Pub Date : 2024-07-16DOI: 10.3389/fonc.2024.1454837
G. G. Loscocco, Barbara Mora, N. Gangat
{"title":"Editorial: Biological and clinical implications of the mutational landscape in myeloproliferative neoplasms","authors":"G. G. Loscocco, Barbara Mora, N. Gangat","doi":"10.3389/fonc.2024.1454837","DOIUrl":"https://doi.org/10.3389/fonc.2024.1454837","url":null,"abstract":"","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"1 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641978","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 : 2024-07-15DOI: 10.3389/fonc.2024.1380453
David O'Reilly, Caroline L. O’Leary, Aislinn Reilly, Min Yuen Teo, Grainne O’Kane, Lizza Hendriks, Kathleen Bennett, Jarushka Naidoo
The combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) can be associated with significant toxicity. We performed a systematic review and meta-analysis of the toxicity of combination treatment of ICIs with TKIs (ICI + TKI) in clinical trials with solid organ malignancies. Our primary endpoint explored the incidence of grade 3 - 5 (G3-5) treatment-related toxicity and our secondary endpoints included the incidence of toxicity by treatment type, disease type and studies with run-in strategies. A total of 9750 abstracts were identified, of which 72 eligible studies were included. The most common disease types were non-small cell lung cancer (n=8, 11.1%), renal cell carcinoma (n=10, 13.8%) and hepatobiliary cancers (n=10, 13.8%). The overall incidence of G3-5 toxicity was 56% (95% CI = 50% – 61%). The most common TKIs combined with ICIs in this analysis were multi-targeted TKIs (n = 52, 72%), VEGF specific (n = 9, 12.5%), or oncogene-targeting TKIs (EGFR, ALK, BRAF, MEK) (n =11, 15.3%). Oncogene-targeted TKIs were associated a higher incidence of rashes and immune related adverse events (irAEs) and lower incidence of hypertension. In studies which used a TKI ‘run-in’ to mitigate toxicity, the pooled estimate of G3-5 toxicity was 71% (95% CI 57-81%). Almost half of studies (48%) omitted the incidence of G3-5 irAEs. Our work suggests that the majority of patients who receive ICI-TKI combinations will experience high grade toxicity (G3-G5) and that toxicity may be specific to TKI partner (Oncogene targeted TKIs: Rash, irAEs; VEGF/Multitargeted: Hypertension). These data did not suggest that a TKI ‘run-in’ was associated with a lower incidence of G3-5 toxicity. Reporting of irAEs was inconsistent supporting the need for harmonisation of adverse event reporting to include onset, duration and treatment.https://www.crd.york.ac.uk/prospero/, identifier CRD42022367416.
{"title":"Toxicity of immune checkpoint inhibitors and tyrosine kinase inhibitor combinations in solid tumours: a systematic review and meta-analysis","authors":"David O'Reilly, Caroline L. O’Leary, Aislinn Reilly, Min Yuen Teo, Grainne O’Kane, Lizza Hendriks, Kathleen Bennett, Jarushka Naidoo","doi":"10.3389/fonc.2024.1380453","DOIUrl":"https://doi.org/10.3389/fonc.2024.1380453","url":null,"abstract":"The combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) can be associated with significant toxicity. We performed a systematic review and meta-analysis of the toxicity of combination treatment of ICIs with TKIs (ICI + TKI) in clinical trials with solid organ malignancies. Our primary endpoint explored the incidence of grade 3 - 5 (G3-5) treatment-related toxicity and our secondary endpoints included the incidence of toxicity by treatment type, disease type and studies with run-in strategies. A total of 9750 abstracts were identified, of which 72 eligible studies were included. The most common disease types were non-small cell lung cancer (n=8, 11.1%), renal cell carcinoma (n=10, 13.8%) and hepatobiliary cancers (n=10, 13.8%). The overall incidence of G3-5 toxicity was 56% (95% CI = 50% – 61%). The most common TKIs combined with ICIs in this analysis were multi-targeted TKIs (n = 52, 72%), VEGF specific (n = 9, 12.5%), or oncogene-targeting TKIs (EGFR, ALK, BRAF, MEK) (n =11, 15.3%). Oncogene-targeted TKIs were associated a higher incidence of rashes and immune related adverse events (irAEs) and lower incidence of hypertension. In studies which used a TKI ‘run-in’ to mitigate toxicity, the pooled estimate of G3-5 toxicity was 71% (95% CI 57-81%). Almost half of studies (48%) omitted the incidence of G3-5 irAEs. Our work suggests that the majority of patients who receive ICI-TKI combinations will experience high grade toxicity (G3-G5) and that toxicity may be specific to TKI partner (Oncogene targeted TKIs: Rash, irAEs; VEGF/Multitargeted: Hypertension). These data did not suggest that a TKI ‘run-in’ was associated with a lower incidence of G3-5 toxicity. Reporting of irAEs was inconsistent supporting the need for harmonisation of adverse event reporting to include onset, duration and treatment.https://www.crd.york.ac.uk/prospero/, identifier CRD42022367416.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"5 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141646160","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 : 2024-07-15DOI: 10.3389/fonc.2024.1383939
