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Graff SL, Tolaney SM, Hart LL, Razavi P, Janni W, Schwartzberg LS, Danyliv A, Akdere M, Ferrusi I, Adhikary RR, O’Shaughnessy JA. Correlation analysis of invasive disease-free survival and overall survival in a real-world population of patients with HR+/HER2- early breast cancer. Cancer 2025; 131:e35817. [PMID: 40159245 PMCID: PMC11955092 DOI: 10.1002/cncr.35817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/27/2025] [Accepted: 02/07/2025] [Indexed: 04/02/2025]
Abstract
BACKGROUND Overall survival (OS) is the gold standard for assessing clinical benefit in oncology but requires extended follow-up to detect sufficient events. Invasive disease-free survival (iDFS) requires shorter follow-up times and is considered an objective and clinically meaningful end point in early breast cancer (EBC) trials. The authors assessed iDFS as a surrogate end point for OS in adjuvant HR+/HER2- EBC using real-world patient-level data. METHODS A retrospective analysis was conducted on patient data from the ConcertAI Patient360 database (January 1995-April 2021). Key inclusion criteria: age ≥18 years, stage II or III (AJCC 8th Edition) HR+/HER2- EBC, prior surgery, adjuvant endocrine therapy (ET). Spearman ρ, iterative multiple imputation ρ (IMI; 0.8-1 considered "very strong"), and R2 (clinical relevance R2 ≥ 0.70) were used to assess iDFS-OS relationship. Subgroup analyses included ET (nonsteroidal aromatase inhibitor or tamoxifen), stage, menopausal status, nodal status, prior (neo)adjuvant chemotherapy, and prior radiotherapy. RESULTS A total of 3133 patients were included (1103 [35.2%] iDFS events; 554 [17.7%] OS events); mean age was 58.4 years, 98.8% were female, 29.9% were premenopausal, and 80.9% had stage II disease. Median follow-up time was 55.1 months. iDFS and OS exhibited a positive, very strong, clinically relevant correlation (Spearman ρ: 0.88 [0.87-0.89]; IMI ρ: 0.83 [0.79-0.86]; both p < .0001). iDFS accounted for 82% of variation in OS (R2 = 0.82). Results of all subgroup analyses were consistent with overall population. CONCLUSIONS This patient-level real-world analysis demonstrated very strong, positive correlations between iDFS and OS, supporting the use of iDFS as a reliable primary end point in adjuvant HR+/HER2- EBC.
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Affiliation(s)
- Stephanie L. Graff
- Brown University Health Cancer InstituteLegorreta Cancer Center at Brown UniversityProvidenceRhode IslandUSA
| | | | - Lowell L. Hart
- Florida Cancer SpecialistsSarah Cannon Research InstituteFort MyersFloridaUSA
- Wake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Pedram Razavi
- Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA
| | - Wolfgang Janni
- Department of Gynecology and ObstetricsUniversity Hospital UlmUlmGermany
| | | | | | | | - Ilia Ferrusi
- Novartis Pharmaceuticals CorporationEast HanoverNew JerseyUSA
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Socha J, Michalski W, Gerard JP, Bujko K. Does total neoadjuvant therapy improve overall survival in rectal cancer? Interpretation of the PRODIGE-23 and other studies. Ann Oncol 2024; 35:1204-1205. [PMID: 39241961 DOI: 10.1016/j.annonc.2024.08.2346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 08/28/2024] [Indexed: 09/09/2024] Open
Affiliation(s)
- J Socha
- Department of Radiotherapy, Regional Oncology Center, Częstochowa; Faculty of Medicine, Jan Dlugosz University, Częstochowa.
| | - W Michalski
- Department of Computational Oncology, M. Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - J P Gerard
- Centre Antoine Lacassagne, Nice; Université Cote d'Azur, Nice, France
| | - K Bujko
- Department of Radiotherapy I, M. Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
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Conroy T, Castan F, Etienne PL, Rio E, Mesgouez-Nebout N, Evesque L, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Boilève A, Delaye M, Gourgou S, Pezzella V, Borg C. Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial. Ann Oncol 2024; 35:873-881. [PMID: 38986769 DOI: 10.1016/j.annonc.2024.06.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 05/27/2024] [Accepted: 06/28/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here. PATIENTS AND METHODS The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate. RESULTS With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P = 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P = 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P = 0.033). The safety profile remained unchanged since the previous analysis. CONCLUSIONS Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in LARC patients, and should be considered as one of the best options of care for these patients.
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Affiliation(s)
- T Conroy
- Institut de Cancérologie de Lorraine and INSERM, INSPIIRE, Université de Lorraine, Nancy.
| | - F Castan
- Institut Régional du Cancer de Montpellier, Université de Montpellier, Montpellier
| | - P-L Etienne
- CARIO, Hôpital Privé des côtes d'Armor, Plérin
| | - E Rio
- Institut de Cancérologie de l'Ouest-Site René Gauducheau, Saint-Herblain
| | | | | | - V Vendrely
- Centre Hospitalier et Universitaire de Bordeaux, Hôpital Haut-Lévêque, Pessac
| | - X Artignan
- Centre Hospitalier Privé Saint-Grégoire, Saint-Grégoire
| | - O Bouché
- CHU Reims, Université de Reims Champagne-Ardenne, Reims
| | - D Gargot
- Centre Hospitalier de Blois, Blois
| | | | | | - C Louvet
- Institut Mutualiste Montsouris, Paris
| | - C Morand
- Centre Hospitalier Départemental Vendée, site de la Roche-sur-Yon, La Roche-sur-Yon
| | | | | | | | - S Gourgou
- Institut Régional du Cancer de Montpellier, Université de Montpellier, Montpellier
| | | | - C Borg
- University Hospital of Besançon, CIC-BT1431, Besançon, France
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Ogata Y, Sadahiro S, Sakamoto K, Tsuchiya T, Takahashi T, Ohge H, Sato T, Kondo K, Baba H, Itabashi M, Ikeda M, Hamada M, Maeda K, Masuko H, Takahashi K, Kusano M, Hyodo I, Sakamoto J, Taguri M, Morita S. Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201). Int J Clin Oncol 2024; 29:1284-1292. [PMID: 38833114 PMCID: PMC11347494 DOI: 10.1007/s10147-024-02565-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 05/28/2024] [Indexed: 06/06/2024]
Abstract
BACKGROUND The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. METHODS In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. RESULTS Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. CONCLUSION The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. TRIAL REGISTRATION Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).
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Affiliation(s)
- Yutaka Ogata
- Department of Surgery, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, Fukuoka, 830-0011, Japan.
| | - Sotaro Sadahiro
- Department of Surgery, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Kazuhiro Sakamoto
- Department of Coloproctological Surgery, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Takashi Tsuchiya
- Department of Surgery, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-Ku, Sendai, Miyagi, 983-0824, Japan
| | - Takao Takahashi
- Department of Digestive Surgery, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan
- Department of Surgery, Seino Kosei Hospital, 293-1 Shimoiso Ono-Cho, Ibi-Gun, Gifu, 501-0532, Japan
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Toshihiko Sato
- Department of Surgery, Yamagata Prefectural Central Hospital, 1800 Aoyagi, Yamagata, 990-2292, Japan
| | - Ken Kondo
- Department of Surgery, Nagoya Medical Center, 4-1-1 Sannomaru, Naka-Ku, Nagoya, Aichi, 460-0001, Japan
| | - Hideo Baba
- Department of Gastroen- Terological Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Michio Itabashi
- Department of Surgery, Division of Inflammatory Bowel Disease Surgery, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan
| | - Masataka Ikeda
- Department of Gastroenterological Surgery, Division of Lower GI, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Madoka Hamada
- Department of Gastrointestinal Surgery, Kansai Medical University Hospital, 2-3-1 Shinmachi Hirakata, Osaka, 573-1191, Japan
| | - Kiyoshi Maeda
- Department of Gastroenterological Surgery, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Hiroyuki Masuko
- Department of Surgery, Nikko Memorial Hospital, 1-5-13 Shintomi-Cho, Muroran, Hokkaido, 051-8501, Japan
| | - Keiichi Takahashi
- Tokyo Metropolitan Health and Hospitals Corporation Ohkubo Hospital, 2-44-1 Kabuki-Cho, Shinjuku-Ku, Tokyo, 160-8488, Japan
| | - Mitsuo Kusano
- Department of Physical Medicine, Yoichi Hospital, 19-1-1 Kurokawa-Cho Yoichi, Hokkaido, 046-0003, Japan
| | - Ichinosuke Hyodo
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto, Matsuyama, Ehime, 791-0280, Japan
| | - Junichi Sakamoto
- Tokai Central Hospital, 4-6-2 Sohara Higashijima-Cho, Kakamigahara, Gifu, 504-8601, Japan
| | - Masataka Taguri
- Department of Health Data Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-Ku, Tokyo, 160-8402, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
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Li J, Pang C, Liu G, Xie X, Zhang DZ, Li K, Li Z, He G, Xu E, Zhong H, Yang H, Lu M, Lou K, Xie X, Lan S, Li Q, Dai G, Yu J, Liang P. Thermal ablation with and without adjuvant systemic therapy: a nationwide multicenter observational cohort study of solitary colorectal liver metastases. Int J Surg 2024; 110:4240-4248. [PMID: 38597399 PMCID: PMC11254207 DOI: 10.1097/js9.0000000000001397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 03/11/2024] [Indexed: 04/11/2024]
Abstract
BACKGROUND Thermal ablation is routinely used for solitary colorectal liver metastases (SCLM), but the added value of adjuvant systemic therapy in SCLM remains unclear. This study aimed to compare the long-term outcomes for SCLM treated by ablation alone (AB) versus ablation plus systemic therapy (AS). METHODS This multicenter retrospective study using nationwide data from fourteen institutions between October 2010 and May 2023, 369 patients with initial SCLM smaller than 5 cm, no extrahepatic metastases, and colorectal cancer R0 resection treated by thermal ablation were included. The crude analysis was used to analyze eligible cases between the two groups. The propensity score matching to control for potential confounders in each matched group. Subgroup analyses were performed to identify specific survival benefits. RESULTS 61.2% (226/369) of eligible patients were treated with AS and 38.8% (143/369) with AB. During the median follow-up period of 8.8 years, 1-/3-/5-year DFS/OS rates did not differ between the two groups, when analyzed via propensity score matching ( P =0.52/0.08). Subgroup analysis revealed that AS was significantly associated with better OS than AB in patients with plasma CEA >5 ug/l ( P =0.036), T (III-IV) category of primary cancer ( P =0.034), or clinical risk score (1-2) ( P =0.041). In each matched group, the authors did find a significant difference in drug-related adverse events ( P <0.001) between AS group (24.1%, 28/116) and AB group (0.0%, 0/116). CONCLUSIONS For patients with plasma CEA >5 ug/l, T (III-IV) category of primary cancer, or clinical risk score (1-2), thermal ablation plus systemic therapy appeared to be associated with improved overall survival. Thermal ablation was equally effective in disease-free survival for treating SCLM, whether with or without adjuvant systemic therapy.
