Efficacy and Tolerability of Selective Internal Radiotherapy With Yttrium-90 as Consolidation Treatment After Chemotherapy in Metastatic Colorectal Cancer

BackgroundSelective internal radiotherapy (SIRT) with yttrium-90 (Y-90)-labeled resin microspheres may have a role in consolidating the response to chemotherapy in patients with metastatic colorectal cancer unamenable to resection after assessment of the best response to first-line chemotherapy.Patients and MethodsThis was a retrospective analysis of outcomes in patients who had received SIRT as consolidation therapy after one or more lines of chemotherapy. Eligible patients were 18 years or older, had confirmed colorectal liver metastases, and had disease unsuitable for surgical resection or local ablation with curative intent. The primary endpoint was progression-free survival.ResultsSixty-eight patients with colorectal liver metastases were treated with at least one SIRT procedure after receiving one or more lines of chemotherapy. Median progression-free survival was significantly longer in patients who received SIRT after prior first-line chemotherapy compared to those who received SIRT after two or more lines of chemotherapy (9 vs. 3 months, respectively; hazard ratio = 0.07; 95% confidence interval, 0.02854‒0.2039; P < .001), and in patients with liver-only disease compared to those who had extrahepatic metastases (6.4 vs. 4.1 months, respectively; hazard ratio = 0.57; 95% confidence interval, 0.34-0.95; P = .0318). There were no grade 3 or higher adverse events.ConclusionSIRT represents a valid option for the treatment of colorectal liver metastases. Earlier use of SIRT may provide a greater survival benefit compared to that afforded by the procedure when used in salvage settings.     

Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases

Background

In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response.

Prognostic Value of the Combination of Circulating Tumor Cells Plus KRAS in Patients With Metastatic Colorectal Cancer Treated With Chemotherapy Plus Bevacizumab

ObjectiveCirculating tumor cells (CTCs) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) status were identified as prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab in analyses of the MACRO (Maintenance Treatment in Advanced Colorectal Cancer) trial. In this post hoc analysis of the MACRO trial, the potential additive effect of these 2 factors on patient outcomes was explored.MethodsA total of 158 of the 480 patients involved in the MACRO trial were included in the biological marker substudy. CTC isolation and enumeration were centralized and performed using the CellSearch System (Veridex LLC, Raritan, NJ) in 7.5 mL of whole blood. Evaluation of KRAS status was performed retrospectively by the standard method used at each center. PFS and OS were analyzed by the Kaplan–Meier method according to CTC count and KRAS status.ResultsPatients with < 3 CTC per 7.5 mL blood at baseline and KRAS wild-type tumors had a median PFS of 14.2 months compared with 6.2 months in patients with ≥ 3 CTCs and KRAS mutated tumors (P < .0001; hazard ratio, 3.0; 95% confidence interval, 1.8-5.2). Similar findings were observed for OS (28.9 and 13.7 months, respectively, P = .0004; hazard ratio 2.8; 95% confidence interval, 1.6-4.9). Multivariate analyses showed that CTC count ≥ 3 and KRAS status were the only independent prognostic factors for both PFS and OS.ConclusionsThis post hoc analysis showed that CTC count and KRAS status were independent prognostic factors for outcomes in patients with metastatic colorectal cancer treated with bevacizumab ± chemotherapy. These factors should be taken into account in the design of future phase III trials.     

Cost-effectiveness of Trifluridine/tipiracil for Previously Treated Metastatic Colorectal Cancer in England and Wales

Background

Treatment options at third-line and beyond for patients with late-line metastatic colorectal cancer (mCRC) are limited, and outcomes are poor with best supportive care (BSC). This study investigated the cost-effectiveness of trifluridine/tipiracil and regorafenib relative to BSC alone in patients with mCRC who have been previously treated with, or are not considered candidates for, standard chemotherapies.