Anjana Sajeev, Bandari BharathwajChetty, Mukesh Kumar Manickasamy, Mohammed S. Alqahtani, Mohamed Abbas, Mehdi Shakibaei, Gautam Sethi, Zhaowu Ma, A. Kunnumakkara
Ovarian cancer (OVC) is one of the most common causes of cancer-related deaths in women worldwide. Despite advancements in detection and therapy, the prognosis of OVC remains poor due to late diagnosis and the lack of effective therapeutic options at advanced stages. Therefore, a better understanding of the biology underlying OVC is essential for the development of effective strategies for early detection and targeted therapies. Nuclear receptors (NRs) are a superfamily of 48 transcription factors that, upon binding to their specific ligand, play a vital role in regulating various cellular processes such as growth, development, metabolism, and homeostasis. Accumulating evidence from several studies has shown that their aberrant expression is associated with multiple human diseases. Numerous NRs have shown significant effects in the development of various cancers, including OVC. This review summarizes the recent findings on the role of NRs in OVC, as well as their potential as prognostic and therapeutic markers. Further, the basic structure and signaling mechanism of NRs have also been discussed briefly. Moreover, this review highlights their cellular and molecular mechanisms in chemoresistance and chemosensitization. Further, the clinical trials targeting NRs for the treatment of OVC have also been discussed.
{"title":"Nuclear receptors in ovarian cancer: changing paradigms in cancer therapeutics","authors":"Anjana Sajeev, Bandari BharathwajChetty, Mukesh Kumar Manickasamy, Mohammed S. Alqahtani, Mohamed Abbas, Mehdi Shakibaei, Gautam Sethi, Zhaowu Ma, A. Kunnumakkara","doi":"10.3389/fonc.2024.1383939","DOIUrl":"https://doi.org/10.3389/fonc.2024.1383939","url":null,"abstract":"Ovarian cancer (OVC) is one of the most common causes of cancer-related deaths in women worldwide. Despite advancements in detection and therapy, the prognosis of OVC remains poor due to late diagnosis and the lack of effective therapeutic options at advanced stages. Therefore, a better understanding of the biology underlying OVC is essential for the development of effective strategies for early detection and targeted therapies. Nuclear receptors (NRs) are a superfamily of 48 transcription factors that, upon binding to their specific ligand, play a vital role in regulating various cellular processes such as growth, development, metabolism, and homeostasis. Accumulating evidence from several studies has shown that their aberrant expression is associated with multiple human diseases. Numerous NRs have shown significant effects in the development of various cancers, including OVC. This review summarizes the recent findings on the role of NRs in OVC, as well as their potential as prognostic and therapeutic markers. Further, the basic structure and signaling mechanism of NRs have also been discussed briefly. Moreover, this review highlights their cellular and molecular mechanisms in chemoresistance and chemosensitization. Further, the clinical trials targeting NRs for the treatment of OVC have also been discussed.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"52 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644541","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 : 2024-07-15DOI: 10.3389/fonc.2024.1425240
B. W. Gjaldbæk, M. Arendt, E. Konradsson, K. Bastholm Jensen, S. Bäck, Per Munck af Rosenschöld, C. Ceberg, K. Petersson, B. Børresen
FLASH radiotherapy (RT) has emerged as a promising modality, demonstrating both a normal tissue sparing effect and anticancer efficacy. We have previously reported on the safety and efficacy of single fraction FLASH RT in the treatment of oral tumors in canine cancer patients, showing tumor response but also a risk of radiation-induced severe late adverse effects (osteoradionecrosis) for doses ≥35 Gy. Accordingly, the objective in this study was to investigate if single fraction high dose FLASH RT is safe for treating non-oral tumors.Privately-owned dogs with superficial tumors or microscopic residual disease were included. Treatment was generally delivered as a single fraction of 15-35 Gy 10 MeV electron FLASH RT, although two dogs were re-irradiated at a later timepoint. Follow-up visits were conducted up to 12 months post-treatment to evaluate treatment efficiency and adverse effects.Fourteen dogs with 16 tumors were included, of which nine tumors were treated for gross disease whilst seven tumors were treated post-surgery for microscopic residual disease. Four treatment sites treated with 35 Gy had ulceration post irradiation, which was graded as severe adverse effect. Only mild adverse effects were observed for the remaining treatment sites. None of the patients with microscopic disease experienced recurrence (0/7), and all patients with macroscopic disease showed either a complete (5/9) or a partial response (4/9). Five dogs were euthanized due to clinical disease