER2) breast cancer (BC) to determine the aggressiveness of the disease based on the calculation of Recurrence Score (RS).Methods: In this retrospective study the authors correlated pathological characteristics and Recurrence Score (RS) by traditional statistical methods and Observed Oriented Modeling (OOM) in a realistic cohort of BC patients.Results: OncotypeDX tests were performed in 94 tumour specimens of 90 BC patients. >83% of node-negative (pN0) and >72% of node-positive (pN1) cases could avoid chemotherapy. For pN0 cases, non-parametric correlation and tests demonstrated significant association in eight types of characteristics [progesterone receptor (PR) expression, Ki-67 value, Ki-67 group, PR group, grade, estrogen receptor (ER) expression, Nottingham Prognostic Index (NPI) and Clinical Risk]. For pN1 cases, parametric correlation and tests showed significant association in six characteristic types (number of positive nodes, ER and PR expression, PR group, Ki-67 group and NPI). Based on OOM for pN0 cases, significant associations were established in three characteristics (Ki-67 group, grade and NPI group). For pN1 cases OOM found significant associations in seven characteristics (PR group, PNI, LVI, Ki-67 group, grade, NPI group and number of positive nodes).Conclusion: First in oncology, OOM was applied, which found some other significant characteristics associated with RS than traditional statistical methods. There were few patients, where no clinical associations were found between characteristics and RS contrary to statistically significant differences. Therefore, the results of these statistical analyses can be neither applied for individual cases nor able to provide the bases for screening patients, i.e., whether they need for OncotypeDX testing or not. OncotypeDX still provides a personalised approach in BC.
{"title":"Association between pathological characteristics and recurrence score by OncotypeDX in resected T1-3 and N0-1 breast cancer: a real-life experience of a North Hungarian regional center","authors":"Dániel Deme, B. Tamaskovics, Nizar Jammoul, Sándor Kovács, Emmanuel Oladunjoye Kayode, James W. Grice, András Telekes","doi":"10.3389/pore.2024.1611735","DOIUrl":"https://doi.org/10.3389/pore.2024.1611735","url":null,"abstract":"Introduction: The 21-gene analysis (OncotypeDX) is validated test for pT1-3, pN0-1 with hormone receptor (HR) positive and normal expression of human epidermal growth factor receptor-2 (HER2) breast cancer (BC) to determine the aggressiveness of the disease based on the calculation of Recurrence Score (RS).Methods: In this retrospective study the authors correlated pathological characteristics and Recurrence Score (RS) by traditional statistical methods and Observed Oriented Modeling (OOM) in a realistic cohort of BC patients.Results: OncotypeDX tests were performed in 94 tumour specimens of 90 BC patients. >83% of node-negative (pN0) and >72% of node-positive (pN1) cases could avoid chemotherapy. For pN0 cases, non-parametric correlation and tests demonstrated significant association in eight types of characteristics [progesterone receptor (PR) expression, Ki-67 value, Ki-67 group, PR group, grade, estrogen receptor (ER) expression, Nottingham Prognostic Index (NPI) and Clinical Risk]. For pN1 cases, parametric correlation and tests showed significant association in six characteristic types (number of positive nodes, ER and PR expression, PR group, Ki-67 group and NPI). Based on OOM for pN0 cases, significant associations were established in three characteristics (Ki-67 group, grade and NPI group). For pN1 cases OOM found significant associations in seven characteristics (PR group, PNI, LVI, Ki-67 group, grade, NPI group and number of positive nodes).Conclusion: First in oncology, OOM was applied, which found some other significant characteristics associated with RS than traditional statistical methods. There were few patients, where no clinical associations were found between characteristics and RS contrary to statistically significant differences. Therefore, the results of these statistical analyses can be neither applied for individual cases nor able to provide the bases for screening patients, i.e., whether they need for OncotypeDX testing or not. OncotypeDX still provides a personalised approach in BC.","PeriodicalId":20037,"journal":{"name":"Pathology and Oncology Research","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140695673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.3389/pore.2024.1611586
Korie A. Grayson, Joshua D. Greenlee, Lauren E. Himmel, Lauren A. Hapach, Cynthia A. Reinhart-King, Michael R. King
Mounting evidence suggests that the immune landscape within prostate tumors influences progression, metastasis, treatment response, and patient outcomes. In this study, we investigated the spatial density of innate immune cell populations within NOD.SCID orthotopic prostate cancer xenografts following microinjection of human DU145 prostate cancer cells. Our laboratory has previously developed nanoscale liposomes that attach to leukocytes via conjugated E-selectin (ES) and kill cancer cells via TNF-related apoptosis inducing ligand (TRAIL). Immunohistochemistry (IHC) staining was performed on tumor samples to identify and quantify leukocyte infiltration for different periods of tumor growth and E-selectin/TRAIL (EST) liposome treatments. We examined the spatial-temporal dynamics of three different immune cell types infiltrating tumors using QuPath image analysis software. IHC staining revealed that F4/80+ tumor-associated macrophages (TAMs) were the most abundant immune cells in all groups, irrespective of time or treatment. The density of TAMs decreased over the course of tumor growth and decreased in response to EST liposome treatments. Intratumoral versus marginal analysis showed a greater presence of TAMs in the marginal regions at 3 weeks of tumor growth which became more evenly distributed over time and in tumors treated with EST liposomes. TUNEL staining indicated that EST liposomes significantly increased cell apoptosis in treated tumors. Additionally, confocal microscopy identified liposome-coated TAMs in both the core and periphery of tumors, highlighting the ability of liposomes to infiltrate tumors by “piggybacking” on macrophages. The results of this study indicate that TAMs represent the majority of innate immune cells within NOD.SCID orthotopic prostate tumors, and spatial density varies widely as a function of tumor size, duration of tumor growth, and treatment of EST liposomes.
