Introduction: DNA ploidy (P), stroma fraction (S), and nucleotyping (N) collectively known as PSN, have proven prognostic accuracy in stage II colorectal cancer (CRC). However, few studies have reported on the prognostic value of the PSN panel in stage III colon cancer patients receiving capecitabine and oxaliplatin adjuvant chemotherapy.
Objectives: This study aimed to validate PSN's prognostic impact on stage III colon cancer, identifying candidates for optimized adjuvant chemotherapy duration.
Design: A retrospective analysis was conducted on a cohort of stage III colon cancer patients from April 2008 to June 2020.
Methods: Postoperative pathological samples from stage III colon cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy at Sun Yat-sen University Cancer Center were retrospectively collected. Automated digital imaging assessed PSN, categorizing risk groups. Kaplan-Meier, Cox regression, and time-dependent receiver operating characteristic analysis compared model validity.
Results: Significant differences in 5-year disease-free survival (DFS) and overall survival (OS) were noted among PSN-based low-, moderate-, and high-risk groups (DFS: 92.10% versus 83.62% versus 79.80%, p = 0.029; OS: 96.69% versus 93.99% versus 90.12%, p = 0.016). PSN emerged as an independent prognostic factor for DFS [hazard ratio (HR) = 1.409, 95% confidence interval (CI): 1.002-1.981, p = 0.049] and OS (HR = 1.720, 95% CI: 1.127-2.624, p = 0.012). The PSN model, incorporating perineural invasion and tumor location, displayed superior area under the curve for 5-year (0.692 versus 0.553, p = 0.020) and 10-year (0.694 versus 0.532, p = 0.006) DFS than TNM stage. In the PSN high-risk group, completing eight cycles of adjuvant chemotherapy significantly improved 5-year DFS and OS compared to four to seven cycles (DFS: 89.43% versus 71.52%, p = 0.026; OS: 96.77% versus 85.46%, p = 0.007).
Conclusion: The PSN panel effectively stratifies stage III colon cancer, aiding in optimized adjuvant chemotherapy duration determination.
{"title":"Combination of DNA ploidy, stroma, and nucleotyping predicting prognosis and tailoring adjuvant chemotherapy duration in stage III colon cancer.","authors":"Jianhong Peng, Weili Zhang, Jiahua He, Weifeng Wang, Weihao Li, Lijun Mao, Yuejin Dong, Zhenhai Lu, Zhizhong Pan, Chi Zhou, Xiaojun Wu","doi":"10.1177/17588359241260575","DOIUrl":"10.1177/17588359241260575","url":null,"abstract":"<p><strong>Introduction: </strong>DNA ploidy (P), stroma fraction (S), and nucleotyping (N) collectively known as PSN, have proven prognostic accuracy in stage II colorectal cancer (CRC). However, few studies have reported on the prognostic value of the PSN panel in stage III colon cancer patients receiving capecitabine and oxaliplatin adjuvant chemotherapy.</p><p><strong>Objectives: </strong>This study aimed to validate PSN's prognostic impact on stage III colon cancer, identifying candidates for optimized adjuvant chemotherapy duration.</p><p><strong>Design: </strong>A retrospective analysis was conducted on a cohort of stage III colon cancer patients from April 2008 to June 2020.</p><p><strong>Methods: </strong>Postoperative pathological samples from stage III colon cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy at Sun Yat-sen University Cancer Center were retrospectively collected. Automated digital imaging assessed PSN, categorizing risk groups. Kaplan-Meier, Cox regression, and time-dependent receiver operating characteristic analysis compared model validity.</p><p><strong>Results: </strong>Significant differences in 5-year disease-free survival (DFS) and overall survival (OS) were noted among PSN-based low-, moderate-, and high-risk groups (DFS: 92.10% <i>versus</i> 83.62% <i>versus</i> 79.80%, <i>p</i> = 0.029; OS: 96.69% <i>versus</i> 93.99% <i>versus</i> 90.12%, <i>p</i> = 0.016). PSN emerged as an independent prognostic factor for DFS [hazard ratio (HR) = 1.409, 95% confidence interval (CI): 1.002-1.981, <i>p</i> = 0.049] and OS (HR = 1.720, 95% CI: 1.127-2.624, <i>p</i> = 0.012). The PSN model, incorporating perineural invasion and tumor location, displayed superior area under the curve for 5-year (0.692 <i>versus</i> 0.553, <i>p</i> = 0.020) and 10-year (0.694 <i>versus</i> 0.532, <i>p</i> = 0.006) DFS than TNM stage. In the PSN high-risk group, completing eight cycles of adjuvant chemotherapy significantly improved 5-year DFS and OS compared to four to seven cycles (DFS: 89.43% <i>versus</i> 71.52%, <i>p</i> = 0.026; OS: 96.77% <i>versus</i> 85.46%, <i>p</i> = 0.007).</p><p><strong>Conclusion: </strong>The PSN panel effectively stratifies stage III colon cancer, aiding in optimized adjuvant chemotherapy duration determination.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11185039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Age is a known prognostic factor for various cancers. However, few studies explored the association between age and prognosis of esophageal cancer (EC) comprehensively, especially from a nonlinear perspective.
Design: Retrospective cohort study.
Objectives: Our study aims to explore the possible nonlinear associations between age and prognosis in EC patients receiving curative surgery and radiotherapy, respectively.
Methods: Cox regression models with restricted cubic splines were used to model the possible nonlinear relationship between age and prognosis in surgical and radiotherapy groups, respectively. Surveillance, Epidemiology, and End Results database was used to validate the age-prognosis patterns found in Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group database. Age-prognosis patterns were further validated by survival comparisons between different age subgroups and in subsequent sensitivity and subgroup analyses. Primary endpoint is overall survival. Secondary endpoints are cancer-specific survival and progression-free survival.
