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Wang F, Chen G, Zhang Z, Yuan Y, Wang Y, Gao Y, Sheng W, Wang Z, Li X, Yuan X, Cai S, Ren L, Liu Y, Xu J, Zhang Y, Liang H, Wang X, Zhou A, Ying J, Li G, Cai M, Ji G, Li T, Wang J, Hu H, Nan K, Wang L, Zhang S, Li J, Xu R. The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update. Cancer Commun (Lond) 2025; 45:332-379. [PMID: 39739441 PMCID: PMC11947620 DOI: 10.1002/cac2.12639] [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: 11/27/2024] [Accepted: 12/02/2024] [Indexed: 01/02/2025] Open
Abstract
The 2024 updates of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China, highlighting the latest advancements in evidence-based medicine, healthcare resource access, and precision medicine in oncology. These updates address disparities in epidemiological trends, clinicopathological characteristics, tumor biology, treatment approaches, and drug selection for colorectal cancer patients across diverse regions and backgrounds. Key revisions include adjustments to evidence levels for intensive treatment strategies, updates to regimens for deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) patients, proficient mismatch repair (pMMR)/ microsatellite stability (MSS) patients who have failed standard therapies, and rectal cancer patients with low recurrence risk. Additionally, recommendations for digital rectal examination and DNA polymerase epsilon (POLE)/ DNA polymerase delta 1 (POLD1) gene mutation testing have been strengthened. The 2024 CSCO Guidelines are based on both Chinese and international clinical research, as well as expert consensus, ensuring their relevance and applicability in clinical practice, while maintaining a commitment to scientific rigor, impartiality, and timely updates.
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Affiliation(s)
- Feng Wang
- Department of Medical OncologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical SciencesGuangzhouGuangdongP. R. China
| | - Gong Chen
- Department of Colorectal SurgerySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerGuangzhouGuangdongP. R. China
| | - Zhen Zhang
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Ying Yuan
- Department of Medical OncologyThe Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Yi Wang
- Department of RadiologyPeking University People's HospitalBeijingP. R. China
| | - Yuan‐Hong Gao
- Department of Radiation OncologySun Yat‐sen University Cancer Centre, The State Key Laboratory of Oncology in South ChinaGuangzhouGuangdongP. R. China
| | - Weiqi Sheng
- Department of PathologyFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Zixian Wang
- Department of Medical OncologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical SciencesGuangzhouGuangdongP. R. China
| | - Xinxiang Li
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Xianglin Yuan
- Department of OncologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanHubeiP. R. China
| | - Sanjun Cai
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Li Ren
- Department of General SurgeryZhongshan HospitalFudan UniversityShanghaiP. R. China
| | - Yunpeng Liu
- Department of Medical OncologyThe First Hospital of China Medical UniversityShenyangLiaoningP. R. China
| | - Jianmin Xu
- Department of General SurgeryZhongshan HospitalFudan UniversityShanghaiP. R. China
| | - Yanqiao Zhang
- Department of OncologyHarbin Medical University Cancer HospitalHarbinHeilongjiangP. R. China
| | - Houjie Liang
- Department of OncologySouthwest HospitalThird Military Medical University (Army Medical University)ChongqingP. R. China
| | - Xicheng Wang
- Department of Gastrointestinal OncologyCancer Medical Center, Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina
| | - Aiping Zhou
- Department of Medical OncologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Jianming Ying
- Department of PathologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Guichao Li
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Muyan Cai
- Department of PathologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South ChinaGuangzhouGuangdongP. R. China
| | - Gang Ji
- Department of Gastrointestinal SurgeryXijing HospitalAir Force Military Medical UniversityXi'anShaanxiP. R. China
| | - Taiyuan Li
- Department of General SurgeryThe First Affiliated Hospital of Nanchang UniversityNanchangJiangxiP. R. China
| | - Jingyu Wang
- Department of RadiologyThe First Hospital of Jilin UniversityChangchunJilinP. R. China
| | - Hanguang Hu
- Department of Medical OncologyThe Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Kejun Nan
- Department of Medical OncologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiP. R. China
| | - Liuhong Wang
- Department of RadiologySecond Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Suzhan Zhang
- Department of Colorectal SurgeryThe Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Jin Li
- Department of Medical OncologyShanghai GoBroad Cancer HospitalChina Pharmaceutical UniversityShanghaiP. R. China
| | - Rui‐Hua Xu
- Department of Medical OncologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat‐sen University, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical SciencesGuangzhouGuangdongP. R. China
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Takakura T, Shimizu T, Yamamoto N. Antibody-drug conjugates in solid tumors; new strategy for cancer therapy. Jpn J Clin Oncol 2024; 54:837-846. [PMID: 38704241 PMCID: PMC11322887 DOI: 10.1093/jjco/hyae054] [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: 12/30/2023] [Accepted: 04/12/2024] [Indexed: 05/06/2024] Open
Abstract
Antibody-drug conjugates (ADCs) have emerged as a novel class of anticancer treatment. ADCs are composed of three parts: a monoclonal antibody, a linker and a payload. A monoclonal antibody binds to the specific antigen present at the cancer cells, allowing selective delivery of the cytotoxic agents to the tumor site. Several ADCs are approved by the US Food and Drug Administration for the treatment of hematologic cancers and solid tumors with clinically meaningful survival benefit. However, the development of ADCs faces a lot of challenges and there is a need to get better understanding of ADCs in order to improve patient outcomes. Here, we briefly discuss the structure and mechanism of ADCs, as well as the clinical data of current approved ADCs in solid tumors.
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Affiliation(s)
- Toshiaki Takakura
- Department of Pulmonary Medicine and Medical Oncology, Wakayama Medical University Faculty of Medicine, 811-1 Kimiidera, Wakayama, Wakayama 641-8510, Japan
| | - Toshio Shimizu
- Department of Pulmonary Medicine and Medical Oncology, Wakayama Medical University Faculty of Medicine, 811-1 Kimiidera, Wakayama, Wakayama 641-8510, Japan
| | - Nobuyuki Yamamoto
- Department of Pulmonary Medicine and Medical Oncology, Wakayama Medical University Faculty of Medicine, 811-1 Kimiidera, Wakayama, Wakayama 641-8510, Japan
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Tarantino P, Ricciuti B, Pradhan SM, Tolaney SM. Optimizing the safety of antibody-drug conjugates for patients with solid tumours. Nat Rev Clin Oncol 2023:10.1038/s41571-023-00783-w. [PMID: 37296177 DOI: 10.1038/s41571-023-00783-w] [Citation(s) in RCA: 91] [Impact Index Per Article: 45.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/11/2023] [Indexed: 06/12/2023]
Abstract
Over the past 5 years, improvements in the design of antibody-drug conjugates (ADCs) have enabled major advances that have reshaped the treatment of several advanced-stage solid tumours. Considering the intended rationale behind the design of ADCs, which is to achieve targeted delivery of cytotoxic molecules by linking them to antibodies targeting tumour-specific antigens, ADCs would be expected to be less toxic than conventional chemotherapy. However, most ADCs are still burdened by off-target toxicities that resemble those of the cytotoxic payload as well as on-target toxicities and other poorly understood and potentially life-threatening adverse effects. Given the rapid expansion in the clinical indications of ADCs, including use in curative settings and various combinations, extensive efforts are ongoing to improve their safety. Approaches currently being pursued include clinical trials optimizing the dose and treatment schedule, modifications of each ADC component, identification of predictive biomarkers for toxicities, and the development of innovative diagnostic tools. In this Review, we describe the determinants of the toxicities of ADCs in patients with solid tumours, highlighting key strategies that are expected to improve tolerability and enable improvements in the treatment outcomes of patients with advanced-stage and those with early stage cancers in the years to come.
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Affiliation(s)
- Paolo Tarantino
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
- Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Biagio Ricciuti
- Harvard Medical School, Boston, MA, USA
- Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Shan M Pradhan
- Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA
| | - Sara M Tolaney
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
- Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.
- Harvard Medical School, Boston, MA, USA.
