Adjuvant Therapy For Colon Cancer Research Articles

Machine Learning Predicts Oxaliplatin Benefit in Early Colon Cancer.

A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who benefit from oxaliplatin would maximize efficacy and minimize unnecessary adverse side effects. We trained a new machine learning model, referred to as the colon oxaliplatin signature (COLOXIS) model, for predicting response to oxaliplatin-containing regimens. We examined whether COLOXIS was predictive of oxaliplatin benefits in the CC adjuvant setting among 1,065 patients treated with 5-fluorouracil plus leucovorin (FULV; n = 421) or FULV + oxaliplatin (FOLFOX; n = 644) from NSABP C-07 and C-08 phase III trials. The COLOXIS model dichotomizes patients into COLOXIS+ (oxaliplatin responder) and COLOXIS- (nonresponder) groups. Eight-year recurrence-free survival was used to evaluate oxaliplatin benefits within each of the groups, and the predictive value of the COLOXIS model was assessed using the P value associated with the interaction term (int P) between the model prediction and the treatment effect. Among 1,065 patients, 526 were predicted as COLOXIS+ and 539 as COLOXIS-. The COLOXIS+ prediction was associated with prognosis for FULV-treated patients (hazard ratio [HR], 1.52 [95% CI, 1.07 to 2.15]; P = .017). The model was predictive of oxaliplatin benefits: COLOXIS+ patients benefited from oxaliplatin (HR, 0.65 [95% CI, 0.48 to 0.89]; P = .0065; int P = .03), but COLOXIS- patients did not (COLOXIS- HR, 1.08 [95% CI, 0.77 to 1.52]; P = .65). The COLOXIS model is predictive of oxaliplatin benefits in the CC adjuvant setting. The results provide evidence supporting a change in CC adjuvant therapy: reserve oxaliplatin only for COLOXIS+ patients, but further investigation is warranted.

Silybin Showed Higher Cytotoxic, Antiproliferative, and Anti-Inflammatory Activities in the CaCo Cancer Cell Line while Retaining Viability and Proliferation in Normal Intestinal IPEC-1 Cells.

The anticancer potential of silymarin is well known, including its anti-inflammatory as well as antiproliferative effect mediated by influencing the cell cycle, suppression of apoptosis, and inhibition of cell-survival kinases. However, less is known about silybin, the main component of the silymarin complex, where studies indicate its dual effect on the proliferation and immune response of various cell types in a dose-dependent manner. Moreover, there is a lack of studies comparing the effect of silybin on the same type of healthy and tumor cells, especially intestinal ones. Therefore, our study aimed to investigate the concentration-dependent effect of silybin on the normal intestinal porcine epithelial cell line-1 (IPEC-1) and the human epithelial colorectal adenocarcinoma cell line (CaCo-2). The metabolic viability, cell cycle, mitochondrial membrane potential, apoptosis, and the relative gene expression for pro- and anti-inflammatory cytokines were monitored in cells treated with silybin. Silybin stimulates metabolic viability as well as proliferation in IPEC-1 cells, protects the mitochondrial membrane, and thus exerts a cytoprotective effect, and has only a minimal effect on the gene expression of pro-inflammatory cytokines but significantly increases the expression of anti-inflammatory TGF-β. In contrast, it inhibits metabolic viability in tumor intestinal CaCo-2 cells, has an antiproliferative effect accompanied by increased apoptosis, and significantly reduces the expression of genes for pro-inflammatory interleukins as well as TGF-β. The antiproliferative and anti-inflammatory effect of silybin on tumor intestinal cells without a negative effect on healthy cells is a prerequisite for its potential use in the adjuvant therapy of colon cancer; however, further studies are necessary.

Current Perspectives on the Importance of Pathological Features in Prognostication and Guidance of Adjuvant Chemotherapy in Colon Cancer.

