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BACKGROUND: Primary tumor (PT) sidedness is an established prognostic marker in metastatic colorectal cancer (mCRC) and has a predictive impact on the efficacy of anti-epidermal growth factor receptor (anti-EGFR) antibody [monoclonal antibody (mAb)] in patients with RAS wild-type mCRC. This investigation focuses on patients with BRAFV600E-mutated (BRAFmt) mCRC and examines the efficacy of anti-EGFR mAbs in relation to primary tumor sidedness (PTS). PATIENT AND METHODS: This pooled analysis was carried out using individual patient data from five randomized studies in the first-line setting of mCRC. The population of interest was limited to patients with BRAFmt mCRC and known PTS. For analysis, treatment was stratified into two groups: those treated with anti-EGFR mAbs and those without. Dichotomous variables, such as overall response rate and objective response rate (ORR), were compared using chi-square or Fisher's exact test. Time-to-event endpoints [progression-free survival (PFS) and overall survival (OS)] were analyzed using the Kaplan-Meier method, log-rank test, and Cox regression. An interaction test was carried out via Cox regression. RESULTS: A total of 102 patients with BRAFmt mCRC were identified. The type of targeted therapy (anti-EGFR-based versus non-anti-EGFR) did not significantly impact the outcome. However, in patients with left-sided primary tumors, anti-EGFR mAb-based treatment, compared with non-anti-EGFR, was associated with a higher ORR (58% versus 34%; P < 0.01), trended toward improved PFS [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.34-1.13; P = 0.12], and demonstrated prolonged OS (HR 0.38; 95% CI 0.20-0.72; P < 0.01). In patients with right-sided primary tumors, anti-EGFR-based therapy had no effect on ORR (33% versus 36%; P > 0.99), induced inferior PFS (HR 1.97; 95% CI 1.12-3.47; P = 0.02), and trended toward a worse OS (HR 1.76; 95% CI 0.99-3.13; P = 0.05). CONCLUSION: This analysis suggests that PTS has predictive value for the efficacy of anti-EGFR mAb in the first-line treatment of BRAFmt mCRC.
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Background: Stage II colon cancer has varying risks for metastasis, and treatment strategies depend on molecular and clinicopathological features. While tumor-sidedness is a well-accepted prognostic factor for stage III/IV colon cancer, its role in stage II is controversial. Understanding its effect in stage II is crucial for improving treatment strategies. Methods: We analyzed clinical and follow-up data of colon cancer from the Surveillance, Epidemiology, and End Results database (2004-2017). Patients were divided into a primary study cohort (2010-2017) and a validation cohort (2004-2009). The baseline characteristics between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) groups were compared. Moreover, the effect of tumor size on cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis. Results: The study involved 87,355 patients in the study cohort and 65,858 in the validation cohort. Of the study cohort, 52.3% were diagnosed with RCC. The median age was 64 years old, with 48.5% females and 76.8% of white people. In addition, stage II RCC showed better CSS compared with LCC (5-year CSS 88.0% vs 85.5%, P < 0.001), while stage III/IV RCC demonstrated poorer outcomes. Multivariate Cox regression analysis identified that the right-sidedness was a positive prognostic factor in stages I/II but negative in stages III (HR 1.10, P < 0.001) and IV (HR 1.26, P < 0.001). Chemotherapy rates decreased in RCC, particularly in stage II (RCC vs LCC: 16.2% vs 28.5%, P < 0.001). Subgroup analysis, stratified by T3/T4 stages and chemotherapy status, further highlighted better survival outcomes in RCC. Conclusions: RCC is associated with a significantly better prognosis in stage II. The importance of considering tumor-sidedness in clinical decision-making and the design of future clinical trials should be emphasized.