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Chen Y, Shankaran V, Hahn EE, Haupt EC, Bansal A. Underutilization or appropriate care? Assessing adjuvant chemotherapy use and survival in 3 heterogenous subpopulations with stage II/III colorectal cancer within a large integrated health system. J Manag Care Spec Pharm 2023; 29:635-646. [PMID: 37276035 PMCID: PMC10387960 DOI: 10.18553/jmcp.2023.29.6.635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
BACKGROUND: Clinical guidelines have recommended adjuvant chemotherapy (ACT) for patients with high-risk stage II colon cancer, although the survival benefit is unclear. ACT is also recommended for patients with stage III colon cancer to reduce the risk of recurrence and mortality. For stage II/III rectal cancer, however, the role of perioperative chemotherapy (PCT, adjuvant or neoadjuvant) remains controversial, resulting in substantial variation in its use in clinical practice. OBJECTIVES: To understand real-world use and predictors of ACT or PCT use and survival outcomes in 3 heterogeneous patient groups with colorectal cancer (CRC), and to inform the evidence gap between guideline-based care and clinical practice. METHODS: This retrospective cohort study included patients with an initial stage II/III CRC diagnosis between 2008 and 2013 identified from Kaiser Permanente Southern California electronic health record databases. Patients were eligible if they were aged 18-74 years at diagnosis and received primary curative surgery. We fitted mixed effects logistic regression models to evaluate predictors of ACT receipt and Cox proportional hazards models on propensity score-matched (PS-matched) samples to assess the association between ACT/PCT receipt and survival. RESULTS: We included 1,690 patients with colon cancer (stage II: 820 and stage III: 870) and 587 patients with rectal cancer (stage II: 241 and stage III: 346). We found that 65% of patients with high-risk stage II colon cancer, 15% of those with stage III colon, and 15% of those with stage II/III rectal cancer did not receive ACT/PCT. Patients with stage II colon cancer with T4 stage (odds ratio [OR] = 5.79, 95% CI = 3.33 - 10.06) and a lower comorbidity score were more likely to receive ACT (high vs low Charlson score: OR = 0.69, 95% CI = 0.55 - 0.87). Patients with stage III rectal cancer were more likely to receive PCT than those with stage II disease (OR = 7.85, 95% CI = 2.07 - 29.74). Patients with another cancer diagnosis prior to CRC diagnosis were less likely to receive PCT (OR = 0.37, 95% CI = 0.16 - 0.85). ACT/PCT use was associated with improved overall survival among patients with high-risk stage II colon cancer (PS-matched hazard ratio [HR] = 0.42, 95% CI = 0.25 - 0.70) and those with stage III CRC (stage III colon: PS-matched HR = 0.3, 95% CI = 0.25 - 0.36; stage III rectal: PS-matched HR = 0.2, 95% CI = 0.13 - 0.31). CONCLUSIONS: We found potential underuse of appropriate chemotherapy treatment in patients with high-risk stage II colon cancer and stage III CRC. Clinicians' and providers' decisions on ACT administration may not be fully guided by the risk of recurrence and 5-year survival benefits in stage II colon cancer. DISCLOSURES: This research was supported by the National Cancer Institute of the National Institutes of Health (NIH) (under R37-CA218413). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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Affiliation(s)
- Yilin Chen
- CHOICE Institute, School of Pharmacy, University of Washington, Seattle
| | - Veena Shankaran
- Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, and Division of Medical Oncology, University of Washington, Seattle
| | - Erin E Hahn
- Department of Health Systems Sciences, Bernard J. Tyson School of Medicine, Kaiser Permanente, Pasadena, CA
- Department of Research and Evaluation, Kaiser Permanente, Pasadena, CA
| | - Eric C Haupt
- Department of Research and Evaluation, Kaiser Permanente, Pasadena, CA
| | - Aasthaa Bansal
- CHOICE Institute, School of Pharmacy, University of Washington, Seattle
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Atci MM, Akagunduz B, Demir M, Arikan R, Ay S, Ozer M, Ayhan M, Cil I, Demir N, Ozyurt N, Karakaya G, Cevik GT, Onder AH, Selvi O, Sakin A. The impact of adjuvant oxaliplatin and tumor sidedness on the overall survival of stage IIB colon cancer patients: a multicentre study. J Chemother 2023; 35:19-28. [PMID: 35174772 DOI: 10.1080/1120009x.2022.2040770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
The aim of this multicentre retrospective study was to compare the efficacy of adjuvant chemotherapy regimens both with and without oxaliplatin and tumor sidedness in stage IIB (pT4aN0) colon cancer patients. This study included patients with stage IIB colon cancer who underwent curative surgery and received adjuvant chemotherapy. The patients were divided into two groups (one with and one without oxaliplatin) to compare the overall survival (OS) in right- and left-sided tumors. The study population included 298 patients with stage IIB colon cancer (median age: 57) of whom 69.1% were male. Forty-four per cent of these patients (n = 131) were diagnosed with right-sided colon cancer. The median follow-up duration was 35.9 months. In the entire population, a median OS was not reached, and the five-year OS was 83%. The median disease-free survival (DFS) was 12 months. There was no significant difference in terms of the five-year OS between right- (82%) and left-sided (84%) colon tumors (p = 0.67). In addition, the five-year OS of patients treated with and without oxaliplatin were 76% and 89%, respectively, and there was no statistically significant difference (p = 0.23). The five-year OS of the patients treated with and without oxaliplatin were 83% and 96.5%, respectively, (p = 0.8) in right-sided colon tumors, while it was 75% and 93% (p = 0.06), respectively, in left-sided colon tumors. Tumor sidedness and the addition of oxaliplatin to adjuvant chemotherapy were not found to be associated with the OS in stage IIB colon cancer patients in our study. Further large prospective studies that also include MSI, RAS and BRAF status data are warranted in colon cancer patients.
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Affiliation(s)
- Muhammed Mustafa Atci
- Department of Medical Oncology, University of Health Sciences, Professor Doctor Cemil Tascioglu Istanbul City Hospital, İstanbul, Turkey
| | - Baran Akagunduz
- Department of Medical Oncology, Erzincan Binali Yıldrıım University Medical School, Erzincan, Turkey
| | - Metin Demir
- Department of Medical Oncology, Erzurum Training and Research Hospital, Erzurum, Turkey
| | - Rukiye Arikan
- Department of Medical Oncology, Marmara University Medical School, Istanbul, Turkey
| | - Seval Ay
- Department of Medical Oncology, Istanbul Medeniyet University, Goztepe Education and Research Hospital, Istanbul, Turkey
| | - Muhammet Ozer
- Department of Internal Medicine, Capital Health Regional Medical Center, Trenton, United States
| | - Murat Ayhan
- Department of Medical Oncology, Kartal Lutfi Kırdar Research Hospital, Istanbul, Turkey
| | - Ibrahim Cil
- Department of Medical Oncology, University of Health Sciences, Umranıye training and Research hospital, Istanbul, Turkey
| | - Nazan Demir
- Department of Medical Oncology, Eskisehir Osmangazi University Medical School, Eskişehir
| | - Neslihan Ozyurt
- Department of Medical Oncology, Gıresun Research Hospital, Gıresun, Turkey
| | - Gökhan Karakaya
- Department of Medical Oncology, Mardın, Research Hospital, Mardın, Turkey
| | | | - Arif Hakan Onder
- Department of Medical Oncology, University of Health Sciences, Antalya training and Research hospital, Antalya, Turkey
| | - Oguzhan Selvi
- Department of Medical Oncology, University of Health Sciences, Professor Doctor Cemil Tascioglu Istanbul City Hospital, İstanbul, Turkey
| | - Abdullah Sakin
- Department of Medical Oncology, University of Health Sciences, Professor Doctor Cemil Tascioglu Istanbul City Hospital, İstanbul, Turkey
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Hanna CR, Lemmon E, Hall PS, Ennis H, Morris E, McLoone P, Boyd KA, Jones RJ. Cancer Trial Impact: Understanding Implementation of the Short Course Oncology Treatment (SCOT) Trial Findings in colorectal cancer at a National Level. Clin Oncol (R Coll Radiol) 2022; 34:554-560. [PMID: 35370039 DOI: 10.1016/j.clon.2022.03.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 02/16/2022] [Accepted: 03/16/2022] [Indexed: 11/28/2022]
Abstract
AIMS The Short Course Oncology Treatment (SCOT) trial indicated that 3 months of adjuvant doublet chemotherapy was non-inferior to 6 months of treatment for patients with colorectal cancer, with considerably less toxicity. The SCOT trial results were disseminated in June 2017. The aim of this study was to understand if SCOT trial findings were implemented in Scotland. MATERIALS AND METHODS A retrospective analysis was carried out on a dataset derived from a source population of 5.4 million people. Eligible patients were those with stage II or III colorectal cancer who received adjuvant chemotherapy. Logistic regression was applied to understand the extent of practice change to a 3-month adjuvant chemotherapy duration after the SCOT trial results were disseminated. Interrupted time series analysis was used to visualise differences in prescribing trends before and after June 2017 for the overall cohort, and by SCOT trial eligibility. RESULTS In total, 2310 patients were included in the study; 1957 and 353 treated pre- and post-June 2017, respectively. The median treatment duration decreased from 21 weeks (interquartile range 14-24) prior to June 2017 to 12 weeks (interquartile range 12-21 weeks) after June 2017 (P < 0.001). The proportion of patients receiving over 3 months of adjuvant treatment decreased from 75% to 42% (P < 0.001). This change was most noticeable for patients who met the SCOT trial eligibility criteria, and specifically for those with low-risk stage III disease and those treated with capecitabine and oxaliplatin (CAPOX). Although practice change occurred in all locations, there were differences between regions that could be explained by pre-SCOT trial prescribing trends. DISCUSSION A significant change in chemotherapy prescribing occurred after dissemination of the SCOT trial results. National, real-world data can be used to capture the extent of implementation of clinical trial results. In this case, implementation was aligned with clinical trial subgroup findings. This type of analysis could be conducted to evaluate the impact of other clinical trials.