{"title":"Spatial distribution of tumor-associated macrophages in an orthotopic prostate cancer mouse model","authors":"Korie A. Grayson, Joshua D. Greenlee, Lauren E. Himmel, Lauren A. Hapach, Cynthia A. Reinhart-King, Michael R. King","doi":"10.3389/pore.2024.1611586","DOIUrl":"https://doi.org/10.3389/pore.2024.1611586","url":null,"abstract":"Mounting evidence suggests that the immune landscape within prostate tumors influences progression, metastasis, treatment response, and patient outcomes. In this study, we investigated the spatial density of innate immune cell populations within NOD.SCID orthotopic prostate cancer xenografts following microinjection of human DU145 prostate cancer cells. Our laboratory has previously developed nanoscale liposomes that attach to leukocytes via conjugated E-selectin (ES) and kill cancer cells via TNF-related apoptosis inducing ligand (TRAIL). Immunohistochemistry (IHC) staining was performed on tumor samples to identify and quantify leukocyte infiltration for different periods of tumor growth and E-selectin/TRAIL (EST) liposome treatments. We examined the spatial-temporal dynamics of three different immune cell types infiltrating tumors using QuPath image analysis software. IHC staining revealed that F4/80+ tumor-associated macrophages (TAMs) were the most abundant immune cells in all groups, irrespective of time or treatment. The density of TAMs decreased over the course of tumor growth and decreased in response to EST liposome treatments. Intratumoral versus marginal analysis showed a greater presence of TAMs in the marginal regions at 3 weeks of tumor growth which became more evenly distributed over time and in tumors treated with EST liposomes. TUNEL staining indicated that EST liposomes significantly increased cell apoptosis in treated tumors. Additionally, confocal microscopy identified liposome-coated TAMs in both the core and periphery of tumors, highlighting the ability of liposomes to infiltrate tumors by “piggybacking” on macrophages. The results of this study indicate that TAMs represent the majority of innate immune cells within NOD.SCID orthotopic prostate tumors, and spatial density varies widely as a function of tumor size, duration of tumor growth, and treatment of EST liposomes.","PeriodicalId":20037,"journal":{"name":"Pathology and Oncology Research","volume":"7 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140697728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-09DOI: 10.3389/pore.2024.1611719
Maja L. Nádorvári, Gábor Lotz, Janina Kulka, András Kiss, József Tímár
Current clinical guidelines recommend mismatch repair (MMR) protein immunohistochemistry (IHC) or molecular microsatellite instability (MSI) tests as predictive markers of immunotherapies. Most of the pathological guidelines consider MMR protein IHC as the gold standard test to identify cancers with MMR deficiency and recommend molecular MSI tests only in special circumstances or to screen for Lynch syndrome. However, there are data in the literature which suggest that the two test types may not be equal. For example, molecular epidemiology studies reported different rates of deficient MMR (dMMR) and MSI in various cancer types. Additionally, direct comparisons of the two tests revealed relatively frequent discrepancies between MMR IHC and MSI tests, especially in non-colorectal and non-endometrial cancers and in cases with unusual dMMR phenotypes. There are also scattered clinical data showing that the efficacy of immune checkpoint inhibitors is different if the patient selection was based on dMMR versus MSI status of the cancers. All these observations question the current dogma that dMMR phenotype and genetic MSI status are equal predictive markers of the immunotherapies.
{"title":"Microsatellite instability and mismatch repair protein deficiency: equal predictive markers?","authors":"Maja L. Nádorvári, Gábor Lotz, Janina Kulka, András Kiss, József Tímár","doi":"10.3389/pore.2024.1611719","DOIUrl":"https://doi.org/10.3389/pore.2024.1611719","url":null,"abstract":"Current clinical guidelines recommend mismatch repair (MMR) protein immunohistochemistry (IHC) or molecular microsatellite instability (MSI) tests as predictive markers of immunotherapies. Most of the pathological guidelines consider MMR protein IHC as the gold standard test to identify cancers with MMR deficiency and recommend molecular MSI tests only in special circumstances or to screen for Lynch syndrome. However, there are data in the literature which suggest that the two test types may not be equal. For example, molecular epidemiology studies reported different rates of deficient MMR (dMMR) and MSI in various cancer types. Additionally, direct comparisons of the two tests revealed relatively frequent discrepancies between MMR IHC and MSI tests, especially in non-colorectal and non-endometrial cancers and in cases with unusual dMMR phenotypes. There are also scattered clinical data showing that the efficacy of immune checkpoint inhibitors is different if the patient selection was based on dMMR versus MSI status of the cancers. All these observations question the current dogma that dMMR phenotype and genetic MSI status are equal predictive markers of the immunotherapies.","PeriodicalId":20037,"journal":{"name":"Pathology and Oncology Research","volume":"23 S1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140727126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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