Glasgow Prognostic Score As a Prognostic Factor in Metastatic Castration-Resistant Prostate Cancer Treated With Docetaxel-Based Chemotherapy

BackgroundThe modified Glasgow Prognostic Score (mGPS), derived from C-reactive protein (CRP) and albumin levels, and the neutrophil-lymphocyte ratio (NLR) have demonstrated prognostic significance in a number of malignancies.Patients and MethodsBaseline mGPS and NLR were calculated in a prospective cohort of chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC) (AT-101-CS-205 trial) who received docetaxel and prednisone ± AT101. Cox proportional hazards regression models estimated their effects on overall survival (OS).ResultsOf 220 eligible patients, mGPS and neutrophil and lymphocyte counts were available for 184, 193, and 112 patients, respectively. Albumin (hazard ratio [HR], 0.28; 95% confidence interval [CI]: 0.14-0.56; P < .001) and CRP (HR, 1.22; 95% CI, 1.00-1.48; P = .048) were independently prognostic for OS. An association between mGPS and OS was found (HR, 1.87; 95% CI, 1.35-2.59; P < .001; median survival, 23.5 months at mGPS 0 vs. 9.8 months at mGPS 2). mGPS was significant after controlling for 3 previously published nomograms or NLR (P ≤ .001). NLR was not prognostic for OS (HR, 0.98; P = .91), and no association between mGPS and toxicity was noted.ConclusionOur results demonstrate the prognostic role of the mGPS in mCRPC over variables previously identified. mGPS is inexpensive, easily measured, and could be incorporated into routine clinical testing if our results are confirmed in a subsequent validation study. The utility of the NLR in mCRPC remains uncertain despite evidence in other malignancies.     

Mean Platelet Volume as a Prognostic Marker in Metastatic Colorectal Cancer Patients Treated with Bevacizumab-Combined Chemotherapy

Background: Recent studies have revealed a prognostic impact of the MPV (mean platelet volume)/platelet count ratio in terms of survival in advanced non-small cell lung cancer. However, there has been no direct analysis of the survival impact of MPV in patients with mCRC. The aim of the study is to evaluate the pretreatment MPV of patients with metastatic and non-metastatic colorectal cancer (non-mCRC) and also the prognostic significance of pretreatment MPV to progression in mCRC patients treated with bevacizumab-combined chemotherapy. Materials and Methods: Fifty-three metastatic and ninety-five non-metastatic colorectal cancer patients were included into the study. Data on sex, age, lymph node status, MPV, platelet and platecrit (PCT) levels were obtained retrospectively from the patient medical records. Results: The MPV was significantly higher in the patients with mCRC compared to those with non-mCRC (7.895±1.060 versus 7.322±1.136, p=0.013). The benefit of bevacizumab on PFS was significantly greater among the patients with low MPV than those with high MPV. The hazard ratio (HR) of disease progression was 0.41 (95%CI, 0.174-0.986; p=0.04). In conclusion, despite the retrospective design and small sample size, MPV can be considered a prognostic factor for mCRC patients treated with bevacizumab-combined chemotherapy.     

Real-World Data: Fruquintinib in Treating Metastatic Colorectal Cancer

Fruquintinib, also called HMPL-013, was first discovered by Hutchison Whampoa Pharmaceuticals Co. Ltd., Shanghai, China, and it is an oral vascular endothelial growth factor receptor (VEGFR) inhibitor. In clinical trials, fruquintinib has demonstrated a survival benefit in metastatic colorectal cancer (mCRC) patients. The purpose of this study was to retrospectively evaluate the efficacy and toxicity of fruquintinib in real-world patients. We collected data from patients with mCRC treated with oral fruquintinib from 2018 to 2020 in six different institutions. Patients with mCRC initially received 5 mg of oral fruquintinib daily for 3 weeks. Progression-free survival (PFS) was evaluated using the Kaplan–Meier method. The efficacy and safety of fruquintinib were also assessed. Seventy-five patients were involved in our study, and 29.3% of patients achieved stable disease (SD). Median PFS was 5.4 months (95% CI: 4.841–5.959). The treatment-emergent adverse events (TEAEs) with fruquintinib were acceptable with grade 3 TEAEs of 6%. The grade 3 TEAEs were hand–foot skin reaction (HFSR), fatigue, and stomatitis. The ECOG performance status was associated with PFS. In this real-world study, the clinical activity of fruquintinib was consistent with what has been reported in previous clinical trials. The level of safety was acceptable, and the side effects were manageable.     