Results: A total of 56,457 patients from two large cancer databases were included. Patients receiving surgery and radiotherapy showed two distinct nonlinear age-prognosis patterns. Age showed a U-/J-shaped association with prognosis in the radiotherapy group, with a nadir at approximately 65- to 70-years-old. As for surgical cohort, relative risk for all-cause mortality and cancer-specific mortality increased with age with p for nonlinearity <0.05. The above age-prognosis relationships were validated by sensitivity, subgroup, and comparative survival analyses. Youngest and middle-aged patients showed better survival results compared to that of other age subgroups in surgical and radiotherapy cohorts, respectively [Radiotherapy, youngest/middle: hazard ratio (HR) = 1.06, 95% confidence interval (CI): 1.02-1.10, p = 0.001; Radiotherapy, oldest/middle: HR = 1.21, 95% CI: 1.18-1.24, p < 0.001; Surgical, middle/youngest: HR = 1.19, 95% CI: 1.14-1.25, p < 0.001; surgical, oldest/youngest: HR = 1.85, 95% CI: 1.75-1.97, p < 0.001].
Conclusion: Patients receiving surgery and radiotherapy showed two distinct age-prognosis patterns. Younger and middle-aged patients were associated with better survival in surgical and radiotherapy groups, respectively. Additional studies are warranted to explore the underlying mechanisms and clinical implications of this phenomenon.
背景:众所周知,年龄是各种癌症的预后因素之一。然而,很少有研究全面探讨年龄与食管癌(EC)预后之间的关系,尤其是从非线性角度进行探讨:设计:回顾性队列研究:我们的研究旨在探讨分别接受根治性手术和放射治疗的食管癌患者的年龄与预后之间可能存在的非线性关系:方法:使用带限制性三次样条的 Cox 回归模型分别模拟手术组和放疗组患者年龄与预后之间可能存在的非线性关系。监测、流行病学和最终结果数据库用于验证京津冀食管癌和食管胃癌放疗肿瘤学组数据库中发现的年龄-预后模式。不同年龄亚组之间的生存期比较以及随后的敏感性和亚组分析进一步验证了年龄-预后模式。主要终点是总生存期。次要终点是癌症特异性生存期和无进展生存期:两个大型癌症数据库共纳入了 56 457 名患者。接受手术和放疗的患者呈现出两种不同的非线性年龄-预后模式。放疗组患者的年龄与预后呈 U/J 型关系,在 65 至 70 岁左右达到最低点。至于手术组,全因死亡率和癌症特异性死亡率的相对风险随着年龄的增长而增加,非线性 p = 0.001;放疗组,最年长者/中间年龄:HR = 1.21,95% CI:1.18-1.24,p p p 结论:接受手术和放疗的患者呈现出两种不同的年龄预后模式。年轻和中年患者分别与手术组和放疗组较好的生存率相关。有必要进行更多的研究来探讨这一现象的内在机制和临床意义。
{"title":"Two distinct age-prognosis patterns in patients with esophageal cancer undergoing surgical and radiotherapy treatments: a combined analysis of 3JECROG and SEER databases.","authors":"Chen Li, Xiao Chang, Qifeng Wang, Qingsong Pang, Zefen Xiao, Wencheng Zhang, Zhiyong Yuan","doi":"10.1177/17588359241261009","DOIUrl":"10.1177/17588359241261009","url":null,"abstract":"<p><strong>Background: </strong>Age is a known prognostic factor for various cancers. However, few studies explored the association between age and prognosis of esophageal cancer (EC) comprehensively, especially from a nonlinear perspective.</p><p><strong>Design: </strong>Retrospective cohort study.</p><p><strong>Objectives: </strong>Our study aims to explore the possible nonlinear associations between age and prognosis in EC patients receiving curative surgery and radiotherapy, respectively.</p><p><strong>Methods: </strong>Cox regression models with restricted cubic splines were used to model the possible nonlinear relationship between age and prognosis in surgical and radiotherapy groups, respectively. Surveillance, Epidemiology, and End Results database was used to validate the age-prognosis patterns found in Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group database. Age-prognosis patterns were further validated by survival comparisons between different age subgroups and in subsequent sensitivity and subgroup analyses. Primary endpoint is overall survival. Secondary endpoints are cancer-specific survival and progression-free survival.</p><p><strong>Results: </strong>A total of 56,457 patients from two large cancer databases were included. Patients receiving surgery and radiotherapy showed two distinct nonlinear age-prognosis patterns. Age showed a U-/J-shaped association with prognosis in the radiotherapy group, with a nadir at approximately 65- to 70-years-old. As for surgical cohort, relative risk for all-cause mortality and cancer-specific mortality increased with age with <i>p</i> for nonlinearity <0.05. The above age-prognosis relationships were validated by sensitivity, subgroup, and comparative survival analyses. Youngest and middle-aged patients showed better survival results compared to that of other age subgroups in surgical and radiotherapy cohorts, respectively [Radiotherapy, youngest/middle: hazard ratio (HR) = 1.06, 95% confidence interval (CI): 1.02-1.10, <i>p</i> = 0.001; Radiotherapy, oldest/middle: HR = 1.21, 95% CI: 1.18-1.24, <i>p</i> < 0.001; Surgical, middle/youngest: HR = 1.19, 95% CI: 1.14-1.25, <i>p</i> < 0.001; surgical, oldest/youngest: HR = 1.85, 95% CI: 1.75-1.97, <i>p</i> < 0.001].</p><p><strong>Conclusion: </strong>Patients receiving surgery and radiotherapy showed two distinct age-prognosis patterns. Younger and middle-aged patients were associated with better survival in surgical and radiotherapy groups, respectively. Additional studies are warranted to explore the underlying mechanisms and clinical implications of this phenomenon.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-14eCollection Date: 2024-01-01DOI: 10.1177/17588359241260985
Shukui Qin, Yusheng Wang, Jun Yao, Yanyan Liu, Tienan Yi, Yueyin Pan, Zhendong Chen, Xizhi Zhang, Jin Lu, Junyan Yu, Yanjun Zhang, Peng Cheng, Yong Mao, Jian Zhang, Meiyu Fang, Yanming Zhang, Jing Lv, Runzi Li, Ning Dou, Qian Tang, Jun Ma
Background: Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis.