There is not a clear consensus on which pathological features and biomarkers are important in guiding prognosis and adjuvant therapy in colon cancer. The Pathology in Colon Cancer, Prognosis and Uptake of Adjuvant Therapy (PiCC UP) Australia and New Zealand questionnaire was distributed to colorectal surgeons, medical oncologists and pathologists after institutional board approval. The aim of this study was to understand current specialist attitudes towards pathological features in the prognostication of colon cancer and adjuvant therapy in stage II disease. A 5-scale Likert score was used to assess attitudes towards 23 pathological features for prognosis and 18 features for adjuvant therapy. Data were analysed using a rating scale and graded response model in item response theory (IRT) on STATA (Stata MP, version 15; StataCorp LP). One hundred and sixty-four specialists (45 oncologists, 86 surgeons and 33 pathologists) participated. Based on IRT modelling, the most important pathological features for prognosis in colon cancer were distant metastases, lymph node metastases and liver metastases. Other features seen as important were tumour rupture, involved margin, radial margin, CRM, lymphovascular invasion and grade of differentiation. Size of tumour, location, lymph node ratio and EGFR status were considered less important. The most important features in decision making for adjuvant therapy in stage II colon cancer were tumour rupture, lymphovascular invasion and microsatellite instability. BRAF status, size of tumour, location, tumour budding and tumour infiltrating lymphocytes were factored as lesser importance. Biomarkers such as CDX2, EGFR, KRAS and BRAF status present areas for further research to improve precision oncology. This study provides the most current status on the importance of pathological features in prognostication and recommendations for adjuvant therapy in Australia and New Zealand. Results of this nationwide study may be useful to help in guiding prognosis and adjuvant treatment in colon cancer.

Advances in the exploration of adjuvant therapy of colon cancer with Chinese medicine

Advances in the exploration of adjuvant therapy of colon cancer with Chinese medicine

Reality of care of colorectal cancer in the State of Brandenburg : With special consideration of the number of hospital cases and certification as a colorectal cancer center

Analysis of the quality of care for colorectal cancer is an essential foundation for further development and is based on the comparison of the goals set and the actual quality of care. This publication presents the reality of care in the State of Brandenburg covering the complete spectrum of treating clinics based on the data of the clinical cancer register. This study analyzed the number of resected and examined lymph nodes, the quality of total mesorectal excision (TME), the residual tumor (R0) resection rate and the proportion of adjuvant therapy of colon cancer in Union internationale contre le cancer (UICC) stage III depending on the operation quota of hospitals and the certification as bowel cancer center according to Onkozert. Apart from the R status, the analyses showed no differences in the qualitative operation data from the clinical cancer register depending on the hospital volume.

Effect of Celecoxib Added to Standard Adjuvant Therapy for Colon Cancer

Aspirin use may reduce the risk for developing colorectal cancer. After surgery and adjuvant therapy, aspirin may also reduce the risk for colorectal

Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in older patients: A subgroup analysis from the TOSCA trial

BackgroundPrevious studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methodsWe assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged <70 years and 693 ≥ 70 years) randomised to receive 3 or 6 months of FOLFOX or CAPOX within the frame of the phase III, TOSCA study. ResultsOlder patients compared with younger ones presented more frequently an Eastern Cooperative Oncology Group performance status equal to 1 (10.5% vs 3.3%, p < 0.001), a greater number of right-sided tumours (40.9% vs 26.6%, p < 0.001), and were at higher clinical risk (37.2% vs 33.2%, p = 0.062). The treatments were almost identical in the two cohorts (p = 0.965). We found a greater proportion of dose reductions (46.7% vs 41.4%, p = 0.018), treatment interruptions (26.1% vs 19.3%, p < 0.001) and a higher proportion of recurrences (24.2% vs 20.3%, p = 0.033) in the older patients. The multivariable analysis of the TTR did not indicate a statistically significant effect of age (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 0.98–1.44; p = 0.082). The HR comparing older with younger patients was 1.34 (95% CI: 1.12–1.59; p = 0.001) for DFS, 1.58 (95% CI: 1.26–1.99; p < 0.001) for OS, and 1.28 (95% CI: 0.96–1.70; p = 0.089) for CSS. ConclusionsWorse prognostic factors and reduced treatment compliance have a negative impact on the efficacy of oxaliplatin-based adjuvant therapy in older patients.