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Affiliation(s)
- Jianming Li
- Department of Interventional Ultrasound PLA Medical College The Fifth Medical Center of Chinese PLA General Hospital, Beijing
| | - Chuan Pang
- Department of Interventional Ultrasound PLA Medical College The Fifth Medical Center of Chinese PLA General Hospital, Beijing
| | - Guangjian Liu
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital of Sun Yat-Sen University Guangzhou
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University Guangzhou
| | - De-zhi Zhang
- Department of Abdominal Ultrasound, The First Affiliated Hospital of Jilin University, Chaoyang District, Changchun, People’s Republic of China
| | - Kai Li
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou
| | - Zhishuai Li
- Biliary Tract Surgery Department I, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai
| | - Guangbin He
- Department of Ultrasound, Xijing Hospital, The Fourth Military Medical University, Xian
| | - Erjiao Xu
- Department of Medical Ultrasonics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen
| | - Huage Zhong
- Department of Gastrointestinal Surgery, Guangxi Clinical Research Center for CRC, Guangxi Medical University Cancer HospitalNanning, Guangxi Zhuang Autonomous Region
| | - Hong Yang
- Department of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region
| | - Man Lu
- Department of Ultrasound Medicine and Laboratory of Translational Research in Ultrasound Theranostics, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu
| | - Kexin Lou
- Department of Medical Ultrasound, Xuzhou Central Hospital, Xuzhou
| | - Xiang Xie
- Department of Interventional Ultrasound, The Second Hospital of Anhui Medical University, Hefei
| | - Sirong Lan
- Department of Ultrasound, Meizhou People’s Hospital, Meizhou
| | - Qian Li
- Department of Ultrasound, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan
| | - Guanghai Dai
- Department of Medical Oncology, PLA Medical College and Fifth Medical Center of Chinese PLA General Hospital, Beijing
| | - Jie Yu
- Department of Interventional Ultrasound PLA Medical College The Fifth Medical Center of Chinese PLA General Hospital, Beijing
| | - Ping Liang
- Department of Interventional Ultrasound PLA Medical College The Fifth Medical Center of Chinese PLA General Hospital, Beijing
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Imamura T, Ohgi K, Mori K, Ashida R, Yamada M, Otsuka S, Uesaka K, Sugiura T. Surrogacy of Recurrence-free Survival for Overall Survival as an Endpoint of Clinical Trials of Perioperative Adjuvant Therapy in Hepatobiliary-pancreatic Cancers: A Retrospective Study and Meta-analysis. Ann Surg 2024; 279:1025-1035. [PMID: 37638472 DOI: 10.1097/sla.0000000000006084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
OBJECTIVE To assess the correlation between recurrence-free survival (RFS) and overall survival (OS) in the hepatobiliary-pancreatic (HBP) surgical setting to validate RFS as a surrogate endpoint. BACKGROUND Reliable surrogate endpoints for OS are still limited in the field of HBP surgery. METHODS We analyzed patients who underwent curative resection for HBP disease [986 patients with pancreatic ductal adenocarcinoma (PDAC), 1168 with biliary tract cancer (BTC), 1043 with hepatocellular carcinoma, and 1071 with colorectal liver metastasis] from September 2002 to June 2022. We also conducted meta-analyses of randomized controlled trials of neoadjuvant or adjuvant therapy to validate the surrogacy in PDAC and BTC. RESULTS Correlation coefficients between RFS and OS were low for hepatocellular carcinoma ( p = 0.67) and colorectal liver metastasis ( p = 0.53) but strong for PDAC ( p = 0.80) and BTC ( p = 0.75). In a landmark analysis, the concordance rates between survival or death at 5 years postoperatively and the presence or absence of recurrence at each time point (1, 2, 3, and 4 years) were 50%, 70%, 74%, and 77% for PDAC and 54%, 67%, 73%, and 78% for BTC, respectively, both increasing and reaching a plateau at 3 years. In a meta-analysis, the correlation coefficients for the RFS hazard ratio and OS hazard ratio in PDAC and BTC were p = 0.88 ( P < 0.001) and p = 0.87 ( P < 0.001), respectively. CONCLUSIONS Three-year RFS can be a reliable surrogate endpoint for OS in clinical trials of neoadjuvant or adjuvant therapy for PDAC and BTC.
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Affiliation(s)
- Taisuke Imamura
- Division of HepatoBiliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhisa Ohgi
- Division of HepatoBiliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Keita Mori
- Clinical Research Center, Shizuoka Cancer Center, Shizuoka, Japan
| | - Ryo Ashida
- Division of HepatoBiliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Mihoko Yamada
- Division of HepatoBiliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Shimpei Otsuka
- Division of HepatoBiliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of HepatoBiliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Teiichi Sugiura
- Division of HepatoBiliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
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Murakawa Y, Ootsuka K, Kusaka J, Miura K. Correlation between overall survival and quality of life in colon cancer patients with chemotherapy. BMC Cancer 2023; 23:492. [PMID: 37259045 DOI: 10.1186/s12885-023-10989-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 05/21/2023] [Indexed: 06/02/2023] Open
Abstract
BACKGROUND Patients presenting with inoperable colon cancer at first onset (ICF) or at time of relapse (ICR) are considered in unrecoverable. The therapeutic goal for unrecoverable cancer is to prolong overall survival (OS) and maintain a high quality of life (QOL). As data on objective indicators of QOL in cancer patients, such as length of hospitalisation (LOH), outpatient consultation times (OCT), and hospital-free survival (HFS), is limited, this study compared ICF and ICR with respect to OS and QOL over the entire clinical course. METHODS We retrospectively evaluated 90 inoperable colon cancer patients with chemotherapy and compared ICF and ICR in terms of OS, LOH, OCT, and HFS. RESULTS Patients with ICF had a worse OS than those with ICR. In patients with ICF and ICR, OS and LOH were not correlated but OS and OCT and OS and HFS were strongly correlated. In patients with ICF and ICR, OCT and HFS accounted for approximately 8% and 90% of their OS, respectively. CONCLUSIONS The LOH, OCT, and HFS are important factors for evaluating objective QOL of patients with inoperable colon cancer and should be considered when making treatment decisions.
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Affiliation(s)
- Yasuko Murakawa
- Department of Cancer Chemotherapy, Miyagi Cancer Center, Nodayama 47-1, Medeshima, Natori, Miyagi, 981-1293, Japan.
| | - Kazunori Ootsuka
- Department of Cancer Chemotherapy, Miyagi Cancer Center, Nodayama 47-1, Medeshima, Natori, Miyagi, 981-1293, Japan
| | - Jun Kusaka
- Department of Gastroenterology, Miyagi Cancer Center, Natori, Japan
| | - Kou Miura
- Department of Digestive Surgery, Miyagi Cancer Center, Natori, Japan
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Canonical Wnt Pathway Is Involved in Chemoresistance and Cell Cycle Arrest Induction in Colon Cancer Cell Line Spheroids. Int J Mol Sci 2023; 24:ijms24065252. [PMID: 36982333 PMCID: PMC10049556 DOI: 10.3390/ijms24065252] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/14/2023] [Accepted: 02/15/2023] [Indexed: 03/12/2023] Open
Abstract
The presence of cancer stem cells (CSCs) has been associated with the induction of drug resistance and disease recurrence after therapy. 5-Fluorouracil (5FU) is widely used as the first-line treatment of colorectal cancer (CRC). However, its effectiveness may be limited by the induction of drug resistance in tumor cells. The Wnt pathway plays a key role in the development and CRC progression, but it is not clearly established how it is involved in CSCs resistance to treatment. This work aimed to investigate the role played by the canonical Wnt/β-catenin pathway in CSCs resistance to 5FU treatment. Using tumor spheroids as a model of CSCs enrichment of CRC cell lines with different Wnt/β-catenin contexts, we found that 5FU induces in all CRC spheroids tested cell death, DNA damage, and quiescence, but in different proportions for each one: RKO spheroids were very sensitive to 5FU, while SW480 were less susceptible, and the SW620 spheroids, the metastatic derivative of SW480 cells, displayed the highest resistance to death, high clonogenic capacity, and the highest ability for regrowth after 5FU treatment. Activating the canonical Wnt pathway with Wnt3a in RKO spheroids decreased the 5FU-induced cell death. But the Wnt/β-catenin pathway inhibition with Adavivint alone or in combination with 5FU in spheroids with aberrant activation of this pathway produced a severe cytostatic effect compromising their clonogenic capacity and diminishing the stem cell markers expression. Remarkably, this combined treatment also induced the survival of a small cell subpopulation that could exit the arrest, recover SOX2 levels, and re-grow after treatment.
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Does the Gain of Total Neoadjuvant Therapy Outweigh the Harm in Rectal Cancer? Importance of the ATRESS (neoAdjuvant Therapy-RElated Shortening of Survival) Phenomenon: A Systematic Review. Cancers (Basel) 2023; 15:cancers15041016. [PMID: 36831360 PMCID: PMC9954766 DOI: 10.3390/cancers15041016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/01/2023] [Accepted: 02/03/2023] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND We aimed to evaluate whether total neoadjuvant therapy (TNT) results in long-term overall survival (OS) or quality of life (QoL) benefit compared with chemoradiation if all patients are being considered for radical resection, and whether the ATRESS phenomenon (i.e., reduction in post-metastatic survival) impacts OS after TNT. METHODS Systematic review of randomised trials comparing TNT with neoadjuvant (chemo)radiation. RESULTS Six trials were identified. Follow-ups were too short to resolve whether TNT improves long-term OS. QoL analysis in one trial showed worse long-term neurotoxicity-related QoL (any neurotoxicity: 14% vs. 3%), higher rate of grade III+ acute toxicity (48% vs. 25%), longer duration of neoadjuvant treatment (19 vs. 6 weeks) and higher rate of locoregional failure (10% vs. 7%) in TNT vs. chemoradiation. This should be weighed against an absolute 8% reduction in the incidence of distant metastases (DM) after TNT. ATRESS could explain a discrepancy between reduction of DM and the absence of OS improvement after TNT in one trial. CONCLUSION In the light of unproven OS benefit, the gain of TNT (reduction of DM) does not seem to outweigh the harm (excess of toxicity). ATRESS can be a reason for the absence of the OS benefit despite the reduction in DM.
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Sobrero AF, Pastorino A, Zalcberg JR. You're Cured Till You're Not: Should Disease-Free Survival Be Used as a Regulatory or Clinical End Point for Adjuvant Therapy of Cancer? J Clin Oncol 2022; 40:4044-4047. [PMID: 36315927 DOI: 10.1200/jco.22.01531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Affiliation(s)
- Alberto F Sobrero
- IRCCS Ospedale Policlinico San Martino, Medical Oncology Unit 1, Genova, Italy
| | | | - John R Zalcberg
- School of Public Health, Monash University and Department of Medical Oncology, Alfred Health, Melbourne, Victoria, Australia
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11
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Ozemir IA, Aydemir MA, Gapbarov A, Ekinci O, Alimoglu O. The Effect of the Mucinous Component Presence on the Clinical Outcomes of Colorectal Cancer. GALICIAN MEDICAL JOURNAL 2022. [DOI: 10.21802/gmj.2022.4.6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Background. The effect of colorectal cancer (CRC) histological subtypes on the prognosis is still a controversial issue. We aimed to compare clinical findings, histopathologic data, and survival outcomes in CRC patients with classical and mucinous subtypes.
Methods. Patients who were operated on for CRC between 2010 and 2017 were included in the study. Patients were classified into two groups according to the presence of a mucinous component: mucinous adenocarcinoma (MAC) - mucinous component > 50% and classical adenocarcinoma (CAC). Clinical and histopathologic findings, recurrence, metastasis, and survival rates were compared.