Neutrophil-related Variables Have Different Prognostic Effect Based on Primary Tumor Location in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy

BackgroundClinical data reported a relationship between neutrophil-related variables and poor prognosis in patients with metastatic colorectal cancer (mCRC), but only platelet-to-lymphocyte ratio has been reported as prognostic.Patients and MethodsA retrospective analysis of 145 patients with mCRC, who received chemotherapy at the department of Oncology of the Ospedale Civile di Sanremo in 2010 to 2013, was performed, and a Cox model was built.ResultsIn the model, some variables were independently related with overall survival (OS) (resection of the primary tumor, number of drugs included in the first-line chemotherapy regimen), whereas neutrophil-related ones were not. However, after stratification by tumor location, neutrophil-related variables appeared associated with a poor survival among patients with a left-sided mCRC, and in particular, among those ones with a rectal tumor (hazard ratio, 3.732; 95% confidence interval, 1.575-8.845).ConclusionNeutrophil-related variables predicted outcome in patients with left-sided mCRC only. A high prevalence of consensus molecular subtype 4 CRC in patients with metastatic cancer of the rectum is suggested.     

Regorafenib Is Associated With Increased Skeletal Muscle Loss Compared to TAS-102 in Metastatic Colorectal Cancer

BackgroundCurrent guidelines of the National Comprehensive Cancer Network and the European Society of Medical Oncology recommend regorafenib or trifluridine/tipiracil (TAS-102) for third-line therapy of metastatic colorectal cancer (mCRC). We evaluated the impact of regorafenib and TAS-102 treatment on skeletal muscle dynamics and sarcopenia.Patients and MethodsThis retrospective analysis was based on unselected, consecutive mCRC patients treated with regorafenib and/or TAS-102 during third or later line of therapy at our tertiary-care cancer center in Salzburg, Austria. The skeletal muscle index (SMI, cm²/m²) and sarcopenia were evaluated from cross-sectional computed tomographic images at the level of the third lumbar vertebra.ResultsBetween January 2013 and April 2018, a total of 45 patients had received regorafenib and/or TAS-102. At initial mCRC diagnosis and at initiation of third-line therapy, 24% and 54% of patients presented with sarcopenia. A statistically significant skeletal muscle loss was observed during regorafenib treatment (median SMI change: −2.75 cm²/m² [−6.3%]; P < .0001), which was not the case during TAS-102 therapy (−1.5 cm²/m² [−3.5%]; P = .575). Furthermore, subclassification of patients into 3 groups—normal muscle mass, stable sarcopenia, and new-onset sarcopenia—at initiation of third-line therapy permitted discrimination of overall survival, with 1-year overall survival rates of 61%, 29%, and 16%, respectively (P = .04).ConclusionThe frequency of sarcopenia increases during the course of mCRC and negatively affects survival. In contrast to TAS-102, regorafenib is associated with increased skeletal muscle loss during mCRC treatment and should therefore be used with caution in mCRC patients with preexisting sarcopenia or a history of recent weight loss.     

Effect of Primary Tumor Side on Survival Outcomes in Untreated Patients With Metastatic Colorectal Cancer When Selective Internal Radiation Therapy Is Added to Chemotherapy: Combined Analysis of Two Randomized Controlled Studies

Background

The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone.

Effect of Primary Tumor Location on Second- or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies

Background

The primary tumor location has a prognostic impact in metastatic colorectal cancer (mCRC). We report the results from retrospective analyses assessing the effect of tumor location on prognosis and efficacy of second- and later-line panitumumab treatment in patients with RAS wild-type (WT) mCRC and on prognosis in all lines of treatment in patients with RAS mutant (MT) mCRC.

The Prognostic Role of CD73/A2AR Expression and Tumor Immune Response in Periampullary Carcinoma Subtypes