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Affiliation(s)
- C R Hanna
- CRUK Glasgow Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
| | - E Lemmon
- Edinburgh Health Economics, Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK
| | - P S Hall
- Edinburgh Health Economics, Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK; Edinburgh Cancer Research Centre, Western General Hospital, Edinburgh, UK
| | - H Ennis
- Edinburgh Health Economics, Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK
| | - E Morris
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - P McLoone
- Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK
| | - K A Boyd
- Health Economics & Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - R J Jones
- CRUK Glasgow Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
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Chen Y, Xu M, Ye Q, Xiang J, Xue T, Yang T, Liu L, Yan B. Irregular delay of adjuvant chemotherapy correlated with poor outcome in stage II-III colorectal cancer. BMC Cancer 2022; 22:670. [PMID: 35715761 PMCID: PMC9206266 DOI: 10.1186/s12885-022-09767-y] [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: 03/17/2022] [Accepted: 06/10/2022] [Indexed: 11/10/2022] Open
Abstract
AIMS Adjuvant chemotherapy (ACT) plays an important role in improving the survival of stage II-III colorectal cancer (CRC) patients after curative surgery. However, the prognostic role of irregular delay of ACT (IDacT) for these patients has been less studied. MATERIALS AND METHODS A total of 117 stage II-III CRC patients who underwent radical resection and received at least 3 months ACT were enrolled retrospectively. The significance of IDacT, including total delay (TD) and delay per cycle (DpC), in predicting disease-free survival (DFS) was determined using receiver operating characteristic curve (ROC) analysis. The survival differences between the TD, DpC-short and DpC-long subgroups were tested using Kaplan-Meier analysis, and risk factors for prognosis were determined using a Cox proportional hazards model. RESULTS Using 35.50 and 3.27 days as the optimal cut-off points for TD and DpC, respectively, ROC analysis revealed that TD and DpC had sensitivities of 43.60% and 59.00% and specificities of 83.30% and 62.80%, respectively, in predicting DFS (both P < 0.05). No differences in the clinicopathological parameters were found between the TD, DpC-short or -long subgroups except histological differentiation in different TD subgroups and combined T stages in different DpC subgroups (both P = 0.04). Patients in the TD or DpC-long group exhibited significantly worse survival than in the -short group (TD: Log rank = 9.11, P < 0.01; DpC: Log rank = 6.09, P = 0.01). DpC was an independent risk factor for prognosis (HR = 2.54, 95% CI: 1.32-4.88, P = 0.01). CONCLUSIONS IDacT had a profound effect on the outcome for stage II-III CRC. Although TD and DpC were significant for the prognosis, DpC was more robust, and patients who presented DpC for a long time had a significantly worse DFS.
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Affiliation(s)
- Yuanyuan Chen
- Department of General Medicine, Hainan Hospital of Chinese PLA General Hospital, Sanya City, Hainan, P.R. China
| | - Mingyue Xu
- Department of General Surgery, Hainan Hospital of Chinese PLA General Hospital, Sanya City, Hainan, P.R. China
| | - Qianwen Ye
- Department of Oncology, Hainan Hospital of Chinese PLA General Hospital, No. 80 of Jianglin Road, Haitang District, Sanya City, Hainan province, 572000, P.R. China
| | - Jia Xiang
- Department of Oncology, Hainan Hospital of Chinese PLA General Hospital, No. 80 of Jianglin Road, Haitang District, Sanya City, Hainan province, 572000, P.R. China
| | - Tianhui Xue
- Department of Oncology, Hainan Hospital of Chinese PLA General Hospital, No. 80 of Jianglin Road, Haitang District, Sanya City, Hainan province, 572000, P.R. China
| | - Tao Yang
- Department of Oncology, Hainan Hospital of Chinese PLA General Hospital, No. 80 of Jianglin Road, Haitang District, Sanya City, Hainan province, 572000, P.R. China
| | - Long Liu
- Department Traditional Chinese Medicine, Tianyou Hospital of Tongji University, No. 528 of Zhennan Road, Putuo District, Shanghai, 200331, P.R. China.
| | - Bing Yan
- Department of Oncology, Hainan Hospital of Chinese PLA General Hospital, No. 80 of Jianglin Road, Haitang District, Sanya City, Hainan province, 572000, P.R. China.
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Hanna CR, Boyd KA, Wincenciak J, Graham J, Iveson T, Jones RJ, Wilson R. Do clinical trials change practice? A longitudinal, international assessment of colorectal cancer prescribing practices. Cancer Treat Res Commun 2021; 28:100445. [PMID: 34425469 DOI: 10.1016/j.ctarc.2021.100445] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Revised: 08/08/2021] [Accepted: 08/10/2021] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Over half of the 1.5 million individuals globally who are diagnosed with colorectal cancer (CRC) present with stage II-III disease. Understanding clinician attitudes towards treatment for this group is paramount to contextualise real-world outcomes and plan future trials. The aim of this study was to assess clinician awareness of trials assessing the optimal duration of CRC adjuvant therapy, their attitudes towards shorter treatment and their self-reported practice. METHODS A survey was developed using OnlineSurveys® and distributed to clinicians in April 2019, with a follow-up survey disseminated to a subset of respondents in August 2020. Microsoft Excel® and Stata® were used for analysis. RESULTS 265 clinicians replied to the first survey, with the majority aware of findings from the International Duration Evaluation of Adjuvant Therapy collaboration and contributory trials. Practice change was greatest for patients under 70 with low-risk stage III CRC, with most uncertainty around using 3-months of doublet chemotherapy for high-risk stage II disease. In August 2020, clinicians (n = 106) were more likely to use 3-months of FOLFOX for low-risk stage III disease and 3-months of CAPOX for stage II disease compared to April 2019. There was no indication that the COVID-19 pandemic had enduring changes on treatment decisions beyond those made in response to trial evidence. DISCUSSION Clinicians use a risk-stratified approach to treat CRC the adjuvant setting. Lower utilisation of doublet chemotherapy for older and stage II patients has affected the extent of trial implementation. Active dialogue regarding how trial results apply to these groups may improve consensus.