Prevention of Colon Cancer Recurrence From Minimal Residual Disease: Computer Optimized Dose Schedules of Intermittent Apoptotic Adjuvant Therapy.

Adjuvant chemotherapy is used after surgery for stages II and III colorectal cancer to reduce recurrence. Nevertheless, recurrence may occur years later with the emergence of initially undetected minimal residual disease (MRD). Attempts to reduce recurrence by increasing the dose intensity and increasing the time of adjuvant therapy have been limited by the adverse effects of the recommended cytotoxic agents. The goals of this study were to suggest an alternative to the recommended cytotoxic agents and to determine optimal adjuvant therapy dose schedules that would reduce the percentage of recurrence at 5 years while retaining colon crypt function. A total of 84,400 dose schedules with different duration, interval between doses, and intensity of treatment were simulated with a high-performance computer. Simulated treatments used the drug sulindac, which had previously been used in primary prevention. With appropriate dose schedules, it can induce apoptosis at the crypt lumen surface while retaining crypt function. We used a computer model of cell dynamics in colon crypts that had been calibrated with measurements of human biopsy specimens. Proliferating mutant cells were assumed to emerge from MRD within crypts. Simulated outcomes included the recurrence percentage at 5 years and the retention of crypt function. Optimal dose schedules were determined for adjuvant treatment of MRD that reduced the percentage of recurrence at 5 years of stages I, II, and III colon cancer to zero. A new adjuvant therapy for colon cancer based upon optimum dose schedules of intermittent apoptotic treatment may prevent the recurrence of colon cancer from MRD and avoid the adverse effects of cytotoxic treatments.

Current status on microsatellite instability, prognosis and adjuvant therapy in colon cancer: A nationwide survey of medical oncologists, colorectal surgeons and gastrointestinal pathologists.

BackgroundThere is significant variation in attitude both towards the role of microsatellite instability (MSI) in predicting prognosis, and towards its role in guiding which Stage II colon cancer patients may benefit from adjuvant chemotherapy.AimTo examine the current status of specialist attitudes towards MSI in guiding prognosis and adjuvant therapy in stage II colon cancer.MethodsThe Pathology in Colon Cancer, Prognosis and Uptake of Adjuvant Therapy (PiCC UP) Australia and New Zealand questionnaire was distributed to colorectal surgeons, medical oncologists and pathologists after institutional board approval. A 5‐scale Likert score was used to assess attitudes towards 23 pathological features for prognosis and 18 features for adjuvant therapy. Data were analysed using a rating scale and graded response model in item response theory (IRT) on STATA (Stata MP, version 15; StataCorp LP).Results164 specialists (45 oncologists, 86 surgeons and 33 pathologists) participated. 80.5% regularly attended colorectal multidisciplinary team (MDT) meetings. 89.63% and 59.26% of specialists reported that MSI status was likely or definitely to influence prognosis in colon cancer and recommendations for adjuvant therapy in Stage II colon cancer respectively.IRT modelling was achieved in 17 pathological features for prognosis. MSI IRT score was 4.47 (95% CI: 4.05‐4.68). IRT modelling was achieved in 10 pathological features for adjuvant therapy. MSI IRT score was 3.62 (2.89‐4.15). MSI ranked 10 (of 17) in order of importance in determining prognosis and ranked three (of 10) in guiding adjuvant therapy.ConclusionMSI status is considered an important biomarker when selecting patients for adjuvant therapy in Stage II colon cancer. MSI is also considered useful in prognostication of colon cancer. MSI status was ranked similar to the tumour grade of differentiation and the presence of perineural invasion.

399O Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in elderly patients: A subgroup analysis from TOSCA trial

Previous studies stating the combination of oxaliplatin and fluoropyrimidines as the standard of care for the adjuvant therapy of stage III colon cancer (CC) patients (pts) obtained non-convergent results and a reduced benefit for those over the age of 70 years.