Introduction: Periampullary adenocarcinoma (PAAC) is a rare, lethal heterogeneous group of malignancy that differs in their molecular phenotypes. Ecto-5′-nucleotidase (CD73)/adenosine A2A Receptor (A2AR) pathway has shown an emerging role in cancer therapy through modulating the immune response. Therefore, this study aimed to explore the functional role of CD73 and A2AR in pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (AC). Material and methods: An immunohistochemical study for CD73 and A2AR carried on 48 PDAC cases, 21 AC cases and 34 adjacent non-tumor tissues that were taken from the farthest point of normal pancreatic tissue away from the tumor. Results: CD73 was overexpressed in the PDAC (p < 0.001), and AC (p = 0.004) groups compared to their non-tumor tissues. However, A2AR was overexpressed in the PDAC group (p = 0.003) but not in the AC group (p = 0.359) compared to non-tumor tissue. In the PDAC group, CD73 overexpression was significantly associated with longer overall survival (p = 0.018). In contrary, A2AR overexpression was significantly associated with high grade (p = 0.001) and late- stage (p = 0.01). Both markers had no prognostic impact on AC. In the meantime, tumor immune response showed a negative prognostic role in PDAC and AC. The prognostic role of tumor immune response in the PDAC group was strongly modulated by CD73 and A2AR expression. Conclusions: PDAC and AC shared CD73 Overexpression while A2AR was overexpressed in PDAC only. In PDAC, CD73 and A2AR showed an opposed  prognostic effect but both had no prognostic impact on AC. In addition, tumor immune response showed a controversial impact on the prognosis of PDAC and AC.     

Occurrence and Management of Thrombocytopenia in Metastatic Colorectal Cancer Patients Receiving Chemotherapy: Secondary Analysis of Data From Prospective Clinical Trials

IntroductionChemotherapy-induced thrombocytopenia (CIT) contributes to treatment dose delay and/or modification, often resulting in poorer survival and disease progression. We explored the incidence and clinical consequences of CIT among metastatic colorectal cancer (mCRC) patients.Materials and MethodsData from two prospective randomized phase 3 trials of mCRC patients receiving either first-line FOLFOX4 (fluorouracil, leucovorin, oxaliplatin) or second-line FOLFIRI (fluorouracil, leucovorin, irinotecan) were analyzed. Thrombocytopenia was defined by platelet count < 100 × 10⁹/L (further categorized by grade) and by recorded adverse events (AEs). Co-occurrence of anemia (hemoglobin < 12 g/dL) and neutropenia (neutrophil count < 2 × 10⁹/L) and clinical consequences of CIT were also evaluated.ResultsAmong 1078 mCRC patients in the FOLFOX4 study, cumulative incidence of CIT based on platelet count was 37% (grade 3, 2%; grade 4, 1%) during an average 8 months’ follow-up. Neutropenia or anemia were absent in 44% of CIT episodes; 62% of CIT AEs led to chemotherapy dose delay, change, and/or discontinuation. Among 1067 mCRC patients in the FOLFIRI study, cumulative incidence of CIT based on platelet count was 4% (grade 3, < 1%; grade 4, 0) during an average 4 months’ follow-up. Neutropenia or anemia were absent in 22% of CIT episodes; 32% of CIT AEs led to chemotherapy dose delay, change, and/or discontinuation. With both regimens, transfusions and hospitalizations after CIT AEs were rare (< 3%).ConclusionCIT was common among mCRC patients receiving the FOLFOX4 regimen. The most frequent consequence of CIT was a delay in chemotherapy, highlighting the unmet need in CIT management.     

Adverse Events Associated With Bevacizumab and Chemotherapy in Older Patients With Metastatic Colorectal Cancer

BackgroundThe safety of bevacizumab in older mCRC patients is poorly understood. The purpose of this analysis was to determine the prevalence, incidence, and risk factors for treatment-related AEs in older bevacizumab recipients.Patients and MethodsPatients age ≥65 were identified from SEER–Medicare and categorized by mCRC diagnosis pre and post bevacizumab approval (2001-2003 vs. 2005-2007). Preexisting conditions known to increase bevacizumab-related AE risk were identified in the year before diagnosis. Factors associated with bevacizumab receipt were identified using logistic regression. Incidence rates for all AEs and specific serious AEs were determined. Risk factors for first AE were determined by competing risks regression.ResultsOf 6821 patients, 3282 (48%) were diagnosed in 2005-2007 of whom 19% received first-line bevacizumab. Likelihood of bevacizumab receipt was lower in patients age ≥ 75 (odds ratio [OR], 0.41; 95% confidence interval [CI], 0.36-0.47), nonwhite patients (OR, 0.67; 95% CI, 0.55-0.81), patients with higher comorbidity index (OR, 0.52; 95% CI, 0.43-0.62), and patients with preexisting cerebrovascular disease (OR, 0.49; 95% CI, 0.33-0.73). AE incidence rate was not increased among first-line bevacizumab recipients relative to first-line chemotherapy recipients. In a competing risk regression adjusting for potential confounders, bevacizumab receipt (2005-2007) was not associated with an increased risk of first AE compared with chemotherapy alone (2001-2007) (hazard ratio, 0.97; 95% CI, 0.87-1.08).ConclusionIn an older mCRC population, bevacizumab receipt was less likely in older (age ≥ 75) nonwhite patients with preexisting cerebrovascular comorbidities. First-line bevacizumab was not associated with increased AE incidence or risk of first AE compared with chemotherapy alone.     