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Affiliation(s)
- Catherine R Hanna
- CRUK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow CRUK Clinical Trials Unit Glasgow, 1042 Great Western Road, Glasgow G12 0YN, United Kingdom.
| | - Kathleen A Boyd
- Health Economic and Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow 1 Lilybank Gardens, Glasgow G12 8RZ, United Kingdom
| | - Joanna Wincenciak
- School of Education, University of Glasgow 1 Eldon St, Glasgow G3 6NH, United Kingdom
| | - Janet Graham
- Beatson West of Scotland Cancer Centre and Institute of Cancer Sciences, University of Glasgow 1053 Great Western Road, G12 0YN Wolfson Wohl Cancer Research Centre, Glasgow, United Kingdom.
| | - Timothy Iveson
- University of Southampton University Hospital NHS Foundation Trust, Tremona Road, Southampton SO16 0YD, United Kingdom.
| | - Robert J Jones
- CRUK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow CRUK Clinical Trials Unit Glasgow, 1042 Great Western Road, Glasgow G12 0YN, United Kingdom
| | - Richard Wilson
- Beatson West of Scotland Cancer Centre and Institute of Cancer Sciences, University of Glasgow 1053 Great Western Road, G12 0YN Wolfson Wohl Cancer Research Centre, Glasgow, United Kingdom
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Chen W, Dong H, Wang G, Chen J, Wang W. Effect of the duration of the capecitabine regimen following colon cancer surgery in an elderly population: a retrospective cohort study. World J Surg Oncol 2021; 19:238. [PMID: 34380513 PMCID: PMC8359119 DOI: 10.1186/s12957-021-02348-6] [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: 04/07/2021] [Accepted: 07/28/2021] [Indexed: 12/16/2022] Open
Abstract
Background Only 50–70% of elderly colon cancer patients could complete the recommended 6 months of postoperative chemotherapy. It is unknown whether a shorter duration of postoperative capecitabine-alone chemotherapy would compromise survival. We thus conducted this study to analyze the association between postoperative chemotherapy duration of a capecitabine-alone regimen and cancer-specific survival (CSS) and disease-free survival (DFS) of surgery-treated elderly colon cancer patients. Methods We performed a retrospective cohort study of surgically treated stage III and high-risk stage II colon cancer patients aged ≥ 70 treated at two medical centers. Cox proportional hazard regression models were utilized to calculate crude and adjusted hazard ratios (HRs). The nonlinear relationship between postoperative chemotherapy duration and survival was analyzed through restricted cubic spline regression analysis, and the threshold effect was calculated by the two-piecewise Cox proportional hazard model. Results A total of 1217 surgery-treated colon cancer patients between August 1, 2013, and September 1, 2019, were reviewed, and 257 stage III and high-risk stage II patients aged ≥ 70 were enrolled. Postoperative chemotherapy with capecitabine was administered to 114 patients, and 143 patients only received surgery. As the duration of chemotherapy increased by 1 week, the risk of cancer-specific death was reduced by 11% (HR = 0.89, 95% confidence interval (CI) 0.82–0.96), and the risk of recurrence was reduced by 10% (HR = 0.90, 0.82–0.96). Nonlinearity exploration suggested a threshold effect of capecitabine duration on CSS in stage III disease. The HR for death was 0.79 (95% CI, 0.68–0.92) with duration ≤ 16 weeks and 1.34 (95% CI, 0.91–1.97) with duration > 16 weeks. Conclusions The postoperative capecitabine duration was significantly associated with a decrease in death risk and recurrence risk in elderly colon cancer patients. However, the threshold effect of capecitabine duration on survival suggests that short-term chemotherapy may improve survival in elderly stage III colon cancer patients.
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Affiliation(s)
- Weiwei Chen
- Department of Clinical Medicine, Guizhou Medical University, Guiyang, China.,Department of Abdominal Oncology, Guizhou Province Cancer Hospital, Guiyang, China
| | - Hongmin Dong
- Department of Abdominal Oncology, Guizhou Province Cancer Hospital, Guiyang, China.,Department of Oncology, Affiliated Hospital of Guizhou Medical University, No. 1 Beijing West Road, Guiyang, Guizhou, 550001, China
| | - Gang Wang
- Department of Abdominal Oncology, Guizhou Province Cancer Hospital, Guiyang, China.,Department of Oncology, Affiliated Hospital of Guizhou Medical University, No. 1 Beijing West Road, Guiyang, Guizhou, 550001, China
| | - Juan Chen
- Department of Clinical Medicine, Guizhou Medical University, Guiyang, China.,Department of Abdominal Oncology, Guizhou Province Cancer Hospital, Guiyang, China
| | - Wenling Wang
- Department of Abdominal Oncology, Guizhou Province Cancer Hospital, Guiyang, China. .,Department of Oncology, Affiliated Hospital of Guizhou Medical University, No. 1 Beijing West Road, Guiyang, Guizhou, 550001, China.
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10
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Prasanna T, Yip D. Adjuvant Therapies in Colon Cancer. COLORECTAL CANCER 2021. [DOI: 10.5772/intechopen.93874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Most of the patients with localized colon cancer undergo curative resection. However, significant number of patients will recur with metastatic disease, especially those with node positive cancer. Adjuvant chemotherapy has shown to improve cure rate and survival by eradicating micrometastases. The benefit of adjuvant therapy is well established in node-positive cancers, while their role in stage II cancer is not well defined. A number of molecular markers have been identified that are prognostic and/or predictive in colon cancer. Such molecular markers, and other clinicopathological features play an important role in selection of appropriate therapy and duration of treatment. Emerging evidence for the utility of genomic profiling or detection of circulating tumor DNA (ctDNA) are promising which may further facilitate decision making in the future. This chapter reviews the evolution of adjuvant therapy for resected colon cancer, the current evidence and the factors influence the choice of therapy.
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11
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Taieb J, Karoui M, Basile D. How I treat stage II colon cancer patients. ESMO Open 2021; 6:100184. [PMID: 34237612 PMCID: PMC8264531 DOI: 10.1016/j.esmoop.2021.100184] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 05/19/2021] [Accepted: 05/19/2021] [Indexed: 11/23/2022] Open
Abstract
Stage II colon cancer (CC) is probably one of the best prognosis gastrointestinal tumors seen in our consultations, but often takes a lot of time for physicians to determine appropriate treatment because of the limited benefit of adjuvant chemotherapy (CT) in these patients, together with the limited evidence in this situation. How to choose the best treatment for each individual patient is thus dependent on molecular (microsatellite instability/microsatellite stability status) and clinico-pathological features relevant enough to classify these tumors into low-, intermediate- and high-risk stage II disease and to choose an appropriate attitude for each of these subgroups. In practice, the first step in treatment decision making must be to assess the patient's status and comorbidities to see if the patient is eligible for an adjuvant treatment. Then, as fluoropyrimidines (FPs) are the corner stone of CC adjuvant treatment, screening for dihydropyrimidine dehydrogenase deficiency is mandatory in western countries. Finally, depending on the patient's characteristics and tumor risk stage, the strategy may be surveillance, adjuvant FP alone or oxaliplatin-based adjuvant CT. In the near future, new tools such as Immunoscore® (HalioDx; Luminy Biotech Enterprises, Marseille Cedex, France) and circulating tumor DNA may help to identify more precisely patients with minimal residual disease for more personalized adjuvant treatment approaches.
Stage II CC is a heterogeneous disease with a complex management due to the limited data and benefit of adjuvant CT. Risk stratification through prognostic parameters is crucial to aid clinicians in determining the appropriate therapy. Lymph node sampling <12 and pT4 are currently recognized as the major prognostic features associated with worse survival. Adjuvant CT should be considered by incorporating prognostic features and balanced against patient's age and comorbidities.