progression.Our study demonstrates that single fraction high dose FLASH RT is generally safe, with few severe adverse effects, particularly in areas less susceptible to radiation-induced damage. In addition, our study indicates that FLASH has anti-tumor efficacy in a clinical setting. No osteoradionecrosis was observed in this study, although other types of high-grade adverse effects including ulcer-formations were observed for the highest delivered dose (35 Gy). Overall, we conclude that osteoradionecrosis following single fraction, high dose FLASH does not appear to be a general problem for non-oral tumor locations. Also, as has been shown previously for oral tumors, 30 Gy appeared to be the maximum safe dose to deliver with single fraction FLASH RT.
{"title":"Long-term toxicity and efficacy of FLASH radiotherapy in dogs with superficial malignant tumors","authors":"B. W. Gjaldbæk, M. Arendt, E. Konradsson, K. Bastholm Jensen, S. Bäck, Per Munck af Rosenschöld, C. Ceberg, K. Petersson, B. Børresen","doi":"10.3389/fonc.2024.1425240","DOIUrl":"https://doi.org/10.3389/fonc.2024.1425240","url":null,"abstract":"FLASH radiotherapy (RT) has emerged as a promising modality, demonstrating both a normal tissue sparing effect and anticancer efficacy. We have previously reported on the safety and efficacy of single fraction FLASH RT in the treatment of oral tumors in canine cancer patients, showing tumor response but also a risk of radiation-induced severe late adverse effects (osteoradionecrosis) for doses ≥35 Gy. Accordingly, the objective in this study was to investigate if single fraction high dose FLASH RT is safe for treating non-oral tumors.Privately-owned dogs with superficial tumors or microscopic residual disease were included. Treatment was generally delivered as a single fraction of 15-35 Gy 10 MeV electron FLASH RT, although two dogs were re-irradiated at a later timepoint. Follow-up visits were conducted up to 12 months post-treatment to evaluate treatment efficiency and adverse effects.Fourteen dogs with 16 tumors were included, of which nine tumors were treated for gross disease whilst seven tumors were treated post-surgery for microscopic residual disease. Four treatment sites treated with 35 Gy had ulceration post irradiation, which was graded as severe adverse effect. Only mild adverse effects were observed for the remaining treatment sites. None of the patients with microscopic disease experienced recurrence (0/7), and all patients with macroscopic disease showed either a complete (5/9) or a partial response (4/9). Five dogs were euthanized due to clinical disease progression.Our study demonstrates that single fraction high dose FLASH RT is generally safe, with few severe adverse effects, particularly in areas less susceptible to radiation-induced damage. In addition, our study indicates that FLASH has anti-tumor efficacy in a clinical setting. No osteoradionecrosis was observed in this study, although other types of high-grade adverse effects including ulcer-formations were observed for the highest delivered dose (35 Gy). Overall, we conclude that osteoradionecrosis following single fraction, high dose FLASH does not appear to be a general problem for non-oral tumor locations. Also, as has been shown previously for oral tumors, 30 Gy appeared to be the maximum safe dose to deliver with single fraction FLASH RT.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"32 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141645613","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 : 2024-07-15DOI: 10.3389/fonc.2024.1340430
Federico Pinto, Marco Di Pangrazio, Alessandro Martinino, Letizia Todeschini, Francesco Toti, Luca Cristin, M. Caimano, Amelia Mattia, Giuseppe Bianco, G. Spoletini, Francesco Giovinazzo
This study comprehensively compared laparoscopic liver resection (LLR) to open liver resection (OLR) in treating colorectal cancer liver metastasis (CRLM).A systematic review of relevant literature was conducted to assess a range of crucial surgical and oncological outcomes.Findings indicate that minimally invasive surgery (MIS) did not significantly prolong the duration of surgery compared to open liver resection and notably demonstrated lower blood transfusion rates and reduced intraoperative blood loss. While some studies favored MIS for its lower complication rates, others did not establish a statistically significant difference. One study identified a lower post-operative mortality rate in the MIS group. Furthermore, MIS consistently correlated with shorter hospital stays, indicative of expedited post-operative recovery. Concerning oncological outcomes, while certain meta-analyses reported a lower rate of cancer recurrence in the MIS group, others found no significant disparity. Overall survival and disease-free survival remained comparable between the MIS and open liver resection groups.The analysis emphasizes the potential advantages of LLR in terms of surgical outcomes and aligns with existing literature findings in this field.[website], identifier [registration number].
