Introduction: Evidence of biliary invasion as a prognostic factor in patients with hepatocellular carcinoma (HCC) is unclear. We aimed to verify the significance of clinically diagnosed biliary involvement in patients with Barcelona Clinic Liver Cancer stage B-C (BCLC B-C) HCC.
Methods: The Korean Liver Cancer Study Group randomly extracted data of patients with HCC enrolled in the Korean Central Cancer Registry between 2011 and 2016 from approximately 50 hospitals nationwide. After excluding records without information regarding serum bilirubin level, alpha-fetoprotein (AFP) level, and Child-Pugh class, a pre-propensity score matching cohort comprising 4,077 patients was included. Considering age, sex, body mass index, viral cause, serum bilirubin level, AFP, Child-Pugh class, tumor size, multiplicity, portal invasion, and extrahepatic metastasis, patients with and without bile duct invasion at initial imaging diagnosis were matched at a ratio of 1:2 from the pre-propensity score matching cohort to form a matched cohort (propensity score matching cohort).
Results: The pre-propensity score matching cohort included 4,077 patients with BCLC B-C and 165 (4.0%) with biliary invasion at diagnosis. Regarding biliary invasion at diagnosis, 1- and 2-year overall survival (OS) rates were 41.2% and 29.1% (with invasion) and 54% and 40.9% (without invasion), respectively (p < 0.0001). Corresponding cancer-specific survival (CSS) rates at 1 and 2 years were 43.4% and 30.7% (with invasion) and 56.6% and 44% (without invasion), respectively (p < 0.0001). Although biliary invasion was a significant factor affecting overall and CSS rates in a univariate analysis, it was not statistically significant in multivariate analyses for overall (p = 0.153) and cancer-specific (p = 0.198) survival rates. The propensity score matching cohort included 165 patients with biliary invasion at diagnosis and 330 without biliary invasion. In the propensity score matching cohort, biliary invasion at diagnosis was not a significant factor affecting overall (p = 0.603) or cancer-specific (p = 0.960) survival rates in the univariate analyses. One- and 2-year OS were 41.2% and 29.1% (with invasion) and 36.1% and 28.2% (without invasion), respectively. The corresponding CSS at one and 2 years were 43.4% and 30.7% (with invasion) and 39.8% and 31.4% (without invasion), respectively. Multivariate analyses revealed that AFP levels, Child-Pugh class, tumor singularity, tumor size, portal invasion, lymph node metastases, and distant metastases significantly affected both overall and CSS rates.
Conclusion: Biliary invasion at diagnosis in patients with BCLC B-C does not affect overall or CSS rates; however, other prognostic factors associated with biliary invasion could have a greater impact.
{"title":"Clinical Significance of Biliary Invasion at Diagnosis in Barcelona Clinic Liver Cancer Stage B-C Hepatocellular Carcinoma: A Nationwide Cohort Analysis in South Korea.","authors":"Chai Hong Rim, Won Sup Yoon, Sunmin Park","doi":"10.1159/000541545","DOIUrl":"10.1159/000541545","url":null,"abstract":"<p><strong>Introduction: </strong>Evidence of biliary invasion as a prognostic factor in patients with hepatocellular carcinoma (HCC) is unclear. We aimed to verify the significance of clinically diagnosed biliary involvement in patients with Barcelona Clinic Liver Cancer stage B-C (BCLC B-C) HCC.</p><p><strong>Methods: </strong>The Korean Liver Cancer Study Group randomly extracted data of patients with HCC enrolled in the Korean Central Cancer Registry between 2011 and 2016 from approximately 50 hospitals nationwide. After excluding records without information regarding serum bilirubin level, alpha-fetoprotein (AFP) level, and Child-Pugh class, a pre-propensity score matching cohort comprising 4,077 patients was included. Considering age, sex, body mass index, viral cause, serum bilirubin level, AFP, Child-Pugh class, tumor size, multiplicity, portal invasion, and extrahepatic metastasis, patients with and without bile duct invasion at initial imaging diagnosis were matched at a ratio of 1:2 from the pre-propensity score matching cohort to form a matched cohort (propensity score matching cohort).</p><p><strong>Results: </strong>The pre-propensity score matching cohort included 4,077 patients with BCLC B-C and 165 (4.0%) with biliary invasion at diagnosis. Regarding biliary invasion at diagnosis, 1- and 2-year overall survival (OS) rates were 41.2% and 29.1% (with invasion) and 54% and 40.9% (without invasion), respectively (p < 0.0001). Corresponding cancer-specific survival (CSS) rates at 1 and 2 years were 43.4% and 30.7% (with invasion) and 56.6% and 44% (without invasion), respectively (p < 0.0001). Although biliary invasion was a significant factor affecting overall and CSS rates in a univariate analysis, it was not statistically significant in multivariate analyses for overall (p = 0.153) and cancer-specific (p = 0.198) survival rates. The propensity score matching cohort included 165 patients with biliary invasion at diagnosis and 330 without biliary invasion. In the propensity score matching cohort, biliary invasion at diagnosis was not a significant factor affecting overall (p = 0.603) or cancer-specific (p = 0.960) survival rates in the univariate analyses. One- and 2-year OS were 41.2% and 29.1% (with invasion) and 36.1% and 28.2% (without invasion), respectively. The corresponding CSS at one and 2 years were 43.4% and 30.7% (with invasion) and 39.8% and 31.4% (without invasion), respectively. Multivariate analyses revealed that AFP levels, Child-Pugh class, tumor singularity, tumor size, portal invasion, lymph node metastases, and distant metastases significantly affected both overall and CSS rates.</p><p><strong>Conclusion: </strong>Biliary invasion at diagnosis in patients with BCLC B-C does not affect overall or CSS rates; however, other prognostic factors associated with biliary invasion could have a greater impact.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"1-13"},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292660","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}
Ahmed A Refae, Rafat I Abu Shakra, Ezzeldin M Ibrahim
Introduction: Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations face poor outcomes after progression on tyrosine kinase inhibitors (TKIs). The efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in these patients remains uncertain.