Objectives: This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors.
Design: A multicenter, randomized, double-blind, placebo-controlled, phase II study.
Methods: Patients with advanced solid tumors who experienced a chemotherapy delay of ⩾7 days due to thrombocytopenia (platelet count <75 × 109/L) were randomly assigned (1:1) to receive oral hetrombopag at an initial dose of 7.5 mg once daily or a matching placebo. The primary endpoint was the proportion of treatment responders, defined as patients resuming chemotherapy within 14 days (platelet count ⩾100 × 109/L) and not requiring a chemotherapy dose reduction of ⩾15% or a delay of ⩾4 days or rescue therapy for two consecutive cycles.
Results: Between 9 October 2021 and 5 May 2022, 60 patients were randomized, with 59 receiving ⩾1 dose of assigned treatment (hetrombopag/placebo arm, n = 28/31). The proportion of treatment responders was significantly higher in the hetrombopag arm than in the placebo arm [60.7% (17/28) versus 12.9% (4/31); difference of proportion: 47.6% (95% confidence interval (CI): 26.0-69.3); odds ratio = 10.44 (95% CI: 2.82-38.65); p value (nominal) based on the Cochran-Mantel-Haenszel: <0.001)]. During the double-blind treatment period, grade 3 or higher adverse events (AEs) occurred in 35.7% (10/28) of patients with hetrombopag and 38.7% (12/31) of patients on placebo. The most common grade 3 or higher AEs were decreased neutrophil count [35.7% (10/28) versus 35.5% (11/31)] and decreased white blood cell count [17.9% (5/28) versus 19.4% (6/31)]. Serious AEs were reported in 3.6% (1/28) of patients with hetrombopag and 9.7% (3/31) of patients with placebo.
Conclusion: Hetrombopag is an effective and well-tolerated alternative for managing CIT in patients with solid tumors.
{"title":"Hetrombopag for the management of chemotherapy-induced thrombocytopenia in patients with advanced solid tumors: a multicenter, randomized, double-blind, placebo-controlled, phase II study.","authors":"Shukui Qin, Yusheng Wang, Jun Yao, Yanyan Liu, Tienan Yi, Yueyin Pan, Zhendong Chen, Xizhi Zhang, Jin Lu, Junyan Yu, Yanjun Zhang, Peng Cheng, Yong Mao, Jian Zhang, Meiyu Fang, Yanming Zhang, Jing Lv, Runzi Li, Ning Dou, Qian Tang, Jun Ma","doi":"10.1177/17588359241260985","DOIUrl":"10.1177/17588359241260985","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis.</p><p><strong>Objectives: </strong>This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors.</p><p><strong>Design: </strong>A multicenter, randomized, double-blind, placebo-controlled, phase II study.</p><p><strong>Methods: </strong>Patients with advanced solid tumors who experienced a chemotherapy delay of ⩾7 days due to thrombocytopenia (platelet count <75 × 10<sup>9</sup>/L) were randomly assigned (1:1) to receive oral hetrombopag at an initial dose of 7.5 mg once daily or a matching placebo. The primary endpoint was the proportion of treatment responders, defined as patients resuming chemotherapy within 14 days (platelet count ⩾100 × 10<sup>9</sup>/L) and not requiring a chemotherapy dose reduction of ⩾15% or a delay of ⩾4 days or rescue therapy for two consecutive cycles.</p><p><strong>Results: </strong>Between 9 October 2021 and 5 May 2022, 60 patients were randomized, with 59 receiving ⩾1 dose of assigned treatment (hetrombopag/placebo arm, <i>n</i> = 28/31). The proportion of treatment responders was significantly higher in the hetrombopag arm than in the placebo arm [60.7% (17/28) <i>versus</i> 12.9% (4/31); difference of proportion: 47.6% (95% confidence interval (CI): 26.0-69.3); odds ratio = 10.44 (95% CI: 2.82-38.65); <i>p</i> value (nominal) based on the Cochran-Mantel-Haenszel: <0.001)]. During the double-blind treatment period, grade 3 or higher adverse events (AEs) occurred in 35.7% (10/28) of patients with hetrombopag and 38.7% (12/31) of patients on placebo. The most common grade 3 or higher AEs were decreased neutrophil count [35.7% (10/28) <i>versus</i> 35.5% (11/31)] and decreased white blood cell count [17.9% (5/28) <i>versus</i> 19.4% (6/31)]. Serious AEs were reported in 3.6% (1/28) of patients with hetrombopag and 9.7% (3/31) of patients with placebo.</p><p><strong>Conclusion: </strong>Hetrombopag is an effective and well-tolerated alternative for managing CIT in patients with solid tumors.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03976882.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-13eCollection Date: 2024-01-01DOI: 10.1177/17588359241249602
Lorenzo Gervaso, Davide Ciardiello, Giuliana Gregato, Lorenzo Guidi, Carmine Valenza, Liliana Ascione, Laura Boldrini, Samuele Frassoni, Chiara Alessandra Cella, Francesca Spada, Luigi Funicelli, Giuseppe De Roberto, Wanda Petz, Simona Borin, Marianna Alessandra Gerardi, Luca Bottiglieri, Darina Tamayo, Emilio Bertani, Uberto Fumagalli Romario, Vincenzo Bagnardi, Giuseppe Curigliano, Francesco Bertolini, Nicola Fazio, Maria Giulia Zampino
Background: The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy.
Objectives: We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes.
Design: Between November 2014 and November 2019, we conducted a monocentric prospective observational study enrolling consecutive patients with LARC managed with neoadjuvant standard CRT (capecitabine and concomitant pelvic long-course radiotherapy), followed by consolidation capecitabine in selected cases and surgery.
Methods: Blood samples for ctDNA were obtained at pre-planned timepoints. We evaluated the correlation of baseline variant allele frequency (VAF) with pathologic complete response (pCR) down-staging, node regression (pN0), event-free survival (EFS), and overall survival (OS).