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Affiliation(s)
- J Taieb
- Departments of Gastroenterology and Digestive Oncology, Assistance Publique-Hôpitaux de Paris (AP-HP-Paris Centre), Université de Paris, Paris, France; Georges-Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP-Paris Centre), Université de Paris, Paris, France.
| | - M Karoui
- Departments of Gastroenterology and Digestive Oncology, Assistance Publique-Hôpitaux de Paris (AP-HP-Paris Centre), Université de Paris, Paris, France; Georges-Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP-Paris Centre), Université de Paris, Paris, France
| | - D Basile
- Departments of Gastroenterology and Digestive Oncology, Assistance Publique-Hôpitaux de Paris (AP-HP-Paris Centre), Université de Paris, Paris, France; Department of Medicine (DAME), University of Udine, Udine, Italy; Department of Oncology, San Bortolo Hospital, AULSS8 Berica, Vicenza, Italy
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12
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Azcue P, Encío I, Guerrero Setas D, Suarez Alecha J, Galbete A, Mercado M, Vera R, Gomez-Dorronsoro ML. PD-L1 as a Prognostic Factor in Early-Stage Colon Carcinoma within the Immunohistochemical Molecular Subtype Classification. Cancers (Basel) 2021; 13:1943. [PMID: 33920689 PMCID: PMC8073668 DOI: 10.3390/cancers13081943] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 04/10/2021] [Accepted: 04/12/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND There is a patent need to better characterize early-stage colorectal cancer (CRC) patients. PD-1 ligand (PD-L1) expression has been proposed as a prognostic factor but yields mixed results in different settings. The Consensus Molecular Subtype (CMS) classification has yet to be integrated into clinical practice. We sought to evaluate the prognostic value of PD-L1 expression overall and within CMS in early-stage colon cancer patients, in the hope of assisting treatment choice in this setting. METHODS Tissue-microarrays were constructed from tumor samples of 162 stage II/III CRC patients. They underwent automatic immunohistochemical staining for PD-L1 and the proposed CMS panel. Primary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS PD-L1 expression was significantly and independently associated with better prognosis (HR = 0.46 (0.26-0.82), p = 0.009) and was mostly seen in immune cells of the tumor-related stroma. CMS4 five-folds the risk of mortalitycompared with CMS1 (HR = 5.58 (1.36, 22.0), p = 0.034). In the subgroup CMS2/CMS3 analysis, PD-L1 expression significantly differentiated individuals with better OS (p = 0.004) and DFS (p < 0.001). CONCLUSIONS Our study suggests that PD-L1 expression is an independent prognostic factor in patients with stage II/III colon cancer. Additionally, it successfully differentiates patients with better prognosis in the CMS2/CMS3 group and may prove significant for the clinical relevance of the CMS classification.
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Affiliation(s)
- Pablo Azcue
- Department of Health Science, Public University of Navarra (UPNA), 31008 Pamplona, Spain;
| | - Ignacio Encío
- Department of Health Science, Public University of Navarra (UPNA), 31008 Pamplona, Spain;
- Institute for Health Research Navarra (IdISNA), 31008 Pamplona, Spain; (A.G.); (R.V.)
| | - David Guerrero Setas
- Department of Molecular Pathology, Hospital Complex of Navarra (CHN), 31008 Pamplona, Spain; (D.G.S.); (M.M.)
- Campus Arrosadia, Public University of Navarra (UPNA), 31006 Pamplona, Spain
- Molecular Pathology of Cancer Group–Navarrabiomed, 31008 Pamplona, Spain
- Department of Medical Oncology, Hospital Complex of Navarra (CHN), 31008 Pamplona, Spain
| | - Javier Suarez Alecha
- Department of Surgery, Hospital Complex of Navarra (CHN), 31008 Pamplona, Spain;
| | - Arkaitz Galbete
- Institute for Health Research Navarra (IdISNA), 31008 Pamplona, Spain; (A.G.); (R.V.)
- Campus Arrosadia, Public University of Navarra (UPNA), 31006 Pamplona, Spain
- Navarrabiomed-Hospital Complex of Navarra (CHN), Redissec, 31008 Pamplona, Spain
| | - María Mercado
- Department of Molecular Pathology, Hospital Complex of Navarra (CHN), 31008 Pamplona, Spain; (D.G.S.); (M.M.)
| | - Ruth Vera
- Institute for Health Research Navarra (IdISNA), 31008 Pamplona, Spain; (A.G.); (R.V.)
- Department of Medical Oncology, Hospital Complex of Navarra (CHN), 31008 Pamplona, Spain
| | - Maria Luisa Gomez-Dorronsoro
- Institute for Health Research Navarra (IdISNA), 31008 Pamplona, Spain; (A.G.); (R.V.)
- Department of Molecular Pathology, Hospital Complex of Navarra (CHN), 31008 Pamplona, Spain; (D.G.S.); (M.M.)
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13
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Jongeneel G, Greuter MJE, van Erning FN, Koopman M, Vink GR, Punt CJA, Coupé VMH. Model-based effectiveness and cost-effectiveness of risk-based selection strategies for adjuvant chemotherapy in Dutch stage II colon cancer patients. Therap Adv Gastroenterol 2021; 14:1756284821995715. [PMID: 33786064 PMCID: PMC7958170 DOI: 10.1177/1756284821995715] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 01/28/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND We aimed to evaluate the cost-effectiveness of risk-based strategies to improve the selection of surgically treated stage II colon cancer (CC) patients for adjuvant chemotherapy. METHODS Using the 'Personalized Adjuvant TreaTment in EaRly stage coloN cancer' (PATTERN) model, we evaluated five selection strategies: (1) no chemotherapy, (2) Dutch guideline recommendations assuming observed adherence, (3) Dutch guideline recommendations assuming perfect adherence, (4) biomarker mutation OR pT4 stage strategy in which patients with MSS status combined with a pT4 stage or a mutation in BRAF and/or KRAS receive chemotherapy assuming perfect adherence and (5) biomarker mutation AND pT4 stage strategy in which patients with MSS status combined with a pT4 stage tumor and a BRAF and/or KRAS mutation receive chemotherapy assuming perfect adherence. Outcomes were number of CC deaths per 1000 patients and total discounted costs and quality-adjusted life-years (QALYs) per patient (pp). Analyses were conducted from a societal perspective. The robustness of model predictions was assessed in sensitivity analyses. RESULTS The reference strategy, that is, no adjuvant chemotherapy, resulted in 139 CC deaths in a cohort of 1000 patients, 8.077 QALYs pp and total costs of €22,032 pp. Strategies 2-5 were more effective (range 8.094-8.217 QALYs pp and range 118-136 CC deaths per 1000 patients) and more costly (range €22,404-€25,102 pp). Given a threshold of €50,000/QALY, the optimal use of resources would be to treat patients with either the full adherence strategy and biomarker mutation OR pT4 stage strategy. CONCLUSION Selection of stage II CC patients for chemotherapy can be improved by either including biomarker status in the selection strategy or by improving adherence to the Dutch guideline recommendations.
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Affiliation(s)
- Gabrielle Jongeneel
- Department of Epidemiology and Data Science,
Amsterdam UMC, VU University, PO Box 7057, MF F-wing, Amsterdam, 1007 MB,
the Netherlands
| | - Marjolein J. E. Greuter
- Department of Epidemiology and Data Science,
Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Felice N. van Erning
- Department of Research and Development,
Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The
Netherlands
| | - Miriam Koopman
- Department of medical oncology, University
Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Geraldine R. Vink
- Department of Research and Development,
Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The
Netherlands
- Department of medical oncology, University
Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Cornelis J. A. Punt
- Department of Epidemiology, University Medical
Center Utrecht, Julius Center for Health Sciences, Utrecht, The
Netherlands
| | - Veerle M. H. Coupé
- Department of Epidemiology and Data Science,
Amsterdam UMC, VU University, Amsterdam, The Netherlands
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14
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Abstract
PURPOSE OF REVIEW This article will review the results of recent studies, which have investigated the duration of adjuvant chemotherapy and also suggest, which aspects of adjuvant treatment need investigation in future studies. RECENT FINDINGS The IDEA collaboration investigated whether the duration of adjuvant chemotherapy with an oxaliplatin doublet could be reduced from 6 to 3 months. Although this study did not demonstrate noninferiority for 3 months treatment, it did show noninferiority for patients receiving 3 months CAPOX chemotherapy and for those patients with low-risk stage III disease receiving 3 months' treatment. There was also significantly less toxicity seen with 3 months' treatment. Recent studies have shown that detectable ctDNA postoperatively can predict those patients most likely to relapse and so benefit from adjuvant treatment. SUMMARY It has been shown that for patients receiving adjuvant CAPOX chemotherapy, or those receiving adjuvant chemotherapy for low-risk stage III colon 3 months' chemotherapy gives similar outcomes to 6 months' treatment with significantly less toxicity.
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15
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Alonso S, Saltz L. The Landmark Series: Chemotherapy for Non-Metastatic Colon Cancer. Ann Surg Oncol 2020; 28:995-1001. [PMID: 33230749 DOI: 10.1245/s10434-020-09375-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 11/02/2020] [Indexed: 02/06/2023]
Abstract
Micrometastatic disease that is present at the time of surgery is responsible for the overwhelming majority of deaths in patients with what is otherwise perceived to be local and regional colon cancer. The goal of perioperative therapy is to eliminate microscopic residual disease that would otherwise be left behind following surgery. A secondary goal specific to neoadjuvant (preoperative) therapy is to downstage tumors deemed potentially not amenable to an R0 resection on the basis of a suspected T4b primary (locally invading into a surrounding structure). In this landmark series paper, we review the current standard for perioperative therapy in patients with colon cancer.