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Background: Colorectal liver metastasis (CRLM) exhibits highly heterogeneity, with clinically and molecularly defined subgroups that differ in their prognosis. The aim of this study is to explore whether left-sided tumors is clinically and gnomically distinct from right-sided tumors in CRLM. Methods: This retrospective study included 1,307 patients who underwent primary tumor and metastases resection at three academic centers in China from January 1, 2012, to December 31, 2020. Propensity score matching with 1:1 ratio matching was performed. The prognostic impact of tumor sidedness was determined after stratifying by the KRAS mutational status. Moreover, whole-exome sequencing (WES) of 200 liver tumor tissues were performed to describe the heterogeneity across the analysis of somatic and germline profiles. Results: The median follow-up was 68 months. Matching yielded 481 pairs of patients. Compared to right-sided CRLM, left-sided patients experienced with better 5-year overall survival (OS) in surgery responsiveness, with a 14.6 lower risk of death [hazard ratio (HR), 1.36, 95% confidence interval (CI), 1.10-1.69, P=0.004]. Interaction between tumor sidedness and KRAS status was statistically significant: left-sidedness was associated with better prognosis among KRAS wild-type patients (HR 1.71; 95% CI: 1.20-2.45; P=0.003), but not among KRAS mutated-type patients. Integrated molecular analyses showed that right-sided tumors more frequently harbored TP53, APC, KRAS, and BRAF alterations, and identified a critical role of KRAS mutation in correlation with their survival differences. Higher pathogenic germline variants were identified in the right-sided tumors compared with left-sided tumors (29.3% vs. 15.5%, P=0.03). Conclusions: We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors. Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.
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BACKGROUND AND OBJECTIVES: The number of young patients with colorectal cancer (CRC) is increasing. However, sex-dependent differences in the prognosis of young CRC remain unknown. METHODS: We investigated patients aged <70 years with stage III CRC treated between January 2000 and December 2010 in 24 Japanese referral hospitals. Patients were divided into subgroups by age of 50 years (early-onset and late-onset groups) and sex, and clinical characteristics and survival outcomes were compared. Risk factors associated with poor survival outcomes were also analyzed. RESULTS: Among 4758 consecutive patients, 771 (16%) were <50 years. Regardless of sex, there were more patients with rectal cancer and treated with adjuvant chemotherapy in the early-onset group. Among males, tumors in the early-onset group were poorly differentiated (p < 0.001), and patients were diagnosed at an advanced N stage (p = 0.010). Among females, there were more patients with left-sided cancer in the early-onset group (p < 0.001). Relapse-free survival (RFS) and overall survival (OS) were worse in the early-onset group than in the late-onset group (5-year RFS rates: 58% and 63%, p = 0.024; 5-year OS rates: 76% and 81%, p = 0.041, respectively), while there were no age-dependent differences in the survival outcomes of female CRC patients. A multivariate analysis identified age <50 years as one of the independent risk factors associated with poor RFS in male stage III CRC patients (p = 0.032) CONCLUSIONS: Young male patients with stage III CRC showed poorer survival outcomes than their older counterparts. Therefore, age- and sex-related differences in the incidence of CRC recurrence need to be considered.
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Neoplasias Colorrectales , Humanos , Masculino , Femenino , Estudios Retrospectivos , Estadificación de Neoplasias , Pronóstico , Quimioterapia AdyuvanteRESUMEN
BACKGROUND/AIM: Systemic treatment for metastatic colorectal cancer (CRC) includes chemotherapy in combination with a targeted antibody. Novel targeted therapies and immunotherapies are introduced for specific molecular subgroups. Prognostic relevant determinants are still under investigation. PATIENTS AND METHODS: Systemic therapies of an unselected patient cohort with metastatic CRC were retrospectively analyzed. Treatment outcome was evaluated according to time-to-next-treatment (TTNT) and frequency of conversion surgery and compared between subgroups stratified by primary tumor side, molecular profile, sex and age, and metastases sites. RESULTS: More than 50% of patients with locally advanced or metastatic CRC underwent secondary resection after first-line systemic therapy. Rectum carcinoma had the best prognosis under anti-EGFR-antibody treatment. Female patients had a worse prognosis than male patients in late disease stage. Young patients demonstrated poor response to systemic therapy, but a high rate of conversion surgeries. Conversely, elderly patients benefited from systemic therapy but underwent surgery less frequently. Liver and lung metastases had a worse prognosis than other metastases sites, whereas lung metastases were more likely to be resected than liver metastases in early disease stage. CONCLUSION: Patient age, sex, primary tumor localization, and metastatic sites are prognostic factors that could guide future treatment decisions for the therapy of metastatic CRC.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias del Recto , Humanos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Neoplasias Colorrectales/patología , Neoplasias del Colon/patología , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Pronóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Hepáticas/secundarioRESUMEN
BACKGROUND: FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin) combined with or without anti-VEGF therapy represents one of the primary first-line treatment options for metastatic colorectal carcinoma (mCRC). However, there is limited comparative data on the impact of anti-VEGF therapy on treatment effectiveness, survival outcomes, and tumor location. METHODS: This retrospective, comparative study utilized data from the AIM Cancer Care Quality Program and commercially insured patients treated at medical oncology clinics in the US. We analyzed 1652 mCRC patients who received FOLFOX, of which 1015 (61.4%) were also treated with anti-VEGF therapy (VEGF cohort). RESULTS: Patients in the VEGF cohort exhibited a higher frequency of lung (33% vs 23%; P < .001) and liver metastases (74% vs 62%; P < .001), underwent fewer liver surgeries prior to treatment (1.2% vs 3.6%; P = .002), and had a higher proportion of right-sided tumors (27% vs 18%; P = .001). Adjusted analysis revealed no significant difference in overall survival (OS) between patients treated with and without anti-VEGF (median survival: 25.4 vs 26.0 months; P = .4). FOLFOX-only treated patients experienced higher rates of post-treatment hospitalizations (22% vs 15%; P < .001). Notably, left-sided tumors treated with anti-VEGF showed a trend toward decreased OS (median survival: 26.8 vs 33 months; P = .09). CONCLUSION: Our real-world data analysis suggests that the addition of anti-VEGF to FOLFOX offers limited and short-lived benefits in the context of mCRC and may provide differential survival benefit based on tumor sidedness.