Use of STAT6 Phosphorylation Inhibitor and Trimethylglycine as New Adjuvant Therapies for 5-Fluorouracil in Colitis-Associated Tumorigenesis.

Colorectal cancer (CRC) is one of the most widespread and deadly types of neoplasia around the world, where the inflammatory microenvironment has critical importance in the process of tumor growth, metastasis, and drug resistance. Despite its limited effectiveness, 5-fluorouracil (5-FU) is the main drug utilized for CRC treatment. The combination of 5-FU with other agents modestly increases its effectiveness in patients. Here, we evaluated the anti-inflammatory Trimethylglycine and the Signal transducer and activator of transcription (STAT6) inhibitor AS1517499, as possible adjuvants to 5-FU in already established cancers, using a model of colitis-associated colon cancer (CAC). We found that these adjuvant therapies induced a remarkable reduction of tumor growth when administrated together with 5-FU, correlating with a reduction in STAT6-phosphorylation. This reduction upgraded the effect of 5-FU by increasing both levels of apoptosis and markers of cell adhesion such as E-cadherin, whereas decreased epithelial–mesenchymal transition markers were associated with aggressive phenotypes and drug resistance, such as β-catenin nuclear translocation and Zinc finger protein SNAI1 (SNAI1). Additionally, Il-10, Tgf-β, and Il-17a, critical pro-tumorigenic cytokines, were downmodulated in the colon by these adjuvant therapies. In vitro assays on human colon cancer cells showed that Trimethylglycine also reduced STAT6-phosphorylation. Our study is relatively unique in focusing on the effects of the combined administration of AS1517499 and Trimethylglycine together with 5-FU on already established CAC which synergizes to markedly reduce the colon tumor load. Together, these data point to STAT6 as a valuable target for adjuvant therapy in colon cancer.

PH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer.

PurposeIn this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(β-amino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenograft model.MethodsThe as-prepared polymer prodrugs are tended to self-assemble into polymeric micelles in aqueous milieu, with PEOz segment as hydrophilic shell and PLA-PBAE segment as hydrophobic core.ResultsThe pH sensitivity of the as-prepared copolymers was confirmed by acid-base titration with pKb values around 6.5. The drug-conjugated polymer micelles showed high stability for at least 96 h in PBS and 37°C, respectively. The as-prepared copolymer prodrugs showed high drug loading content, with 9.57%±1.24% of drug loading for PEOz-PLA-PBAE-ART4. The conjugated ART could be released in a sustained and pH-dependent manner, with 92% of released drug at pH 6.0 and 57% of drug released at pH 7.4, respectively. In addition, in vitro experiments showed higher inhibitory effect of the prodrugs on rodent CT-26 cells than that of free ART. Animal studies also demonstrated the enhanced inhibitory efficacy of PEOz-PLA-PBAE-ART2 micelles on the growth of rodent xenograft tumor.ConclusionThe pH-responsive artesunate polymer prodrugs are promising candidates for colon cancer adjuvant therapy.

Development and Evaluation of Bioresponsive Tablets of a Selective COX-2 Inhibitor for Colonic Delivery

Background: We report the effectiveness of a targeted delivery system containing Meloxicam using polysaccharides for the treatment of colorectal cancer. We also propose a novel biorelevant dissolution method to overcome drawbacks of existing dissolution methodologies of polysaccharidebased systems. The proposed method includes a mixture of probiotics cultured under anaerobic conditions in the presence of prebiotic in the in vitro dissolution study to surrogate colonic conditions. Polysaccharide- based system can be simple, safe and effective drug delivery system to target drugs to colon. Methods: Press-coated tablets of Meloxicam were prepared by direct compression using various polysaccharides, such as xanthan gum, guar gum and pectin as coating polysaccharides. Developed tablets were evaluated for physical parameters, lag phase and in vitro drug release. Developed probioticsbased dissolution method was validated and explored for versatility using other polysaccharides. Results: Press-coated tablets of Meloxicam were successfully developed exhibiting targeted delivery to the colon using guar gum as coat and releasing more than 80% of drug in simulated colonic fluid. The developed probiotics based dissolution method may prove to be useful as a bio-relevant and discriminatory method. Conclusion: Developed Meloxicam tablets press-coated with guar gum can be taken orally for treatment or as an adjuvant therapy in colon cancer. Polymers used in this formulation are abundant, nontoxic, biodegradable and inexpensive which make this a a very promising approach for the treatment of different colonic diseases. The proposed biorelevant, animal sparing, probiotics based dissolution medium was found to be versatile to study drug release from other polysaccharide based formulations for colonic delivery.