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Affiliation(s)
- Salvador Alonso
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Leonard Saltz
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.,Department of Medicine, Weill Cornell Medicine, New York, NY, USA
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16
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Yamazaki K, Yamanaka T, Shiozawa M, Manaka D, Kotaka M, Gamoh M, Shiomi A, Makiyama A, Munemoto Y, Rikiyama T, Fukunaga M, Ueki T, Shitara K, Shinkai H, Tanida N, Oki E, Sunami E, Ohtsu A, Maehara Y, Yoshino T. Oxaliplatin-based adjuvant chemotherapy duration (3 versus 6 months) for high-risk stage II colon cancer: the randomized phase III ACHIEVE-2 trial. Ann Oncol 2020; 32:77-84. [PMID: 33121997 DOI: 10.1016/j.annonc.2020.10.480] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 09/24/2020] [Accepted: 10/16/2020] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Oxaliplatin-based adjuvant chemotherapy may be associated with debilitating peripheral sensory neuropathy (PSN) in patients with high-risk stage II colon cancer. This open-label, multicenter, randomized phase III trial was conducted as a prospective pooled analysis to investigate the non-inferiority of 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy. PATIENTS AND METHODS From 12 February 2014 to 31 January 2017, 525 Asian patients with high-risk stage II colon cancer were randomly assigned to 3- and 6-month treatment arms. The treatment consisted of either modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine combined with oxaliplatin (CAPOX). The primary end point was disease-free survival (DFS). The secondary end points were treatment compliance and safety. RESULTS Of the 525 randomized patients, 11 were not treated. Among the 514 participating patients (255 in the 3-month arm; 259 in the 6-month arm), 432 (84%) received CAPOX, and 184 (36%) presented with T4 as a high-risk factor for recurrence. The 3-year DFS rate was 88.2% in the 3-month arm and 87.9% in the 6-month arm [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.67-1.87]. With CAPOX, the 3-year DFS rate was 88.2% in the 3-month arm and 88.4% in the 6-month arm (HR, 1.13; 95% CI, 0.65-1.96). The discontinuation rate in the 3- and 6-month arms was 10% and 31% for mFOLFOX6 (P = 0.0193), and 15% and 35% for CAPOX (P < 0.0001), respectively. The incidence of grade ≥2 PSN was significantly lower in the 3-month arm than in the 6-month arm (16% and 43%, respectively, P < 0.0001). CONCLUSIONS Three months of combination therapy presented significantly less grade ≥2 PSN than the respective 6-month regimen. The shortened therapy duration did not affect the 3-year DFS rate, suggesting that a 3-month course of CAPOX can be an effective treatment option. CLINICAL TRIAL INFORMATION UMIN Clinical Trials Registry, UMIN000013036 and Japan Registry of Clinical Trials, jRCTs031180128.
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Affiliation(s)
- K Yamazaki
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - T Yamanaka
- Department of Biostatistics, Yokohama City University School of Medicine, Kanagawa, Japan
| | - M Shiozawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Kanagawa, Japan
| | - D Manaka
- Department of Surgery, Gastrointestinal Center, Kyoto Katsura Hospital, Kyoto, Japan
| | - M Kotaka
- Department of Gastrointestinal Cancer Center, Sano Hospital, Hyogo, Japan
| | - M Gamoh
- Department of Medical Oncology, Osaki Citizen Hospital, Miyagi, Japan
| | - A Shiomi
- Division of Colon and Rectal Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - A Makiyama
- Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka, Japan
| | - Y Munemoto
- Department of Surgery, Fukui-ken Saiseikai Hospital, Fukui, Japan
| | - T Rikiyama
- Department of Surgery, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - M Fukunaga
- Department of Surgery, Hyogo Prefectural Nishinomiya Hospital, Hyogo, Japan
| | - T Ueki
- Department of Surgery, Hamanomachi Hospital, Fukuoka, Japan
| | - K Shitara
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - H Shinkai
- Department of Surgery, Chigasaki Municipal Hospital, Kanagawa, Japan
| | - N Tanida
- Department of Surgery, Japanese Red Cross Kochi Hospital, Kochi, Japan
| | - E Oki
- Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - E Sunami
- Department of Tumor Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - A Ohtsu
- National Cancer Center Hospital East, Chiba, Japan
| | - Y Maehara
- Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan
| | - T Yoshino
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
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17
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Argilés G, Tabernero J, Labianca R, Hochhauser D, Salazar R, Iveson T, Laurent-Puig P, Quirke P, Yoshino T, Taieb J, Martinelli E, Arnold D. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020; 31:1291-1305. [PMID: 32702383 DOI: 10.1016/j.annonc.2020.06.022] [Citation(s) in RCA: 760] [Impact Index Per Article: 152.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 06/26/2020] [Accepted: 06/26/2020] [Indexed: 02/07/2023] Open
Affiliation(s)
- G Argilés
- Department of Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Spain
| | - J Tabernero
- Department of Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), UVic-UCC, IOB-Quiron, Barcelona, Spain
| | - R Labianca
- Department Oncology, Ospedale Papa Giovanni XXIII, Bergamo, Italy
| | | | - R Salazar
- Department of Medical Oncology, Catalan Institute of Oncology, Oncobell Program (IDIBELL), CIBERONC, Hospitalet de Llobregat, Barcelona, Spain
| | - T Iveson
- University Hospital Southampton, NHS Foundation Trust, Southampton, UK
| | - P Laurent-Puig
- Assitance Publique-Hôpitaux de Paris AP-HP Paris Centre, Paris, France; Paris Cancer Institute CARPEM, Centre de Recherche des Cordeliers, Paris Sorbonne University, Paris University, Paris, France; INSERM, CNRS, Paris, France
| | - P Quirke
- Pathology and Data Analytics, School of Medicine, University of Leeds, Leeds, UK
| | - T Yoshino
- National Cancer Centre Hospital East, Kashiwa, Japan
| | - J Taieb
- Assitance Publique-Hôpitaux de Paris AP-HP Paris Centre, Paris, France; Paris Cancer Institute CARPEM, Centre de Recherche des Cordeliers, Paris Sorbonne University, Paris University, Paris, France; INSERM, CNRS, Paris, France; Department of Gastroenterology and GI Oncology, Georges Pompidou European Hospital, Paris Descartes University, Paris, France
| | - E Martinelli
- Università degli Studi della Campania Luigi Vanvitelli, Department of Precision Medicine, Naples, Italy
| | - D Arnold
- Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Germany
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18
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Lee MW, Kim JS, Kim JY, Lee KH. Prognostic Factor and Survival Benefit of Adjuvant Chemotherapy in Stage IIA Colon Cancer. Ann Coloproctol 2020; 37:35-43. [PMID: 32972104 PMCID: PMC7989565 DOI: 10.3393/ac.2020.09.03] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 09/03/2020] [Indexed: 01/04/2023] Open
Abstract
Purpose There is no clear evidence of the benefit of adjuvant chemotherapy (AC) in stage IIA colon cancer. Therefore, we aimed to evaluate the prognostic factors and survival benefit of AC in this disease. Methods A retrospective data collection for patients who underwent radical surgery for colon cancer between January 2008 and December 2015 was undertaken. The cohort was divided into the no-AC and AC groups. Results We included 227 patients with stage IIA colon cancer in our study cohort, including 67 and 160 patients in the no-AC and AC groups, respectively. The number of retrieved lymph nodes and the presence of tumor complications as obstruction or perforation were independent risk factors for survival. In the no-AC group, there was a significant difference in survival according to the number of retrieved lymph nodes. In the AC group, there were significant differences in survival according to sidedness and preoperative carcinoembryonic antigen (CEA). There was no significant difference in survival between the no-AC and the AC groups. Conclusion The number of retrieved lymph nodes and the presence of tumor complications were prognostic factors for stage IIA colon cancer but lymphovascular and perineural invasion were not. Sidedness and preoperative CEA could be used as factors to predict the benefit of adjuvant chemotherapy. Currently, it is believed that there is no benefit of AC for stage IIA colon cancer. Further studies are needed to determine the survival benefit of adjuvant chemotherapy in stage IIA colon cancer.