Results. Data of the 484 CRC patients were documented. Sixty-nine patients (14.3%) were in the MAC group and 415 (85.7%) patients were in the CAC group. The mean age of patients with MAC and CAC was 63.4 ± 13.5 and 68.5 ± 12.7 years, respectively (p = 0.002). Proximal colon localization was found in 30 (43.5%) MAC patients and 123 (29.6%) CAC patients (p = 0.029). The number of patients with metastatic lymph nodes was higher in the MAC group (58% vs. 41.2%, p = 0.03). Nevertheless, there was no significant difference between the CAC and MAC groups in terms of disease-free survival (63.1% vs. 69.6%, p = 0.37) and disease-related mortality (23.6% vs. 23.2%, p = 0.94) over the follow-up period. Multivariate analysis showed that the presence of perineural invasion, patient’s age, and disease stage were associated with mortality in CRC patients.
Conclusions. MACs occurred at a younger age than CACs and were more likely localized in the proximal colon as compared to CACs. Despite increased lymph node metastasis in MAC patients, no statistical significance was detected in overall survival or disease-free survival. Multivariate analysis revealed that age, perineural invasion, and disease stage were relevant to mortality in CRC patients.
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Ecker BL, Lee J, Saadat LV, Aparicio T, Buisman FE, Balachandran VP, Drebin JA, Hasegawa K, Jarnagin WR, Kemeny NE, Kingham TP, Groot Koerkamp B, Kokudo N, Matsuyama Y, Portier G, Saltz LB, Soares KC, Wei AC, Gonen M, D'Angelica MI. Recurrence-free survival versus overall survival as a primary endpoint for studies of resected colorectal liver metastasis: a retrospective study and meta-analysis. Lancet Oncol 2022; 23:1332-1342. [PMID: 36058227 DOI: 10.1016/s1470-2045(22)00506-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 07/28/2022] [Accepted: 08/01/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Recurrence-free survival has been used as a surrogate endpoint for overall survival in trials involving patients with resected colorectal liver metastases. We aimed to assess the correlation between recurrence-free survival and overall survival after resection of colorectal liver metastases to determine the adequacy of this surrogate endpoint. METHODS In this retrospective study and meta-analysis, we compiled an institutional cohort of consecutive patients who had complete resection of colorectal liver metastases from the Memorial Sloan Kettering Cancer Center (New York, NY, USA) prospective database. Patients were eligible for inclusion if they were aged 18 years or older, and underwent hepatectomy, with or without operative ablation, between Jan 1, 1991, and April 30, 2019. We estimated overall survival and recurrence-free survival probabilities at various timepoints using the Kaplan-Meier method, and we assessed pairwise associations between these endpoints using Spearman's rank correlation. We also did a meta-analysis of adjuvant phase 3 clinical trials for colorectal liver metastases to assess the correlation between hazard ratios (HRs) for recurrence-free survival and overall survival. We searched MEDLINE for articles of phase 3 randomised controlled trials analysing adjuvant treatment strategies for resected colorectal metastases from database inception to Jan 1, 2022. The titles and abstracts of identified studies were screened before full-text screening and summary data were either recalculated or extracted manually from the published Kaplan-Meier curves (depending on data availability). FINDINGS Data were available for 3299 patients in the institutional database, of whom 2983 were eligible for inclusion in our cohort. Median follow-up was 8·4 years (95% CI 7·9-9·1) , during which time there were 1995 (67%) disease recurrences and 1684 (56%) deaths. Median recurrence-free survival was 1·3 years (95% CI 1·3-1·4) and median overall survival was 5·2 years (95% CI 5·0-5·5). 1428 (85%) of 1684 deaths were preceded by recurrence, and median time from recurrence to death was 2·0 years (IQR 1·0-3·4). Pairwise correlations between recurrence-free survival and overall survival were low to moderate, with a correlation estimate ranging from 0·30 (SD 0·17) to 0·56 (0·13). In the meta-analysis of adjuvant clinical trials, the Spearman's correlation coefficient between recurrence-free survival HR and overall survival HR was r=0·20 (p=0·71). INTERPRETATION We found a minimal correlation between recurrence-free survival and overall survival after resection of colorectal liver metastases. Recurrence-free survival is an inadequate surrogate endpoint for overall survival in this disease setting. FUNDING US National Cancer Institute.
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Affiliation(s)
- Brett L Ecker
- Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Jasme Lee
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Lily V Saadat
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Thomas Aparicio
- Gastroenterology and Digestive Oncology Department, Centre Hospitalo-Universitaire Saint Louis, Paris, France
| | - Florian E Buisman
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jeffrey A Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nancy E Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | - Norihiro Kokudo
- Department of Hepato-Biliary-Pancreatic Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yutaka Matsuyama
- Department of Biostatistics, The University of Tokyo, Tokyo, Japan
| | | | - Leonard B Saltz
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kevin C Soares
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Livadaru C, Moscalu M, Ghitun FA, Huluta AR, Terinte C, Ferariu D, Lunca S, Dimofte GM. Postoperative Quality Assessment Score Can Select Patients with High Risk for Locoregional Recurrence in Colon Cancer. Diagnostics (Basel) 2022; 12:363. [PMID: 35204454 PMCID: PMC8871190 DOI: 10.3390/diagnostics12020363] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 01/28/2022] [Accepted: 01/30/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Monitoring surgical quality has been shown to reduce locoregional recurrence (LRR). We previously showed that the arterial stump length (ASL) after complete mesocolic excision (CME) is a reproducible quality instrument and correlates with the lymph-node (LN) yield. We hypothesized that generating an LRR prediction score by integrating the ASL would predict the risk of LRR after suboptimal surgery. METHODS 502 patients with curative resections for stage I-III colon cancer were divided in two groups (CME vs. non-CME) and compared in terms of surgical data, ASL-derived parameters, pathological parameters, LRR and LRR-free survival. A prediction score was generated to stratify patients at high risk for LRR. RESULTS The ASL showed significantly higher values (50.77 mm ± 28.5 mm) with LRR vs. (45.59 mm ± 28.1 mm) without LRR (p < 0.001). Kaplan-Meier survival analysis showed a significant increase in LRR-free survival at 5.58 years when CME was performed (Group A: 81%), in contrast to non-CME surgery (Group B: 67.2%). CONCLUSIONS The prediction score placed 76.6% of patients with LRR in the high-risk category, with a strong predictive value. Patients with long vascular stumps and positive nodes could benefit from second surgery to complete the mesocolic excision.
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Affiliation(s)
- Cristian Livadaru
- Surgical Department, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- Radiology and Medical Imaging Department, St. Spiridon Emergency County Clinical Hospital, 700111 Iasi, Romania
| | - Mihaela Moscalu
- Department of Preventive Medicine and Interdisciplinarity, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
| | | | | | - Cristina Terinte
- Department of Pathology, Regional Oncology Institute, 700483 Iasi, Romania
| | - Dan Ferariu
- Department of Pathology, Regional Oncology Institute, 700483 Iasi, Romania
| | - Sorinel Lunca
- Surgical Department, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- 2nd Clinic of Surgical Oncology, Regional Oncology Institute, 700483 Iasi, Romania
| | - Gabriel Mihail Dimofte
- Surgical Department, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- 2nd Clinic of Surgical Oncology, Regional Oncology Institute, 700483 Iasi, Romania
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Socha J, Bujko K. Does Total Neoadjuvant Treatment Improve Overall Survival in Rectal Cancer? No, It Does Not. Ann Surg Oncol 2021; 28:797-800. [PMID: 34258722 DOI: 10.1245/s10434-021-10432-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 05/27/2021] [Indexed: 11/18/2022]
Affiliation(s)
- Joanna Socha
- Department of Radiotherapy, Military Institute of Medicine, Warsaw, Poland. .,Department of Radiotherapy, Regional Oncology Centre, Czestochowa, Poland.
| | - Krzysztof Bujko
- Department of Radiotherapy I, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
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15
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Socha J, Bujko K. Are we already in the era of total neoadjuvant treatment for rectal cancer? Lancet Oncol 2021; 22:575-577. [PMID: 33861999 DOI: 10.1016/s1470-2045(21)00127-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 02/23/2021] [Indexed: 11/20/2022]
Affiliation(s)
- Joanna Socha
- Department of Radiotherapy, Military Institute of Medicine, Warsaw, Poland; Department of Radiotherapy, Regional Oncology Centre, Czestochowa, Poland
| | - Krzysztof Bujko
- Department of Radiotherapy I, Maria Skłodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
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Markowiak T, Dakkak B, Loch E, Großer C, Klinkhammer-Schalke M, Hofmann HS, Ried M. Video-assisted pulmonary metastectomy is equivalent to thoracotomy regarding resection status and survival. J Cardiothorac Surg 2021; 16:84. [PMID: 33858453 PMCID: PMC8048191 DOI: 10.1186/s13019-021-01460-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Accepted: 04/05/2021] [Indexed: 12/29/2022] Open
Abstract
Background Surgical resection of pulmonary metastases leads to prolonged survival if strictly indicated. Usually, thoracotomy with manual palpation of the entire lung with lymph node dissection or sampling is performed. The aim of this study was to evaluate the role of video-assisted thoracoscopic surgery (VATS) in pulmonary metastectomy with curative intent. Methods In this study, all patients with suspected pulmonary metastasis (n = 483) who visited the Center for Thoracic Surgery in Regensburg, between January 2009 and December 2017 were analysed retrospectively. Results A total of 251 patients underwent metastectomy with curative intent. VATS was performed in 63 (25.1%) patients, 54 (85.7%) of whom had a solitary metastasis. Wedge resection was the most performed procedure in patients treated with VATS (82.5%, n = 52) and thoracotomy (72.3%, n = 136). Postoperative revisions were necessary in nine patients (4.8%), and one patient died of pulmonary embolism after thoracotomy (0.5%). Patients were discharged significantly faster after VATS than after thoracotomy (p < 0.001). Complete (R0) resection was achieved in 89% of patients. The median recurrence-free survival was 11 months (95% confidence interval 7.9–14.1). During follow-up, eight (12.7%) patients in the VATS group and 42 (22.3%) patients in the thoracotomy group experienced recurrence (p = 0.98). The median overall survival was 61 months (95% confidence interval 46.1–75.9), and there was no significant difference with regard to the surgical method used (p = 0.34). Conclusions VATS metastasectomy can be considered in patients with a solitary lung metastasis. An open surgical approach with palpation of the lung showed no advantage in terms of surgical outcome or survival.
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Affiliation(s)
- Till Markowiak
- Department of Thoracic Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - Beshir Dakkak
- Department of Thoracic Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - Elena Loch
- Department of Thoracic Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - Christian Großer
- Department of Thoracic Surgery, Hospital Barmherzige Brüder Regensburg, Regensburg, Germany
| | - Monika Klinkhammer-Schalke
- Tumor Center, University Institute of Quality Assurance and Health Services Research, Regensburg, Germany
| | - Hans-Stefan Hofmann
- Department of Thoracic Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.,Department of Thoracic Surgery, Hospital Barmherzige Brüder Regensburg, Regensburg, Germany
| | - Michael Ried
- Department of Thoracic Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
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Statistical aspects in adjuvant and neoadjuvant trials for gastrointestinal cancer in 2020: focus on time-to-event endpoints. Curr Opin Oncol 2020; 32:384-390. [PMID: 32541329 DOI: 10.1097/cco.0000000000000636] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
PURPOSE OF REVIEW Clinical-trial design, analysis, and interpretation entails the use of efficient and reliable endpoints. Statistical issues related to endpoints warrant continued attention, as they may have a substantial impact on the conduct of clinical trials and on interpretation of their results. RECENT FINDINGS We review concepts and discuss recent developments related to the use of time-to-event endpoints in studies on adjuvant and neoadjuvant therapy for colon, pancreatic, and gastric adenocarcinomas. The definition of endpoints has varied to a considerable extent in these settings. Although these variations are relevant in interpreting results from individual trials, they probably have a small impact when considered in aggregate. In terms of surrogacy, most published reports so far have used aggregated data. A few studies based on the preferred method of a metaanalysis of individual-patient data have shown that disease-free survival (DFS) is a surrogate for overall survival in the adjuvant therapy of stage III colon cancer and in gastric cancer, whereas DFS with a landmark of six months is a surrogate for overall survival in the neoadjuvant therapy of adenocarcinoma of the esophagus, gastroesophageal junction, or stomach. SUMMARY Testing novel agents in gastrointestinal cancer requires continued attention to statistical issues related to endpoints.