Role of Predictive Value of the Modified Glasgow Prognostic Score for Later-line Chemotherapy in Patients With Metastatic Colorectal Cancer

Background

Assessment of patient factors is essential for selecting later-line chemotherapy in patients with metastatic colorectal cancer (mCRC). The efficacy, prognosis, and safety of each treatment regimen according to nutritional and inflammatory status still remain to be elucidated.

MicroRNA Signature in Metastatic Colorectal Cancer Patients Treated With Anti-EGFR Monoclonal Antibodies

BackgroundTo investigate whether microRNAs are predictive of sensitivity to anti–epidermal growth factor receptor (EGFR) monoclonal antibodies in patients with metastatic colorectal cancer (mCRC).MethodsA total of 183 mCRC cases from 2 independent cohorts (cohort 1: 74 cases; validation cohort: 109 cases) treated with cetuximab or panitumumab were included in the study. MiRNA arrays were analyzed using Agilent's miRNA platform.ResultsThe study identified the cluster Let-7c/miR-99a/miR-125b as a signature associated with an outcome different from that of anti-EGFR therapies. In the first cohort, patients with high-intensity signatures had a significantly longer progression-free survival (PFS) (6.1 vs. 2.3 mo; P = .02) and longer overall survival (OS) ( 29.8 vs. 7.0 mo, P = .08) than patients with low-intensity signatures. In the validation cohort, patients with high signature had significantly longer PFS and OS than individuals with low-intensity signatures (PFS 7.8 vs. 4.3 mo, P = .02; OS 12.8 vs. 7.5 mo, P = .02). In the KRAS wild-type population (n = 120), high-intensity signature patients had a significantly longer PFS (7.8 vs. 4.6 mo, P = .016) and longer OS (16.1 vs. 10.9 mo, P = .09) than low-signature individuals, with no difference in KRAS mutated patients.ConclusionThe MiR-99a/Let-7c/miR-125b signature may improve the selection of patients with KRAS wild-type mCRC as good candidates for anti-EGFR therapy.     

Capecitabine Plus Oxaliplatin and Bevacizumab,Followed by Maintenance Treatment With Capecitabine and Bevacizumab for Patients Aged > 75 Years With Metastatic Colorectal Cancer

BackgroundThe aim of the present study was to evaluate the efficacy and safety of the combination of CAPOX-Bev (capecitabine [Cap] plus oxaliplatin and bevacizumab [Bev]), followed by maintenance Cap and Bev, for patients with metastatic colorectal cancer (mCRC) and aged > 75 years.Patients and MethodsThe regimen consisted of intravenous oxaliplatin 130 to 100 mg/m² on day 1, oral Cap 750 to 1000 mg/m² twice daily on days 1 to 14, and Bev 7.5 mg/kg on day 1, every 3 weeks. After 4 cycles of CAPOX-Bev, the patients without evidence of disease progression received maintenance treatment with Cap 1000 to 1250 mg/m² twice daily on days 1 to 14 and Bev 7.5 mg/kg on day 1, every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint was the 9-month disease control rate. Progression-free survival (PFS), overall survival (OS), and safety were the secondary endpoints.ResultsOverall, 36 patients were enrolled from March 2012 to April 2017 at our institution. After completion of CAPOX/Bev, 15 patients (41.7%) had a partial response, 18 (50.0%) had stable disease, and 3 (8.3%) had progressive disease. Thirty-three patients (91.7%) received the Cap/Bev regimen as maintenance treatment for a median of 8.6 cycles (range, 3-14 cycles). The 9-month DCR was 58.3% (95% confidence interval [CI], 40.8-74.5), the median PFS was 8.8 months (95% CI, 6.7-10.3 months), and the median OS was 20.8 months (95% CI, 16.1-25.4 months). With the CAPOX/Bev regimen, the most common grade 3 toxicity included neutropenia (11.1%), diarrhea (5.5%), nausea/vomiting (2.8%), and fatigue (2.8%). Grade 3 neurotoxicity was not observed. With Cap/Bev maintenance therapy, grade 3 hand-foot syndrome was observed in 2 patients (6.0%).ConclusionCAPOX/Bev, followed by Cap/Bev as maintenance treatment, is safe and effective in terms of PFS and OS for elderly patients aged > 75 years with mCRC.     

