Identification of odontogenic ameloblast associated as a novel target gene of the Wnt/ß-catenin signaling pathway.

The Wnt/ß-catenin signaling pathway plays a key role in development and carcinogenesis. Although some target genes of this signaling have been identified in various tissues and neoplasms, the comprehensive understanding of the target genes and their roles in the development of human cancer, including hepatoma and colorectal cancer remain to be fully elucidated. In this study, we searched for genes regulated by the Wnt signaling in liver cancer using HuH-7 hepatoma cells. A comparison of the expression profiles between cells expressing an active form of mutant ß-catenin and cells expressing enhanced green fluorescent protein (EGFP) identified seven genes upregulated by the mutant ß-catenin gene (CTNNB1). Among the seven genes, we focused in this study on ODAM, odontogenic, ameloblast associated, as a novel target gene. Interestingly, its expression was frequently upregulated in hepatocellular carcinoma, colorectal adenocarcinoma, and hepatoblastoma. We additionally identified a distant enhancer region that was associated with the ß-catenin/TCF7L2 complex. Further analyses revealed that ODAM plays an important role in the regulation of the cell cycle, DNA synthesis, and cell proliferation. These data may be useful for clarification of the main molecular mechanism(s) underlying these cancers.

Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910.

Large-scale genomic sequencing of colorectal cancers has been reported mainly for Western populations. Differences by stage and ethnicity in the genomic landscape and their prognostic impact remain poorly understood. We investigated 534 Japanese stage III colorectal cancer samples from the Phase III trial, JCOG0910. Targeted-capture sequencing of 171 potentially colorectal cancer-associated genes was performed, and somatic single-nucleotide variants and insertion-deletions were determined. Hypermutated tumors were defined as tumors with MSIsensor score >7 and ultra-mutated tumors with POLE mutations. Genes with alterations associated with relapse-free survival were analyzed using multivariable Cox regression models. In all patients (184 right-sided, 350 left-sided), mutation frequencies were TP53, 75.3%; APC, 75.1%; KRAS, 43.6%; PIK3CA, 19.7%; FBXW7, 18.5%; SOX9, 11.8%; COL6A3, 8.2%; NOTCH3, 4.5%; NRAS, 4.1%; and RNF43, 3.7%. Thirty-one tumors were hypermutated (5.8%; 14.1% right-sided, 1.4% left-sided). Modest associations were observed: poorer relapse-free survival was seen with mutant KRAS (hazard ratio 1.66; p = 0.011) and mutant RNF43 (2.17; p = 0.055), whereas better relapse-free survival was seen with mutant COL6A3 (0.35; p = 0.040) and mutant NOTCH3 (0.18; p = 0.093). Relapse-free survival tended to be better for hypermutated tumors (0.53; p = 0.229). In conclusion, the overall spectrum of mutations in our Japanese stage III colorectal cancer cohort was similar to that in Western populations, but the frequencies of mutation for TP53, SOX9, and FBXW7 were higher, and the proportion of hypermutated tumors was lower. Multiple gene mutations appeared to impact relapse-free survival, suggesting that tumor genomic profiling can support precision medicine for colorectal cancer.

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study.

INTRODUCTION: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

Prognostic Factors of Bone Metastases From Colorectal Cancer in the Era of Targeted Therapy.

BACKGROUND: Various prognostic factors have been reported for bone metastases from different primary tumor sites. However, bone metastases from colorectal cancer are very rare, and the prognostic factors have not been investigated in detail. OBJECTIVE: This study aimed to identify prognostic factors of bone metastases from colorectal cancer. DESIGN: This is a retrospective cohort study using data from a prospectively collected database. SETTINGS: This study was conducted at a single tertiary care cancer center in Japan. PATIENTS: Patients who developed bone metastases from colorectal cancer during the study period among all patients who received initial treatment for colorectal cancer at our hospital between 2005 and 2016 (n = 4538) were included. MAIN OUTCOME MEASURES: Overall survival after diagnosis of bone metastases from colorectal cancer was the main outcome measure. RESULTS: Ninety-four patients developed bone metastases during the study period. The 5-year overall survival rate was 11.0%. Multivariable analysis identified the following independent risk factors associated with poor prognosis: ≥70 years of age at diagnosis of bone metastases (HR, 2.48; 95% CI, 1.24-4.95; p < 0.01), curative surgery not performed as initial treatment (HR, 2.54; 95% CI, 1.24-5.19; p = 0.01), multiple bone metastases (HR, 2.44; 95% CI, 1.30-4.57; p < 0.01), albumin level <3.7 g/dL (HR, 3.80; 95% CI, 1.95-7.39; p < 0.01), CEA ≥30 ng/mL (HR, 1.94; 95% CI, 1.09-3.46; p = 0.02), and less than 3 chemotherapy options remaining at diagnosis of bone metastases (HR, 2.83; 95% CI, 1.51-5.30; p < 0.01). The median survival times for patients with 0-2, 3, and 4-6 risk factors were 25.0, 8.8, and 4.3 months, respectively. LIMITATIONS: The main limitation is the single-center, retrospective design of this study. CONCLUSIONS: Our results may facilitate multidisciplinary decision-making in patients with bone metastases from colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B930 . FACTORES PRONSTICOS DE LAS METSTASIS SEAS DEL CNCER COLORRECTAL EN LA ERA DE LA TERAPIA DIRIGIDA: ANTECEDENTES:Se han reportado varios factores pronósticos para las metástasis óseas de diferentes sitios de tumores primarios. Sin embargo, las metástasis óseas del cáncer colorrectal son muy raras y los factores pronósticos no se han investigado en detalle.OBJETIVO:Identificar los factores pronósticos de las metástasis óseas del cáncer colorrectal.DISEÑO:Estudio de cohorte retrospectivo utilizando datos de una base de datos recolectada prospectivamente.ENTORNO CLINICO:Un solo centro oncológico de atención terciaria en Japón.PACIENTES:Se seleccionaron pacientes que desarrollaron metástasis óseas de cáncer colorrectal durante el período de estudio entre todos los pacientes que recibieron tratamiento inicial para el cáncer colorrectal en nuestro hospital entre 2005 y 2016 (n = 4538).MEDIDA DE RESULTADO PRINCIPAL:Supervivencia general después del diagnóstico de metástasis óseas por cáncer colorrectal.RESULTADOS:Noventa y cuatro pacientes desarrollaron metástasis óseas, lo que representa el 2,0% de todos los pacientes con cáncer colorrectal que comenzaron el tratamiento durante el período de estudio. La tasa de supervivencia global a 5 años fue del 11,0 %. El análisis multivariable identificó los siguientes factores de riesgo independientes asociados con mal pronóstico: edad ≥70 años al momento del diagnóstico de metástasis óseas (hazard ratio 2,48, CI del 95 % 1,24-4,95, p < 0,01), cirugía curativa no realizada como tratamiento inicial (hazard ratio 2,54, CI 95 % 1,24-5,19, p = 0,01), metástasis óseas múltiples (hazard ratio 2,44, CI del 95 % 1,30-4,57, p < 0,01), nivel de albúmina <3,7 g/dL (hazard ratio 3,80, CI del 95 % 1,95 -7,39, p < 0,01), antígeno carcinoembrionario ≥30 ng/mL (hazard ratio 1,94, CI del 95 % 1,09-3,46, p = 0,02) y menos de 3 opciones de quimioterapia restantes al momento del diagnóstico de metástasis óseas (hazard ratio 2,83, 95 % CI 1,51-5,30, p < 0,01). La mediana de los tiempos de supervivencia para los pacientes con 0-2, 3 y 4-6 factores de riesgo fue de 25,0, 8,8 y 4,3 meses, respectivamente.LIMITACIONES:Diseño retrospectivo de un solo centro.CONCLUSIÓN:Nuestros resultados pueden facilitar la toma de decisiones multidisciplinares en pacientes con metástasis óseas de cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B930 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Prognostic Role for Primary Tumor Location in Patients With Colorectal Liver Metastases: A Comparison of Right-Sided Colon, Left-Sided Colon, and Rectum.