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18
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Statistical Considerations for Trials in Adjuvant Treatment of Colorectal Cancer. Cancers (Basel) 2020; 12:cancers12113442. [PMID: 33228149 PMCID: PMC7699469 DOI: 10.3390/cancers12113442] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 10/29/2020] [Accepted: 11/17/2020] [Indexed: 12/26/2022] Open
Abstract
The design of the best possible clinical trials of adjuvant interventions in colorectal cancer will entail the use of both time-tested and novel methods that allow efficient, reliable and patient-relevant therapeutic development. The ultimate goal of this endeavor is to safely and expeditiously bring to clinical practice novel interventions that impact patient lives. In this paper, we discuss statistical aspects and provide suggestions to optimize trial design, data collection, study implementation, and the use of predictive biomarkers and endpoints in phase 3 trials of systemic adjuvant therapy. We also discuss the issues of collaboration and patient centricity, expecting that several novel agents with activity in the (neo)adjuvant therapy of colon and rectal cancers will become available in the near future.
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Zhang N, Ning F, Guo R, Pei J, Qiao Y, Fan J, Jiang B, Liu Y, Chi Z, Mei Z, Abe M, Zhu J, Zhang R, Zhang C. Prognostic Values of Preoperative Inflammatory and Nutritional Markers for Colorectal Cancer. Front Oncol 2020; 10:585083. [PMID: 33215031 PMCID: PMC7670074 DOI: 10.3389/fonc.2020.585083] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 10/12/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Increasing evidence indicates that inflammation and nutritional status are associated with survival outcomes in patients with colorectal cancer (CRC). This study aimed to investigate the prognostic values of preoperative inflammatory and nutritional factors and develop a prognostic model individually predicting overall survival (OS) and disease-free survival (DFS) in patients with CRC. METHODS We retrospectively collected data on patients with CRC who underwent radical surgery. Independent prognostic inflammatory and nutritional markers were identified and novel prognostic models were developed incorporating the identified factors. The discriminative ability and model-fitting performance were evaluated by receiver operating characteristic curves and Akaike information criteria. Clinical usefulness was assessed by decision curve analysis. RESULTS A total of 400 eligible patients were identified. Multivariate analysis identified pN stage, tumor differentiation grade, neutrophil count, and body mass index as independent prognostic factors for OS, and pN stage, tumor differentiation grade, neutrophil count, neutrophil-lymphocyte ratio, and serum albumin as prognostic factors for DFS. The combined inflammatory and nutritional prognostic model showed better discriminative ability, model-fitting performance, and net benefits than the inflammatory and nutritional models alone, and the American Joint Committee on Cancer (AJCC) 8th TNM classification for predicting OS and DFS. CONCLUSION Preoperative nutritional and inflammatory factors have significant prognostic value in patients with CRC. A novel prognostic model incorporating preoperative inflammatory and nutritional markers provides better prognostic performance than the AJCC 8th TNM classification. A novel nomogram incorporating preoperative inflammatory and nutritional markers can individually predict OS and DFS in patients with CRC.
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Affiliation(s)
- Nannan Zhang
- State key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Feilong Ning
- Department of General Surgery, Xuzhou Hospital of Traditional Chinese Medicine, Xuzhou, China
| | - Rui Guo
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Junpeng Pei
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Yun Qiao
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Jin Fan
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Bo Jiang
- Department of Colorectal Anal Surgery, Shanxi Province Cancer Hospital & Institute, Taiyuan, China
| | - Yanlong Liu
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Zhaocheng Chi
- Second Department of Gastrointestinal Surgery, Jilin Cancer Hospital, Changchun, China
| | - Zubing Mei
- Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Anorectal Surgery, Anorectal Disease Institute of Shuguang Hospital, Shanghai, China
| | - Masanobu Abe
- Division for Health Service Promotion, University of Tokyo, Tokyo, Japan
| | - Ji Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Rui Zhang
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Chundong Zhang
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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Chakrabarti S, Peterson CY, Sriram D, Mahipal A. Early stage colon cancer: Current treatment standards, evolving paradigms, and future directions. World J Gastrointest Oncol 2020; 12:808-832. [PMID: 32879661 PMCID: PMC7443846 DOI: 10.4251/wjgo.v12.i8.808] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 05/16/2020] [Accepted: 08/01/2020] [Indexed: 02/05/2023] Open
Abstract
Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies. The majority of patients with colon cancer are diagnosed at an early stage (stages I to III), which provides an opportunity for cure. The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients, which is directed at the eradication of minimal residual disease to achieve a cure. Surgery alone is curative for the vast majority of colon cancer patients. Currently, surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement. Adjuvant chemotherapy is recommended for all patients with stage III colon cancer, while the benefit in stage II patients is not unequivocally established despite several large clinical trials. Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques, strategies to limit treatment-related toxicities, precise patient selection for adjuvant therapy, utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology. In this review, we will discuss the current standard treatment, evolving treatment paradigms, and the emerging biomarkers, that will likely help improve patient selection and personalization of therapy leading to superior outcomes.
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Affiliation(s)
- Sakti Chakrabarti
- Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, United States
| | - Carrie Y Peterson
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, United States
| | - Deepika Sriram
- Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, United States
| | - Amit Mahipal
- Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, United States
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Chen QY, Liu ZY, Zhong Q, Xie JW, Wang JB, Lin JX, Lu J, Cao LL, Lin M, Tu RH, Huang ZN, Lin JL, Zheng HL, Li P, Zheng CH, Huang CM. Clinical Impact of Delayed Initiation of Adjuvant Chemotherapy Among Patients With Stage II/III Gastric Cancer: Can We Do Better? Front Oncol 2020; 10:1149. [PMID: 32850326 PMCID: PMC7412732 DOI: 10.3389/fonc.2020.01149] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 06/08/2020] [Indexed: 12/24/2022] Open
Abstract
Background: To investigate the prognostic effects and risk factors of the omission and delay of postoperative chemotherapy of stage II/III gastric cancer (GC). Methods: The clinicopathological data of 1,520 patients undergoing radical gastrectomy for stage II/III GC were collected and retrospectively analyzed. We defined the chemotherapy delayed until more than 60 days after radical gastrectomy and the complete omission of chemotherapy as unacceptable chemotherapy initiation (UAC), whereas the chemotherapy conducted within 60 days of radical gastrectomy was defined as acceptable chemotherapy initiation (AC). The survival between the two groups was compared, and the trends and risk factors of UAC were analyzed. Results: There were 539 (35.5%) patients with UAC. The overall survival (OS) and disease-free survival of the UAC group patients were significantly inferior to those in the AC group (p < 0.001). Cox multivariate analysis demonstrated that UAC is an independent predictor of OS (p < 0.05). The OS and disease-free survival of the patients in the UAC group were close to those of the patients without chemotherapy (p > 0.05). Logistic analysis showed that female, old age, a self-paid status, a very low social status, high American Society of Anesthesiologists scores, intra-abdominal surgery history, and serious postoperative complications were independent risk factors of UAC (all p < 0.05). The radar chart shows the risk factors of UAC changed with time. Conclusions: UAC after radical gastrectomy is an independent risk factor for the prognosis of stage II/III GC patients. However, no significant decline of UAC has been achieved recently and should call for the attention of both government and clinicians.
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Affiliation(s)
- Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Zhi-Yu Liu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Qing Zhong
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ze-Ning Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ju-Li Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Hua-Long Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
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22
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Bridgewater J. Adjuvant therapy for colorectal cancer in 2020: has anything changed this millennium? Ann Oncol 2020; 31:447-448. [PMID: 32093918 DOI: 10.1016/j.annonc.2020.01.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 01/12/2020] [Indexed: 02/02/2023] Open
Affiliation(s)
- J Bridgewater
- Department of Oncology, UCL Cancer Institute, London, UK.
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23
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Salem ME, Yin J, Goldberg RM, Pederson LD, Wolmark N, Alberts SR, Taieb J, Marshall JL, Lonardi S, Yoshino T, Kerr RS, Yothers G, Grothey A, Andre T, De Gramont A, Shi Q. Evaluation of the change of outcomes over a 10-year period in patients with stage III colon cancer: pooled analysis of 6501 patients treated with fluorouracil, leucovorin, and oxaliplatin in the ACCENT database. Ann Oncol 2020; 31:480-486. [PMID: 32085892 PMCID: PMC10688027 DOI: 10.1016/j.annonc.2019.12.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 12/16/2019] [Accepted: 12/17/2019] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Since 2004, adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX or FLOX) have been the standard of care for patients with resected colon cancer. Herein we examine the change of outcomes over a 10-year period in patients with stage III colon cancer who received this regimen. PATIENTS AND METHODS Individual patient data from the ACCENT database was used to compare the outcomes in older (1998-2003) and newer (2004-2009) treatment eras for patients with stage III colon cancer who received adjuvant FOLFOX or FLOX. The outcomes were compared between the two groups by the multivariate Cox proportional-hazards model adjusting for age, sex, performance score, T stage, N stage, tumor sidedness, and histological grade. RESULTS A total of 6501 patients with stage III colon cancer who received adjuvant FOLFOX or FLOX in six randomized trials were included in the analysis. Patients enrolled in the new era group experienced statistically significant improvement in time to recurrence [3-year rate, 76.1% versus 73.0%; adjusted hazard ratio (HRadj) = 0.83 (95% CI, 0.74-0.92), P = 0.0008], disease-free survival (DFS) [3-year rate, 74.7% versus 72.3%; HRadj = 0.88 (0.79-0.98), P = 0.024], survival after recurrence (SAR) [median time, 27.0 versus 17.7 months; HRadj = 0.65 (0.57-0.74), P < 0.0001], and overall survival (OS) [5-year rate, 80.9% versus 75.7%; HRadj = 0.78 (0.69-0.88), P < 0.0001]. The improved outcomes remained in patients diagnosed at 45 years of age or older, low-risk patients (T1-3 and N1), left colon, mismatch repair proficient (pMMR), BRAF, and KRAS wild-type tumors. CONCLUSION Improved outcomes were observed in patients with stage III colon cancer enrolled in clinical trials who received adjuvant FOLFOX/FLOX therapy in 2004 or later compared with patients in the older era. Prolonged SAR calls for revalidation of 3-year DFS as the surrogate endpoint of OS in adjuvant clinical trials and reevaluation of optimal follow-up of OS to confirm the trial findings based on the DFS endpoints. CLINICAL TRIALS NUMBERS NCT00079274; NCT00096278; NCT00004931; NCT00275210; NCT00265811; NCT00112918.