本研究对腹腔镜肝切除术（LLR）和开腹肝切除术（OLR）治疗结直肠癌肝转移（CRLM）进行了全面比较。研究结果表明，与开腹肝切除术相比，微创手术（MIS）并没有明显延长手术时间，而且输血率明显较低，术中失血量也有所减少。虽然一些研究认为 MIS 的并发症发生率较低，但其他研究并未发现统计学上的显著差异。一项研究发现，MIS 组的术后死亡率较低。此外，MIS 始终与住院时间缩短相关，表明术后恢复更快。关于肿瘤结果，虽然某些荟萃分析报告称 MIS 组癌症复发率较低，但其他研究并未发现明显差异。该分析强调了LLR在手术效果方面的潜在优势，并与该领域现有的文献研究结果相一致。
{"title":"Laparoscopic versus open liver resection for colorectal liver metastasis: an umbrella review","authors":"Federico Pinto, Marco Di Pangrazio, Alessandro Martinino, Letizia Todeschini, Francesco Toti, Luca Cristin, M. Caimano, Amelia Mattia, Giuseppe Bianco, G. Spoletini, Francesco Giovinazzo","doi":"10.3389/fonc.2024.1340430","DOIUrl":"https://doi.org/10.3389/fonc.2024.1340430","url":null,"abstract":"This study comprehensively compared laparoscopic liver resection (LLR) to open liver resection (OLR) in treating colorectal cancer liver metastasis (CRLM).A systematic review of relevant literature was conducted to assess a range of crucial surgical and oncological outcomes.Findings indicate that minimally invasive surgery (MIS) did not significantly prolong the duration of surgery compared to open liver resection and notably demonstrated lower blood transfusion rates and reduced intraoperative blood loss. While some studies favored MIS for its lower complication rates, others did not establish a statistically significant difference. One study identified a lower post-operative mortality rate in the MIS group. Furthermore, MIS consistently correlated with shorter hospital stays, indicative of expedited post-operative recovery. Concerning oncological outcomes, while certain meta-analyses reported a lower rate of cancer recurrence in the MIS group, others found no significant disparity. Overall survival and disease-free survival remained comparable between the MIS and open liver resection groups.The analysis emphasizes the potential advantages of LLR in terms of surgical outcomes and aligns with existing literature findings in this field.[website], identifier [registration number].","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"25 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141645607","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 : 2024-07-15DOI: 10.3389/fonc.2024.1435516
Ashna Fathima, Mohammad Ali Farboodniay Jahromi, S. Begum, Trinath Jamma
Withanolides are a group of naturally occurring plant-based small molecules known for their wide range of host cellular functions. The anticancer potential of withanolides has been explored in varying cancer cell lines in vitro. Based on our prior studies, among the tested withanolides, withametelin (WM) has shown significant cytotoxicity with the highest efficacy on HCT-116 colon cancer cells (IC50 0.719 ± 0.12μM). Treatment with WM reduced the TGF-β driven proliferation, colony-forming ability, migration, and invasiveness of HCT-116 cells in vitro. WM also downregulated the expression of mesenchymal markers such as N-CADHERIN, SNAIL, and SLUG in HCT-116 cells. At the molecular level, WM inhibited TGF-β induced phosphorylation of SMAD2/3 and reduced the expression of an immune checkpoint inhibitor programmed-death ligand-1 (PD-L1). Our study highlights the possible anticancer mechanisms of WM involving modulation of the TGF-β pathway and associated target gene expression, suggesting its potential utility in cancer therapy.