BACKGROUND: Although right-sided colon cancer is increasingly recognized as having a worse prognosis than left-sided colorectal cancer for colorectal liver metastases, little is known about the differences between the left-sided colon and rectum. OBJECTIVE: This study evaluated the prognostic value of primary tumor location in patients with colorectal liver metastases by examining the left-sided colon and rectum separately. DESIGN: This was a retrospective study from 2003 to 2017. SETTINGS: The study was conducted in a National Cancer Center Hospital. PATIENTS: The study cohort included 489 patients with colorectal liver metastases from right-sided colon cancer ( n = 119, 24%), left-sided colon cancer ( n = 251, 51%), or rectal cancer ( n = 119, 24%) who underwent hepatic resection. MAIN OUTCOME MEASURES: Primary outcomes were relapse-free survival and overall survival. RESULTS: Five-year relapse-free survival rates for patients with right-sided colon cancer, left-sided colon cancer, and rectal cancer were 28.6%, 34.1%, and 26.4%, and 5-year overall survival rates were 53.9%, 70.3%, and 60.8%. Multivariable analysis revealed significant differences in relapse-free survival and overall survival between left-sided colon cancer and rectal cancer (relapse-free survival: HR = 1.37, p = 0.03; overall survival: HR = 1.49, p = 0.03) and between left-sided colon cancer and right-sided colon cancer (relapse-free survival: HR = 1.39, p = 0.02; overall survival: HR = 1.60, p = 0.01), but not between right-sided colon cancer and rectal cancer. In patients with recurrence ( n = 325), left-sided colon cancer had the lowest multiple-site recurrence rate and the highest surgical resection rate for recurrence (left-sided colon cancer, 20%/46%; right-sided colon cancer, 32%/30%; rectal cancer, 26%/39%). LIMITATIONS: This study was retrospective in design. CONCLUSIONS: Rectal cancer was associated with worse relapse-free survival and overall survival compared with left-sided colon cancer in patients with colorectal liver metastases who underwent hepatic resection. Our findings suggest that the left-sided colon and rectum should be considered distinct entities in colorectal liver metastases. See Video Abstract at http://links.lww.com/DCR/B882 . PAPEL PRONSTICO DE LA UBICACIN DEL TUMOR PRIMARIO EN PACIENTES CON METSTASIS HEPTICAS COLORRECTALES UNA COMPARACIN ENTRE COLON DERECHO, COLON IZQUIERDO Y RECTO: ANTECEDENTES:Aunque se reconoce cada vez más que el cáncer de colon del lado derecho tiene un peor pronóstico que el cáncer colorrectal del lado izquierdo para las metástasis hepáticas colorrectales, se sabe poco acerca de las diferencias entre el recto y el colon del lado izquierdo.OBJETIVO:Este estudio evaluó el valor pronóstico de la ubicación del tumor primario en pacientes con metástasis hepáticas colorrectales examinando el recto y el colon del lado izquierdo por separado.DISEÑO:Este fue un estudio retrospectivo de 2003 a 2017.ENTORNO CLÍNICO:El estudio se llevó a cabo en un Hospital del Centro Nacional de Cáncer.PACIENTES:La cohorte del estudio incluyó a 489 pacientes con metástasis hepáticas colorrectales de cáncer de colon del lado derecho (n = 119, 24%), cáncer de colon del lado izquierdo (n = 251, 51%) o cáncer de recto (n = 119, 24%). %) que fueron sometidos a resección hepática.PRINCIPALES MEDIDAS DE VALORACIÓN:Los resultados primarios fueron la supervivencia sin recaídas y la supervivencia general.RESULTADOS:Las tasas de supervivencia sin recaída a cinco años para los pacientes con cáncer de colon derecho, cáncer de colon izquierdo y cáncer de recto fueron del 28,6%, 34,1%, y 26,4%, respectivamente, y las tasas de supervivencia general a los 5 años fueron del 53,9%, 70,3%, y 60,8%, respectivamente. El análisis multivariable reveló diferencias significativas en la supervivencia sin recaída y la supervivencia general entre el cáncer de colon izquierdo y el cáncer de recto (supervivencia sin recaída: HR = 1,37, p = 0,03; supervivencia general: HR = 1,49, p = 0,03) y entre el cáncer de colon izquierdo y el cáncer de colon del lado derecho (supervivencia libre de recaídas: HR = 1,39, p = 0,02; supervivencia global: HR = 1,60, p = 0,01), pero no entre el cáncer de colon del lado derecho y el cáncer de recto. En pacientes con recurrencia (n = 325), el cáncer de colon izquierdo tuvo la tasa de recurrencia en sitios múltiples más baja y la tasa de resección quirúrgica más alta por recurrencia (cáncer de colon izquierdo, 20%/46%; cáncer de colon derecho, 32%/30%; cáncer de recto, 26%/39%).LIMITACIONES:Este estudio fue de diseño retrospectivo.CONCLUSIONES:El cáncer de recto se asoció con una peor supervivencia sin recaída y una supervivencia general peor en comparación con el cáncer de colon izquierdo en pacientes con metástasis hepáticas colorrectales que se sometieron a resección hepática. Nuestros hallazgos sugieren que el colon y el recto del lado izquierdo deben considerarse entidades distintas en las metástasis hepáticas colorrectales. Consulte Video Resumen en http://links.lww.com/DCR/B882 . (Tradducción-Dr. Ingrid Melo ).