Results: Among 112 screened patients, 61 were enrolled. In all, 38 (62%) had a positive ctDNA at baseline with VAF > 0 and 23 had negative ctDNA (VAF = 0). Among patients with negative ctDNA, 30% had a complete response, while only 13% of positive ctDNA patients had pCR [odds ratio (OR) 0.35 (95% confidence interval (CI): 0.10-1.26), p = 0.11]. Similarly, 96% and 74% of pN0 were observed among negative and positive ctDNA patients, respectively [OR 0.13 (95% CI: 0.02-1.07), p = 0.058]. The presence of a baseline VAF > 0 was associated with a trend toward a lower EFS compared with VAF = 0 patients [hazard ratio (HR) = 2.30, 95% CI: 0.63-8.36, p = 0.21]. Within the limitations of small sample size, no difference in OS was observed according to the baseline ctDNA status (HR = 1.18, 95% CI: 0.35-4.06, p = 0.79).
Conclusion: Within the limitations of a reduced number of patients, patients with baseline negative ctDNA seem to show a higher probability of pN0 status and a trend toward improved EFS. Prospective translational studies are required to define the role of ctDNA analysis in the multimodal treatment of LARC.
{"title":"Circulating tumor DNA in patients with locally advanced rectal cancer treated with multimodal treatment.","authors":"Lorenzo Gervaso, Davide Ciardiello, Giuliana Gregato, Lorenzo Guidi, Carmine Valenza, Liliana Ascione, Laura Boldrini, Samuele Frassoni, Chiara Alessandra Cella, Francesca Spada, Luigi Funicelli, Giuseppe De Roberto, Wanda Petz, Simona Borin, Marianna Alessandra Gerardi, Luca Bottiglieri, Darina Tamayo, Emilio Bertani, Uberto Fumagalli Romario, Vincenzo Bagnardi, Giuseppe Curigliano, Francesco Bertolini, Nicola Fazio, Maria Giulia Zampino","doi":"10.1177/17588359241249602","DOIUrl":"10.1177/17588359241249602","url":null,"abstract":"<p><strong>Background: </strong>The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy.</p><p><strong>Objectives: </strong>We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes.</p><p><strong>Design: </strong>Between November 2014 and November 2019, we conducted a monocentric prospective observational study enrolling consecutive patients with LARC managed with neoadjuvant standard CRT (capecitabine and concomitant pelvic long-course radiotherapy), followed by consolidation capecitabine in selected cases and surgery.</p><p><strong>Methods: </strong>Blood samples for ctDNA were obtained at pre-planned timepoints. We evaluated the correlation of baseline variant allele frequency (VAF) with pathologic complete response (pCR) down-staging, node regression (pN0), event-free survival (EFS), and overall survival (OS).</p><p><strong>Results: </strong>Among 112 screened patients, 61 were enrolled. In all, 38 (62%) had a positive ctDNA at baseline with VAF > 0 and 23 had negative ctDNA (VAF = 0). Among patients with negative ctDNA, 30% had a complete response, while only 13% of positive ctDNA patients had pCR [odds ratio (OR) 0.35 (95% confidence interval (CI): 0.10-1.26), <i>p</i> = 0.11]. Similarly, 96% and 74% of pN0 were observed among negative and positive ctDNA patients, respectively [OR 0.13 (95% CI: 0.02-1.07), <i>p</i> = 0.058]. The presence of a baseline VAF > 0 was associated with a trend toward a lower EFS compared with VAF = 0 patients [hazard ratio (HR) = 2.30, 95% CI: 0.63-8.36, <i>p</i> = 0.21]. Within the limitations of small sample size, no difference in OS was observed according to the baseline ctDNA status (HR = 1.18, 95% CI: 0.35-4.06, <i>p</i> = 0.79).</p><p><strong>Conclusion: </strong>Within the limitations of a reduced number of patients, patients with baseline negative ctDNA seem to show a higher probability of pN0 status and a trend toward improved EFS. Prospective translational studies are required to define the role of ctDNA analysis in the multimodal treatment of LARC.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Adjuvant therapy is used to reduce the risk of hepatocellular carcinoma (HCC) recurrence and improve patient prognosis. Exploration of treatment strategies that are both efficacious and safe has been extensively performed in the recent years. Although donafenib has demonstrated good efficacy in the treatment of advanced HCC, its use as adjuvant therapy in HCC has not been reported.
Objectives: To investigate the efficacy and safety of postoperative adjuvant donafenib treatment in patients with HCC at high-risk of recurrence.
Design: Retrospective study.
Methods: A total of 196 patients with HCC at high-risk of recurrence were included in this study. Of these, 49 received adjuvant donafenib treatment, while 147 did not. Survival outcomes and incidence of adverse events (AEs) in the donafenib-treated group were compared. Inverse probability of treatment weighting (IPTW) method was used.
Results: The median follow-up duration was 21.8 months [interquartile range (IQR) 17.2-27.1]. Before IPTW, the donafenib-treated group exhibited a significantly higher 1-year recurrence-free survival (RFS) rate (83.7% versus 66.7%, p = 0.023) than the control group. Contrarily, no significant difference was observed in the 1-year overall survival (OS) rates between the two groups (97.8% versus 91.8%, p = 0.120). After IPTW, the 1-year RFS and OS rates (86.6% versus 64.8%, p = 0.004; 97.9% versus 89.5%, p = 0.043, respectively) were higher than those in the control group. Multivariate analysis revealed that postoperative adjuvant donafenib treatment was an independent protective factor for RFS. The median duration of adjuvant donafenib treatment was 13.6 (IQR, 10.7-18.1) months, with 44 patients (89.8%) experienced AEs, primarily grade 1-2 AEs.
Conclusion: Postoperative adjuvant donafenib treatment effectively reduced early recurrence among patients with HCC at high-risk of recurrence, while exhibiting favorable safety and tolerability profile. However, these findings warrant further investigation.