{"title":"Withametelin inhibits TGF-β induced Epithelial-to-Mesenchymal Transition and Programmed-Death Ligand-1 expression in vitro","authors":"Ashna Fathima, Mohammad Ali Farboodniay Jahromi, S. Begum, Trinath Jamma","doi":"10.3389/fonc.2024.1435516","DOIUrl":"https://doi.org/10.3389/fonc.2024.1435516","url":null,"abstract":"Withanolides are a group of naturally occurring plant-based small molecules known for their wide range of host cellular functions. The anticancer potential of withanolides has been explored in varying cancer cell lines in vitro. Based on our prior studies, among the tested withanolides, withametelin (WM) has shown significant cytotoxicity with the highest efficacy on HCT-116 colon cancer cells (IC50 0.719 ± 0.12μM). Treatment with WM reduced the TGF-β driven proliferation, colony-forming ability, migration, and invasiveness of HCT-116 cells in vitro. WM also downregulated the expression of mesenchymal markers such as N-CADHERIN, SNAIL, and SLUG in HCT-116 cells. At the molecular level, WM inhibited TGF-β induced phosphorylation of SMAD2/3 and reduced the expression of an immune checkpoint inhibitor programmed-death ligand-1 (PD-L1). Our study highlights the possible anticancer mechanisms of WM involving modulation of the TGF-β pathway and associated target gene expression, suggesting its potential utility in cancer therapy.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"13 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141646059","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 : 2024-07-15DOI: 10.3389/fonc.2024.1421418
G. Palenzuela, Camille Schiffler, Didier Frappaz, A. Peyrl, N. Gerber, R. Kortmann, Michael Philippe, Martin Zimmermann, Matthew J Murray, James C Nicholson, G. Calaminus, Cécile Faure-Conter
SIOP-CNS-GCT-II European trial was opened for the treatment of patients of any age with central nervous system germ cell tumour (CNS-GCT). Four courses of pre-irradiation chemotherapy were delivered. The influence of patient age on chemotherapy related acute toxicity (CRAT) was assessed.CRAT was analysed according to age-groups: children (aged ≤11 years), adolescents (aged 12-17 years), adults (aged ≥18 years) and to chemotherapy type: CarboPEI (alternating etoposide-carboplatin/etoposide-ifosfamide) for non-metastatic germinoma; PEI (cisplatin-etoposide-ifosfamide) for standard-risk non-germinomatous GCT (NGGCT); PEI and high-dose PEI (HD-PEI), for high-risk or poorly responsive NGGCTs.296 patients were assessable for CRAT: 105 children, 121 adolescents, 70 adults (max age: 41 years). Median cumulative doses/m² of chemotherapy were similar among age-groups. The proportion of germinoma over NGGCT (and accordingly use of CarboPEI chemotherapy) was higher in the adult groups (79%) versus the other two groups (62%). Delay in chemotherapy ≥7 days was noticed in 27%, 38%, and 19% of children, adolescents, and adults, respectively. Grade ≥3 haematological and non-haematological adverse events (AEs) were observed in 94%/31%, 97%/36%, and 77%/21% of children, adolescents, and adults, respectively. No toxic death was reported. Grade ≥3 AEs and delayed chemotherapies were significantly rarer in adults when compared with adolescents, even when adjusted on chemotherapy type: odds ratio: 0.1 [95%CI 0.02-0.4], and 0.2 [95%CI 0.1-0.4] in the group treated with CarboPEI.Adult patients can be treated safely with a chemotherapy intensive protocol, with even less toxicity than that observed in adolescents. Further work is required to understand age-related differences regarding toxicity.