Prognostic factors associated with the transition in treatment methods for brain metastases from colorectal cancer.

BACKGROUND: Treatment of brain metastases (BMs) from colorectal cancer (CRC) has transitioned with the expansion of indications for stereotactic radiotherapy. Our study aimed to assess changes in prognosis and prognostic factors associated with changes in treatment for BMs from CRC. METHODS: We retrospectively surveyed treatments for and outcomes of BMs from CRC in 208 patients treated during 1997-2018. Patients were divided into two groups according to time of BM diagnosis, i.e., 1997-2013 ("first period") and 2014-2018 ("second period"). We compared overall survival between the periods and assessed how the transition impacted prognostic factors affecting overall survival, including the following prognostic factors such as Karnofsky performance status (KPS), volume-related factors (BM number and diameter), and BM treatment modalities as covariates. RESULTS: Of the 208 patients, 147 were treated in the first period and 61 in the second period. Whole-brain radiotherapy use decreased from 67 to 39% in the second period, and stereotactic radiotherapy use increased from 30 to 62%. Median survival after BM diagnosis improved from 6.1 to 8.5 months (p = 0.0272). Multivariate analysis revealed KPS, control of primary tumor, stereotactic radiotherapy use, and chemotherapy history as independent prognostic factors during the entire observation period. Hazard ratios of KPS, primary tumor control, and stereotactic radiotherapy were higher in the second period, whereas prognostic impact of chemotherapy history before BM diagnosis was similar in both periods. CONCLUSION: Overall survival of patients with BMs from CRC improved since 2014, which can be attributed to advances in chemotherapy and the more widespread use of stereotactic radiotherapy.

Clinicopathological and molecular characteristics of RSPO fusion-positive colorectal cancer.

BACKGROUND: RSPO fusions that lead to WNT pathway activation are potential therapeutic targets in colorectal cancer (CRC), but their clinicopathological significance remains unclear. METHODS: We screened 1019 CRCs for RSPO fusions using multiplex reverse transcription-PCR. The RSPO fusion-positive tumours were subjected to whole-exome sequencing (WES). RESULTS: Our analysis identified 29 CRCs with RSPO fusions (2.8%), consisting of five with an EIF3E-RSPO2 fusion and 24 with PTPRK-RSPO3 fusions. The patients were 17 women and 12 men. Thirteen tumours (45%) were right-sided. Histologically, approximately half of the tumours (13/29, 45%) had a focal or extensive mucinous component that was significantly more frequent than the RSPO fusion-negative tumours (13%; P = 8.1 × 10-7). Four tumours (14%) were mismatch repair-deficient. WES identified KRAS, BRAF, and NRAS mutations in a total of 27 tumours (93%). In contrast, pathogenic mutations in major WNT pathway genes, such as APC, CTNNB1 and RNF43, were absent. RSPO fusion status did not have a statistically significant influence on the overall or recurrence-free survival. These clinicopathological and genetic features were also confirmed in a pooled analysis of previous studies. CONCLUSION: RSPO fusion-positive CRCs constitute a rare subgroup of CRCs with several characteristic clinicopathological and genetic features.

Evaluation of Recurrence Risk After Curative Resection for Patients With Stage I to III Colorectal Cancer Using the Hazard Function: Retrospective Analysis of a Single-institution Large Cohort.

OBJECTIVE: This study aimed to investigate transitions of recurrence hazard and peak recurrence time in patients with nonmetastatic CRC using the hazard function. SUMMARY OF BACKGROUND DATA: A postoperative surveillance period of 5 years is consistent across major guidelines for patients with nonmetastatic CRC, but surveillance intervals differ. Estimates of instantaneous conditional recurrence rate can help set appropriate intervals. METHODS: The study population consisted of 4330 patients with stage I to III CRC who underwent curative resection at the National Cancer Center Hospital between January 2000 and December 2013. Hazard rates of recurrence were calculated using the hazard function. RESULTS: Recurrence rates in patients with stage I, II, and III CRC were 4% (50/1432), 11% (136/1231), and 25% (424/1667), respectively. The hazard curve for stage I was relatively flat and hazard rates were consistently low (<0.0015) for 5 years after surgery. The hazard curve for stage II had a peak hazard rate of 0.0046 at 13.7 months, after which the curve had a long hem to the right. The hazard curve for stage III had an earlier and higher peak than that of stage II (0.0105 at 11.6 months), with a long hem to the right. CONCLUSIONS: Changes in recurrence hazard for CRC patients varied considerably by stage. Our findings suggest that short-interval surveillance might be unnecessary for stage I patients for the first 3 years after surgery, whereas short-interval surveillance for the first 3 years should be considered for stage III patients.

The Conventional Technique Versus the No-touch Isolation Technique for Primary Tumor Resection in Patients With Colon Cancer (JCOG1006): A Multicenter, Open-label, Randomized, Phase III Trial.