Methods: We searched for studies published between randomized controlled trials of ICIs in combination therapies in advanced NSCLC patients post-EGFR TKI progression. Data on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were extracted and analyzed.
Results: Six studies with a total of 2,225 patients were analyzed. The pooled hazard ratio (HR) for PFS was 0.60 (95% CI, 0.55-0.65; p < 0.0001), indicating a significant improvement in PFS with ICIs. Subgroup analysis suggested that patients with prior exposure to third-generation TKIs showed a more pronounced benefit (HR = 0.61; 95% CI, 0.49-0.76; p < 0.0001). However, no benefit was found in patients without prior exposure. The efficacy of the experimental interventions was also shown on the pooled estimates of OS (HR = 0.87; 95% CI, 0.77-0.0.99; p value = 0.04) and ORR (OR = 1.91; 95% CI, 1.32-2.76; p < 0.0001).
Conclusion: ICIs may significantly benefit PFS among patients with EGFR-mutated NSCLC who have progressed on TKI treatment. Future research should continue stratifying patients based on prior treatment exposure to optimize therapeutic strategies.
{"title":"Immunotherapy plus Chemotherapy for Patients with EGFR-Mutated Non-Squamous Cell Lung Cancer for Disease Progression after EGFR Tyrosine-Kinase Inhibitor: A Meta-Analysis of Randomized Controlled Trials.","authors":"Ahmed A Refae, Rafat I Abu Shakra, Ezzeldin M Ibrahim","doi":"10.1159/000541415","DOIUrl":"10.1159/000541415","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations face poor outcomes after progression on tyrosine kinase inhibitors (TKIs). The efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in these patients remains uncertain.</p><p><strong>Methods: </strong>We searched for studies published between randomized controlled trials of ICIs in combination therapies in advanced NSCLC patients post-EGFR TKI progression. Data on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were extracted and analyzed.</p><p><strong>Results: </strong>Six studies with a total of 2,225 patients were analyzed. The pooled hazard ratio (HR) for PFS was 0.60 (95% CI, 0.55-0.65; p < 0.0001), indicating a significant improvement in PFS with ICIs. Subgroup analysis suggested that patients with prior exposure to third-generation TKIs showed a more pronounced benefit (HR = 0.61; 95% CI, 0.49-0.76; p < 0.0001). However, no benefit was found in patients without prior exposure. The efficacy of the experimental interventions was also shown on the pooled estimates of OS (HR = 0.87; 95% CI, 0.77-0.0.99; p value = 0.04) and ORR (OR = 1.91; 95% CI, 1.32-2.76; p < 0.0001).</p><p><strong>Conclusion: </strong>ICIs may significantly benefit PFS among patients with EGFR-mutated NSCLC who have progressed on TKI treatment. Future research should continue stratifying patients based on prior treatment exposure to optimize therapeutic strategies.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"1-13"},"PeriodicalIF":2.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292672","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}
Su Ho Kim, Jung Suk Oh, Chang Ho Jeon, Ho Jong Chun, Byung Gil Choi
Introduction: This study aimed to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in 2 groups of patients: those who receive lipiodol (referred to as the lipiodol group) and those who do not receive lipiodol (referred to as the control group).
Methods: From January 2016 through December 2023, 85 patients with advanced hepatocellular carcinoma were enrolled in this retrospective study. In total, 40 patients received HAIC with lipiodol, while 45 patients were given HAIC without lipiodol. The modified response evaluation criteria for solid tumors were used to evaluate the tumor response, which was assessed through an imaging study. The two groups were compared regarding their overall survival (OS), progression-free survival (PFS), and safety.
Results: The outcomes between the lipiodol group and control group demonstrated no significant difference: the objective response rates (p = 0.066) were 32.5% and 15.6%; the disease control rates (p = 0.556) were 67.5% and 73.3%; the median OS times (p = 0.339) were 224 days and 398 days; the median PFS (p = 0.334) times were 191 days and 286 days in the lipiodol group and the control group, respectively. Adverse events also showed no significant difference between the two groups: elevation of total bilirubin (p = 0.834) rates were 40.0% and 37.8%; elevation of alanine aminotransferase (p = 0.191) percentages were 35.0% and 22.2%; and elevation of aspartate aminotransferase values (p = 0.058) were 65.0% and 44.4% in the lipiodol group and the control group, respectively.
Conclusions: HAIC without lipiodol was non-inferior to HAIC with lipiodol in the clinical outcome.