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Affiliation(s)
- M E Salem
- Levine Cancer Institute, Carolinas HealthCare System, Charlotte, USA
| | - J Yin
- Department of Health Science Research, Mayo Clinic, Rochester, USA
| | - R M Goldberg
- West Virginia University Cancer Institute, Morgantown, USA
| | - L D Pederson
- Department of Health Science Research, Mayo Clinic, Rochester, USA
| | - N Wolmark
- National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, USA
| | - S R Alberts
- Department of Oncology, Mayo Clinic, Rochester, USA
| | - J Taieb
- Department of Gastroenterology and GI Oncology, Georges Pompidou European Hospital, Paris Descartes University, Paris, France
| | - J L Marshall
- Lombardi Comprehensive Cancer Center, Georgetown University, Washington, USA
| | - S Lonardi
- Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto, IRCCS, Padua, Italy
| | - T Yoshino
- Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - R S Kerr
- Department of Oncology, University of Oxford, Oxford, UK
| | - G Yothers
- Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, USA
| | - A Grothey
- West Cancer Center and Research Institute, Germantown, USA
| | - T Andre
- Sorbonne University and Department of Medical Oncology, Hôspital St Antoine, Paris, France
| | - A De Gramont
- Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France
| | - Q Shi
- Department of Health Science Research, Mayo Clinic, Rochester, USA.
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24
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Wang Q, Wei J, Chen Z, Zhang T, Zhong J, Zhong B, Yang P, Li W, Cao J. Establishment of multiple diagnosis models for colorectal cancer with artificial neural networks. Oncol Lett 2019; 17:3314-3322. [PMID: 30867765 PMCID: PMC6396131 DOI: 10.3892/ol.2019.10010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Accepted: 09/13/2018] [Indexed: 12/13/2022] Open
Abstract
The current study aimed to develop multiple diagnosis models for colorectal cancer (CRC) based on data from The Cancer Genome Atlas database and analysis with artificial neural networks in order to enhance CRC diagnosis methods. A genetic algorithm and mean impact value were used to select genes to be used as numerical encoded parameters to reflect cancer metastasis or aggression. Back propagation and learning vector quantization neural networks were used to build four diagnosis models: Cancer/Normal, M0/M1, carcinoembryonic antigen (CEA) <5/≥5 and Clinical stage I-II/III-IV. The performance of each model was evaluated by predictive accuracy (ACC), the area under the receiver operating characteristic curve (AUC) and a 10-fold cross-validation test. The ACC and AUC of the Cancer/Normal, M0/M1, CEA and Clinical stage models were 100%, 1.000; 87.14%, 0.670; 100%, 1.000; and 100%, 1.000, respectively. The 10-fold cross-validation test of the ACC values and sensitivity for each test were 93.75-99.39%, 1.0000; 80.58-88.24%, 0.9286-1.0000; 67.21-92.31%, 0.7091-1.0000; and 59.13-68.85%, 0.6017-0.6585, respectively. The diagnosis models developed in the current study combined gene expression profiling data and artificial intelligence algorithms to create tools for improved diagnosis of CRC.
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Affiliation(s)
- Qiang Wang
- Department of General Surgery, Guangzhou Digestive Disease Centre, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510000, P.R. China
| | - Jianchang Wei
- Department of General Surgery, Guangzhou Digestive Disease Centre, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510000, P.R. China
| | - Zhuanpeng Chen
- Department of General Surgery, Guangzhou Digestive Disease Centre, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510000, P.R. China
| | - Tong Zhang
- Department of General Surgery, Guangzhou Digestive Disease Centre, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510000, P.R. China
| | - Junbin Zhong
- Department of General Surgery, Guangzhou Digestive Disease Centre, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510000, P.R. China
| | - Bingzheng Zhong
- Department of General Surgery, Guangzhou Digestive Disease Centre, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510000, P.R. China
| | - Ping Yang
- Department of General Surgery, Guangzhou Digestive Disease Centre, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510000, P.R. China
| | - Wanglin Li
- Department of General Surgery, Guangzhou Digestive Disease Centre, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510000, P.R. China
| | - Jie Cao
- Department of General Surgery, Guangzhou Digestive Disease Centre, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510000, P.R. China
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25
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Peng JH, Fang YJ, Li CX, Ou QJ, Jiang W, Lu SX, Lu ZH, Li PX, Yun JP, Zhang RX, Pan ZZ, Wan DS. A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery. Oncotarget 2017; 7:22939-47. [PMID: 27008710 PMCID: PMC5008413 DOI: 10.18632/oncotarget.8217] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Accepted: 03/10/2016] [Indexed: 01/03/2023] Open
Abstract
Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment.
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Affiliation(s)
- Jian-Hong Peng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, P.R. China
| | - Yu-Jing Fang
- Department of Colorectal Surgery, Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, P. R. China
| | - Cai-Xia Li
- School of Mathematics and Computational Science,Sun Yat-sen University, Guangzhou, P.R. China,.,Guangdong Provincial Key Laboratory of Computational Science, Sun Yat-sen University, Guangzhou, P.R. China
| | - Qing-Jian Ou
- Department of Colorectal Surgery, Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, P. R. China
| | - Wu Jiang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, P.R. China
| | - Shi-Xun Lu
- Department of pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, P. R. China
| | - Zhen-Hai Lu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, P.R. China
| | - Pei-Xing Li
- School of Mathematics and Computational Science,Sun Yat-sen University, Guangzhou, P.R. China,.,Guangdong Provincial Key Laboratory of Computational Science, Sun Yat-sen University, Guangzhou, P.R. China
| | - Jing-Ping Yun
- Department of pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, P. R. China
| | - Rong-Xin Zhang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, P.R. China
| | - Zhi-Zhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, P.R. China
| | - De Sen Wan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, P.R. China
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26
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Shi Q, Liu S, Li W, Zong S, Han S, Yang W, Li H, Hou F. Exploring the medication duration based on the effect of traditional Chinese medicine on postoperative stage I-III colorectal patients: a retrospective cohort study. Oncotarget 2017; 8:13488-13495. [PMID: 28086238 PMCID: PMC5355114 DOI: 10.18632/oncotarget.14567] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Accepted: 12/27/2016] [Indexed: 01/30/2023] Open
Abstract
PURPOSE To clarify the effect of tradional Chinese medicine (TCM) on different stage patients and to explore medication duration based on survival analysis. RESULTS 523 and 294 patients were respectively in the TCM group and the control group. For all patients, 6-year disease-free survival (DFS) was 57.6% after TCM and 46.6% after non-TCM (p = 0.0006). 6-year DFS for patients with stage I disease in the TCM group was 79.5% compared with 89.1% in the control group (p = 0.65). For patients with stage II disease, 6-year DFS was 63.1% in the TCM group compared with 50.2% in the control group (p = 0.054), and for patients with stage III disease, it was 43.3% in the TCM group compared with 22.0% in the control group (p = 0.0000). MATERIALS AND METHODS Data for patients with stage I-III disease between 2004 and 2013 were retrieved for this study, who underwent TCM after surgery were in the TCM group and the others were in the control group. Clinic appointments or phone were used to collect data by research assistants. Survival data were collected on Nov 2015 from the database, which is continuously updated by the researchers. CONCLUSIONS TCM is associated with significantly improved disease-free survival, in particular for patients with stage III disease. Among of these, TCM is not necessary for patients with stage I disease, and postoperative patients with stage II disease should be recommended to take 2 years of TCM. For patients with stage III disease, adherence to medication of TCM during the 6-year follow-up is worthy of being recommended.
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Affiliation(s)
- Qi Shi
- Oncology Department of Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
| | - Shanshan Liu
- Oncology Department of Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
| | - Wen Li
- Oncology Department of Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
| | - Shaoqi Zong
- Oncology Department of Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
| | - Susu Han
- Oncology Department of Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
| | - Wei Yang
- Oncology Department of Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
| | - Hongjia Li
- Oncology Department of Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
| | - Fenggang Hou
- Oncology Department of Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
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27
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Petrelli F, Borgonovo K, Cabiddu M, Ghilardi M, Lonati V, Barni S. Pathologic complete response and disease-free survival are not surrogate endpoints for 5-year survival in rectal cancer: an analysis of 22 randomized trials. J Gastrointest Oncol 2017; 8:39-48. [PMID: 28280607 DOI: 10.21037/jgo.2016.11.03] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND We performed a literature-based analysis of randomized clinical trials to assess the pathologic complete response (pCR) (ypT0N0 after neoadjuvant therapy) and 3-year disease-free survival (DFS) as potential surrogate endpoints for 5-year overall survival (OS) in rectal cancer treated with neoadjuvant (chemo)radiotherapy (CT)RT. METHODS A systematic literature search of PubMed, EMBASE, the Web of Science, SCOPUS, CINAHL, and the Cochrane Library was performed. Treatment effects on 3-year DFS and 5-year OS were expressed as rates of patients alive (%), and those on pCR as differences in pCR rates (∆pCR%). A weighted regression analysis was performed at individual- and trial-level to test the association between treatment effects on surrogate (∆pCR% and ∆3yDFS) and the main clinical outcome (∆5yOS). RESULTS Twenty-two trials involving 10,050 patients, were included in the analysis. The individual level surrogacy showed that the pCR% and 3-year DFS were poorly correlated with 5-year OS (R=0.52; 95% CI, 0.31-0.91; P=0.002; and R=0.60; 95% CI, 0.36-1; P=0.002). The trial-level surrogacy analysis confirmed that the two treatment effects on surrogates (∆pCR% and ∆3yDFS) are not strong surrogates for treatment effects on 5-year OS % (R=0.2; 95% CI, -0.29-0.78; P=0.5 and R=0.64; 95% CI, 0.29-1; P=0.06). These findings were confirmed in neoadjuvant CTRT studies but not in phase III trials were 3-year DFS could still represent a valid surrogate. CONCLUSIONS This analysis does not support the use of pCR and 3-year DFS% as appropriate surrogate endpoints for 5-year OS% in patients with rectal cancer treated with neoadjuvant therapy.
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Affiliation(s)
- Fausto Petrelli
- Oncology Department, UO Oncologia, ASST Bergamo Ovest, 24047 Treviglio, BG, Italy
| | - Karen Borgonovo
- Oncology Department, UO Oncologia, ASST Bergamo Ovest, 24047 Treviglio, BG, Italy
| | - Mary Cabiddu
- Oncology Department, UO Oncologia, ASST Bergamo Ovest, 24047 Treviglio, BG, Italy
| | - Mara Ghilardi
- Oncology Department, UO Oncologia, ASST Bergamo Ovest, 24047 Treviglio, BG, Italy
| | - Veronica Lonati
- Oncology Department, UO Oncologia, ASST Bergamo Ovest, 24047 Treviglio, BG, Italy
| | - Sandro Barni
- Oncology Department, UO Oncologia, ASST Bergamo Ovest, 24047 Treviglio, BG, Italy
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28
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Shi Q, Sargent DJ, Renfro LA. Findings from the Adjuvant Colon Cancer End Points (ACCENT) Collaborative Group: the Power of Pooled Individual Patient Data from Multiple Clinical Trials. CURRENT COLORECTAL CANCER REPORTS 2016. [DOI: 10.1007/s11888-016-0331-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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29
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Renfro LA, Shang H, Sargent DJ. Impact of Copula Directional Specification on Multi-Trial Evaluation of Surrogate End Points. J Biopharm Stat 2016; 25:857-77. [PMID: 24905465 DOI: 10.1080/10543406.2014.920870] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Evaluation of surrogate end points using patient-level data from multiple trials is the gold standard, where multi-trial copula models are used to quantify both patient-level and trial-level surrogacy. While limited consideration has been given in the literature to copula choice (e.g., Clayton), no prior consideration has been given to direction of implementation (via survival vs. distribution functions). We demonstrate that even with the "correct" copula family, directional misspecification leads to biased estimates of patient-level and trial-level surrogacy. We illustrate with a simulation study and a reanalysis of disease-free survival as a surrogate for overall survival in early stage colon cancer.