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Neoplasias Colorrectales , Factor A de Crecimiento Endotelial Vascular , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Colorrectales/patología , Leucovorina/uso terapéutico , Oxaliplatino/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To determine whether N3 nodal involvement predicts outcomes and whether its prognostic implications vary with tumor location in patients with Stage III colon cancer (CC). METHODS: We defined N3 as lymph node metastases near the bases of the major feeding arteries. We retrospectively examined recurrence rates and patterns by tumor location and sites of lymph node metastases in 57 patients with N3 CC who had undergone curative resections between January 2000 and March 2019. Survival analysis was performed to compare the prognoses of patients with and without N3 lymph node metastasis. RESULTS: Most N3 patients had large tumors (T ≥ 3); five had T2 disease. Recurrence occurred quickly in one patient with T2N3M0 disease. Multivariate survival analysis demonstrated that N3 lymph node metastasis is an independent predictor of poor prognosis in Stage III CC patients (P < 0.001). Categorizing N3 patients according to UICC-TNM staging system does not stratify risk of recurrence (P = 0.970). To investigate the impact of tumor location on recurrence risk, we classified N3 CC into two subtypes according to tumor location: metastasis at the base of the superior mesenteric artery in right-sided CC and inferior mesenteric artery in left-sided CC. The former was found to have a statistically significant poorer prognosis than the latter (P = 0.091). CONCLUSION: N3 is a robust prognostic marker in CC patients. Recurrence risk varies by tumor location. N3 right-sided CCs with lymph node metastasis at the base of the superior mesenteric artery have poorer prognoses than do N3 left-sided CCs.
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Neoplasias del Colon , Humanos , Pronóstico , Metástasis Linfática/patología , Estudios Retrospectivos , Neoplasias del Colon/cirugía , Neoplasias del Colon/patología , Estadificación de Neoplasias , Arterias , Ganglios Linfáticos/patología , Escisión del Ganglio LinfáticoRESUMEN
Very recently, emerging evidence demonstrated that laterality might be an independent prognostic factor in patients with advanced ovarian cancer (OC). Based on preliminary provocative observations, our study aimed to investigate the prognostic impact of sidedness in a large cohort of women with OC. Survival was estimated based on Kaplan-Meier method and survival curves were compared using Log-rank test. Cox proportional-hazards model was used to study the association between survival and covariates. A total of 10,177 women with OC were included. Mean age at diagnosis was 59.58 years (±13.5); 36.7% OC right-sided, 36.9% were left- sided, and 26.4% had bilateral OC. The median overall survival (OS) for the entire population was 77 months, with the lowest median OS observed in bilateral OC (median OS: 34 months). The prognostic value of OC sidedness was not confirmed at the univariable analysis (HR = 0.958; 95% CI: 0.888-1.033, p = 0.268). However, women with bilateral OC has a 45% higher risk of death as compared with unilateral diagnosis (HR = 1.453; 95% CI: 1.410-1.497; p< 0.001). The independent prognostic value was further confirmed on multivarible analysis after adjusting for covariates including age, marital status, histological type, CA-125 at diagnosis, grade, stage, chemotherapy and surgery (HR = 1.087; 95% CI: 1.043-1.136, p = 0.02). However, the ultimate prognostic significance appeared less prominent, with bilateral OC conferring a relative increase of 8.7% of mortality. Our real-world study demonstrated that impact of tumor sidedness has no prognostic implication (right vs left OC) but bilateral OCs might be marginally more prognostically unfavorable. Prospective validation might be warranted, to confirm the prognostic significance of OC sidedness, including for the presence of key genetic alterations and lymph nodes asymmetry, to better stratify patients with OC and predict outcomes according to tumor sidedness at diagnosis.