{"title":"Clinical Effects and Safety of Intra-Arterial Infusion Chemotherapy with Lipiodol versus Intra-Arterial Infusion Chemotherapy Alone for Treatment of Advanced Hepatocellular Carcinoma.","authors":"Su Ho Kim, Jung Suk Oh, Chang Ho Jeon, Ho Jong Chun, Byung Gil Choi","doi":"10.1159/000541114","DOIUrl":"10.1159/000541114","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in 2 groups of patients: those who receive lipiodol (referred to as the lipiodol group) and those who do not receive lipiodol (referred to as the control group).</p><p><strong>Methods: </strong>From January 2016 through December 2023, 85 patients with advanced hepatocellular carcinoma were enrolled in this retrospective study. In total, 40 patients received HAIC with lipiodol, while 45 patients were given HAIC without lipiodol. The modified response evaluation criteria for solid tumors were used to evaluate the tumor response, which was assessed through an imaging study. The two groups were compared regarding their overall survival (OS), progression-free survival (PFS), and safety.</p><p><strong>Results: </strong>The outcomes between the lipiodol group and control group demonstrated no significant difference: the objective response rates (p = 0.066) were 32.5% and 15.6%; the disease control rates (p = 0.556) were 67.5% and 73.3%; the median OS times (p = 0.339) were 224 days and 398 days; the median PFS (p = 0.334) times were 191 days and 286 days in the lipiodol group and the control group, respectively. Adverse events also showed no significant difference between the two groups: elevation of total bilirubin (p = 0.834) rates were 40.0% and 37.8%; elevation of alanine aminotransferase (p = 0.191) percentages were 35.0% and 22.2%; and elevation of aspartate aminotransferase values (p = 0.058) were 65.0% and 44.4% in the lipiodol group and the control group, respectively.</p><p><strong>Conclusions: </strong>HAIC without lipiodol was non-inferior to HAIC with lipiodol in the clinical outcome.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"1-8"},"PeriodicalIF":2.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292659","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}
INTRODUCTIONIn atezolizumab plus bevacizumab (Atezo/Bev) combination treatment, both drugs act on the immune system. Previously we reported that immunological changes after Atezo/Bev administration for unresectable hepatocellular carcinoma (uHCC) revealed significant alterations in interleukin (IL)-6, soluble IL-2 receptor, tumor necrosis factor-alpha, and programmed cell death-1 levels. Among these variable factors, serum levels of IL-6 can be easily measured on a commercial baias. Therefore, this study aimed to investigate the utility of serum IL-6 as a predictor of tumor response to Atezo/Bev treatment for uHCC.METHODSThe study included 44 patients with HCC treated with Atezo/Bev. Blood samples were collected before and 3 weeks after treatment, and tumor response was assessed using contrast-enhanced computed tomography 6 weeks after treatment.RESULTSSignificant changes in serum IL-6 levels were observed in patients treated with Atezo/Bev as first-line therapy but not in those treated with it as second line or later-line therapy. In patients treated with Atezo/Bev as first-line therapy, serum IL-6 levels increased significantly after treatment in patients with a complete or partial response but not in patients with stable or progressive disease. Furthermore, compared to other tumor markers such as alpha-fetoprotein, lens culinaris agglutinin-reactive fraction of alpha-fetoprotein, and des-gamma-carboxyprothrombin, serum IL-6 levels exhibited the highest sensitivity in predicting tumor response during the treatment period.CONCLUSIONIn patients with uHCC treated with Atezo/Bev, serum IL-6 levels could serve as a potential predictor of tumor response. Elevated levels after treatment may indicate a favorable tumor response and prognosis.
{"title":"The usefulness of serum interleukin-6 as a predictor of response to atezolizumab plus bevacizumab combination treatment in hepatocellular carcinoma.","authors":"Takanori Mukozu,Hidenari Nagai,Hideki Nagumo,Kunihide Mohri,Naoyuki Yoshimine,Kojiro Kobayashi,Yu Ogino,Teppei Matsui,Yasuko Daido,Noritaka Wakui,Koichi Momiyama,Koji Higai,Takahisa Matsuda,Yoshinori Igarashi","doi":"10.1159/000541372","DOIUrl":"https://doi.org/10.1159/000541372","url":null,"abstract":"INTRODUCTIONIn atezolizumab plus bevacizumab (Atezo/Bev) combination treatment, both drugs act on the immune system. Previously we reported that immunological changes after Atezo/Bev administration for unresectable hepatocellular carcinoma (uHCC) revealed significant alterations in interleukin (IL)-6, soluble IL-2 receptor, tumor necrosis factor-alpha, and programmed cell death-1 levels. Among these variable factors, serum levels of IL-6 can be easily measured on a commercial baias. Therefore, this study aimed to investigate the utility of serum IL-6 as a predictor of tumor response to Atezo/Bev treatment for uHCC.METHODSThe study included 44 patients with HCC treated with Atezo/Bev. Blood samples were collected before and 3 weeks after treatment, and tumor response was assessed using contrast-enhanced computed tomography 6 weeks after treatment.RESULTSSignificant changes in serum IL-6 levels were observed in patients treated with Atezo/Bev as first-line therapy but not in those treated with it as second line or later-line therapy. In patients treated with Atezo/Bev as first-line therapy, serum IL-6 levels increased significantly after treatment in patients with a complete or partial response but not in patients with stable or progressive disease. Furthermore, compared to other tumor markers such as alpha-fetoprotein, lens culinaris agglutinin-reactive fraction of alpha-fetoprotein, and des-gamma-carboxyprothrombin, serum IL-6 levels exhibited the highest sensitivity in predicting tumor response during the treatment period.CONCLUSIONIn patients with uHCC treated with Atezo/Bev, serum IL-6 levels could serve as a potential predictor of tumor response. Elevated levels after treatment may indicate a favorable tumor response and prognosis.","PeriodicalId":19497,"journal":{"name":"Oncology","volume":"43 1","pages":"1-24"},"PeriodicalIF":3.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255258","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}