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Affiliation(s)
- Mok-Won Lee
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Jin-Su Kim
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Ji-Yeon Kim
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Kyung-Ha Lee
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
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19
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Jongeneel G, Greuter MJE, van Erning FN, Koopman M, Vink GR, Punt CJA, Coupé VMH. Model-based evaluation of the cost effectiveness of 3 versus 6 months' adjuvant chemotherapy in high-risk stage II colon cancer patients. Therap Adv Gastroenterol 2020; 13:1756284820954114. [PMID: 32994804 PMCID: PMC7502861 DOI: 10.1177/1756284820954114] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 08/11/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Our aim was to evaluate the cost effectiveness of 3 months' adjuvant chemotherapy versus 6 months in high-risk (T4 stage + microsatellite stable) stage II colon cancer (CC) patients. METHODS Using the validated PATTERN Markov cohort model, which simulates the disease progression of stage II CC patients from diagnosis to death, we first evaluated a reference strategy in which high-risk patients were treated with chemotherapy for 6 months. In the second strategy, treatment duration was shortened to 3 months. Both strategies were evaluated for CAPOX (capecitabine plus oxaliplatin) and FOLFOX (fluorouracil, leucovorin and oxaliplatin). Based on trial data, we assumed that shortened treatment duration compared with a 6-month regimen was equally effective for CAPOX and less effective for FOLFOX. Adverse events were highest in the 6-month strategy. Analyses were conducted from a societal perspective using a lifelong time horizon. Outcomes were number of CC deaths per 1000 patients and total discounted costs and quality-adjusted life-years (QALYs) per patient (pp). Incremental net monetary benefit (iNMB) was calculated using a willingness-to-pay value of €50,000/QALY. RESULTS For CAPOX, the 6-month strategy resulted in 316 CC deaths per 1000 patients, 6.71 QALYs pp and total costs of €41,257 pp. The 3-month strategy resulted in an equal number of CC deaths, but higher QALYs (6.80 pp) and lower costs (€37,645 pp), leading to a iNMB of €8454 per person for 3 months versus 6 months. For FOLFOX, the 6-month strategy resulted in 316 CC deaths per 1000 patients, 6.71 QALYs pp and total costs of €47,135 pp. The 3-month strategy resulted in more CC deaths (393), lower QALYs (6.19 pp) and lower costs (€44,389 pp). An iNMB of -€23,189 was found for 3 months versus 6 months. CONCLUSION Our findings indicate that 3 months' adjuvant chemotherapy should be considered as standard of care in high-risk stage II CC patients for CAPOX, but not for FOLFOX.
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Affiliation(s)
| | | | - Felice N. van Erning
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands
| | - Miriam Koopman
- University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Geraldine R. Vink
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands,University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Cornelis J. A. Punt
- Department of Medical Oncology, University of Amsterdam, Amsterdam, The Netherlands
| | - Veerle M. H. Coupé
- Department of Epidemiology and Biostatistics, VU University, Amsterdam, The Netherlands
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20
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Rebuzzi SE, Pesola G, Martelli V, Sobrero AF. Adjuvant Chemotherapy for Stage II Colon Cancer. Cancers (Basel) 2020; 12:cancers12092584. [PMID: 32927771 PMCID: PMC7565376 DOI: 10.3390/cancers12092584] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 09/04/2020] [Accepted: 09/06/2020] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Stage II colon cancer is defined as an early stage of the tumor disease, without the involvement of lymph nodes or distant organs. In this group of patients, surgery alone is associated with high cure rate and the role of post-operative chemotherapy is still a matter of debate. In patients with tumor features associated with a high risk of recurrence, post-operative chemotherapy is recommended even if it has a small survival benefit. This clinical issue leads to the need for identifying patients who may benefit from post-operative chemotherapy based on their risk of recurrence. The purpose of this review is to highlight and discuss the uncertainties of the previous trials about the risk stratification, the weight of each prognostic factor and the therapeutic benefit of adjuvant chemotherapy in stage II colon cancer patients. Moreover, we summarize the data from previous studies in a decision algorithm that could help clinicians in clinical practice. Abstract In stage II colon cancer management, surgery alone has shown a high cure rate (about 80%), and the role of adjuvant chemotherapy is still a matter of debate. Patients with high-risk features (T4, insufficient nodal sampling, grading, etc.) have a poorer prognosis and, usually, adjuvant chemotherapy is recommended. The purpose of the present study is to highlight and discuss what is still unclear and not completely defined from the previous trials regarding risk stratification and therapeutic benefit of adjuvant chemotherapy. With all the limitations of generalizing, we make the effort of trying to quantify the relative contribution of each prognostic factor and the benefit of adjuvant chemotherapy for stage II colon cancer. Finally, we propose a decision algorithm with the aim of summarizing the current evidence and translating it to clinical practice.
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Affiliation(s)
- Sara Elena Rebuzzi
- Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino of Genova, Largo Rosanna Benzi 10, 16132 Genova, Italy; (S.E.R.); (G.P.); (V.M.)
| | - Guido Pesola
- Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino of Genova, Largo Rosanna Benzi 10, 16132 Genova, Italy; (S.E.R.); (G.P.); (V.M.)
- Medical Oncology Unit, Department of Medicine, Surgery and Neurosciences, Azienda Ospedaliera Universitaria Senese, Viale Bracci, 53100 Siena, Italy
| | - Valentino Martelli
- Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino of Genova, Largo Rosanna Benzi 10, 16132 Genova, Italy; (S.E.R.); (G.P.); (V.M.)
| | - Alberto Felice Sobrero
- Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino of Genova, Largo Rosanna Benzi 10, 16132 Genova, Italy; (S.E.R.); (G.P.); (V.M.)
- Correspondence:
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21
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Collienne M, Arnold D. The Optimal Duration of Adjuvant Chemotherapy in Colon Cancer. Cancers (Basel) 2020; 12:E2509. [PMID: 32899406 PMCID: PMC7563599 DOI: 10.3390/cancers12092509] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 08/30/2020] [Accepted: 08/31/2020] [Indexed: 12/22/2022] Open
Abstract
Adjuvant chemotherapy for colon cancer (UICC stage II and III) has been under investigation over the last 30 years, regarding treatment duration and regimens. In this review, choice of regimen, its duration, possible limitations and future perspectives are discussed. Monotherapy with 5-fluorouracil was followed by addition of oxaliplatin, resulting in improved 3-yr disease free survival (DFS) and overall survival (OS) rates, but also increased peripheral sensory neurotoxicity (PSN). The International Duration Evaluation of Adjuvant therapy (IDEA) collaboration demonstrated less toxicity, especially PSN, when shortening treatment duration to 3 months. However, formally, the anticipated non-inferiority of 3 months with fluoropyrimidine (FP)/oxaliplatin over 6 months (at 3-yr DFS) was not met for all patients groups, although subgroup analyses showed non-inferiority with capecitabine/oxaliplatin (CAPOX) rather than with FOLFOX, and also in relation to the prognostic information (e.g., clinical low-risk group, pT1-3 N0). In addition, first data of newer parameters like Immunoscore® and ctDNA show promising results as stratification parameters. Further investigations to better define clinical risk groups and prognostic factors are mandatory. Besides this, individual decision-making of treatment intensity (FP or FP/oxaliplatin) and duration should always consider patient characteristics and preferences, also given the absolute relatively small differences and their clinical relevance.