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Affiliation(s)
- Lindsay A Renfro
- a Division of Biomedical Statistics and Informatics , Mayo Clinic , Rochester , Minnesota , USA
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Lee SY, Kim DW, Lee HS, Ihn MH, Oh HK, Min BS, Kim WR, Huh JW, Yun JA, Lee KY, Kim NK, Lee WY, Kim HC, Kang SB. Low-Level Microsatellite Instability as a Potential Prognostic Factor in Sporadic Colorectal Cancer. Medicine (Baltimore) 2015; 94:e2260. [PMID: 26683947 PMCID: PMC5058919 DOI: 10.1097/md.0000000000002260] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 10/30/2015] [Accepted: 11/16/2015] [Indexed: 01/12/2023] Open
Abstract
Although microsatellite instability-high (MSI-H) colorectal cancers (CRCs) have been shown to exhibit a distinct phenotype, the clinical value of MSI-low (MSI-L) in CRC remains unclear. We designed this study to examine the clinicopathologic characteristics and oncologic implications associated with MSI-L CRCs. We retrospectively reviewed data of CRC patients from 3 tertiary referral hospitals in Korea, who underwent surgical resection between January 2003 and December 2009 and had available MSI testing results. MSI testing was performed using the pentaplex Bethesda panel. Clinicopathologic features and oncologic outcomes were compared between MSI-L and microsatellite stable (MSS) CRCs; prognostic factors for survival were also examined. Of the 3019 patients reviewed, 2621 (86.8%) were MSS, and 200 (6.6%) were MSI-L; the remaining 198 (6.6%) were MSI-H. MSI-L and MSS CRCs were comparable in terms of their clinicopathologic features, with the exception of proximal tumor location (MSI-L 30.0% vs MSS 22.1%, P = 0.024) and tumor size (MSI-L 5.2 ± 2.6 cm vs MSS 4.6 ± 2.1 cm, P = 0.001). No differences were detected in either 3-year disease-free survival (MSI-L 87.2% vs MSS 82.6%, P = 0.121) or 5-year overall survival (OS) (MSI-L 74.2% vs MSS 78.3%, P = 0.131) by univariable analysis. However, MSI-L was an independent prognostic factor for poor OS by Cox regression analysis (hazard ratio 1.358, 95% confidence interval 1.014-1.819, P = 0.040). MSI-L may be an independent prognostic factor for OS in sporadic CRCs despite their clinicopathologic similarity to MSS. Further studies investigating the significance of MSI-L in the genesis and prognosis of CRCs are needed.
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Affiliation(s)
- Soo Young Lee
- From the Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun (SYL); Department of Surgery, Seoul National University Bundang Hospital, Seongnam (D-WK, MHI, H-KO, S-BK); Korean Hereditary Tumor Registry, Seoul National University College of Medicine, Seoul (D-WK); Department of Pathology, Seoul National University Bundang Hospital, Seongnam (HSL); Department of Surgery, Severance Hospital, Yonsei University College of Medicine (BSM, WRK, KYL, NKK); and Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (JWH, J-AY, WYL, HCK)
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Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Hoersch S, Rittweger K, Haller DG. Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer: Final Results of the NO16968 Randomized Controlled Phase III Trial. J Clin Oncol 2015; 33:3733-40. [PMID: 26324362 DOI: 10.1200/jco.2015.60.9107] [Citation(s) in RCA: 194] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
PURPOSE To report the final efficacy findings and biomarker analysis from the NO16968 trial comparing bolus fluorouracil/folinic acid (FU/FA) with capecitabine plus oxaliplatin (XELOX) in resected stage III colon cancer. PATIENTS AND METHODS After curative resection, patients were randomly assigned to receive XELOX, as oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1,000 mg/m(2) twice daily on days 1 to 14 every 3 weeks, or bolus FU/FA, as the Mayo Clinic or Roswell Park regimens, for 6 months. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS). RESULTS The intention-to-treat population comprised 1,886 patients (XELOX, n = 944; FU/FA, n = 942). Seven-year DFS rates were 63% and 56% in the XELOX and FU/FA groups, respectively (hazard ratio [HR], 0.80; 95% CI, 0.69 to 0.93; P = .004). Seven-year OS rates were 73% and 67% in the XELOX and FU/FA groups, respectively (HR, 0.83; 95% CI, 0.70 to 0.99; P = .04). A total of 68% and 77% of patients who experienced relapse or a new colorectal cancer in the XELOX and FU/FA groups, respectively, received drug treatment for metastatic disease. Four hundred ninety-eight patients consented to the biomarker analysis: 242 in the XELOX group and 256 in the FU/FA group. Low tumor expression of dihydropyrimidine dehydrogenase may be predictive for XELOX efficacy; in the XELOX group, for high versus low dihydropyrimidine dehydrogenase expression levels, DFS HR was 2.45 (95% CI, 1.55 to 3.86; P < .001), and OS HR was 2.75 (95% CI, 1.65 to 4.59; P < .001). In the FU/FA group, no statistically significant associations were observed between any tumor biomarker and outcomes. CONCLUSION XELOX improved OS compared with bolus FU/FA in patients with resected stage III colon cancer after a median follow-up of almost 7 years. XELOX should be considered a standard adjuvant treatment option in patients with stage III disease. Tumoral dihydropyrimidine dehydrogenase expression is a promising predictive, and potentially, highly clinically relevant, biomarker for XELOX efficacy requiring further prospective evaluation.
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Affiliation(s)
- Hans-Joachim Schmoll
- Hans-Joachim Schmoll, Martin Luther University, Halle, Germany; Josep Tabernero, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Jean Maroun, Ottawa Regional Cancer Center, Ottawa, Ontario, Canada; Filippo de Braud, Istituto Europeo di Oncologia, Milan, Italy; Timothy Price, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium; Mark Hill, Kent Oncology Centre, Maidstone, Kent, United Kingdom; Silke Hoersch, F. Hoffmann-La Roche, Basel, Switzerland; Karen Rittweger, F. Hoffmann-La Roche, Nutley, NJ; and Daniel G. Haller, University of Pennsylvania, Philadelphia, PA.
| | - Josep Tabernero
- Hans-Joachim Schmoll, Martin Luther University, Halle, Germany; Josep Tabernero, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Jean Maroun, Ottawa Regional Cancer Center, Ottawa, Ontario, Canada; Filippo de Braud, Istituto Europeo di Oncologia, Milan, Italy; Timothy Price, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium; Mark Hill, Kent Oncology Centre, Maidstone, Kent, United Kingdom; Silke Hoersch, F. Hoffmann-La Roche, Basel, Switzerland; Karen Rittweger, F. Hoffmann-La Roche, Nutley, NJ; and Daniel G. Haller, University of Pennsylvania, Philadelphia, PA
| | - Jean Maroun
- Hans-Joachim Schmoll, Martin Luther University, Halle, Germany; Josep Tabernero, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Jean Maroun, Ottawa Regional Cancer Center, Ottawa, Ontario, Canada; Filippo de Braud, Istituto Europeo di Oncologia, Milan, Italy; Timothy Price, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium; Mark Hill, Kent Oncology Centre, Maidstone, Kent, United Kingdom; Silke Hoersch, F. Hoffmann-La Roche, Basel, Switzerland; Karen Rittweger, F. Hoffmann-La Roche, Nutley, NJ; and Daniel G. Haller, University of Pennsylvania, Philadelphia, PA
| | - Filippo de Braud
- Hans-Joachim Schmoll, Martin Luther University, Halle, Germany; Josep Tabernero, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Jean Maroun, Ottawa Regional Cancer Center, Ottawa, Ontario, Canada; Filippo de Braud, Istituto Europeo di Oncologia, Milan, Italy; Timothy Price, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium; Mark Hill, Kent Oncology Centre, Maidstone, Kent, United Kingdom; Silke Hoersch, F. Hoffmann-La Roche, Basel, Switzerland; Karen Rittweger, F. Hoffmann-La Roche, Nutley, NJ; and Daniel G. Haller, University of Pennsylvania, Philadelphia, PA
| | - Timothy Price
- Hans-Joachim Schmoll, Martin Luther University, Halle, Germany; Josep Tabernero, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Jean Maroun, Ottawa Regional Cancer Center, Ottawa, Ontario, Canada; Filippo de Braud, Istituto Europeo di Oncologia, Milan, Italy; Timothy Price, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium; Mark Hill, Kent Oncology Centre, Maidstone, Kent, United Kingdom; Silke Hoersch, F. Hoffmann-La Roche, Basel, Switzerland; Karen Rittweger, F. Hoffmann-La Roche, Nutley, NJ; and Daniel G. Haller, University of Pennsylvania, Philadelphia, PA
| | - Eric Van Cutsem
- Hans-Joachim Schmoll, Martin Luther University, Halle, Germany; Josep Tabernero, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Jean Maroun, Ottawa Regional Cancer Center, Ottawa, Ontario, Canada; Filippo de Braud, Istituto Europeo di Oncologia, Milan, Italy; Timothy Price, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium; Mark Hill, Kent Oncology Centre, Maidstone, Kent, United Kingdom; Silke Hoersch, F. Hoffmann-La Roche, Basel, Switzerland; Karen Rittweger, F. Hoffmann-La Roche, Nutley, NJ; and Daniel G. Haller, University of Pennsylvania, Philadelphia, PA
| | - Mark Hill
- Hans-Joachim Schmoll, Martin Luther University, Halle, Germany; Josep Tabernero, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Jean Maroun, Ottawa Regional Cancer Center, Ottawa, Ontario, Canada; Filippo de Braud, Istituto Europeo di Oncologia, Milan, Italy; Timothy Price, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium; Mark Hill, Kent Oncology Centre, Maidstone, Kent, United Kingdom; Silke Hoersch, F. Hoffmann-La Roche, Basel, Switzerland; Karen Rittweger, F. Hoffmann-La Roche, Nutley, NJ; and Daniel G. Haller, University of Pennsylvania, Philadelphia, PA
| | - Silke Hoersch
- Hans-Joachim Schmoll, Martin Luther University, Halle, Germany; Josep Tabernero, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Jean Maroun, Ottawa Regional Cancer Center, Ottawa, Ontario, Canada; Filippo de Braud, Istituto Europeo di Oncologia, Milan, Italy; Timothy Price, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium; Mark Hill, Kent Oncology Centre, Maidstone, Kent, United Kingdom; Silke Hoersch, F. Hoffmann-La Roche, Basel, Switzerland; Karen Rittweger, F. Hoffmann-La Roche, Nutley, NJ; and Daniel G. Haller, University of Pennsylvania, Philadelphia, PA
| | - Karen Rittweger
- Hans-Joachim Schmoll, Martin Luther University, Halle, Germany; Josep Tabernero, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Jean Maroun, Ottawa Regional Cancer Center, Ottawa, Ontario, Canada; Filippo de Braud, Istituto Europeo di Oncologia, Milan, Italy; Timothy Price, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium; Mark Hill, Kent Oncology Centre, Maidstone, Kent, United Kingdom; Silke Hoersch, F. Hoffmann-La Roche, Basel, Switzerland; Karen Rittweger, F. Hoffmann-La Roche, Nutley, NJ; and Daniel G. Haller, University of Pennsylvania, Philadelphia, PA
| | - Daniel G Haller
- Hans-Joachim Schmoll, Martin Luther University, Halle, Germany; Josep Tabernero, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Jean Maroun, Ottawa Regional Cancer Center, Ottawa, Ontario, Canada; Filippo de Braud, Istituto Europeo di Oncologia, Milan, Italy; Timothy Price, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium; Mark Hill, Kent Oncology Centre, Maidstone, Kent, United Kingdom; Silke Hoersch, F. Hoffmann-La Roche, Basel, Switzerland; Karen Rittweger, F. Hoffmann-La Roche, Nutley, NJ; and Daniel G. Haller, University of Pennsylvania, Philadelphia, PA
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Renfro LA, Shi Q, Sargent DJ. Mining the ACCENT database: a review and update. Chin Clin Oncol 2015; 2:18. [PMID: 25841498 DOI: 10.3978/j.issn.2304-3865.2013.03.05] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2013] [Accepted: 03/15/2013] [Indexed: 12/27/2022]
Abstract
The database of the Adjuvant Colon Cancer End Points (ACCENT) Group was assembled to address questions in early stage colon cancer that could be best answered by information pooled across many similar trials. Today, the ACCENT database contains individual patient-level data from over 33,000 patients enrolled onto 25 adjuvant colon cancer trials conducted between 1977 and 2008. Since its flagship analysis of 3-year disease-free survival as a surrogate endpoint for 5-year overall survival in 2005, the ACCENT group has produced many noteworthy scientific findings addressing a variety of clinical questions, which we describe here. Additionally, we provide an overview of the history, collaboration, construction, principles, and future of the ACCENT database, as it has set a precedent for multi-trial database creation in other types of cancer.