Background This study aimed to evaluate the clinical impact of skeletal muscle mass and nutritional status in gastric cancer patients treated with nivolumab monotherapy as late-line treatment. Methods We conducted a multi-institutional retrospective study of 90 gastric cancer patients who previously received anti-PD-1 therapy (nivolumab). On computed tomography images captured before nivolumab induction, the skeletal muscle index (SMI, cm2/m2) was defined as the erector muscle area (cm2) divided by the height (m) squared. Patients were divided into two groups: those with SMI-high (n = 45) and those with SMI-low (n = 45). Prognostic nutritional index (PNI) was also calculated before nivolumab induction. The associations of SMI and PNI with response rate (RR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety were analyzed. Results The cutoff values for SMI were determined as 13.45 for males and 10.41 for females. SMI-high was significantly associated with a higher RR (odds ratio = 12.36, p = 0.02) and DCR (odds ratio = 2.97, p = 0.02). Although not significant, PNI-high also tended to be associated with a higher RR. Multivariate analysis showed that SMI-high was independently associated with a higher RR and higher DCR in gastric cancer. Moreover, prognostic analyses revealed that SMI-high (log-rank test p = 0.008) and PNI-high (log-rank test p = 0.0008) were significantly associated with longer OS since nivolumab induction. SMI-high was also associated with longer PFS (log-rank test p = 0.03). There were no significant differences in irAE between SMI-low and SMI-high. Conclusions SMI and PNI were associated with nivolumab efficacy in gastric cancer patients. Management of skeletal muscle loss and nutritional status in gastric cancer patients who will receive nivolumab would be beneficial to enhance survival outcomes.
{"title":"Clinical impact of skeletal muscle mass and nutritional status in patients with recurrent or advanced gastric cancer treated with nivolumab.","authors":"Qingjiang Hu,Kensuke Kudo,Takafumi Yukaya,Hirofumi Hasuda,Ryota Nakanishi,Tomonori Nakanoko,Koji Ando,Mitsuhiko Ota,Yasue Kimura,Tadashi Koga,Tetsuya Kusumoto,Eiji Oki,Tomoharu Yoshizumi","doi":"10.1159/000540840","DOIUrl":"https://doi.org/10.1159/000540840","url":null,"abstract":"Background This study aimed to evaluate the clinical impact of skeletal muscle mass and nutritional status in gastric cancer patients treated with nivolumab monotherapy as late-line treatment. Methods We conducted a multi-institutional retrospective study of 90 gastric cancer patients who previously received anti-PD-1 therapy (nivolumab). On computed tomography images captured before nivolumab induction, the skeletal muscle index (SMI, cm2/m2) was defined as the erector muscle area (cm2) divided by the height (m) squared. Patients were divided into two groups: those with SMI-high (n = 45) and those with SMI-low (n = 45). Prognostic nutritional index (PNI) was also calculated before nivolumab induction. The associations of SMI and PNI with response rate (RR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety were analyzed. Results The cutoff values for SMI were determined as 13.45 for males and 10.41 for females. SMI-high was significantly associated with a higher RR (odds ratio = 12.36, p = 0.02) and DCR (odds ratio = 2.97, p = 0.02). Although not significant, PNI-high also tended to be associated with a higher RR. Multivariate analysis showed that SMI-high was independently associated with a higher RR and higher DCR in gastric cancer. Moreover, prognostic analyses revealed that SMI-high (log-rank test p = 0.008) and PNI-high (log-rank test p = 0.0008) were significantly associated with longer OS since nivolumab induction. SMI-high was also associated with longer PFS (log-rank test p = 0.03). There were no significant differences in irAE between SMI-low and SMI-high. Conclusions SMI and PNI were associated with nivolumab efficacy in gastric cancer patients. Management of skeletal muscle loss and nutritional status in gastric cancer patients who will receive nivolumab would be beneficial to enhance survival outcomes.","PeriodicalId":19497,"journal":{"name":"Oncology","volume":"7 1","pages":"1-17"},"PeriodicalIF":3.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269060","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}
INTRODUCTIONAtezolizumab (ATZ) and bevacizumab (BEV) combination therapy is widely used in patients with unresectable hepatocellular carcinoma (HCC). However, combination therapy is typically interrupted or discontinued owing to BEV-related adverse events. In this study, we examined the effects of BEV dose-reduction on the treatment of unresectable HCC using propensity score matching (PSM).METHODOverall, 119 patients with HCC who were treated with ATZ + BEV between November 2020 and October 2022 were enrolled retrospectively at our institute. The therapeutic effects and safety of BEV dose-reduction and non-dose reduction after PSM were compared. Decision-tree analysis was used to investigate treatment duration in the patients.RESULTSSignificant differences were not observed between the two groups after PSM. The objective response rate (ORR) and disease control rate (DCR) assessed by modified RECIST did not differ significantly between the two groups (BEV non-dose-reduction/dose-reduction: ORR; 46/34%, DCR; 80/91%). Progression-free survival (PFS) and overall survival (OS) also did not differ significantly between the two groups (BEV non-dose-reduction /dose-reduction: PFS; 5.6/8.6 months, OS; 18.6/15.5 months). The median duration of treatment in the BEV dose-reduction group was significantly longer than that in the non-dose-reduction group (BEV non-dose-reduction /dose-reduction: 4.8/9.1 months, P = 0.038). Decision-tree analysis revealed that dose-reduction of BEV was the first distinguishae factor for the extension of treatment duration with ATZ + BEV.CONCLUSIONBEV dose-reduction can be effectively used in maintaining the treatment duration of ATZ + BEV while maintaining therapeutic effects and safety in real-world clinical practice.