{"title":"Adjuvant donafenib for hepatocellular carcinoma patients at high-risk of recurrence after radical resection: a real-world experience.","authors":"Shenyu Zhang, Guibin Yang, Ruipeng Song, Wei Wang, Fanzheng Meng, Dalong Yin, Jiabei Wang, Shugeng Zhang, Wei Cai, Yao Liu, Dayong Luo, Jizhou Wang, Lianxin Liu","doi":"10.1177/17588359241258394","DOIUrl":"10.1177/17588359241258394","url":null,"abstract":"<p><strong>Background: </strong>Adjuvant therapy is used to reduce the risk of hepatocellular carcinoma (HCC) recurrence and improve patient prognosis. Exploration of treatment strategies that are both efficacious and safe has been extensively performed in the recent years. Although donafenib has demonstrated good efficacy in the treatment of advanced HCC, its use as adjuvant therapy in HCC has not been reported.</p><p><strong>Objectives: </strong>To investigate the efficacy and safety of postoperative adjuvant donafenib treatment in patients with HCC at high-risk of recurrence.</p><p><strong>Design: </strong>Retrospective study.</p><p><strong>Methods: </strong>A total of 196 patients with HCC at high-risk of recurrence were included in this study. Of these, 49 received adjuvant donafenib treatment, while 147 did not. Survival outcomes and incidence of adverse events (AEs) in the donafenib-treated group were compared. Inverse probability of treatment weighting (IPTW) method was used.</p><p><strong>Results: </strong>The median follow-up duration was 21.8 months [interquartile range (IQR) 17.2-27.1]. Before IPTW, the donafenib-treated group exhibited a significantly higher 1-year recurrence-free survival (RFS) rate (83.7% <i>versus</i> 66.7%, <i>p</i> = 0.023) than the control group. Contrarily, no significant difference was observed in the 1-year overall survival (OS) rates between the two groups (97.8% <i>versus</i> 91.8%, <i>p</i> = 0.120). After IPTW, the 1-year RFS and OS rates (86.6% <i>versus</i> 64.8%, <i>p</i> = 0.004; 97.9% <i>versus</i> 89.5%, <i>p</i> = 0.043, respectively) were higher than those in the control group. Multivariate analysis revealed that postoperative adjuvant donafenib treatment was an independent protective factor for RFS. The median duration of adjuvant donafenib treatment was 13.6 (IQR, 10.7-18.1) months, with 44 patients (89.8%) experienced AEs, primarily grade 1-2 AEs.</p><p><strong>Conclusion: </strong>Postoperative adjuvant donafenib treatment effectively reduced early recurrence among patients with HCC at high-risk of recurrence, while exhibiting favorable safety and tolerability profile. However, these findings warrant further investigation.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-12eCollection Date: 2024-01-01DOI: 10.1177/17588359241255174
Italo Fernandes, Rania Chehade, Helen MacKay
Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have transformed the treatment of ovarian cancer, particularly benefiting patients whose tumors harbor genomic events that result in impaired homologous recombination (HR) repair. The use of PARPi over recent years has expanded to include subpopulations of patients with breast, pancreatic, and prostate cancers. Their potential to benefit patients with non-ovarian gynecologic cancers is being recognized. This review examines the underlying biological rationale for exploring PARPi in non-ovarian gynecologic cancers. We consider the clinical data and place this in the context of the current treatment landscape. We review the development of PARPi strategies for treating patients with endometrial, cervical, uterine leiomyosarcoma, and vulvar cancers. Furthermore, we discuss future directions and the importance of understanding HR deficiency in the context of each cancer type.
{"title":"PARP inhibitors in non-ovarian gynecologic cancers.","authors":"Italo Fernandes, Rania Chehade, Helen MacKay","doi":"10.1177/17588359241255174","DOIUrl":"10.1177/17588359241255174","url":null,"abstract":"<p><p>Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have transformed the treatment of ovarian cancer, particularly benefiting patients whose tumors harbor genomic events that result in impaired homologous recombination (HR) repair. The use of PARPi over recent years has expanded to include subpopulations of patients with breast, pancreatic, and prostate cancers. Their potential to benefit patients with non-ovarian gynecologic cancers is being recognized. This review examines the underlying biological rationale for exploring PARPi in non-ovarian gynecologic cancers. We consider the clinical data and place this in the context of the current treatment landscape. We review the development of PARPi strategies for treating patients with endometrial, cervical, uterine leiomyosarcoma, and vulvar cancers. Furthermore, we discuss future directions and the importance of understanding HR deficiency in the context of each cancer type.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-12eCollection Date: 2024-01-01DOI: 10.1177/17588359241259635
Amaury Demaziere, Charline Mourgues, Céline Lambert, Sophie Trevis, Hélène Bertucat, Isabelle Grange, Denis Pezet, Valérie Sautou, Marine Jary, Johan Gagnière
Context: In France, gemcitabine plus nab-paclitaxel (GEM-NAB) is heterogeneously used in metastatic pancreatic cancer due to disparities in its financial accessibility in the institutions.
Objectives: GEM-NAB conduct a French multi-institutional cost-effectiveness analysis of GEM-NAB versus gemcitabine alone (GEM) as second-line treatment in pancreatic cancer patients.
Design: All the unresected metastatic pancreatic ductal adenocarcinoma (PDAC) consecutive patients who received GEM-NAB (institution 1) or GEM alone (institutions 2 and 3) as second-line treatment after failure of a 5-fluorouracil based systemic chemotherapy regimen were screened.
Methods: This study was conducted from the French national healthcare insurance perspective. The primary endpoint was the overall survival (OS) expressed in months, calculated from the date of the first second-line chemotherapy administration to death. Only direct (medical and non-medical) costs have been considered for this analysis. Data were collected retrospectively in one university hospital and two general hospitals.