OBJECTIVE: This phase III trial evaluated whether the no touch was superior to the conventional in patients with cT3/T4 colon cancer. BACKGROUND: No touch involves ligating blood vessels that feed the primary tumor to limit cancer cell spreading. However, previous studies did not confirm the efficacy of the no touch. METHODS: This open-label, randomized, phase III trial was conducted at 30 Japanese centers. The eligibility criteria were histologically proven colon cancer; clinical classification of T3-4, N0-2, andM0; and patients aged 20 to 80years. Patients were randomized (1:1) to undergo open surgery with conventional or the no touch. Patients with pathological stage III disease received adjuvant capecitabine chemotherapy. The primary endpoint was disease-free survival (DFS) according to the intention-to-treat principle. RESULTS: Between January 2011 and November 2015, 853 patients were randomized to the conventional group (427 patients) or the no touch group (426 patients). The 3-year DFS were 77.3% [95% confidence interval (CI) 73.1%-81.0%] and 76.2% (95% CI 71.9%-80.0%) in the conventional and no touch groups, respectively. The superiority of no touch was not confirmed: hazard ratio for DFS = 1.029 (95% CI 0.800- 1.324; 1-sided P = 0.59). Operative morbidity was observed in 31 of 427 conventional patients (7%) and 26 of 426 no touch patients (6%). All grade adverse events were similar between the conventional and no touch groups. No in-hospital mortality occurred in either group. CONCLUSION: The present study failed to confirm the superiority of the no touch.

Study protocol of a single-arm phase 2 study evaluating the preventive effect of topical hydrocortisone for capecitabine-induced hand-foot syndrome in colorectal cancer patients receiving adjuvant chemotherapy with capecitabine plus oxaliplatin (T-CRACC study).

BACKGROUNDS: Clinical evidence of the preventive effectiveness of medium-class topical corticosteroids for capecitabine-induced hand foot syndrome (HFS) is limited. Although the pathogenesis and mechanism of HFS are unclear, inflammatory reactions are thought to be involved in HFS development. This study aimed to evaluate the preventive effect of medium-class topical corticosteroids (hydrocortisone butyrate 0.1% topical therapy) for capecitabine-induced HFS in patients with colorectal cancer receiving adjuvant chemotherapy with capecitabine plus oxaliplatin. METHODS: This is a single-center, single-arm, phase 2 study. Patients with colorectal cancer scheduled to receive adjuvant chemotherapy with capecitabine plus oxaliplatin are enrolled, and topical hydrocortisone butyrate 0.1% is applied prophylactically in addition to standard moisturizing therapy. The primary endpoint is the incidence of grade ≥ 2 HFS within three months. The secondary endpoints are the time to onset of HFS, rates of dose reduction, schedule delay, discontinuation caused by capecitabine-induced HFS, and other adverse events. All adverse events are evaluated by clinical pharmacists and attending physicians. DISCUSSION: This study is expected to contribute to the establishment of new supportive care for preventing HFS, not only for colorectal cancer patients receiving adjuvant chemotherapy, but also for various cancer patients receiving capecitabine-based chemotherapy. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCTs031220002. Registered 5 April 2022, https://jrct.niph.go.jp/search Protocol version V.1.0, 16 February 2022.

A delay in the diagnosis of colorectal cancer screened by fecal immunochemical tests during the COVID-19 pandemic: a longitudinal cohort study.

PURPOSE: There is concern that the COVID-19 pandemic may cause people to refrain from undergoing examination resulting in delayed detection of colorectal cancer (CRC). The purpose of this study was to investigate whether there was a delay in CRC detection due to withholding of screening. METHODS: The colonoscopy screening rate and the CRC detection rate were calculated for patients who underwent fecal immunochemical tests (FITs) from 2018 to 2021 in the longitudinal cohort. The stages of CRC cases detected as a result of positive FIT in each year were compared. RESULTS: A total of 39,521 patients were initially screened by FIT over a 4-year period. The FIT-positive rate was 4.7% (441 /9,349) in 2018, 4.6% (420 /9,156) in 2019, 4.9% (453 /9,255) in 2020, and 4.3% (504 /11,760) in 2021. The colonoscopy screening rate for positive FIT results was lower in 2020 than in 2019 (25.8% vs. 38.1%, P < 0.001), and higher in 2021 than in 2020 (56.7% vs. 25.8%, P < 0.001). The CRC detection rate among colonoscopy recipients was higher in 2021 than in 2020 (13% vs. 4%, P = 0.014). Stage 1 or higher CRC accounted for 25.0% (1/4) in 2020, and 78% (18/23) in 2021. Among the CRC cases detected each year, 1 (14%), 1 (25%), and 10 (43%) did not undergo colonoscopy despite positive FIT results in the previous year. CONCLUSIONS: The COVID-19 pandemic has reduced the detection of CRC by screening colonoscopy following FIT and might have led to a delay in the detection of CRC.

Challenges needed to be overcome in multi-institutional surgical trials: accumulated experience in the JCOG Colorectal Cancer Study Group (CCSG).

JCOG-CCSG has been conducting several surgical trials and experienced several challenges. The first point is the appropriate timing of conducting the trial. Once a certain number of surgeons acquire the new technique and its utility is accepted, it suddenly becomes difficult to maintain 'equipoise' between the standard and new treatment, which may lead to poor patient accrual. Smooth preparation and commencement of the trial at an appropriate timing is necessary for its success. Second is the appropriate quality assurance of surgery. High-level quality assurance will strengthen the comparability of randomized control trials and minimize the heterogeneity among hospitals. On the other hand, it may impair the generalizability of the trial. Large observational studies help to bridge the gap of heterogeneity among hospitals. Third is the selection of an appropriate endpoint. Overall survival (OS) is the gold-standard primary endpoint; however, the number of events is much less due to more effective treatment. JCOG0212 and JCOG0404 were unable to demonstrate the non-inferiority of omission of lateral lymph node dissection and laparoscopic surgery partly due to a lack of power. Disease-free survival (DFS) is also a promising candidate for primary endpoint, but as in JCOG0603, special attention must be paid when DFS does not correlate with OS. Although careful discussion is required because the precision of the hazard ratio depends on the number of events, an alternative population-level summary of variables, including restricted mean survival time, can be considered as the primary endpoint. Future surgical trials should be planned considering these points.

Severe thrombocytopenia induced by chemotherapy after total gastrectomy: A report of three cases.