{"title":"Dose-reduction of bevacizumab in atezolizumab plus bevacizumab therapy extends treatment duration with disease control in patients with hepatocellular carcinoma.","authors":"Miwa Sakai,Hideki Iwamoto,Shigeo Shimose,Takashi Niizeki,Masahito Nakano,Tomotake Shirono,Yu Noda,Etsuko Moriyama,Hiroyuki Suzuki,Hironori Koga,Ryoko Kuromatsu,Takumi Kawaguchi","doi":"10.1159/000541082","DOIUrl":"https://doi.org/10.1159/000541082","url":null,"abstract":"INTRODUCTIONAtezolizumab (ATZ) and bevacizumab (BEV) combination therapy is widely used in patients with unresectable hepatocellular carcinoma (HCC). However, combination therapy is typically interrupted or discontinued owing to BEV-related adverse events. In this study, we examined the effects of BEV dose-reduction on the treatment of unresectable HCC using propensity score matching (PSM).METHODOverall, 119 patients with HCC who were treated with ATZ + BEV between November 2020 and October 2022 were enrolled retrospectively at our institute. The therapeutic effects and safety of BEV dose-reduction and non-dose reduction after PSM were compared. Decision-tree analysis was used to investigate treatment duration in the patients.RESULTSSignificant differences were not observed between the two groups after PSM. The objective response rate (ORR) and disease control rate (DCR) assessed by modified RECIST did not differ significantly between the two groups (BEV non-dose-reduction/dose-reduction: ORR; 46/34%, DCR; 80/91%). Progression-free survival (PFS) and overall survival (OS) also did not differ significantly between the two groups (BEV non-dose-reduction /dose-reduction: PFS; 5.6/8.6 months, OS; 18.6/15.5 months). The median duration of treatment in the BEV dose-reduction group was significantly longer than that in the non-dose-reduction group (BEV non-dose-reduction /dose-reduction: 4.8/9.1 months, P = 0.038). Decision-tree analysis revealed that dose-reduction of BEV was the first distinguishae factor for the extension of treatment duration with ATZ + BEV.CONCLUSIONBEV dose-reduction can be effectively used in maintaining the treatment duration of ATZ + BEV while maintaining therapeutic effects and safety in real-world clinical practice.","PeriodicalId":19497,"journal":{"name":"Oncology","volume":"70 1","pages":"1-21"},"PeriodicalIF":3.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255261","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}
Sarah Childs,Udit Nindra,Gowri Shivasabesan,Robert Yoon,Sana Haider,Martin Hong,Adam Cooper,Aflah Roohullah,Kate Wilkinson,Wei Chua,Abhijit Pal
Introduction Early phase clinical trials (EPCT) enable access to novel therapies for patients who have exhausted standard of care treatment and contribute a crucial role in drug development and research. Culturally and linguistically diverse (CALD) or socially disadvantaged patients have notably lower rates of participation in these trials. We aimed to characterise the social and cultural demographics of patients enrolled on an EPCT in South Western Sydney. Methods We conducted a 10-year retrospective review of patients enrolled on a EPCT at Liverpool Hospital. CALD patients were defined as those born overseas or whose preferred language was other than English. The patient residential address was used to calculate distance travelled and the Index of Relative Socio-economic advantage and disadvantage (IRSD and IRSAD) scores were calculated and used as a surrogate for socioeconomic status (SES). Results Our study included 233 patients across 39 EPCTs. Ninety-one patients (39%) were identified as CALD. The median IRSD and IRSAD scores were 941 and 944 respectively with 62.7% - 67.4% of patients residing in an area with greater disadvantage compared to the median of Australia. The median distance travelled was 17 kilometres with only 12% of participants travelling more than 50 kilometres. CALD patients were more likely to reside in an area of low SES (OR 3.4, 95% CI 1.8 - 6.5, p<0.01) and travelled shorter median distances (10 vs 23 kilometres) when compared to non-CALD patients. Conclusion Our study cohort contained a lower proportion of CALD patients and a higher SES than what we might have expected from our local population. Furthermore, there was a trend toward greater SES disadvantage (lower IRSD/IRSAD scores) for the CALD population. This study provides novel Australian data to support the underrepresentation of culturally diverse or disadvantaged patients on EPCTs. Future efforts should be made to reduce barriers to participation and improve equity in clinical trial participation.