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Affiliation(s)
- Lindsay A Renfro
- Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
| | - Qian Shi
- Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Daniel J Sargent
- Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
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Bai L, Zhang DS, Wu WJ, Ren C, Wang DS, Wang F, Qiu MZ, Xu RH. Clinical outcomes of Chinese patients with metastatic colorectal cancer receiving first-line bevacizumab-containing treatment. Med Oncol 2015; 32:469. [PMID: 25582893 DOI: 10.1007/s12032-014-0469-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2014] [Accepted: 12/16/2014] [Indexed: 12/15/2022]
Abstract
After the approval of bevacizumab for the first-line treatment of metastatic colorectal cancer (mCRC) in China, published information was still limited. This observational cohort study enrolled 175 mCRC patients who initiated bevacizumab-containing first-line chemotherapies at Sun Yet-sen University Cancer Center. Backbone chemotherapies included FOLFIRI (45.6 %), FOLFOX (34.9 %), and XELOX (19.5 %). Effectiveness data, safety profiles, and treatment patterns were collected and compared between oxaliplatin- and irinotecan-based groups. The median treatment durations of bevacizumab in first-line and total were equivalent between oxaliplatin- and irinotecan-based group (5.0 vs. 4.8 and 6.0 vs. 5.9 months, respectively). Median progression-free survival (PFS) was 10.6 months, and median overall survival (OS) was 24.2 months in entire population. No significant difference was found between irinotecan- and oxaliplatin-based groups in PFS (10.8 vs. 10.1 months, p = 0.21) or in OS (27.5 vs. 23.7 months, p = 0.68). Overall response rate in entire population was 38.3 %, and the disease control rate was 86.3 %. Bevacizumab-associated serious adverse events included hypertension (4.2 %), bleeding (3.6 %), proteinuria (3.0 %), venous thromboembolism (0.6 %), and wound-healing complications (0.6 %). Curative-intent surgery after conversion chemotherapy was carried out in 23 patients (13.7 %). Multivariate analyses showed that maintenance therapy (p = 0.001), resection of metastatic sites (p = 0.002), and disease-free interval (p = 0.003) were independent prognostic factors for OS survival. In spite of small discrepancies in treatment patterns, irinotecan- and oxaliplatin-based chemotherapeutic regimens are equally compatible partners for bevacizumab in first-line Chinese mCRC treatment.
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Affiliation(s)
- Long Bai
- Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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Accuracy of Predefined Hypotheses in Colon Cancer Adjuvant Phase III Trials: Observations and Recommendations. CURRENT COLORECTAL CANCER REPORTS 2014. [DOI: 10.1007/s11888-014-0229-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Wang L, Gu GL, Li ZW, Peng YF, Gu J. Abdominoperineal excision following preoperative radiotherapy for rectal cancer: unfavorable prognosis even with negative circumferential resection margin. World J Gastroenterol 2014; 20:9138-9145. [PMID: 25083087 PMCID: PMC4112869 DOI: 10.3748/wjg.v20.i27.9138] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2014] [Revised: 03/10/2014] [Accepted: 04/15/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate whether an abdominoperineal excision (APE) is associated with increased local recurrence (LR) and shortened disease-free survival (DFS) in mid-low rectal cancer with a negative circumferential resection margin (CRM). METHODS 283 consecutive cases of mid-low rectal cancer underwent preoperative 30 Gy/10 F radiotherapy and surgery in Peking University Cancer Hospital between August 2003 and August 2009. Patients with positive CRM and intraoperative distant metastasis were precluded according to exclusion criteria. Survival analyses were performed in patients with APE or non-APE procedures. RESULTS 256 of the 283 (90.5%) cases were enrolled in the analysis, including 78 (30.5%) and 178 (69.5%) cases who received APE and non-APE procedures. Fewer female patients (P = 0.016), lower level of tumor (P = 0.000) and higher body mass index (P = 0.006) were found in the APE group. On univariate analysis, the APE group had a higher LR rate (5.1% vs 1.1%, P = 0.036) and decreased DFS (73.1% vs 83.4%, P = 0.021). On multivariate analysis, APE procedure was also an independent risk factor for LR (HR = 5.960, 1.085-32.728, P = 0.040) and decreased DFS (HR = 2.304, 1.298-4.092, P = 0.004). In stratified analysis for lower rectal cancer, APE procedure was still an independent risk factor for higher LR rate (5.6% vs 0%, P = 0.024) and shortened DFS (91.5% vs 73.6%, P = 0.002). CONCLUSION Following preoperative 30 Gy/10 F radiotherapy, APE procedure was still a predictor for LR and decreased DFS even with negative CRM. More intensive preoperative treatment should be planned for the candidates who are scheduled to receive APE with optimal imaging assessment.
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Abstract
INTRODUCTION Debate persists regarding the relationship between mucin expression and outcome in colon cancer. This arises due to discrepancy in the definition of mucinous adenocarcinoma and the combination of both colon and rectal cancers in analyses. This study examines the relationship between increased mucin production and outcomes in colon cancer. METHODS Cases were classified according to the World Health Organization classification of mucinous adenocarcinoma of the colon. Accordingly, tumors were categorized as either (a) mucinous adenocarcinoma of the colon (greater than 50% of the extracellular matrix occupied by mucin) or (b) non-mucinous adenocarcinoma of the colon. Overall survival and disease-free survival were calculated. A stepwise Cox proportional hazards regression model was employed to determine the risk of death/disease recurrence. Kaplan-Meier estimates of overall survival and disease-free survival were plotted for each group and compared using a log-rank test. RESULTS On univariate analysis, mucinous adenocarcinoma was associated with reduced risk of death (P = 0.01). On multivariate analysis, mucinous adenocarcinoma was also associated with reduced risk of death (hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.14-0.79, P = 0.01). Kaplan-Meier estimates confirmed improved rate of survival in the mucinous vs. non-mucinous group (P = 0.01). Mucinous adenocarcinoma did not affect disease-free survival (HR 0.75, 95% CI 0.46-1.21, P = 0.22). A comparison of Kaplan-Meier estimates for systemic recurrence demonstrated significant increases in systemic recurrence in the group with no mucin production (P = 0.04) but not for locoregional recurrence (P = 0.24). CONCLUSIONS Histopathological evidence of mucinous adenocarcinoma in colon cancer is associated with improved outcomes.
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Assessment of progression-free survival as a surrogate end-point for overall survival in patients with metastatic renal cell carcinoma. Eur J Cancer 2014; 50:1766-1771. [PMID: 24768571 DOI: 10.1016/j.ejca.2014.03.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Revised: 03/07/2014] [Accepted: 03/11/2014] [Indexed: 11/22/2022]
Abstract
BACKGROUND To determine suitability of progression-free survival (PFS) as a surrogate end-point for overall survival (OS), we evaluated the relationship between PFS and OS in 750 treatment-naïve metastatic renal cell carcinoma (mRCC) patients who received sunitinib or interferon-alpha (IFN-α) in a phase III study. METHODS The relationship between PFS and post-progression survival (PPS; the difference between PFS and OS) was studied, which correctly removes inherent dependencies between PFS and OS, to properly estimate whether and to what extent PFS can serve as a surrogate for OS. A Weibull parametric model to failure time data was fit to determine whether longer PFS was significantly and meaningfully predictive of longer PPS. In a sensitivity analysis by Kaplan-Meier non-parametric method, PPS curves for three approximately equal numbered groups of patients categorised by PFS were compared by log-rank test. RESULTS In the Weibull parametric model, longer PFS was significantly predictive of longer PPS (P<0.001). The model also allowed prediction of estimated median PPS duration from actual PFS times. In the Kaplan-Meier (non-parametric) analysis, incrementally longer PFS was also associated with longer PPS, and the PPS curves for the three PFS groups were significantly different (P<0.0001). CONCLUSIONS A positive relationship was found between PFS and PPS duration in individual mRCC patients randomised to first-line treatment with sunitinib or IFN-α. These results indicate that PFS can act as a surrogate end-point for OS in the first-line mRCC setting and provide clinical researchers with a potentially useful approach to estimate median PPS based on PFS.
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Jeon J, Sato K, Niedzwiecki D, Ye X, Saltz LB, Mayer RJ, Mowat RB, Whittom R, Hantel A, Benson A, Wigler DS, Atienza D, Messino M, Kindler H, Venook A, Fuchs CS, Meyerhardt JA. Impact of physical activity after cancer diagnosis on survival in patients with recurrent colon cancer: Findings from CALGB 89803/Alliance. Clin Colorectal Cancer 2013; 12:233-8. [PMID: 24035029 PMCID: PMC3818492 DOI: 10.1016/j.clcc.2013.06.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2013] [Revised: 05/24/2013] [Accepted: 06/17/2013] [Indexed: 12/17/2022]
Abstract
BACKGROUND The impact of physical activity on survival outcomes in patients with recurrent colon cancer has not been studied. We tested the association between the level of postdiagnosis physical activity and survival outcomes of patients with recurrent colon cancer. PATIENTS AND METHODS We conducted a prospective observational study of 237 patients with stage III colon cancer who had recurrence of disease. Physical activity was measured approximately 6 months after the completion of therapy (14 months after surgical resection) but before detection of recurrent disease. The primary end point of the study was survival time after recurrence. RESULTS The hazard ratio comparing patients who reported at least 18 metabolic equivalent task (MET) hours per week of physical activity with those engaging in < 3 MET hours per week was 0.71 (95% confidence interval, 0.46-1.11). Increasing total MET hours of physical activity per week was associated with a borderline statistical significance trend for improved survival after recurrence (P = .052). The benefit of physical activity on survival was not significantly modified by sex, body mass index (BMI), number of positive lymph nodes, age, baseline performance status, adjuvant chemotherapy regimen, or recurrence-free survival period. CONCLUSION To our knowledge, this is the first study investigating the association of physical activity with survival outcome of patients with recurrent colon cancer. Although the association exceeded our predefined P trend < .05 for statistical significance, these findings warrant further studies of physical activity in patients with recurrent colorectal cancer.