{"title":"Acute toxicity of chemotherapy in central nervous system germ cell tumour patients according to age","authors":"G. Palenzuela, Camille Schiffler, Didier Frappaz, A. Peyrl, N. Gerber, R. Kortmann, Michael Philippe, Martin Zimmermann, Matthew J Murray, James C Nicholson, G. Calaminus, Cécile Faure-Conter","doi":"10.3389/fonc.2024.1421418","DOIUrl":"https://doi.org/10.3389/fonc.2024.1421418","url":null,"abstract":"SIOP-CNS-GCT-II European trial was opened for the treatment of patients of any age with central nervous system germ cell tumour (CNS-GCT). Four courses of pre-irradiation chemotherapy were delivered. The influence of patient age on chemotherapy related acute toxicity (CRAT) was assessed.CRAT was analysed according to age-groups: children (aged ≤11 years), adolescents (aged 12-17 years), adults (aged ≥18 years) and to chemotherapy type: CarboPEI (alternating etoposide-carboplatin/etoposide-ifosfamide) for non-metastatic germinoma; PEI (cisplatin-etoposide-ifosfamide) for standard-risk non-germinomatous GCT (NGGCT); PEI and high-dose PEI (HD-PEI), for high-risk or poorly responsive NGGCTs.296 patients were assessable for CRAT: 105 children, 121 adolescents, 70 adults (max age: 41 years). Median cumulative doses/m² of chemotherapy were similar among age-groups. The proportion of germinoma over NGGCT (and accordingly use of CarboPEI chemotherapy) was higher in the adult groups (79%) versus the other two groups (62%). Delay in chemotherapy ≥7 days was noticed in 27%, 38%, and 19% of children, adolescents, and adults, respectively. Grade ≥3 haematological and non-haematological adverse events (AEs) were observed in 94%/31%, 97%/36%, and 77%/21% of children, adolescents, and adults, respectively. No toxic death was reported. Grade ≥3 AEs and delayed chemotherapies were significantly rarer in adults when compared with adolescents, even when adjusted on chemotherapy type: odds ratio: 0.1 [95%CI 0.02-0.4], and 0.2 [95%CI 0.1-0.4] in the group treated with CarboPEI.Adult patients can be treated safely with a chemotherapy intensive protocol, with even less toxicity than that observed in adolescents. Further work is required to understand age-related differences regarding toxicity.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141646151","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 : 2024-07-15DOI: 10.3389/fonc.2024.1374149
Qi Liu, Ying Zhang, Jingwen Zhang, Luhao Chen, Yi Yang, Yan Liu
To evaluate the efficacy and safety of mFOLFOX-based hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT)This retrospective study included patients who received mFOLFOX-based HAIC combined with TKIs and ICIs from January 2021 to January 2023. The primary outcome was the objective response rate of PVTT response, and the secondary outcomes were 6-month, 1-year survival rate, overall survival (OS), and corresponding adverse events and complications were also evaluated. PVTT responses were assessed using ITK-SNAP software.A total of 37 patients were included in the analysis, 18.92% achieved a complete response and 56.76% achieved a partial response in PVTT response. The objective response rate (ORR) of PVTT was 75.68%. The 6-month survival rate was 89%, the 1-year survival rate was 66%, and the median OS was 15.8 months. In univariate analysis, Child-Pugh score (P=0.010) was important factor for predicting OS; in multivariate analysis, Child-Pugh score (P=0.015, HR= 3.089, 95%CI: 1.250–7.633) was the important factor for predicting OS. In terms of adverse reactions, the most common adverse reactions associated with HAIC are pain and thrombocytopenia associated with oxaliplatin.FOLFOX-based HAIC combined with TKIs and ICIs induced an objective response rate of 75.68% in PVTT.FOLFOX-based HAIC combined with TKIs and ICIs provides more treatment options for PVTT.