{"title":"Social characteristics of culturally and linguistically diverse cancer patients enrolled in early phase clinical trials in South-Western Sydney.","authors":"Sarah Childs,Udit Nindra,Gowri Shivasabesan,Robert Yoon,Sana Haider,Martin Hong,Adam Cooper,Aflah Roohullah,Kate Wilkinson,Wei Chua,Abhijit Pal","doi":"10.1159/000540462","DOIUrl":"https://doi.org/10.1159/000540462","url":null,"abstract":"Introduction Early phase clinical trials (EPCT) enable access to novel therapies for patients who have exhausted standard of care treatment and contribute a crucial role in drug development and research. Culturally and linguistically diverse (CALD) or socially disadvantaged patients have notably lower rates of participation in these trials. We aimed to characterise the social and cultural demographics of patients enrolled on an EPCT in South Western Sydney. Methods We conducted a 10-year retrospective review of patients enrolled on a EPCT at Liverpool Hospital. CALD patients were defined as those born overseas or whose preferred language was other than English. The patient residential address was used to calculate distance travelled and the Index of Relative Socio-economic advantage and disadvantage (IRSD and IRSAD) scores were calculated and used as a surrogate for socioeconomic status (SES). Results Our study included 233 patients across 39 EPCTs. Ninety-one patients (39%) were identified as CALD. The median IRSD and IRSAD scores were 941 and 944 respectively with 62.7% - 67.4% of patients residing in an area with greater disadvantage compared to the median of Australia. The median distance travelled was 17 kilometres with only 12% of participants travelling more than 50 kilometres. CALD patients were more likely to reside in an area of low SES (OR 3.4, 95% CI 1.8 - 6.5, p<0.01) and travelled shorter median distances (10 vs 23 kilometres) when compared to non-CALD patients. Conclusion Our study cohort contained a lower proportion of CALD patients and a higher SES than what we might have expected from our local population. Furthermore, there was a trend toward greater SES disadvantage (lower IRSD/IRSAD scores) for the CALD population. This study provides novel Australian data to support the underrepresentation of culturally diverse or disadvantaged patients on EPCTs. Future efforts should be made to reduce barriers to participation and improve equity in clinical trial participation.","PeriodicalId":19497,"journal":{"name":"Oncology","volume":"10 1","pages":"1-12"},"PeriodicalIF":3.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268828","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}
INTRODUCTIONIn this study, we aimed to identify biomarkers for predicting treatment outcomes and efficacy of chemotherapy plus nivolumab, as well as predict immune-related adverse events (irAEs) characteristics of immune checkpoint inhibitors.METHODSThis multicenter study included 104 patients who received chemotherapy plus nivolumab as the primary treatment for unresectable advanced recurrent gastric cancer. Blood test results were collected before the start and after two courses of treatment. The neutrophil-lymphocyte ratio, prognostic nutritional index (PNI), and lactate dehydrogenase/albumin ratio (LAR) were examined after treatment in each case to determine changes compared to values before the start of treatment.RESULTSA total of 57 (54.8%) patients experienced a complete or partial response. The LAR of the stable disease (SD)/progressive disease (PD) group significantly increased (p=0.018). An examination of the presence of grade ≥3 irAEs and changes in related factors showed that the LAR of all patients increased.CONCLUSIONThe LAR was correlated with the best therapeutic response; therefore, it may be a potential biomarker of treatment outcomes and efficacy.
{"title":"Identification of biomarkers for assessing treatment efficacy of chemotherapy plus nivolumab as the first line in patients with unresectable advanced or recurrent gastric cancer: a multicenter study.","authors":"Nobuhiro Nakazawa,Makoto Sohda,Nobuhiro Hosoi,Takayoshi Watanabe,Yuji Kumakura,Toshiki Yamashita,Naritaka Tanaka,Kana Saito,Akiharu Kimura,Kengo Kasuga,Kenji Nakazato,Daisuke Yoshinari,Hisashi Shimizu,Yasunari Ubukata,Hisashi Hosaka,Akihiko Sano,Makoto Sakai,Hiroomi Ogawa,Ken Shirabe,Hiroshi Saeki","doi":"10.1159/000540841","DOIUrl":"https://doi.org/10.1159/000540841","url":null,"abstract":"INTRODUCTIONIn this study, we aimed to identify biomarkers for predicting treatment outcomes and efficacy of chemotherapy plus nivolumab, as well as predict immune-related adverse events (irAEs) characteristics of immune checkpoint inhibitors.METHODSThis multicenter study included 104 patients who received chemotherapy plus nivolumab as the primary treatment for unresectable advanced recurrent gastric cancer. Blood test results were collected before the start and after two courses of treatment. The neutrophil-lymphocyte ratio, prognostic nutritional index (PNI), and lactate dehydrogenase/albumin ratio (LAR) were examined after treatment in each case to determine changes compared to values before the start of treatment.RESULTSA total of 57 (54.8%) patients experienced a complete or partial response. The LAR of the stable disease (SD)/progressive disease (PD) group significantly increased (p=0.018). An examination of the presence of grade ≥3 irAEs and changes in related factors showed that the LAR of all patients increased.CONCLUSIONThe LAR was correlated with the best therapeutic response; therefore, it may be a potential biomarker of treatment outcomes and efficacy.","PeriodicalId":19497,"journal":{"name":"Oncology","volume":"19 1","pages":"1-17"},"PeriodicalIF":3.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255259","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}