Circulating Cell Free DNA Integrity Index as a Biomarker for Response to Chemotherapy in Patients with Metastatic Colorectal Carcinoma

Objective: Assessing plasma Cell Free DNA (cfDNA) integrity index as a biomarker for response prediction and early response evaluation in mCRC patients receiving chemotherapy, in comparison to Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9), to be used as an additional tool to computed tomography (CT). Methods: CEA, CA19-9, cfDNA concentration and cfDNA integrity index (ALU 247/115) measurements were conducted on 86 subjects divided into 43 healthy volunteers and 43 mCRC patients, before starting chemotherapy and then after 6-12 weeks of therapy initiation (3-4 cycles FOLFOX) at first response assessment. Plasma cfDNA integrity index was calculated as the ratio of long to short DNA fragments (ALU 247/115) amplified and detected by real-time PCR. Serum CEA and CA19-9 were measured by chemiluminescent immunometric assay. Results: Baseline cfDNA integrity index was statistically significantly different between responders and non-responders (p=0.03). It was found that at cut off 0.608, sensitivity was 73.7%, specificity was 66.7% and diagnostic accuracy=69.77%. Markers with statistical significant difference between responders and non-responders after chemotherapy were CEA % change (p=0.035), CA19-9 (p=0.024), cfDNA integrity index (p=0.035) and cfDNA integrity index % change (p<0.001). Among these markers, cfDNA integrity index % change had the best sensitivity (84.2%), specificity (95.2%) and diagnostic accuracy (90.7%) at cut off -17.827%. Conclusion: Baseline cfDNA integrity index can be used as a potential marker to predict response to chemotherapy. cfDNA integrity index (ALU 247/115) % change rather than its absolute value is superior to CEA, CA19-9, cfDNA concentration and their % changes in early assessment of response to chemotherapy.     

Skin Disorders and Primary Tumor Location as Prognostic Factors in Patients with Metastatic Colorectal Cancer Treated with Cetuximab and Chemotherapy

Background: Cetuximab-induced skin disorder is common in colorectal cancer (CRC), and is known to affectprolonged overall survival (OS). Patients with left-sided CRC survive longer than those with right-sided CRC, amongthose treated with combination cetuximab and chemotherapy. However, no study has evaluated patient prognosisin terms of OS and progression-free survival (PFS) in relation to both tumor location and skin disorder. This studyaimed to determine the incidence of skin disorder according to tumor location and analyze the relationship of tumorlocation and skin disorder with OS. Methods: Patients with metastatic colorectal cancer (mCRC) treated with standardchemotherapy and cetuximab as first-line therapy were included. Differences in the incidence of skin disorders due tothe location of the primary tumors were compared in the same patient. The OS and PFS in relation to the location ofthe primary tumors and presence or absence of skin disorder were also compared. Results: Total frequency of eachskin disorder as rash acneiform, paronychia, and dry skin in patients with left- and right-sided mCRC was 70%, 70%,and 43% and 27%, 36%, and 27%, respectively. The median OS was 8.9 months for mCRC on the left-sided withoutskin disorder and 56.3 months for mCRC on the left-sided with skin disorder. In comparison, the median OS was 10.4months for mCRC on the right-sided without skin disorder and 11.3 months for mCRC on the right-sided with skindisease (left-sided with skin disorder versus other three group; P<0.001). Conclusions: Primary tumor location andthe presence of skin disorder are important factors in patients with mCRC who receive cetuximab. In particular, ourresults show the new fact that the left-sided and right-sided mCRC survival time were comparable if there is no skindisorder caused by cetuximab.