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Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Pronóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/terapia , Carcinoma Epitelial de Ovario , Análisis de Supervivencia , Ganglios Linfáticos/patologíaRESUMEN
Background and objectives. In colorectal cancers, the embryologic origin of the primary tumor determines important molecular dissimilarities between right-sided (RS) and left-sided (LS) carcinomas. Although important prognostic differences have been revealed between RS- and LS-patients with resected colorectal liver metastases (CLMs), it is still unclear if this observation depends on the RAS mutational status. To refine the impact of primary tumor location (PTL) on the long-term outcomes of patients with resected CLMs, the rates of overall survival (OS), relapse-free survival (RFS) and survival after recurrence (SAR) were compared between RS- vs. LS-patients, according to their RAS status. Material and Methods. All patients with known RAS status, operated until December 2019, were selected from a prospectively maintained database, including all patients who underwent hepatectomy for histologically-proven CLMs. A log-rank test was used to compare survival rates between the RS- vs. LS-group, in RAS-mut and RAS-wt patients, respectively. A multivariate analysis was performed to assess if PTL was independently associated with OS, RFS or SAR. Results. In 53 patients with RAS-mut CLMs, the OS, RFS and SAR rates were not significantly different (p = 0.753, 0.945 and 0.973, respectively) between the RS and LS group. In 89 patients with RAS-wt CLMs, the OS and SAR rates were significantly higher (p = 0.007 and 0.001, respectively) in the LS group vs. RS group, while RFS rates were similar (p = 0.438). The multivariate analysis performed in RAS-wt patients revealed that RS primary (p = 0.009), extrahepatic metastases (p = 0.001), N-positive (p = 0.014), age higher than 65 (p = 0.002) and preoperative chemotherapy (p = 0.004) were independently associated with worse OS, while RS location (p < 0.001) and N-positive (p = 0.007) were independent prognostic factors for poor SAR. Conclusions. After resection of CLMs, PTL had no impact on long-term outcomes in RAS-mut patients, while in RAS-wt patients, the RS primary was independently associated with worse OS and SAR.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Hepatectomía/métodos , Humanos , Neoplasias Hepáticas/cirugía , Mutación , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Purpose: Vascular invasion is a well-known independent prognostic factor in colon cancer and tumor sidedness is also being considered a prognostic factor. The aim of this study was to compare the oncological impact of vascular invasion depending on the tumor location in stages I to III colon cancer. Methods: A retrospective analysis was performed using data from patients who underwent curative resection between 2004 and 2015. Patients were divided into right-sided colon cancer (RCC) and left-sided colon cancer (LCC) groups according to the tumor location. Disease-free survival (DFS) and overall survival (OS) were compared between the RCC and LCC groups, depending on the presence of vascular invasion. Results: A total of 793 patients were included, of which 304 (38.3%) had RCC and 489 (61.7%) had LCC. DFS and OS did not differ significantly between the RCC and LCC groups. Vascular invasion was a poor prognostic factor for DFS in both RCC (hazard ratio [HR], 2.291; 95% confidence interval [CI], 1.186-4.425; p = 0.010) and LCC (HR, 1.848; 95% CI, 1.139-2.998; p = 0.011). Additionally, it was associated with significantly worse OS in the RCC (HR, 3.503; 95% CI, 1.681-7.300; p < 0.001), but not in the LCC group (HR, 1.676; 95% CI, 0.885-3.175; p = 0.109). Multivariate analysis revealed that vascular invasion was independently poor prognostic factor for OS in the RCC (HR, 3.186; 95% CI, 1.391-7.300; p = 0.006). Conclusion: This study demonstrated that RCC with vascular invasion had worse OS than LCC with vascular invasion.