Pancytopenia associated with vitamin B12 and folic acid deficiency has been reported in patients who have undergone total gastrectomy. Therefore, myelosuppression due to chemotherapy following total gastrectomy is considered to be more serious. We encountered three cases of severe thrombocytopenia in patients who received chemotherapy after total gastrectomy. The lowest platelet levels in these patients were 1.7 × 104/mm3, 2.3 × 104/mm3, and 0.9 × 104/mm3, respectively. None of the patients presented with vitamin B12 deficiency, and one patient presented with folic acid deficiency. The association between serum vitamin levels and chemotherapy-related adverse events is controversial. Since folic acid has a shorter half-life (6 hours) and cannot accumulate in the body, unlike vitamin B12 that is stored for a long time in the liver, folic acid deficiency is suspected to be associated with thrombocytopenia induced by post-total gastrectomy chemotherapy. However, serum folic acid levels fluctuate depending on the timing of evaluation and require a few days to evaluate. In conclusion, patients who undergo chemotherapy after total gastrectomy should be monitored for severe thrombocytopenia but serum vitamin B12 levels are not necessarily clinically important. By measuring serum folic acid levels at appropriate times, folic acid deficiency may prove to be a reference for predicting severe thrombocytopenia.

Postoperative, but not preoperative, inflammation-based prognostic markers are prognostic factors in stage III colorectal cancer patients.

BACKGROUND: Recent evidence suggests that both preoperative and postoperative inflammation-based prognostic markers are useful for predicting the survival of colorectal cancer (CRC) patients. However, associations between longitudinal changes in inflammation-based prognostic markers and prognosis are controversial. METHODS: The subjects of this study were 568 patients with stage III CRC between 2008 and 2014. Preoperative and postoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein/albumin ratio (CAR) and lymphocyte-to-C-reactive protein ratio (LCR) were calculated to assess the inflammatory state of subjects. Subjects were stratified into three groups for each marker: preoperatively low inflammatory state (normal group), preoperatively high but postoperatively low inflammatory state (normalised group) and persistently high inflammatory state (elevated group). Multivariable analyses for overall survival (OS) and recurrence-free survival (RFS) were performed to adjust for well-established clinicopathologic factors. RESULTS: For all assessed markers, the normalised group had a significantly better prognosis than the elevated group and a similar prognosis as the normal group for both OS and RFS. CONCLUSIONS: Postoperative, but not preoperative, inflammation-based prognostic markers more accurately predict OS and RFS in patients with stage III CRC.

Spontaneous Regression of Mismatch Repair-Deficient Colon Cancer: A Case Series.

Spontaneous regression of cancer is a rare phenomenon, with 33 colorectal cancer cases reported between 1900 and 2020.1-4 Spontaneous regression is defined as the partial or complete disappearance of a tumor without treatment.1,3 Several factors may be involved in this process, including biopsy, mechanical stress, humoral factors, and infection.1,5 However, no concrete evidence for the mechanistic insights has been indicated.

Laparoscopic versus Open Colectomy for Elderly Patients with Colon Cancer: A Propensity Score Analysis with the Controlling Nutritional Status (CONUT) Score.

The feasibility of laparoscopic surgery for elderly patients remains unclear, as these patients usually present with comorbidities. Recently, the controlling nutritional status (CONUT) score has drawn attention as an evaluation score of patients' general status as well as a predictor of survival. We retrospectively analyzed overall survival in 424 patients aged ≥75 years with colon cancer, who underwent curative surgery (laparoscopic (n = 167) or open surgery (n = 257)) between January 2004 and December 2013. To adjust for heterogeneity in both groups, a propensity score-matched analysis was performed, with the CONUT score as a confounding covariate. 5-year overall survival rates of patients with normal (0-1), mildly abnormal (2-4), or abnormal (≥5) CONUT score were 88.6%, 79.4%, and 41.4%, respectively (p < 0.001). T3 or less, N negative, late period (2009-2013), and normal CONUT score were associated with the tendency to undergo laparoscopic surgery (p < 0.001). The analysis of the propensity score-matched cohort (124 pairs) revealed that patients in the laparoscopic surgery group had a similar prognosis to those in the open surgery group, with a 5-year overall survival of 91.9% vs. 82.0%, respectively (p = 0.102). Laparoscopic surgery for colon cancer is an acceptable surgical approach in elderly patients.

Primary Tumor-Related Complications Among Patients With Unresectable Stage IV Colorectal Cancer in the Era of Targeted Therapy: A Competing Risk Regression Analysis.