The re-evaluation of optimal lymph node yield in stage II right-sided colon cancer: is a minimum of 12 lymph nodes adequate?

Adequate lymphadenectomy is critical for accurate nodal staging and planning adjuvant therapy in colon cancer. However, the optimal lymph node (LN) yield for stage II right-sided colon cancer (RSCC) is still unclear. This population-based study aimed to determine the optimal LN yield associated with survival and LN positivity in patients with stage II RSCC. All patients with stage II-III RSCC were identified from the Surveillance, Epidemiology, and End Results database over a 10-year interval (2006-2015). The optimal threshold for LN yield was explored using an outcome-oriented approach based on survival and LN positivity. The median number of LNs examined for all 17,385 patients with stage II RSCC was 17 (IQR 12-23). Nineteen LNs were determined as the optimal cut-off point to maximize survival benefit from lymphadenectomy. Increased LN yield was associated with a gradual increase in the risk of node positivity, with no change after 19 nodes. Compared with patients with 19 or more LNs examined, the group with fewer LNs had a significantly poor cancer-specific survival (< 12 nodes: hazard ratio (HR) 2.26, P < 0.001; 12-18 nodes: HR 1.58, P < 0.001) and overall survival (< 12 nodes: HR 1.80, P < 0.001; 12-18 nodes: HR 1.31, P < 0.001). Similar survival results were found in the validation cohort. Patients with older age, small tumor size, and appendix and transverse colon cancer were more likely to receive inadequate LN harvest. A minimum of 19 LNs is needed to be examined for optimal survival and adequate node staging in lymph node-negative RSCC.

Hyaluronic Acid Binding to TLR4 Promotes Proliferation and Blocks Apoptosis in Colon Cancer.

Hyaluronic acid (HA), a constituent of the extracellular matrix, promotes colorectal cancer growth. CD44 is a relevant HA receptor in this context. However, HA is also a ligand for TLR4, a receptor of significance in colorectal cancer. In this study, we examine the relative contribution of HA interactions with CD44 and TLR4 in colon tumorigenesis. Colorectal cancer models included ApcMin/+ mice, azoxymethane/dextran sodium sulfate (AOM-DSS), and CT26 tumor isografts. We used knockout mice and CT26 colorectal cancer cells with CRISPR knockdown of CD44 and TLR4. HA activity was modulated by PEP1 (a 12-mer peptide that blocks HA from binding its receptors), hyaluronidase (which promotes HA degradation), or 4-MU (HA synthesis inhibitor). Blockade of HA binding via PEP1 decreased growth in all colorectal cancer models and in cell culture. The effects were significant in WT and with CD44 deletion, but not with TLR4 deletion. In the AOM-DSS model, mice deficient in CD44 or TLR4 had fewer tumors. CD44- and TLR4-deficient CT26 isografts grew more slowly, exhibiting decreased tumor cell proliferation and increased apoptosis. In vitro, endogenous HA blocked LPS binding to TLR4 suggesting that HA is a relevant TLR4 ligand in colon cancer. Finally, PEP1 enhanced tumor radiation sensitivity in the isograft model. Together, these results indicate that HA binding to TLR4, as well as CD44, plays a key role in colon tumorigenesis. These findings also raise the possibility that an agent that blocks HA binding, such as PEP1, may be useful as an adjuvant therapy in colon cancer.