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BACKGROUND: Primary tumor location is considered a predictor of overall survival (OS) in RAS wild-type (WT) metastatic colorectal cancer (mCRC) treated with bevacizumab (BEV) or an anti-epidermal growth factor antibody (cetuximab or panitumumab [CET/PAN]) as first-line molecularly targeted therapy. BEV is recommended for right-sided mCRC and CET/PAN for left-sided mCRC based on post-hoc analyses of clinical trial data, but real-world evidence is lacking. METHODS: We retrospectively collected data of patients who started BEV or CET/PAN plus 5-fluorouracil-based doublet chemotherapy between January 2013 and December 2016 as first-line treatment for RAS WT mCRC at any of 24 Japanese institutions. OS was compared between the BEV and CET/PAN groups according to primary tumor location by Cox multivariate regression analysis in the full cohort and in a propensity score-matched cohort. RESULTS: In total, 935 patients were enrolled. Median OS was 24.6 months with BEV and 20.9 months with CET/PAN in right-sided mCRC (n = 213; adjusted hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.50-1.06) and 35.7 months and 30.0 months, respectively, in left-sided mCRC (n = 722; adjusted HR 0.92, 95% CI 0.74-1.13). In the propensity score-matched cohort, OS was significantly better in the BEV group than in the CET/PAN group in right-sided mCRC (HR 0.52, 95% CI 0.28-0.96) but was not significantly different in left-sided mCRC (HR 0.78, 95% CI 0.53-1.07). CONCLUSION: Real-world data showed that OS was better with BEV than with CET/PAN in right-sided mCRC. However, there was no significant difference in OS in left-sided mCRC.
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Neoplasias del Colon , Neoplasias Colorrectales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Fluorouracilo , Humanos , Japón , Panitumumab/uso terapéutico , Recto/patología , Estudios RetrospectivosRESUMEN
INTRODUCTION: Guidelines recommend regional lymphadenectomy with a lymph node yield (LNY) of at least 12 lymph nodes (LN) for adequate colon cancer (CC) staging. LNY ≥22LN may improve survival, especially in right-sided CC [Lee et al., Surg Oncol, 27(3), 2018]. This multicentric retrospective cohort study evaluated the impact of LNY and tumor laterality on CC staging and survival. MATERIALS AND METHODS: Patients with stage I-III CC that underwent surgery from 2012 to 2018 were grouped according to LNY: <22 and ≥ 22. Primary outcomes were LN positivity (N+ rate) and disease-free survival (DFS). Overall survival (OS) was the secondary outcome. Exploratory analyses were performed for laterality and stage. RESULTS: We included 795 patients (417 < 22LN, 378 ≥ 22LN); 53% had left-sided CC and 29%/37%/38% had stage I/II/III tumors. There was no association between LNY ≥22LN and N+ rate after adjustment for grade, T stage, lymphovascular invasion (LVI) and perineural invasion; a trend for a higher N+ rate in left-sided CC was identified (interaction p = 0.033). With a median follow-up of 63.6 months for DFS and 73.2 months for OS, 254 patients (31.9%) relapsed and 207 (26.0%) died. In multivariate analysis adjusted for age, ASA score, laparoscopic approach, T/N stage, mucinous histology, LVI and adjuvant chemotherapy, LNY ≥22LN was significantly associated with both DFS (HR 0.75, p = 0.031) and OS (HR 0.71, p = 0.025). Restricted cubic spline analysis showed a more significant benefit for right-sided CC. CONCLUSION: LNY ≥22LN was associated with longer DFS and OS in patients with operable CC, especially for right-sided CC.
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Neoplasias del Colon , Ganglios Linfáticos , Neoplasias del Colon/patología , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
AIM: In recent years, the prognostic and predictive value of primary tumor localization in colon cancer has become increasingly important. This study aimed to retrospectively analyze the effect of colon cancer tumor localization on progression-free survival, overall survival, and response to treatments and present real-life data. METHOD: Retrospective evaluation was made of 465 patients who were diagnosed with metastatic colorectal carcinoma between 2010 and 2015 in our clinic. The effect of primary tumor localization on progression-free survival, overall survival, and response to therapy was investigated. RESULTS: The right colon cancer (RCC) was determined in 66 patients, 14.2% of the whole group, and left colorectal cancer (LCRC) in 399 patients which is 85.8% of patients. Mucinous adenocarcinoma was 16.7% in RCC; however, only 6.4% of LCRC had a mucinous tumor (p < 0.05). Nodal involvement in any stage (N1 and N2) was 46.9% in right colon cancer whereas in LCRC, it was 41.2% (p < 0.05). Primary tumor surgery (74.2% vs. 70.2%) and metastasectomy (33.3% vs. 19.4%) were also more common in RCC(p < 0.05). k-ras mutation status was similar in both groups (28.8% in RCC vs 26.8% in LCRC, p > 0.05). Median progression-free survival was 12.6 months in RCC, and 15.5 in LCRC (p > 0.05). Median overall survival was 28.4 months in RCC and 33.5 months in LCRC (p > 0.05). In k-ras wild-type patients, the median overall survival was 32.3 months (95% CI 25.2-39.5) in the anti-VEGF antibody treatment group and 55.1 months (95% CI 36.5-73.7) in the anti-EGFR antibody treatment group (p < 0.05). CONCLUSION: Although tumors located in the right colon have been considered to be worse in terms of progression-free and overall survival in clinical trials, the results of this study showed that in daily practice, there was no difference between left and right colon localized tumors in progression-free and overall survival. Further, in k-ras wild-type colon cancers, tumor localization predicts the treatment response. This study is important with the presentation of real-life data and compatibility with the data of the studies to daily life.