BACKGROUND: Whether prolonged survival with current chemotherapy using molecular target agents has changed the rate of primary tumor-related complications in patients with unresectable stage IV colorectal cancer is unclear. OBJECTIVE: This study aimed to investigate the rate of primary tumor-related complications among patients receiving targeted therapy as compared with patients receiving chemotherapy without molecular target agents. DESIGN: This was a retrospective review of data from a prospectively maintained database. SETTINGS: The study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS: Subjects were 352 consecutive patients with unresectable stage IV colorectal cancer who received systemic chemotherapy without primary tumor resection from 2001 to 2015. Patients were categorized into nontargeted and targeted groups according to the use of molecular target agents. MAIN OUTCOME MEASURES: Complication rates attributed to primary tumors were measured. RESULTS: Of the 352 patients, 159 were categorized into the nontargeted group and 193 patients into the targeted group. Competing risk-adjusted univariate analysis revealed that the primary tumor-related complication rates in the nontargeted group were 6.9% (95% CI, 3.8%-11.9%) at 1 year and 8.2% (95% CI, 4.8%-13.8%) at 2 years, whereas the targeted group had complication rates of 11.5% (95% CI, 7.5%-16.6%) at 1 year and 16.7% (95% CI, 12.4%-23.3%) at 2 years. Multivariate analysis revealed that the targeted group was ≈2 times more likely to have primary tumor-related complications (subdistribution HR = 2.04 (95% CI, 1.12-4.01); p = 0.020). Median survival time was 12.0 months in the nontargeted group and 24.1 months in the targeted group (p < 0.001). LIMITATIONS: This study was limited by the retrospective design. CONCLUSIONS: Targeted therapy was associated with a significantly increased risk of primary tumor-related complications during chemotherapy. However, targeted therapy also improved overall survival, making it a tolerable therapy. See Video Abstract at http://links.lww.com/DCR/B536. COMPLICACIONES PRIMARIAS RELACIONADAS CON EL TUMOR ENTRE PACIENTES CON CNCER COLORRECTAL EN ESTADIO IV IRRESECABLE EN LA ERA DE LA TERAPIA DIRIGIDA UN ANLISIS DE REGRESIN DEL RIESGO COMPETITIVO: ANTECEDENTES:No está claro si la supervivencia prolongada con la quimioterapia actual utilizando agentes moleculares dirigidos ha cambiado la tasa de complicaciones relacionadas con el tumor primario en pacientes con cáncer colorrectal en estadio IV irresecable.OBJETIVO:Este estudio tuvo como objetivo investigar la tasa de complicaciones relacionadas con el tumor primario entre los pacientes que reciben terapia dirigida, en comparación con pacientes que reciben quimioterapia sin agentes moleculares dirigidos.DISEÑO:Revisión retrospectiva de datos de una base de datos mantenida prospectivamente.ESCENARIO CLINICO:Centro oncológico de tercer nivel multidisciplinario de alto volumen en Japón.PACIENTES:352 pacientes consecutivos con cáncer colorrectal en estadio IV irresecable que recibieron quimioterapia sistémica sin resección del tumor primario entre 2001 y 2015. Los pacientes se clasificaron en grupos dirigidos y no dirigidos según el uso de agentes moleculares dirigidos.PRINCIPALES MEDIDAS DE VALORACION:Tasas de complicaciones debidas a tumores primarios.RESULTADOS:De los 352 pacientes, 159 se clasificaron en el grupo no dirigido y 193 pacientes en el grupo dirigido. El análisis univariado ajustado al riesgo competitivo reveló que las tasas de complicaciones primarias relacionadas con el tumor en el grupo no dirigido fueron del 6,9% (intervalo de confianza (IC) del 95%, 3,8 - 11,9%) al año y del 8,2% (IC del 95%, 4,8%). - 13,8%) a los dos años, mientras que el grupo dirigido tuvo tasas de complicaciones del 11,5% (IC del 95%, 7,5 - 16,6%) al año y del 16,7% (IC del 95%, 12,4 - 23,3%) a los dos años. El análisis multivariado reveló que el grupo dirigido tenía aproximadamente dos veces más probabilidades de tener complicaciones relacionadas con el tumor primario (razón de riesgo de subdistribución, 2,04; IC del 95%, 1,12 a 4,01; p = 0,020). La mediana del tiempo de supervivencia fue de 12,0 meses en el grupo no dirigido y de 24,1 meses en el grupo dirigido (p <0,001).LIMITACIONES:Este estudio estuvo limitado por el diseño retrospectivo.CONCLUSIONES:La terapia dirigida se asoció con un riesgo significativamente mayor de complicaciones relacionadas con el tumor primario durante la quimioterapia. Sin embargo, la terapia dirigida también mejoró la SG, convirtiéndola en una terapia tolerable. Consulte Video Resumen en http://links.lww.com/DCR/B536.

Preoperative Nutritional Scores as Host-Related Prognostic Factors for Both Overall Survival and Postoperative Complications in Patients With Stage II to III Colorectal Cancer.

BACKGROUND: In the TNM eighth edition, nutritional status and inflammatory scores are newly described as host-related prognostic factors for esophageal cancer, hepatocellular carcinoma, and pancreatic cancer. However, only age and race are listed as host-related prognostic factors for colorectal cancer. OBJECTIVE: The purpose of this study was to evaluate the prognostic significance of nutritional and inflammatory scores for postoperative outcomes in patients with colorectal cancer. DESIGN: This was a retrospective study using a database that prospectively collects data. SETTINGS: The study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS: Study participants were 1880 consecutive patients with stage II to III colorectal cancer who underwent curative resection at the National Cancer Center Hospital between 2004 and 2012. Two nutritional scores (prognostic nutritional index and controlling nutritional status score) and 4 inflammatory scores (modified Glasgow prognostic score, neutrophil:lymphocyte ratio, platelet:lymphocyte ratio, and C-reactive protein:albumin ratio) were calculated. MAIN OUTCOME MEASURES: Correlations of nutritional scores and inflammatory scores with overall survival and postoperative complications were measured. RESULTS: After adjusting for key clinical and pathologic factors by multivariable analysis, 2 nutritional scores (prognostic nutritional index and controlling nutritional status score) and 2 inflammatory scores (neutrophil:lymphocyte ratio and C-reactive protein:albumin ratio) were independent prognostic factors for overall survival. With respect to discriminative ability, time-dependent receiver operating characteristic curves and Harrell concordance index revealed that prognostic nutritional index and controlling nutritional status score were superior to the 4 inflammatory scores for predicting overall survival. Multivariable logistic regression analyses also revealed that prognostic nutritional index, controlling nutritional status score, and C-reactive protein:albumin ratio were independent predictors for postoperative complications. LIMITATIONS: The retrospective design of the study was a limitation. CONCLUSIONS: Preoperative nutritional scores are promising host-related prognostic factors for overall survival and postoperative complications in patients with stage II and III colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B587. EVALUACIN DE SCORE NUTRICIONALES PREOPERATORIOS COMO FACTORES PRONSTICOS PARA SOBREVIDA Y COMPLICACIONES POSTOPERATORIAS EN PACIENTES CON CANCER COLORECTAL ETAPA II Y III: ANTECEDENTES:En las últimas etapificaciones T-N-M, tanto el estado nutricional como inflamatorio han sido descritos como factores pronósticos en cáncer de esófago, hepático y pancreático. Sin embargo en cáncer colorectal solo la edad y la raza son enumerados como factores pronósticos.OBJETIVO:Evaluar la importancia pronóstica de los scores nutricionales e inflamatorias para los resultados posoperatorios en pacientes con cáncer colorrectal.DISEÑO:Estudio retrospectivo utilizando una base de datos.AJUSTE:Centro oncológico teciario en Japón.PACIENTES:Fueron incluidos en el estudio 1880 pacientes, consecutivos, con cancer colorectal etapa II y III sometidos a reseeción curativa en el National Cancer Center Hospital entre 2004 y 2012. Se aplicaron dos scores: nutricional (índice nutricional pronóstico y puntuación del estado nutricional) e inflamatorias (Glasgow modificada, proporción de neutrófilos a linfocitos, de plaquetas a linfocitos y de proteína C reactiva a albúmina).PRINCIPALES MEDIDAS DE RESULTADO:Evaluar scores nutricional e inflamatorio con sobrevida y complicaciones postoperatoria.RESULTADOS:Después de ajustar los factores clínicos y patológicos clave mediante análisis multivariable, dos scores nutricionales (índice nutricional pronóstico y puntuación del estado nutricional de control) y dos inflamatorias (proporción de neutrófilos a linfocitos y proporción de proteína C reactiva a albúmina) fueron pronósticos independientes factores para la sobrevida. Con respecto a la capacidad discriminativa, las curvas de características operativas del receptor, dependientes del tiempo y el índice de concordancia de Harrell, revelaron que el índice nutricional pronóstico y del estado nutricional de control eran superiores a las cuatro inflamatorias para predecir la sobrevida general. Los análisis de regresión logística multivariable también revelaron que el índice nutricional pronóstico, el estado nutricional de control y la relación proteína C reactiva / albúmina fueron predictores independientes de complicaciones postoperatorias.LIMITACIONES:Estudio de tipo retrospectivo.CONCLUSIONES:Los scores nutricionales preoperatorias son factores pronósticos prometedores relacionados con la sobrevida y las complicaciones postoperatorias en pacientes con cáncer colorrectal en estadio II y III. Consulte Video Resumen en http://links.lww.com/DCR/B587.