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Affiliation(s)
- Justin Jeon
- Dana-Farber Cancer Institute, Boston, MA; Department of Sport and Leisure Studies, College of Science in Education, Yonsei University, Seoul, Korea
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Shi Q, Andre T, Grothey A, Yothers G, Hamilton SR, Bot BM, Haller DG, Van Cutsem E, Twelves C, Benedetti JK, O'Connell MJ, Sargent DJ. Comparison of outcomes after fluorouracil-based adjuvant therapy for stages II and III colon cancer between 1978 to 1995 and 1996 to 2007: evidence of stage migration from the ACCENT database. J Clin Oncol 2013; 31:3656-63. [PMID: 23980089 DOI: 10.1200/jco.2013.49.4344] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
PURPOSE With improved patient care, better diagnosis, and more treatment options after tumor recurrence, outcomes after fluorouracil (FU) -based treatment are expected to have improved over time in early-stage colon cancer. Data from 18,449 patients enrolled onto 21 phase III trials conducted from 1978 to 2002 were evaluated for potential differences in time to recurrence (TTR), time from recurrence to death (TRD), and overall survival (OS) with regard to FU-based adjuvant regimens. METHODS Trials were predefined as old versus newer era using initial accrual before or after 1995. Outcomes were compared between patients enrolled onto old- or newer-era trials, stratified by stage. RESULTS Within the first 3 years, recurrence rates were lower in newer- versus old-era trials for patients with stage II disease, with no differences among those with stage III disease. Both TRD and OS were significantly longer in newer-era trials overall and within each stage. The lymph node (LN) ratio (ie, number of positive nodes divided by total nodes harvested) in those with stage III disease declined over time. TTR improved slightly, with larger number of LNs examined in both stages. CONCLUSION Improved TRD in newer trials supports the premise that more aggressive intervention (oxaliplatin- and irinotecan-based chemotherapy and/or surgery for recurrent disease) improves OS for patients previously treated in the adjuvant setting. Lower recurrence rates with identical treatments in those with stage II disease enrolled onto newer-era trials reflect stage migration over time, calling into question historical data related to the benefit of FU-based adjuvant therapy in such patients.
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Affiliation(s)
- Qian Shi
- Qian Shi, Axel Grothey, Brian M. Bot, and Daniel J. Sargent, North Central Cancer Treatment Group, Mayo Clinic, Rochester, MN; Thierry Andre, Hôpital Saint Antoine, Paris, France; Greg Yothers and Michael J. O'Connell, National Surgical Adjuvant Breast and Bowel Project, Pittsburgh; Daniel G. Haller, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Stanley R. Hamilton, University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Bot, Sage Bionetworks; Jacqueline K. Benedetti, Southwest Oncology Group Statistical Center, Seattle, WA; Eric Van Cutsem, University Hospital Gasthuisberg, Gasthuisberg, Belgium; and Chris Twelves, St James's University Hospital, Leeds, United Kingdom
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Kirkwood JM, Tarhini A, Sparano JA, Patel P, Schiller JH, Vergo MT, Benson Iii AB, Tawbi H. Comparative clinical benefits of systemic adjuvant therapy for paradigm solid tumors. Cancer Treat Rev 2013; 39:27-43. [PMID: 22520262 PMCID: PMC8555872 DOI: 10.1016/j.ctrv.2012.03.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2011] [Revised: 03/16/2012] [Accepted: 03/18/2012] [Indexed: 01/15/2023]
Abstract
Adjuvant therapy employing cytotoxic chemotherapy, molecularly targeted agents, immunologic, and hormonal agents has shown a significant impact upon a variety of solid tumors. The principles that guide adjuvant therapy differ among various tumor types and specific modalities, but generally indicate a greater impact of therapy in the postsurgical setting of micrometastatic disease, for which adjuvant therapy is commonly pursued, vs. the setting of gross unresectable disease. This review of adjuvant therapies in current use for five major solid tumors highlights the rationale for current effective adjuvant therapy, and draws comparisons between the adjuvant regimens that have found application in solid tumors.
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Affiliation(s)
- John M Kirkwood
- University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1862, USA.
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van Steenbergen LN, Lemmens VEPP, Rutten HJT, Wymenga ANM, Nortier JWR, Janssen-Heijnen MLG. Increased adjuvant treatment and improved survival in elderly stage III colon cancer patients in The Netherlands. Ann Oncol 2012; 23:2805-2811. [PMID: 22562836 DOI: 10.1093/annonc/mds102] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND We determined to what extent patients with colon cancer stage III ≥ 75 years received adjuvant chemotherapy and the impact on overall and disease-specific survival. PATIENTS AND METHODS Data from The Netherlands Cancer Registry on all 8051 patients with colon cancer stage III ≥ 75 years diagnosed in 1997-2009 were included. Trends in adjuvant chemotherapy administration were analysed and multivariable overall and disease-specific survival analyses were performed. RESULTS The proportion of stage III colon cancer patients ≥ 75 years who received adjuvant chemotherapy increased from 12%in 1997-2000 to 23% in 2007-2009 (P < 0.0001), with a marked age gradient and large geographic variation. Five-year overall survival increased over time from 28% in 1997-2000 to 35% in 2004-2006 (P < 0.0001). Sixty percent of patients died of colorectal cancer. Adjuvant chemotherapy was the strongest positive predictor of survival in this retrospective study (hazard ratio = 0.5; 95% confidence interval: 0.4-0.5). CONCLUSION There has been an increase in administration of adjuvant chemotherapy to elderly patients with stage III colon cancer in The Netherlands since 1997. Survival of elderly patients with stage III colon cancer increased over time, at least partly due to stage migration. The large effect of adjuvant chemotherapy on survival in this study is likely to be associated with the selection of fitter patients for adjuvant treatment.
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Affiliation(s)
| | - V E P P Lemmens
- Eindhoven Cancer Registry, Comprehensive Cancer Centre South, Eindhoven; Department of Public Health, Erasmus University Medical Centre, Rotterdam
| | - H J T Rutten
- Department of Surgery, Catharina Hospital, Eindhoven
| | - A N M Wymenga
- Department of Internal Medicine, Medisch Spectrum Twente, Enschede
| | | | - M L G Janssen-Heijnen
- Eindhoven Cancer Registry, Comprehensive Cancer Centre South, Eindhoven; Department of Clinical Epidemiology, Viecuri Medical Centre, Venlo, The Netherlands
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Sherrill B, Kaye JA, Sandin R, Cappelleri JC, Chen C. Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology. Onco Targets Ther 2012; 5:287-96. [PMID: 23109809 PMCID: PMC3481854 DOI: 10.2147/ott.s36683] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Overall survival (OS) is the gold standard in measuring the treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data, and surrogate endpoints are often used instead. Meta-analyses have been widely used for the validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology studies and examined the extent of correlation between surrogate endpoints and OS for different cancer types. A search was conducted in October 2010 to compile available published evidence in the English language for the validation of disease progression-related endpoints as surrogates of OS, based on meta-analyses. We summarize published meta-analyses that quantified the correlation between progression-based endpoints and OS for multiple advanced solid-tumor types. We also discuss issues that affect the interpretation of these findings. Progression-free survival is the most commonly used surrogate measure in studies of advanced solid tumors, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and the availability of second-/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on progression-free survival and OS in additional tumor types.
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Affiliation(s)
- Beth Sherrill
- RTI Health Solutions, Biometrics, Research Triangle Park, NC, USA
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Lee SH. From Evidence-based Medicine to Personalized Medicine. JOURNAL OF THE KOREAN SOCIETY OF COLOPROCTOLOGY 2012; 28:228-229. [PMID: 23185701 PMCID: PMC3499422 DOI: 10.3393/jksc.2012.28.5.228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Suk-Hwan Lee
- Department of Surgery, Kyung Hee University School of Medicine, Seoul, Korea
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Mayer RJ. Oxaliplatin as part of adjuvant therapy for colon cancer: more complicated than once thought. J Clin Oncol 2012; 30:3325-7. [PMID: 22915653 DOI: 10.1200/jco.2012.44.1949] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
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Gene Signatures in Stage II Colon Cancer: A Clinical Review. CURRENT COLORECTAL CANCER REPORTS 2012; 8:225-231. [PMID: 23002390 DOI: 10.1007/s11888-012-0132-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
Understanding the biology of cancer is the key to understanding its behavior. Stage II colon cancers represent a unique treatment challenge for medical oncologists because they contain a very heterogeneous group of tumors with a wide range of recurrence risks after resection. Defining these differences in biology can help to explain differences in behavior. To this end, gene signatures have been developed to define various prognostic groups beyond the clinicopathologic features alone. Adjuvant chemotherapy for stage II colon cancers as a group has not shown survival advantage in clinical trials. Future research to develop gene signatures to predict a group that will benefit from adjuvant chemotherapy will be helpful in the clinical decision-making process. The purpose of this review is to present the prognostic gene signatures currently available for use, those in development, and their utility in stratifying recurrence risk in stage II colon cancer patients.
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A systematic review evaluating the relationship between progression free survival and post progression survival in advanced ovarian cancer. Gynecol Oncol 2012; 125:493-9. [DOI: 10.1016/j.ygyno.2011.12.420] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2011] [Revised: 11/28/2011] [Accepted: 12/01/2011] [Indexed: 11/20/2022]
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Adjuvant interferon therapy for patients at high risk for recurrent melanoma: an updated systematic review. Clin Oncol (R Coll Radiol) 2012; 24:410-2. [PMID: 22521078 DOI: 10.1016/j.clon.2012.03.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Accepted: 03/27/2012] [Indexed: 11/23/2022]
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Bonnetain F, Bosset JF, Gerard JP, Calais G, Conroy T, Mineur L, Bouché O, Maingon P, Chapet O, Radosevic-Jelic L, Methy N, Collette L. What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer in a pooled analysis of EORTC 22921 and FFCD 9203 trials: surrogacy in question? Eur J Cancer 2012; 48:1781-90. [PMID: 22507892 DOI: 10.1016/j.ejca.2012.03.016] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2011] [Revised: 02/22/2012] [Accepted: 03/19/2012] [Indexed: 01/08/2023]
Abstract
BACKGROUND Two phase III trials of neoadjuvant treatment in T3-4 rectal cancer established that adding chemotherapy (CRT) to radiotherapy (RT) improves pathological complete response (pCR) and local control (LC). We combined trials to assess the clinical benefit of CRT on overall (OS) and progression free survival (PFS) and to explore the surrogacy of pCR and LC. PATIENTS AND METHODS Individual patient data from European Organisation for Research and Treatment of Cancer (EORTC) 22921 (1011 patients) and FFCD 9203 (756 patients) were pooled. Meta-analysis methodology was used to compare neoadjuvant CRT to RT for OS, PFS LC and distant progression (DP). Weighted linear regression was used to estimate trial-level association (surrogacy R(2)) between treatment effects on candidate surrogate (pCR, LC, DP) and OS. RESULTS The median follow-up was 5.6 years. Compared to RT (881 pts), CRT (886 pts) did not prolong OS, DP or PFS. The 5-y OS-rate was 66.3% with CRT versus 65.9% in RT (hazard ratios (HR) = 1.04 {0.88-1.21}). CRT significantly improved LC (HR = 0.54, 95%confidence interval (CI): 0.41-0.72). PFS was validated as surrogate for OS with R(2) = 0.88. Neoadjuvant treatment effects on LC (R(2) = 0.17) or DP (R(2) = 0.31) did not predict effects on OS. CONCLUSION Preoperative CRT does not prolong OS or PFS. pCR or LC do not qualify as surrogate for PFS or OS while PFS is surrogate. Phase III trials should use OS or PFS as primary endpoint.
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Affiliation(s)
- F Bonnetain
- Biostatistics and Epidemiology Department, EA 4184 Centre Georges François Leclerc & FFCD, Dijon, France.
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