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Adenocarcinoma Mucinoso , Neoplasias del Colon , Neoplasias Colorrectales , Adenocarcinoma Mucinoso/cirugía , Neoplasias del Colon/cirugía , Neoplasias Colorrectales/patología , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
PURPOSE: Right-sided colon tumors with peritoneal metastases (PM) are associated with a poorer prognosis than left-sided tumors. We hypothesized that a different pattern of spread could be characterized with abdominopelvic MRI. The objective of this study was to explore the spread of PM in relation to the primary tumor location on MRI. METHODS: This is a retrospective cohort study of patients with PM from colon cancer referred to be considered for CRS-HIPEC at a single tertiary referral center. Patients with colon cancer were eligible if they had undergone an abdominopelvic MRI scan following a clinical diagnosis of PM. The frequency of affected PCI regions on MRI (MRI-PCI) was assessed and compared between tumor sidedness. RESULTS: One hundred eighteen patients were included with a median age of 65 (IQR: 56-72). 46% percent were male. The median MRI-PCI was 10 (IQR: 5-16) and 8 (IQR: 4-11) for right- and left-sided tumors, respectively (p = 0.39), and the median number of affected regions was 4 (IQR: 2-7 for right-sided and IQR 2-5 for left-sided tumors). PM was most frequently found close to the primary tumor. The odds ratio of patients with PM of left sided to be affected with PM in the upper abdominal regions was 0.42 (95% CI: 0.20-0.90) and with PM on the small bowels or mesentery was 0.42 (95% CI: 0.19-0.92) over a patient with PM of right-sided colon cancer. CONCLUSION: MRI can help to assess the spread of PM in colonic cancer. In right-sided tumors, the small bowel and upper abdominal regions are more frequently affected.
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Neoplasias del Colon , Neoplasias Colorrectales , Intervención Coronaria Percutánea , Neoplasias Peritoneales , Neoplasias del Colon/diagnóstico por imagen , Neoplasias del Colon/patología , Neoplasias Colorrectales/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/secundario , Pronóstico , Estudios RetrospectivosRESUMEN
The aim of this study was to assess primary tumor sidedness of colorectal cancer (CRC), rat sarcoma viral oncogene homolog (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations and microsatellite instability (MSI) status as prognostic factors predicting complications, survival outcomes, and local tumor progression (LTP) following surgery and thermal ablation in patients with colorectal liver metastases (CRLM). This Amsterdam Colorectal Liver Met Registry (AmCORE) based study included 520 patients, 774 procedures, and 2101 tumors undergoing local treatment (resection and/or thermal ablation) from 2000 to 2021. Outcomes following local treatment were analyzed for primary tumor sidedness of CRC, RAS, and BRAF mutations and MSI status. The Kaplan-Meier method was used to estimate local tumor progression-free survival (LTPFS), local control (LC), distant progression-free survival (DPFS), and overall survival (OS). Uni- and multivariable analyses were performed based on Cox proportional hazards model. The chi-square test was used to analyze complications. Complications (p = 0.485), OS (p = 0.252), LTPFS (p = 0.939), and LC (p = 0.423) was not associated with tumor-sidedness. Compared to right-sided colon cancer (CC) (reference HR 1.000), DPFS was superior for left-sided CC and rectal cancer (p = 0.018) with an HR for left-sided CC of 0.742 (95% CI, 0.596-0.923) and for RC of 0.760 (95% CI, 0.597-0.966). Regarding RAS mutations, no significant difference was found in OS (p = 0.116). DPFS (p = 0.001), LTPFS (p = 0.039), and LC (p = 0.025) were significantly lower in the RAS mutation group. Though no difference in LTPFS was found between RAS wildtype and RAS mutated CRLM following resection (p = 0.532), LTPFS was worse for RAS mutated tumors compared to RAS wildtype following thermal ablation (p = 0.037). OS was significantly lower in the BRAF mutation group (p < 0.001) and in the MSI group (p < 0.001) following local treatment, while both did not affect DPFS, LTPFS, and LC. This AmCORE based study suggests the necessity of wider margins to reduce LTP rates in patients with RAS mutated CRLM, especially for thermal ablation. Upfront knowledge regarding molecular biomarkers may contribute to improved oncological outcomes.