Results: The OS was significantly improved in patients receiving GEM-NAB (hazard ratio: 0.54, 95% confidence interval: 0.38-0.77, p = 0.001), with a median OS of 6.2 months (versus 4.1 months in patients receiving GEM alone). Taking into account the cost of GEM-NAB which was afforded by each institution, the incremental cost-effectiveness ratio was €1,449,231 by year of life (€40,256 per patient). In both groups, most of the costs were attributable to readmissions and outpatient chemotherapy administration.
Conclusion: The issues of the article is based on the trade-off between the benefit in terms of OS of patients treated with GEM-NAB, which is minor (a gain of 2 months of survival, with an accumulated rate of grade ⩾ 3 non-hematological adverse effects) and the additional institutional cost (€25k per year of life for each patient treated). The debate is complex and refers to an ethical component, which is the cost of human life when no other therapeutic alternative is offered to the patient.
{"title":"French multi-institutional cost-effectiveness analysis of gemcitabine plus nab-paclitaxel <i>versus</i> gemcitabine alone as second-line treatment in metastatic pancreatic cancer patients.","authors":"Amaury Demaziere, Charline Mourgues, Céline Lambert, Sophie Trevis, Hélène Bertucat, Isabelle Grange, Denis Pezet, Valérie Sautou, Marine Jary, Johan Gagnière","doi":"10.1177/17588359241259635","DOIUrl":"10.1177/17588359241259635","url":null,"abstract":"<p><strong>Context: </strong>In France, gemcitabine plus nab-paclitaxel (GEM-NAB) is heterogeneously used in metastatic pancreatic cancer due to disparities in its financial accessibility in the institutions.</p><p><strong>Objectives: </strong>GEM-NAB conduct a French multi-institutional cost-effectiveness analysis of GEM-NAB <i>versus</i> gemcitabine alone (GEM) as second-line treatment in pancreatic cancer patients.</p><p><strong>Design: </strong>All the unresected metastatic pancreatic ductal adenocarcinoma (PDAC) consecutive patients who received GEM-NAB (institution 1) or GEM alone (institutions 2 and 3) as second-line treatment after failure of a 5-fluorouracil based systemic chemotherapy regimen were screened.</p><p><strong>Methods: </strong>This study was conducted from the French national healthcare insurance perspective. The primary endpoint was the overall survival (OS) expressed in months, calculated from the date of the first second-line chemotherapy administration to death. Only direct (medical and non-medical) costs have been considered for this analysis. Data were collected retrospectively in one university hospital and two general hospitals.</p><p><strong>Results: </strong>The OS was significantly improved in patients receiving GEM-NAB (hazard ratio: 0.54, 95% confidence interval: 0.38-0.77, <i>p</i> = 0.001), with a median OS of 6.2 months (<i>versus</i> 4.1 months in patients receiving GEM alone). Taking into account the cost of GEM-NAB which was afforded by each institution, the incremental cost-effectiveness ratio was €1,449,231 by year of life (€40,256 per patient). In both groups, most of the costs were attributable to readmissions and outpatient chemotherapy administration.</p><p><strong>Conclusion: </strong>The issues of the article is based on the trade-off between the benefit in terms of OS of patients treated with GEM-NAB, which is minor (a gain of 2 months of survival, with an accumulated rate of grade ⩾ 3 non-hematological adverse effects) and the additional institutional cost (€25k per year of life for each patient treated). The debate is complex and refers to an ethical component, which is the cost of human life when no other therapeutic alternative is offered to the patient.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05eCollection Date: 2024-01-01DOI: 10.1177/17588359241258440
Alix Riescher-Tuczkiewicz, Jules Grégory, Frederic Bert, Magaly Zappa, Anna Pellat, Valerie Lalande, Claire Gallois, Jean-Luc Mainardi, Jean-Baptiste Bachet, Jérôme Robert, Anne Sophie Bourrel, Romain Coriat, Dominique Thabut, Pascal Hammel, Vinciane Rebours, Diane Lorenzo
Background: Bacterial peritonitis (BP) in patients with gastrointestinal (GI) cancer has been poorly described, and its prevalence is unknown.
Objectives: This study aimed to evaluate in patients with both GI cancer and ascites the prevalence of BP, associated features, mechanisms, prognosis, and the diagnostic performance of neutrophil count in ascites.
Design: A retrospective, multicenter, observational study.
Methods: All patients with GI cancer and ascites who underwent at least one paracentesis sample analyzed for bacteriology over a 1-year period were included. BP was defined by a positive ascites culture combined with clinical and/or biological signs compatible with infection. Secondary BP was defined as BP related to a direct intra-abdominal infectious source.
Results: Five hundred fifty-seven ascites from 208 patients included were analyzed. Twenty-eight patients had at least one episode of BP and the annual prevalence rate of BP was 14%. Among the 28 patients with BP, 19 (65%) patients had proven secondary BP and 17 (59%) patients had multi-microbial BP, mainly due to Enterobacterales. A neutrophil count greater than 110/mm3 in ascites had negative and positive predictive values of 96% and 39%, respectively, for the diagnosis of BP. The median survival of patients with BP was 10 days (interquartile range 6-40) after the diagnosis.
Conclusion: BP is not rare in patients with GI cancer and is associated with a poor short-term prognosis. When a patient with GI cancer is diagnosed with BP, a secondary cause should be sought. Further studies are needed to better define the best management of these patients.