{"title":"Efficacy and safety of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and immune checkpoint inhibitors in the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombosis in the main trunk","authors":"Qi Liu, Ying Zhang, Jingwen Zhang, Luhao Chen, Yi Yang, Yan Liu","doi":"10.3389/fonc.2024.1374149","DOIUrl":"https://doi.org/10.3389/fonc.2024.1374149","url":null,"abstract":"To evaluate the efficacy and safety of mFOLFOX-based hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT)This retrospective study included patients who received mFOLFOX-based HAIC combined with TKIs and ICIs from January 2021 to January 2023. The primary outcome was the objective response rate of PVTT response, and the secondary outcomes were 6-month, 1-year survival rate, overall survival (OS), and corresponding adverse events and complications were also evaluated. PVTT responses were assessed using ITK-SNAP software.A total of 37 patients were included in the analysis, 18.92% achieved a complete response and 56.76% achieved a partial response in PVTT response. The objective response rate (ORR) of PVTT was 75.68%. The 6-month survival rate was 89%, the 1-year survival rate was 66%, and the median OS was 15.8 months. In univariate analysis, Child-Pugh score (P=0.010) was important factor for predicting OS; in multivariate analysis, Child-Pugh score (P=0.015, HR= 3.089, 95%CI: 1.250–7.633) was the important factor for predicting OS. In terms of adverse reactions, the most common adverse reactions associated with HAIC are pain and thrombocytopenia associated with oxaliplatin.FOLFOX-based HAIC combined with TKIs and ICIs induced an objective response rate of 75.68% in PVTT.FOLFOX-based HAIC combined with TKIs and ICIs provides more treatment options for PVTT.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"35 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141649189","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}
Circular RNAs (circRNAs) constitute a class of endogenous non-coding RNAs (ncRNAs) that lack a 5’-ended cap and 3’-ended poly (A) tail and form a closed ring structure with covalent bonds. Due to its special structure, circRNA is resistant to Exonuclease R (RNaseR), making its distribution in the cytoplasm quite rich. Advanced high-throughput sequencing and bioinformatics methods have revealed that circRNA is highly conserved, stable, and disease- and tissue-specific. Furthermore, increasing research has confirmed that circRNA, as a driver or suppressor, regulates cancer onset and progression by modulating a series of pathophysiological mechanisms. As a result, circRNA has emerged as a clinical biomarker and therapeutic intervention target. This article reviews the biological functions and regulatory mechanisms of circRNA in the context of respiratory cancer onset and progression.
{"title":"Roles and mechanisms of circular RNA in respiratory system cancers","authors":"Nan Yang, Mengwen Jiao, Yuewen Zhang, Shaokang Mo, Ling Wang, Jianqing Liang","doi":"10.3389/fonc.2024.1430051","DOIUrl":"https://doi.org/10.3389/fonc.2024.1430051","url":null,"abstract":"Circular RNAs (circRNAs) constitute a class of endogenous non-coding RNAs (ncRNAs) that lack a 5’-ended cap and 3’-ended poly (A) tail and form a closed ring structure with covalent bonds. Due to its special structure, circRNA is resistant to Exonuclease R (RNaseR), making its distribution in the cytoplasm quite rich. Advanced high-throughput sequencing and bioinformatics methods have revealed that circRNA is highly conserved, stable, and disease- and tissue-specific. Furthermore, increasing research has confirmed that circRNA, as a driver or suppressor, regulates cancer onset and progression by modulating a series of pathophysiological mechanisms. As a result, circRNA has emerged as a clinical biomarker and therapeutic intervention target. This article reviews the biological functions and regulatory mechanisms of circRNA in the context of respiratory cancer onset and progression.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"46 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141645054","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 : 2024-07-15DOI: 10.3389/fonc.2024.1376270
Matthew R. Kroll, Cherry Au, Jessica Slostad, Trevor N. Christ, Sam G. Papas, Alan Tan
Nephroblastoma or Wilms’ tumor (WT) is the most common pediatric renal malignancy but rare in adults. Treatment protocols for adults are typically extrapolated from pediatric guidelines, but there are no standard guidelines for adults due to the rarity of the disease. However, next-generation sequencing has led to new therapeutic options for adult WT patients. We present the first case to our knowledge of a recurrent adult WT treated with dual BRAF/MEK–targeted therapy, which showed initial robust clinical response and was well tolerated.
{"title":"Case report: Metastatic BRAF V600E–mutated adult Wilms’ tumor with robust response to BRAF/MEK inhibitor therapy","authors":"Matthew R. Kroll, Cherry Au, Jessica Slostad, Trevor N. Christ, Sam G. Papas, Alan Tan","doi":"10.3389/fonc.2024.1376270","DOIUrl":"https://doi.org/10.3389/fonc.2024.1376270","url":null,"abstract":"Nephroblastoma or Wilms’ tumor (WT) is the most common pediatric renal malignancy but rare in adults. Treatment protocols for adults are typically extrapolated from pediatric guidelines, but there are no standard guidelines for adults due to the rarity of the disease. However, next-generation sequencing has led to new therapeutic options for adult WT patients. We present the first case to our knowledge of a recurrent adult WT treated with dual BRAF/MEK–targeted therapy, which showed initial robust clinical response and was well tolerated.","PeriodicalId":507440,"journal":{"name":"Frontiers in Oncology","volume":"49 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644580","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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