Youn Joo Jung,Seungju Lee,Seok Kyeong Kang,Jee Yeon Kim,Ki Seok Choo,Kyung Jin Nam,Ji Hyeon Joo,Jae Joon Kim,Hyun Yul Kim
Introduction Human epidermal growth factor receptor 2 (HER2)-targeted therapies have shown effectiveness against HER2-positive breast cancer. This makes neoadjuvant chemotherapy (NAC) a valuable option for treating both early and advanced stages of the disease. The tumor's response to HER2-targeted NAC provides crucial prognostic information. Additionally, it allows for tailoring adjuvant treatment strategies for HER2+ breast cancer based on pathological responses. This study aimed to investigate the clinicopathological factors that influence tumor response. Methods We retrospectively analyzed 122 patients diagnosed with HER2+ breast cancer. These patients received NAC and HER2-directed therapy between January 2018 and December 2022 at the Pusan National University Yangsan Hospital. Following surgery, tumor response was evaluated, categorizing patients into two groups: pathological complete response (pCR) and non-pCR groups. We analyzed data on various factors, including age, NAC regimen, type of breast and axillary surgery, clinical stage (cTNM), historical grade, and pre-operative levels of carcinoembryonic antigen, cancer antigen 15-3 (CA 15-3), estrogen receptor (ER), progesterone receptor (PR), HER2, p53, and KI-67. Results Out of the 122 patients, 75 achieved pCR, while 47 did not. Most clinicopathological factors showed no significant difference between the pCR and non-pCR groups. However, several factors were associated with a higher pCR rate: normal preoperative CA 15-3 levels (odds ratio [OR]: 3.74, confidence interval [CI]: 1.19-11.72, P = 0.02), preoperative-ER positivity (OR: 2.65, CI: 1.25-5.59, P = 0.01), PR negativity (OR: 3.92, CI: 1.82-8.45, P <0.05), and strong preoperative HER2 immunohistochemistry (IHC) 3+ staining. Multivariate analysis confirmed that PR negativity (OR: 2.8, CI: 1.23-6.42, P = 0.01) and strong preoperative-HER2 IHC 3+ staining (OR: 0.18, CI: 0.03-0.84, P = 0.04) were independent predictors of a higher pCR rate. Conclusions A pCR after NAC impacts patient prognosis and influences the choice of adjuvant treatment for HER2+ breast cancer. Clinicopathological factors can help predict responses to HER2-targeted NAC. In our study, pre-ER/PR negativity, high pre-HER2 levels, and normal CA 15-3 levels were found to be potential predictors of pCR. These findings may contribute to developing more effective treatment strategies for HER2+ breast cancer.
{"title":"Clinicopathological factors predicting pathological complete response to neoadjuvant anti-HER2 therapy in HER2-positive breast cancer.","authors":"Youn Joo Jung,Seungju Lee,Seok Kyeong Kang,Jee Yeon Kim,Ki Seok Choo,Kyung Jin Nam,Ji Hyeon Joo,Jae Joon Kim,Hyun Yul Kim","doi":"10.1159/000541019","DOIUrl":"https://doi.org/10.1159/000541019","url":null,"abstract":"Introduction Human epidermal growth factor receptor 2 (HER2)-targeted therapies have shown effectiveness against HER2-positive breast cancer. This makes neoadjuvant chemotherapy (NAC) a valuable option for treating both early and advanced stages of the disease. The tumor's response to HER2-targeted NAC provides crucial prognostic information. Additionally, it allows for tailoring adjuvant treatment strategies for HER2+ breast cancer based on pathological responses. This study aimed to investigate the clinicopathological factors that influence tumor response. Methods We retrospectively analyzed 122 patients diagnosed with HER2+ breast cancer. These patients received NAC and HER2-directed therapy between January 2018 and December 2022 at the Pusan National University Yangsan Hospital. Following surgery, tumor response was evaluated, categorizing patients into two groups: pathological complete response (pCR) and non-pCR groups. We analyzed data on various factors, including age, NAC regimen, type of breast and axillary surgery, clinical stage (cTNM), historical grade, and pre-operative levels of carcinoembryonic antigen, cancer antigen 15-3 (CA 15-3), estrogen receptor (ER), progesterone receptor (PR), HER2, p53, and KI-67. Results Out of the 122 patients, 75 achieved pCR, while 47 did not. Most clinicopathological factors showed no significant difference between the pCR and non-pCR groups. However, several factors were associated with a higher pCR rate: normal preoperative CA 15-3 levels (odds ratio [OR]: 3.74, confidence interval [CI]: 1.19-11.72, P = 0.02), preoperative-ER positivity (OR: 2.65, CI: 1.25-5.59, P = 0.01), PR negativity (OR: 3.92, CI: 1.82-8.45, P <0.05), and strong preoperative HER2 immunohistochemistry (IHC) 3+ staining. Multivariate analysis confirmed that PR negativity (OR: 2.8, CI: 1.23-6.42, P = 0.01) and strong preoperative-HER2 IHC 3+ staining (OR: 0.18, CI: 0.03-0.84, P = 0.04) were independent predictors of a higher pCR rate. Conclusions A pCR after NAC impacts patient prognosis and influences the choice of adjuvant treatment for HER2+ breast cancer. Clinicopathological factors can help predict responses to HER2-targeted NAC. In our study, pre-ER/PR negativity, high pre-HER2 levels, and normal CA 15-3 levels were found to be potential predictors of pCR. These findings may contribute to developing more effective treatment strategies for HER2+ breast cancer.","PeriodicalId":19497,"journal":{"name":"Oncology","volume":"34 1","pages":"1-16"},"PeriodicalIF":3.