Lymphocyte-to-C-Reactive Protein Ratio Is the Most Sensitive Inflammation-Based Prognostic Score in Patients With Unresectable Metastatic Colorectal Cancer.

BACKGROUND: Systemic inflammation contributes to the progression of malignancies. The preoperative lymphocyte-to-C-reactive protein ratio has recently been shown to predict survival of patients with colorectal cancer who undergo surgery, but its prognostic value remains unclear in patients with unresectable metastatic colorectal cancer. OBJECTIVE: This study aimed to examine the prognostic values of inflammation-based prognostic scores in patients with metastatic colorectal cancer, focusing on the lymphocyte-to-C-reactive protein ratio. DESIGN: This is a retrospective study from a prospectively collected database. SETTINGS: This study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS: The subjects were 756 consecutive patients with unresectable metastatic colorectal cancer who received systemic chemotherapy from 2000 to 2015. The prognostic value of the lymphocyte-to-C-reactive protein ratio was evaluated by univariable and multivariable analyses. Time-dependent receiver operating characteristics curve analysis was conducted to compare the prognostic impact of the lymphocyte-to-C-reactive protein ratio with the impact of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, or the modified Glasgow Prognostic Score. MAIN OUTCOME MEASURES: The primary outcomes measured were the correlations of prognostic scores with overall survival. RESULTS: Median survival times of patients with high, intermediate, and low lymphocyte-to-C-reactive protein ratios were 29.4, 19.3, and 13.1 months (p < 0.001). In all subgroups according to key prognostic factors (performance status, use of targeted agents, pretreatment CEA levels, tumor sidedness, M category, and primary tumor resection), patient prognosis could be clearly stratified into 3 groups by the lymphocyte-to-C-reactive protein ratio. Multivariable analysis revealed that decreased lymphocyte-to-C-reactive protein ratio was independently associated with reduced survival (low vs high: HR 1.96, p < 0.001; intermediate vs high: HR 1.44, p < 0.001). The time-dependent receiver operating characteristics curve analysis revealed that the lymphocyte-to-C-reactive protein ratio was the most sensitive predictor of survival among all inflammation-based prognostic scores on a continuous basis. LIMITATIONS: This study was retrospective in nature. CONCLUSIONS: The lymphocyte-to-C-reactive protein ratio is a useful prognostic biomarker for unresectable metastatic colorectal cancer and could contribute to accurate prognostication and therapeutic decision making. See Video Abstract at http://links.lww.com/DCR/B600. RELACIN ENTRE LINFOCITOS Y PROTENA C ES EL SCORE PRONOSTICO INFLAMATORIO MAS SENSIBLE EN PACIENTES CON CNCER COLORRECTAL METASTSICO IRRESECABLE: ANTECEDENTES:La inflamación sistémica contribuye en la progresión de neoplasias malignas. Recientemente se ha demostrado que la proporción preoperatoria de linfocitos -proteína C reactiva predice la supervivencia de los pacientes con cáncer colorrectal que se sometieron a cirugía, pero su valor pronóstico sigue sin estar claro en pacientes con cáncer colorrectal metastásico irresecable.OBJETIVO:Evaluar el valor pronostico de los scores inflamtorios centrandose en linfocito- proteina c reactiva en pacientes con cáncer colorrectal metastásico.DISEÑO:Estudio retrospective evaluando una base de datos.AJUSTE:Este estudio se llevó a cabo en un centro oncológico terciario multidisciplinario de gran volumen en Japón.PACIENTES:Se incluyeron 756 pacientes consecutivos todos con cáncer colorrectal metastásico irresecable que recibieron quimioterapia sistémica de 2000 a 2015. El valor pronóstico de la proteína C reactiva se evaluó mediante análisis univariables y multivariables. Se realizó análisis de la curva de características operativas del receptor dependiente del tiempo para comparar el impacto pronóstico de la proteína linfocito-C-reactiva con el de la proporción de neutrófilos a linfocitos, la proporción de plaquetas a linfocitos, la proporción de linfocitos a monocitos o la proporción de puntuación pronóstica segun escala de Glasgow modificada.PRINCIPALES MEDIDAS DE RESULTADO:Correlacion de las puntuaciones pronósticas con la supervivencia global.RESULTADOS:La mediana de supervivencia de los pacientes con niveles altos, intermedios y bajos de proteína C reactiva de linfocitos fue de 29,4, 19,3 y 13,1 meses, respectivamente (p <0,001). En todos los subgrupos de acuerdo con los factores pronósticos clave (estado funcional, uso de agentes dirigidos, niveles de antígeno carcinoembrionario antes del tratamiento, lado del tumor, categoría M y resección del tumor primario), el pronóstico del paciente podría estratificarse claramente en tres grupos por linfocito a C- proteína reactiva. El análisis multivariable reveló que la disminución de linfocitos a proteína C reactiva se asoció de forma independiente con una supervivencia reducida (baja frente a alta: cociente de riesgo 1,96, p <0,001; intermedio frente a alto: cociente de riesgo 1,44, p <0,001). El análisis de la curva de características operativas del receptor dependiente del tiempo reveló que de linfocito a proteína C reactiva era el predictor de supervivencia más sensible entre todas las puntuaciones de pronóstico basadas en inflamación de forma continua.LIMITACIONES:Este estudio fue de naturaleza retrospectiva.CONCLUSIONES:La proteína C reactiva de linfocitos a C es un biomarcador pronóstico útil para el cáncer colorrectal metastásico irresecable y podría contribuir a un pronóstico preciso y a la toma de decisiones terapéuticas. Consulte Video Resumen en http://links.lww.com/DCR/B600.