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FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab is the preferred first-line treatment for right-sided metastatic colorectal cancer with RAS mutation. However, severe adverse events are common in Japanese patients. We report the successful management of multiple stage IV colorectal cancers in a patient who received multidisciplinary treatment, including chemotherapy and Japanese Kampo medicine. A 68-year-old man presented with epigastralgia and appetite loss and was diagnosed with multiple stage IV colorectal cancers. Colonoscopy identified type II tumors in the ascending colon, sigmoid colon, and upper rectum. Histopathological examination of a biopsy specimen revealed well- to moderately differentiated tubular adenocarcinoma. Enhanced computed tomography of the thorax and abdomen showed multiple pulmonary nodules and para-aortic lymph node swelling. Laparoscopic loop-ileostomy was performed to avoid bowel obstruction due to severe stenosis of ascending colon cancer. Intraoperative observation revealed two white nodules suggestive of metastasis in the lateral area of the liver. Therefore, we diagnosed multiple stage IV colorectal cancers with multiple metastases (lung, liver, and distant lymph nodes). His postoperative course was uneventful, and chemotherapy was started. Since the cancer cells harbored a RAS mutation, he received FOLFOXIRI plus bevacizumab. Japanese Kampo medicine consisting of Hangeshashinto and Juzen-taiho-to, to prevent diarrhea and fatigue, was administered daily. After 12 courses of chemotherapy, though circumferential stenosis still existed in the ascending colon, the tumors in the sigmoid colon and upper rectum were unclear. Enhanced computed tomography showed shrinkage of the pulmonary nodules and para-aortic lymph node; therefore, laparoscopic-assisted ileocecal resection was performed. The postoperative histopathological examination revealed moderately differentiated adenocarcinoma. The patient recovered uneventfully, and Kampo medicine consisting of Ninjin'yoeito was administered for postoperative weakness. Administration of adjuvant chemotherapy in this patient led to a near complete response that has been maintained without recurrence for 2 years and 8 months without reduced quality of life.
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Neoplasias Colorrectales/tratamiento farmacológico , Quimioterapia , Leucovorina/uso terapéutico , Medicina Kampo , Compuestos Organoplatinos/farmacología , Adenocarcinoma/tratamiento farmacológico , Anciano , Bevacizumab/uso terapéutico , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Quimioterapia/métodos , Fluorouracilo/uso terapéutico , Humanos , Japón , Masculino , Medicina Kampo/métodos , Calidad de VidaRESUMEN
Objective To provide guidance for the management of RAS wild-type (wt) metastatic colorectal cancer (mCRC) in daily practice. Methods Nominal group and Delphi techniques were used. A steering committee of seven experts analyzed the current management of RAS wt mCRC, through which they identified controversies, critically analyzed the available evidence, and formulated several guiding statements for clinicians. Subsequently, a group of 30 experts (the expert panel) was selected to test agreement with the statements, through two Delphi rounds. The following response categories were established in both rounds: 1 = totally agree, 2 = basically agree, 3 = basically disagree, 4 = totally disagree. Agreement was defined if ≥ 75% of answers were in categories 1 and 2 (consensus with the agreement) or 3 and 4 (consensus with the disagreement). Results Overall, 71 statements were proposed, which incorporated the following areas: (1) overarching principles; (2) tumor location; (3) triplets; (4) maintenance; (5) second-line and beyond treatments; (6) Rechallenge and liquid biopsy. After the two Delphi rounds, only six statements maintained a lack of clear consensus. Conclusions This document aims to describe the experts attitude when dealing with several common clinical questions regarding patients with RAS wt mCRC (AU)
Asunto(s)
Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/uso terapéutico , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Técnica Delphi , Fluorouracilo/uso terapéutico , Camptotecina/uso terapéutico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Genes ras/genética , Genotipo , RetratamientoRESUMEN
BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is rising. Left-sided colorectal cancer (LCC) is associated with better survival compared to right-sided colon cancer (RCC) in metastatic disease. NCCN guidelines recommend the addition of EGFR inhibitors to KRAS/NRAS WT metastatic CRC originating from the left only. Whether laterality impacts survival in locoregional disease and EOCRC is of interest. METHODS: 65,940 CRC cases from the National VA Cancer Cube Registry (2001-2015) were studied. EOCRC (2096 cases) was defined as CRC diagnosed at <50 years. Using ICD codes, RCC was defined from the cecum to the hepatic flexure (C18.0-C18.3), and LCC from the splenic flexure to the rectum (C18.5-18.7; C19 and C20). RESULTS: EOCRC is more likely to originate from the left side (66.65% LCC in EOCRC vs. 58.77% in CRC). Overall, LCC has better 5-year Overall Survival (OS) than RCC in stages I (61.67% vs. 58.01%) and III (46.1% vs. 42.1%) and better 1-year OS in stage IV (57.79% vs. 49.49%). Stage II RCC has better 5-year OS than LCC (53.39% vs. 49.28%). In EOCRC, there is no statistically significant difference between LCC and RCC in stages I-III. Stage IV EOCRC patients with LCC and RCC have a 1-year OS of 73.23% and 59.84%, respectively. CONCLUSION: In EOCRC, LCC is associated with better OS than RCC only stage IV. In the overall population, LCC is associated with better OS in all stages except stage II. The better prognosis of stage II RCC might be due to the high incidence of mismatch repair deficient tumors in this subpopulation.