{"title":"Diagnosis and treatment of bacterial peritonitis in patients with gastrointestinal cancer: an observational multicenter study.","authors":"Alix Riescher-Tuczkiewicz, Jules Grégory, Frederic Bert, Magaly Zappa, Anna Pellat, Valerie Lalande, Claire Gallois, Jean-Luc Mainardi, Jean-Baptiste Bachet, Jérôme Robert, Anne Sophie Bourrel, Romain Coriat, Dominique Thabut, Pascal Hammel, Vinciane Rebours, Diane Lorenzo","doi":"10.1177/17588359241258440","DOIUrl":"10.1177/17588359241258440","url":null,"abstract":"<p><strong>Background: </strong>Bacterial peritonitis (BP) in patients with gastrointestinal (GI) cancer has been poorly described, and its prevalence is unknown.</p><p><strong>Objectives: </strong>This study aimed to evaluate in patients with both GI cancer and ascites the prevalence of BP, associated features, mechanisms, prognosis, and the diagnostic performance of neutrophil count in ascites.</p><p><strong>Design: </strong>A retrospective, multicenter, observational study.</p><p><strong>Methods: </strong>All patients with GI cancer and ascites who underwent at least one paracentesis sample analyzed for bacteriology over a 1-year period were included. BP was defined by a positive ascites culture combined with clinical and/or biological signs compatible with infection. Secondary BP was defined as BP related to a direct intra-abdominal infectious source.</p><p><strong>Results: </strong>Five hundred fifty-seven ascites from 208 patients included were analyzed. Twenty-eight patients had at least one episode of BP and the annual prevalence rate of BP was 14%. Among the 28 patients with BP, 19 (65%) patients had proven secondary BP and 17 (59%) patients had multi-microbial BP, mainly due to <i>Enterobacterales</i>. A neutrophil count greater than 110/mm<sup>3</sup> in ascites had negative and positive predictive values of 96% and 39%, respectively, for the diagnosis of BP. The median survival of patients with BP was 10 days (interquartile range 6-40) after the diagnosis.</p><p><strong>Conclusion: </strong>BP is not rare in patients with GI cancer and is associated with a poor short-term prognosis. When a patient with GI cancer is diagnosed with BP, a secondary cause should be sought. Further studies are needed to better define the best management of these patients.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05eCollection Date: 2024-01-01DOI: 10.1177/17588359241257874
Susu Zhou, Nobuyuki Horita, Theresa Shao, Matthew Harrington, Yu Fujiwara
Background: Perioperative use of immune checkpoint blockade (ICB) improves survival in patients with early-stage cancer. Treatment-related adverse events (AEs), frequently involve the endocrine system which may increase perioperative complications and affect quality of life.
Objective: We conducted a meta-analysis to elucidate the impact of adding ICB to conventional neoadjuvant/adjuvant therapy on the incidence of endocrine AEs.
Design: A systematic review and meta-analysis of randomize-controlled trials (RCTs).
Data sources and methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed for RCTs comparing groups with and without the addition of ICB to conventional perioperative therapy in patients with cancer. Outcomes included all-grade and grade 3-5 thyroiditis, hyperthyroidism, hypothyroidism, adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, and hyperglycemia. The odds ratios (ORs) of all-grade and grade 3-5 endocrine were pooled using the random-effect model meta-analysis.
Results: Twenty-four RCTs comprising 12,199 patients were identified for meta-analysis. The addition of ICB was associated with higher incidence of thyroiditis [all grade: OR = 3.53 (95% confidence interval (CI): 1.88-6.64)], hyperthyroidism [all-grade: 7.18 (4.30-12.01); grade 3-5: 3.93 (1.21-12.82)], hypothyroidism [all-grade: 5.39 (3.68-7.90); grade 3-5: 3.63 (1.18-11.11)], adrenal insufficiency [all-grade: 3.82 (1.88-7.79); grade 3-5: 5.91 (2.36-14.82)], hypophysitis [all-grade: 10.29 (4.97-21.3); grade 3-5: 5.80 (1.99-16.92)], and type 1 diabetes mellitus [all-grade: 2.24 (1.06-4.74); grade 3-5: 3.49 (1.21-10.08)]. The cumulative incidence of each grade 3-5 endocrine AE was low (<1.3%). No grade 5 AEs leading to death were observed.
Conclusion: The addition of neoadjuvant/adjuvant ICB to conventional therapy was associated with an increased incidence of several endocrine AEs. Clinicians should be aware of the risk of endocrinopathy from the perioperative ICB use to facilitate risk-benefit discussion with patients with early-stage cancer.
Trial registration: The protocol of this research was registered in PROSPERO (CRD42022332624).
{"title":"Endocrine adverse events in patients with cancer receiving perioperative immune checkpoint blockade: a meta-analysis of randomized controlled trials.","authors":"Susu Zhou, Nobuyuki Horita, Theresa Shao, Matthew Harrington, Yu Fujiwara","doi":"10.1177/17588359241257874","DOIUrl":"10.1177/17588359241257874","url":null,"abstract":"<p><strong>Background: </strong>Perioperative use of immune checkpoint blockade (ICB) improves survival in patients with early-stage cancer. Treatment-related adverse events (AEs), frequently involve the endocrine system which may increase perioperative complications and affect quality of life.</p><p><strong>Objective: </strong>We conducted a meta-analysis to elucidate the impact of adding ICB to conventional neoadjuvant/adjuvant therapy on the incidence of endocrine AEs.</p><p><strong>Design: </strong>A systematic review and meta-analysis of randomize-controlled trials (RCTs).</p><p><strong>Data sources and methods: </strong>A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed for RCTs comparing groups with and without the addition of ICB to conventional perioperative therapy in patients with cancer. Outcomes included all-grade and grade 3-5 thyroiditis, hyperthyroidism, hypothyroidism, adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, and hyperglycemia. The odds ratios (ORs) of all-grade and grade 3-5 endocrine were pooled using the random-effect model meta-analysis.</p><p><strong>Results: </strong>Twenty-four RCTs comprising 12,199 patients were identified for meta-analysis. The addition of ICB was associated with higher incidence of thyroiditis [all grade: OR = 3.53 (95% confidence interval (CI): 1.88-6.64)], hyperthyroidism [all-grade: 7.18 (4.30-12.01); grade 3-5: 3.93 (1.21-12.82)], hypothyroidism [all-grade: 5.39 (3.68-7.90); grade 3-5: 3.63 (1.18-11.11)], adrenal insufficiency [all-grade: 3.82 (1.88-7.79); grade 3-5: 5.91 (2.36-14.82)], hypophysitis [all-grade: 10.29 (4.97-21.3); grade 3-5: 5.80 (1.99-16.92)], and type 1 diabetes mellitus [all-grade: 2.24 (1.06-4.74); grade 3-5: 3.49 (1.21-10.08)]. The cumulative incidence of each grade 3-5 endocrine AE was low (<1.3%). No grade 5 AEs leading to death were observed.</p><p><strong>Conclusion: </strong>The addition of neoadjuvant/adjuvant ICB to conventional therapy was associated with an increased incidence of several endocrine AEs. Clinicians should be aware of the risk of endocrinopathy from the perioperative ICB use to facilitate risk-benefit discussion with patients with early-stage cancer.</p><p><strong>Trial registration: </strong>The protocol of this research was registered in PROSPERO (CRD42022332624).</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-02eCollection Date: 2024-01-01DOI: 10.1177/17588359241253115
Nicola L Barclay, Marti Català, Annika M Jödicke, Daniel Prieto-Alhambra, Danielle Newby, Antonella Delmestri, Wai Yi Man, Àlvar Roselló Serrano, Marta Pineda Moncusí
Background: The COVID-19 pandemic affected cancer screening, diagnosis and treatments. Many surgeries were substituted with bridging therapies during the initial lockdown, yet consideration of treatment side effects and their management was not a priority.