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222948","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}
Sean S Kumar,Ninad Khandekar,Komal Dani,Saina R Bhatt,Vinay Duddalwar,Anishka D'Souza
INTRODUCTIONPrevious literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well-studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: Von Hippel-Landau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C (KDM5C). The review compiled genomic diversity data, incidence, and risk factor differences by geographical and racial cohorts.METHODSThe review methodology was created using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) principles from articles on PubMed and Embase through July 31, 2023, written and published in English, with diagnoses of primary or metastatic ccRCC via cytology or pathology, recorded the incidence of one or more of the 6 biomarkers, explored gene aberration via sequencing, were epidemiological in nature; and/or discussed basic science research, cohort studies, or retrospective studies.RESULTSAberrations in vHL, PBRM1, and SETD2 driving ccRCC are studied frequently, but the data is heterogenous; whereas, there is a paucity in the data regarding KDM5C, PBRM1, and mTOR mutations.CONCLUSIONStudying the genetic aberrations that frequently occur in different regions gives insight into what current research lacks. When more genomic landscape research arises, precision therapy, risk calculators, and artificial intelligence may help better prognosticate and individualize treatment for those at risk for ccRCC. Provided the scarcity of existing data, and the rising prevalence of ccRCC, more studies must be conducted at the clinical level.
简介：以往的文献表明，透明细胞肾细胞癌（ccRCC）正成为一种越来越普遍的诊断，其发病率和死亡率在地区和种族上都存在差异。虽然通过活组织检查和测序技术对ccRCC的分子特征进行了区域性研究，但对基因组状况和ccRCC多样性数据的研究还不够深入。我们对 6 种与临床最相关的 ccRCC DNA 生物标记物的已知基因组数据进行了回顾：Von Hippel-Landau (vHL)、Polybromo-1 (PBRM1)、Breast Cancer Gene 1-Associated Protein 1 (BAP1)、Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2)、Mammalian Target of Rapamycin (mTOR) 和 Lysine-Specific Demethylase 5C (KDM5C)。综述汇编了基因组多样性数据、发病率以及不同地域和种族队列的风险因素差异。方法采用系统综述和荟萃分析首选报告项目（Preferred Reporting Items for Systematic Reviews and Meta-Analyses，PRISMA）原则，从PubMed和Embase上截至2023年7月31日用英文撰写和发表的文章中创建综述方法，这些文章通过细胞学或病理学诊断为原发性或转移性ccRCC，记录了6种生物标志物中一种或多种生物标志物的发病率，通过测序探讨了基因畸变，具有流行病学性质；和/或讨论了基础科学研究、队列研究或回顾性研究。结果对驱动ccRCC的vHL、PBRM1和SETD2基因畸变的研究较多，但数据不尽相同；而有关KDM5C、PBRM1和mTOR突变的数据则很少。当出现更多基因组图谱研究时，精准治疗、风险计算器和人工智能可能有助于更好地预测预后，并为ccRCC高危人群提供个体化治疗。鉴于现有数据的匮乏以及 ccRCC 发病率的上升，必须在临床层面开展更多的研究。
{"title":"A Scoping Review of Population Diversity in the Common Genomic Aberrations of Clear Cell Renal Cell Carcinoma.","authors":"Sean S Kumar,Ninad Khandekar,Komal Dani,Saina R Bhatt,Vinay Duddalwar,Anishka D'Souza","doi":"10.1159/000541370","DOIUrl":"https://doi.org/10.1159/000541370","url":null,"abstract":"INTRODUCTIONPrevious literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well-studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: Von Hippel-Landau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C (KDM5C). The review compiled genomic diversity data, incidence, and risk factor differences by geographical and racial cohorts.METHODSThe review methodology was created using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) principles from articles on PubMed and Embase through July 31, 2023, written and published in English, with diagnoses of primary or metastatic ccRCC via cytology or pathology, recorded the incidence of one or more of the 6 biomarkers, explored gene aberration via sequencing, were epidemiological in nature; and/or discussed basic science research, cohort studies, or retrospective studies.RESULTSAberrations in vHL, PBRM1, and SETD2 driving ccRCC are studied frequently, but the data is heterogenous; whereas, there is a paucity in the data regarding KDM5C, PBRM1, and mTOR mutations.CONCLUSIONStudying the genetic aberrations that frequently occur in different regions gives insight into what current research lacks. When more genomic landscape research arises, precision therapy, risk calculators, and artificial intelligence may help better prognosticate and individualize treatment for those at risk for ccRCC. Provided the scarcity of existing data, and the rising prevalence of ccRCC, more studies must be conducted at the clinical level.","PeriodicalId":19497,"journal":{"name":"Oncology","volume":"63 1","pages":"1-15"},"PeriodicalIF":3.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222947","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}
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