Asunto(s)
Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Adulto , Anciano , Colon Ascendente/patología , Colon Descendente/patología , Colon Transverso/patología , Neoplasias del Colon/etnología , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Neoplasias Colorrectales/etnología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/etnología , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Sistema de Registros/estadística & datos numéricos , Estudios Retrospectivos , Estados Unidos/epidemiología , VeteranosRESUMEN
Background: Advances in therapies for patients with metastatic colorectal cancer (mCRC) and improved understanding of prognostic and predictive factors have impacted treatment decisions. Materials & methods: This study used a large oncology database to investigate patterns of monoclonal antibody (mAb) plus chemotherapy treatment in France, Germany, Italy, Spain and the UK in mCRC patients treated in first line in 2018. Results: Anti-EGFR mAbs were most often administered to patients with RAS wild-type mCRC and those with left-sided tumors, while anti-VEGF mAbs were preferred in RAS mutant and right-sided tumors. Adopted treatment strategies differed between countries, largely due to reimbursement. Conclusion: Biomarker status and primary tumor location steered treatment decisions in first line. Adopted treatment strategies differed between participating countries.
Lay abstract Each patient's cancer is unique. For example, colon cancer on the left side is different from colon cancer on the right side. Colon cancer is different from cancer of the rectum. Cancers also have changes in their genes, which means some treatments should work, while others may not. Doctors can select among different medicines to find the drug that works best for each patient. We looked at patients with cancer of the colon or rectum that has spread to other organs. We tried to find out how doctors in Europe select drugs for their patients after performing tests called RAS or BRAF. We found that doctors make different choices in different countries.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/terapia , Pruebas Genéticas/estadística & datos numéricos , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Quimioterapia Adyuvante/métodos , Quimioterapia Adyuvante/estadística & datos numéricos , Toma de Decisiones Clínicas/métodos , Neoplasias Colorrectales/genética , Receptores ErbB/antagonistas & inhibidores , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Medicina de Precisión/métodos , Medicina de Precisión/estadística & datos numéricos , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adulto Joven , Proteínas ras/genéticaRESUMEN
OBJECTIVE: To provide guidance for the management of RAS wild-type (wt) metastatic colorectal cancer (mCRC) in daily practice. METHODS: Nominal group and Delphi techniques were used. A steering committee of seven experts analyzed the current management of RAS wt mCRC, through which they identified controversies, critically analyzed the available evidence, and formulated several guiding statements for clinicians. Subsequently, a group of 30 experts (the expert panel) was selected to test agreement with the statements, through two Delphi rounds. The following response categories were established in both rounds: 1 = totally agree, 2 = basically agree, 3 = basically disagree, 4 = totally disagree. Agreement was defined if ≥ 75% of answers were in categories 1 and 2 (consensus with the agreement) or 3 and 4 (consensus with the disagreement). RESULTS: Overall, 71 statements were proposed, which incorporated the following areas: (1) overarching principles; (2) tumor location; (3) triplets; (4) maintenance; (5) second-line and beyond treatments; (6) Rechallenge and liquid biopsy. After the two Delphi rounds, only six statements maintained a lack of clear consensus. CONCLUSIONS: This document aims to describe the expert's attitude when dealing with several common clinical questions regarding patients with RAS wt mCRC.