PC03.01 Adjuvant Therapy for Resected NSCLC Harboring EGFR Mutation, Chemotherapy or Targeted Therapy - PROs

Lung cancer is so far the leading cause of cancer death worldwide. Complete surgical resection remains the most effective approach for patients with early-stage non-small cell lung cancer (NSCLC). Patients with completely resected stage I NSCLC could have a 5-year survival of ∼80%, whereas it fails to ∼30%. Since 2003, adjuvant chemotherapy became the standard of care showing 4% absolute 5-year survival benefit compared to surgery alone [1]. Following randomized control trials revealed similar results [2-4], yet limited survival benefit, low therapeutic completed rate plus high toxicities rate may somehow hinder its clinical applicability. In the past decade, targeted therapies had achieved tremendous success in oncogene-driven advanced NSCLC showing both high efficacy and low toxicities [5]. As a matter of course, targeted therapy had its baby steps in early-stage NSCLC. However, no positive results were found in these trials which should probably be blame for large proportion of stage IB patients and incorrect detection methods for EGFR mutation. Besides, conservative trial design without head to head comparison could not fully address toxicities issues caused by chemotherapy. Precise target population seemed to be an essential key point to adjuvant targeted therapies and ADJUVANT as well as EVAN trial came into being [6, 7]. Although overall survival (OS) was not mature enough to measure, significantly prolonged disease-free survival (DFS) was observed in both trials along with better tolerability. Indeed, questioning around adjuvant targeted therapy has never been adjourned such as the optimal duration of targeted therapies, study design and lack of OS data. Ross et al brought up with an informative comment for ADJUVANT trial bringing the concept of MRD (molecular residual disease) into adjuvant treatment [8]. Based on the ctDNA testing after standard of care adjuvant chemotherapy, patients of high risk of recurrence will be given further treatments while observation for the others. It highlighted the significant role of discriminating beneficiaries from adjuvant targeted therapies instead of simply providing more efficient treatment modalities. Previous biomarker-based studies regarding adjuvant treatment among different tumor types [9, 10] had provided inspirational examples, and as well shown clinical feasibility and urgent need for personalized adjuvant treatment after complete surgical resection. For ADJUVANT trial, we established a comprehensive signature of genetic-features (MEDUSA) to guide personalized adjuvant treatment in EGFR-mutant stage II-III NSCLC. Results would be unleashed in upcoming ESMO meeting. Through utilizing multi-omics data, we could predict whether additional treatments, adjuvant chemotherapy only or observation would be adequate for each individual and provide optimal sequential treatments. Further translational researches and corresponding trials regarding resectable NSCLC should decipher the issues. Fortunately, several trials regarding dynamic monitoring postoperative ctDNA or genomic profile of primary cancer to guide sequential treatments are ongoing and the results should be expected. 1. Arriagada R, Bergman B, Dunant A et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004; 350: 351-360. 2. Winton T, Livingston R, Johnson D et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005; 352: 2589-2597. 3. Strauss GM, Herndon JE, 2nd, Maddaus MA et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol 2008; 26: 5043-5051. 4. Douillard JY, Rosell R, De Lena M et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol 2006; 7: 719-727. 5. Hirsch FR, Scagliotti GV, Mulshine JL et al. Lung cancer: current therapies and new targeted treatments. Lancet 2017; 389: 299-311. 6. Zhong WZ, Wang Q, Mao WM et al. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol 2018; 19: 139-148. 7. Yue D, Xu S, Wang Q et al. Erlotinib versus vinorelbine plus cisplatin as adjuvant therapy in Chinese patients with stage IIIA EGFR mutation-positive non-small-cell lung cancer (EVAN): a randomised, open-label, phase 2 trial. Lancet Respir Med 2018; 6: 863-873. 8. Ng TL, Camidge DR. Lung cancer's real adjuvant EGFR targeted therapy questions. Lancet Oncol 2018; 19: 15-17. 9. Sparano JA, Gray RJ, Makower DF et al. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2015; 373: 2005-2014. 10. Dienstmann R, Salazar R, Tabernero J. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients. J Clin Oncol 2015; 33: 1787-1796. Adjuvant therapy, EGFR-TKI, Lung cancer