Objectives: To examine how the changing social restrictions imposed by the pandemic affected incidence and trends of endocrine treatment prescriptions in newly diagnosed (incident) breast and prostate cancer patients and, secondarily, endocrine treatment-related outcomes (including bisphosphonate prescriptions, osteopenia and osteoporosis), in UK clinical practice from March 2020 to June 2022.
Design: Population-based cohort study using UK primary care Clinical Practice Research Datalink GOLD database.
Methods: There were 13,701 newly diagnosed breast cancer patients and 12,221 prostate cancer patients with ⩾1-year data availability since diagnosis between January 2017 and June 2022. Incidence rates (IR) and incidence rate ratios (IRR) were calculated across multiple time periods before and after lockdown to examine the impact of changing social restrictions on endocrine treatments and treatment-related outcomes, including osteopenia, osteoporosis and bisphosphonate prescriptions.
Results: In breast cancer patients, aromatase inhibitor (AI) prescriptions increased during lockdown versus pre-pandemic [IRR: 1.22 (95% confidence interval (CI): 1.11-1.34)], followed by a decrease post-first lockdown [IRR: 0.79 (95% CI: 0.69-0.89)]. In prostate cancer patients, first-generation antiandrogen prescriptions increased versus pre-pandemic [IRR: 1.23 (95% CI: 1.08-1.4)]. For breast cancer patients on AIs, diagnoses of osteopenia, osteoporosis and bisphosphonate prescriptions were reduced across all lockdown periods versus pre-pandemic (IRR range: 0.31-0.62).
Conclusion: During the first 2 years of the pandemic, newly diagnosed breast and prostate cancer patients were prescribed more endocrine treatments compared to pre-pandemic due to restrictions on hospital procedures replacing surgeries with bridging therapies. But breast cancer patients had fewer diagnoses of osteopenia and osteoporosis and bisphosphonate prescriptions. These patients should be followed up in the coming years for signs of bone thinning. Evidence of poorer management of treatment-related side effects will help assess resource allocation for patients at high risk for bone-related complications.
{"title":"Collateral effects of the COVID-19 pandemic on endocrine treatments for breast and prostate cancer in the UK: a cohort study.","authors":"Nicola L Barclay, Marti Català, Annika M Jödicke, Daniel Prieto-Alhambra, Danielle Newby, Antonella Delmestri, Wai Yi Man, Àlvar Roselló Serrano, Marta Pineda Moncusí","doi":"10.1177/17588359241253115","DOIUrl":"10.1177/17588359241253115","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic affected cancer screening, diagnosis and treatments. Many surgeries were substituted with bridging therapies during the initial lockdown, yet consideration of treatment side effects and their management was not a priority.</p><p><strong>Objectives: </strong>To examine how the changing social restrictions imposed by the pandemic affected incidence and trends of endocrine treatment prescriptions in newly diagnosed (incident) breast and prostate cancer patients and, secondarily, endocrine treatment-related outcomes (including bisphosphonate prescriptions, osteopenia and osteoporosis), in UK clinical practice from March 2020 to June 2022.</p><p><strong>Design: </strong>Population-based cohort study using UK primary care Clinical Practice Research Datalink GOLD database.</p><p><strong>Methods: </strong>There were 13,701 newly diagnosed breast cancer patients and 12,221 prostate cancer patients with ⩾1-year data availability since diagnosis between January 2017 and June 2022. Incidence rates (IR) and incidence rate ratios (IRR) were calculated across multiple time periods before and after lockdown to examine the impact of changing social restrictions on endocrine treatments and treatment-related outcomes, including osteopenia, osteoporosis and bisphosphonate prescriptions.</p><p><strong>Results: </strong>In breast cancer patients, aromatase inhibitor (AI) prescriptions increased during lockdown <i>versus</i> pre-pandemic [IRR: 1.22 (95% confidence interval (CI): 1.11-1.34)], followed by a decrease post-first lockdown [IRR: 0.79 (95% CI: 0.69-0.89)]. In prostate cancer patients, first-generation antiandrogen prescriptions increased <i>versus</i> pre-pandemic [IRR: 1.23 (95% CI: 1.08-1.4)]. For breast cancer patients on AIs, diagnoses of osteopenia, osteoporosis and bisphosphonate prescriptions were reduced across all lockdown periods <i>versus</i> pre-pandemic (IRR range: 0.31-0.62).</p><p><strong>Conclusion: </strong>During the first 2 years of the pandemic, newly diagnosed breast and prostate cancer patients were prescribed more endocrine treatments compared to pre-pandemic due to restrictions on hospital procedures replacing surgeries with bridging therapies. But breast cancer patients had fewer diagnoses of osteopenia and osteoporosis and bisphosphonate prescriptions. These patients should be followed up in the coming years for signs of bone thinning. Evidence of poorer management of treatment-related side effects will help assess resource allocation for patients at high risk for bone-related complications.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}