Circumferential Resection Margin Status as a Predictive Factor for Recurrence in Preoperative MRI for Advanced Lower Rectal Cancer Without Preoperative Therapy.

BACKGROUND: In Japan, total mesorectal excision plus lateral lymph node dissection without preoperative therapy is the standard treatment for advanced lower rectal cancer. Although long-term oncologic outcomes with preoperative therapy based on circumferential resection margin status in preoperative MRI has been reported, outcomes without preoperative therapy are unknown. OBJECTIVE: This study evaluated long-term oncologic outcomes of radical surgery without preoperative therapy in advanced lower rectal cancer based on circumferential resection margin status in preoperative MRI, with the aim of defining appropriate patient populations for preoperative therapy. DESIGN: This retrospective analysis compared long-term oncologic outcomes with preoperative MRI in patients with lower rectal cancer. SETTINGS: Patients were identified through a database managed by our institute. PATIENTS: In total, 338 patients with lower rectal cancer who underwent radical surgery between 2000 and 2014 at the National Cancer Center Hospital without preoperative therapy were included. MAIN OUTCOME MEASURES: The main outcome was relapse-free survival. RESULTS: The median follow-up period was 61.7 months (range, 3-153 months). Five-year relapse-free survival rates in MRI-predicted circumferential resection margin negative patients and positive patients were 76.0% and 55.6% (p < 0.001). Univariate and multivariate analyses revealed pN stage (HR, 2.35; 95% CI, 1.470-3.770; p < 0.001), lymphatic invasion (HR, 2.03; 95% CI, 1.302-3.176; p = 0.002), venous invasion (HR, 2.15; 95% CI, 1.184-3.9; p = 0.01), surgical procedure (HR, 1.72; 95% CI, 1.115-2.665; p = 0.01), and MRI-predicted circumferential resection margin (HR, 1.850; 95% CI, 1.206-2.838; p = 0.0051) to be independent risk factors for postoperative recurrence. LIMITATIONS: This study was retrospective in design. CONCLUSIONS: Magnetic resonance imaging-predicted circumferential resection margin was associated with relapse-free survival without preoperative therapy, indicating its potential for use in selecting optimal preoperative therapy. See Video Abstract at http://links.lww.com/DCR/B335. ESTADO DEL MARGEN DE RESECCIÓN CIRCUNFERENCIAL COMO FACTOR PREDICTIVO DE RECURRENCIA EN LA RESONANCIA MAGNÉTICA PREOPERATORIA, PARA EL CÁNCER RECTAL BAJO AVANZADO SIN TERAPIA PREOPERATORIA: En Japón, la escisión mesorrectal total con disección de ganglios linfáticos laterales y sin terapia preoperatoria, es el tratamiento estándar para el cáncer rectal bajo avanzado. Aunque se han reportado resultados oncológicos a largo plazo con terapia preoperatoria, basada en el estado del margen de resección circunferencial en la resonancia magnética preoperatoria, se desconocen los resultados sin terapia preoperatoria.Este estudio evaluó los resultados oncológicos a largo plazo de cirugía radical sin terapia preoperatoria, en cáncer rectal bajo avanzado, basado en el estado del margen de resección circunferencial en la resonancia magnética preoperatoria, con el objetivo de definir poblaciones de pacientes apropiadas para terapia preoperatoria.Este análisis retrospectivo comparó los resultados oncológicos a largo plazo con resonancia magnética preoperatoria, en pacientes con cáncer rectal bajo.Los pacientes fueron identificados a través de una base de datos administrada por nuestro instituto.Se incluyeron un total de 338 pacientes con cáncer rectal bajo, que se sometieron a cirugía radical entre 2000 y 2014 en el Hospital Nacional del Centro de Cáncer, sin terapia preoperatoria.El resultado principal fue la supervivencia libre de recaídas.La mediana del período de seguimiento fue de 61,7 meses (rango, 3-153 meses). Las tasas de supervivencia sin recaídas a cinco años, con margen de resección circunferencial predicho por resonancia magnética, en pacientes negativos y pacientes positivos fueron 76.0% y 55.6% (p <0.001), respectivamente. Los análisis univariados y multivariados revelaron estadio pN (razón de riesgo [HR], 2.35; intervalo de confianza [IC] del 95%, 1.470-3.770; p <0.001), invasión linfática (HR, 2.03; IC del 95%, 1.302-3.176; p = 0.002), invasión venosa (HR, 2.15; IC 95%, 1.184-3.9; p = 0.01), procedimiento quirúrgico (HR, 1.72; IC 95%, 1.115-2.665; p = 0.01) y circunferencial predicho por resonancia magnética en margen de resección (HR, 1.850; IC 95%, 1.206-2.838; p = 0.0051), como factores de riesgo independientes, para la recurrencia postoperatoria.Este estudio fue retrospectivo en diseño.El margen de resección circunferencial predicho de resonancia magnética, se asoció con una supervivencia libre de recaída sin terapia preoperatoria, lo que indica su potencial para uso en la selección de la terapia óptima preoperatoria. Consulte Video Resumen en http://links.lww.com/DCR/B335.