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Affiliation(s)
| | - Dirk Arnold
- Department of Oncology and Hematology, Asklepios Klinik Altona, Asklepios Tumorzentrum Hamburg, 22763 Hamburg, Germany;
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22
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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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23
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Parent P, Cohen R, Rassy E, Svrcek M, Taieb J, André T, Turpin A. A comprehensive overview of promising biomarkers in stage II colorectal cancer. Cancer Treat Rev 2020; 88:102059. [DOI: 10.1016/j.ctrv.2020.102059] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 06/11/2020] [Accepted: 06/13/2020] [Indexed: 02/08/2023]
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24
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Battisti NML, Liposits G, De Glas NA, Gomes F, Baldini C, Mohile S. Systemic Therapy of Common Tumours in Older Patients: Challenges and Opportunities. A Young International Society of Geriatric Oncology Review Paper. Curr Oncol Rep 2020; 22:98. [PMID: 32725503 DOI: 10.1007/s11912-020-00958-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE OF REVIEW Decision-making for systemic treatments in older patients with cancer is difficult because of concerns for decreased organ function, risk of toxicity, limited life expectancy due to comorbidities and the lack of evidence available to guide its management in this population. Here, we review the data on the role of systemic agents for the treatment of common malignancies in this age group. RECENT FINDINGS Evidence on the use of systemic treatments for older patients with cancer is increasing, especially for newer options including immune checkpoint inhibitors and targeted agents that provide comparable benefit in older and younger patients. Nonetheless, the risks for short- and long-term toxicities need to be considered. More research is warranted and represents a unique opportunity to increase the knowledge on cancer treatment for older adults. Healthy, older individuals should be considered for standard systemic treatment options, whereas those at risk based on geriatric assessments require adjusted plans. Geriatric assessments are key for decision-making.
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Affiliation(s)
- Nicolò Matteo Luca Battisti
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, UK. .,Breast Cancer Research Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK.
| | - Gabor Liposits
- Department of Oncology, Regional Hospital West Jutland, Gl Landevej 61, 7400, Herning, Denmark
| | - Nienke Aafke De Glas
- Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333, Leiden, ZA, Netherlands
| | - Fabio Gomes
- Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK
| | - Capucine Baldini
- Drug Development Department, Institut Gustave Roussy, Gustave Roussy Cancer Campus, 114 Rue Edouard Vaillant, 94800, Villejuif, France
| | - Supriya Mohile
- Division of Hematology/Oncology, James P. Wilmot Cancer Institute, University of Rochester Medical Center, 601 Elmwood Ave # 704, Rochester, NY, 14642, USA
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25
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Cohen R, Shi Q, André T. Immunotherapy for Early Stage Colorectal Cancer: A Glance into the Future. Cancers (Basel) 2020; 12:E1990. [PMID: 32708216 PMCID: PMC7409300 DOI: 10.3390/cancers12071990] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/10/2020] [Accepted: 07/17/2020] [Indexed: 12/16/2022] Open
Abstract
Immune checkpoint inhibitors (ICI) have reshaped therapeutic strategies for cancer patients. The development of ICI for early stage colorectal cancer is accompanied by specific challenges: (i) the selection of patients who are likely to benefit from these treatments, i.e., patients with tumors harboring predictive factors of efficacy of ICI, such as microsatellite instability and/or mismatch repair deficiency (MSI/dMMR), or other potential parameters (increased T cell infiltration using Immunoscore® or others, high tumor mutational burden, POLE mutation), (ii) the selection of patients at risk of disease recurrence (poor prognostic features), and (iii) the choice of an accurate clinical trial methodological framework. In this review, we will discuss the ins and outs of clinical research of ICI for early stage MSI/dMMR CC patients in adjuvant and neoadjuvant settings. We will then summarize data that might support the development of ICI in localized colorectal cancer beyond MSI/dMMR.
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Affiliation(s)
- Romain Cohen
- Department of Medical Oncology, Hôpital Saint-Antoine, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), F-75012 Paris, France;
- Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA;
| | - Qian Shi
- Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA;
| | - Thierry André
- Department of Medical Oncology, Hôpital Saint-Antoine, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), F-75012 Paris, France;
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26
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Puckett Y, Tran R, Wachtel M. Yellow-Gold Polarized Light Microscopy May Improve Accuracy of Pathological Staging of Colorectal Adenocarcinoma. Cureus 2020; 12:e9007. [PMID: 32775087 PMCID: PMC7402530 DOI: 10.7759/cureus.9007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Introduction Polarized light (PL) has been used in pathology for multiple reasons, including the demonstration of foreign bodies, the evaluation of crystals, and the demonstration of fibrosis. We incidentally found that yellow-gold polarization routinely occurs surrounding desmoplastic scar tissue abutting the invasive glands of colonic adenocarcinoma. We hypothesized that evaluating the use of polarized light over a series of invasive adenocarcinomas of the large intestine might produce evidence of its utility. Methods Large intestinal resections with invasive adenocarcinoma were reviewed with yellow-gold polarized light microscopy by two surgical pathologists postoperatively between January 2017 and March 2019. Specimens were examined under yellow-gold polarized light to evaluate invasion from the submucosa into the muscularis propria, from the muscularis propria into pericolic fat, and to the serosa. The diagnosed location, T stage, history of radiotherapy, mucinous features, and grade were recorded. Photographs were taken when images were deemed to be of value. The two-tailed Fisher's exact test was used to compare the invasion detection of the tumor into fat in scar tissue in colorectal cancer. Results A total of 75 large intestinal resections with invasive adenocarcinoma from 75 patients were accessioned. Concerning the initial stage, three (4%) were T1, nine (12%) were T2, 46 (61%) were T3, and 17 (22%) were T4. A history of previous radiation treatment was seen in 10 (13%). Two (2%) were poorly differentiated. Nine (12%) were mucinous carcinomas; mucinous areas were seen to pose difficulty in 12 (16%). Overall, one out of nine, initially staged as T2, was upstaged to T3 (11%), with the addition of yellow-gold polarized light microscopy. One tumor was downstaged from T2 to T1 (11%). For many T2 and T3 tumors, invasion into the muscularis propria was better defined by yellow-gold polarized light. Conclusion Yellow-gold polarized light microscopy may be a useful adjunct to conventional microscopy in more precisely staged pathological colorectal cancer specimens.
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Affiliation(s)
- Yana Puckett
- Surgical Oncology, University of Wisconsin, Madison, USA.,Surgery, Texas Tech University Health Sciences Center, Lubbock, USA
| | - Ruc Tran
- Pathology, Texas Tech University Health Sciences Center, Lubbock, USA
| | - Mitchell Wachtel
- Pathology, Texas Tech University Health Sciences Center, Lubbock, USA
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27
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Bhethanabhotla S, Pramanik R, Srivastava P, Mehta P, Patel A, Biswas B, Batra A, Gupta VG, Das C, Mahindru S. Colorectal Cancer Chemotherapy during COVID-19 Pandemic. Indian J Med Paediatr Oncol 2020. [DOI: 10.4103/ijmpo.ijmpo_149_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
AbstractThe management of patients with colorectal cancer during the current SARS-CoV2 pandemic opens a Pandora's Box. While the world is facing an unprecedented crisis of fighting a life-threatening infectious disease, patients with colorectal cancer are facing the dual challenge to fight cancer while protecting them from infection. We attempted to critically examine the existing evidence for chemotherapy in colorectal cancer in different stages of disease and suggest treatment options in these vulnerable patients. Treatment options which do not overburden existing health-care resources can be provided for patients with colorectal cancer patients requiring chemotherapy without significant compromise in efficacy or increase the risk of hospital acquired SAR-CoV-2 infection.
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Affiliation(s)
| | - Raja Pramanik
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Priyanka Srivastava
- M.S. Patel Cancer Center, Shreekrishna Hospital and Medical Research Centre, Karamsad, Gujarat, India
| | - Prashant Mehta
- Department of Medical Oncology, Asian Institute of Medical Sciences, Faridabad, Haryana, India
| | - Amol Patel
- Malignant Diseases Treatment Centre, Army Hospital Research and Referral, New Delhi, India
| | - Bivas Biswas
- Department of Medical Oncology, Tata Medical Center, Kolkata, West Bengal, India
| | - Atul Batra
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Chandan Das
- Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shubh Mahindru
- Department of Surgical Oncology, Ivy Hospital, Mohali, Punjab, India
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28
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Moretto R, Falcone A, Cremolini C. Duration of oxaliplatin-based adjuvant chemotherapy in patients with Stage III or high-risk Stage II resected colon cancer. Int J Cancer 2020; 146:2652-2654. [PMID: 31970766 DOI: 10.1002/ijc.32884] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 01/08/2020] [Accepted: 01/20/2020] [Indexed: 11/12/2022]
Affiliation(s)
- Roberto Moretto
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.,Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Alfredo Falcone
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.,Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Chiara Cremolini
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.,Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
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