Disputes and exploration of neoadjuvant and adjuvant therapy for colon cancer

Perioperative treatment combined with radical resection is the major approach to cure non-metastatic colon cancer. A precise evaluation and perioperative treatment would probably improve the R0 resection rate, recurrence-free survival and overall survival of colon cancer patients. Recently, individualized treatment is the mainstream due to the development of molecular pathology and multi-disciplinary therapy. The indications and course of perioperative treatment and preoperative neoadjuvant therapy of colon cancer are still in intense discussion. The present review will mainly discuss three topics. Firstly, the various reaction of adjuvant therapy to stage II colon cancer is caused by patients' heterogeneity. Choosing stratified treatment for these patients according to clinical and molecular pathological features is the future. Secondly, we discuss the adjuvant chemotherapy course for stage III colon cancer according to the Chinese Society of Clinical Oncology (CSCO) guideline and the progress of this field. Lastly, we summarize the status and significance of colon cancer neoadjuvant therapy.

The prognostic impact of primary tumour location in patients with stage II and stage III colon cancer receiving adjuvant therapy. A GISCAD analysis from three large randomised trials

PurposeBecause the role of the primary tumour location in the adjuvant setting has not been clearly established in colon cancer, we analysed the clinical outcome according to the primary tumour location from three Italian trials assessing adjuvant therapy in colon cancer. Patients and methodsOverall survival (OS) and disease-free survival (DFS) were assessed globally and in each trial, according to right-sided, transverse and left-sided primary colon cancer. Analysis was planned to provide overall and stage-specific results. ResultsIndividual data of 5239 patients were included in this analysis. The right-sided tumours were 1540 (29%), tumours originating in the transverse were 815 (16%) and left-sided tumours were 2884 (55%). At the multivariate analysis, DFS findings from the comparison of the right-sided versus left-sided tumours (hazard ratio [HR] = 1.00; 95% confidence interval [CI] = 0.89–1.14) were not statistically associated with clinical outcomes in the overall population. On the contrary, OS findings, from the comparison of the right-sided versus left-sided tumours, were significantly associated with outcomes (HR = 1.20; 95% CI = 1.04–1.39). In stage II patients, there was no difference in terms of DFS and OS among the three different tumour locations, whereas in stage III patients, the left-sided tumours showed an improved prognosis in terms of OS (HR: 1.36 95% CI = 1.14–1.62, p < 0.001). ConclusionThis is the largest analysis demonstrating a prognostic effect of the tumour location on patients with colon cancer receiving adjuvant chemotherapy. Nevertheless, the effect is limited to OS in stage III colon cancer. In stage II tumours, the primary location has a lesser impact. The transverse tumours should be prognostically considered in between the right-sided and left-sided tumours.

Adjuvant Therapy for Colon Cancer: Genes, Genes… and the Patient in the Center

Although molecular subtype-based stratification and genomic signatures of increasing complexity are becoming a new strategy to guide therapeutic decisions in stage II/III colon cancer, several prognostic factors that can be easily obtained from formalin-fixed paraffin-embedded (FFPE) specimens should be considered to create combined models that better define individual patients' needs. Clin Cancer Res; 24(16); 3787-9. ©2018 AACRSee related article by Kandimalla et al., p. 3867.

Precision Medicine Versus Population Medicine in Colon Cancer: From Prospects of Prevention, Adjuvant Chemotherapy, and Surveillance.

With the advances of technologic revolution that provides new insights into human biology, genetics and cancer, as well as advantages of big data which amasses large amounts of information for us to approach cancer treatment and prevention, we are facing challenges of organically combining data from studies based on general population and information from individual testing and setting out precisional recommendations in cancer diagnosis, prevention, and treatment. We are obligated to accelerate the adaptation of new scientific discoveries into effective treatments and prevention for cancer. In this review, we introduce our opinions on bringing knowledge of precision and population medicine together to guide our clinical practice from the prospects of colorectal cancer prevention, stage III colon cancer adjuvant therapy, and postsurgery surveillance.