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BACKGROUND: Patients with familial adenomatous polyposis (FAP) experience psychological and social challenges concerning future events such as marriage and childbirth alongside the medical risks of colorectal cancer (CRC) and FAP-related disease. We retrospectively investigated the rate of marriage and childbirth postoperatively in Japanese patients with FAP. METHODS: We included 161 patients who had colorectal surgery and reported marital status from a national survey of 35 Japanese institutions. Participants were classified according to marital status: married before colectomy (80 patients), married after colectomy (13 patients), and unmarried (68 patients). RESULTS: The marriage rate for all 161 patients (57.8%, standardized ratio 0.95, 95% confidence interval [CI] 0.76-1.14) was comparable to that in the general Japanese population (57.1%). The marriage rate among the 81 patients who were unmarried before colectomy was low (16.0%); however, the standardized marital ratio (0.75, 95% CI 0.34-1.15) was not significantly lower than that of the general population. In multivariable logistic regression, younger age (born after 1980, odds ratio [OR] 0.12, p < 0.001) and genetic testing (OR 4.06, p = 0.001) were associated with postoperative marriage. Seventy-one percent of patients with FAP who married after colectomy became pregnant and achieved delivery. CONCLUSIONS: The marriage rate of patients with FAP was comparable to that of the general population whereas the rate after colectomy was low among patients with FAP. However, in patients with FAP, colorectal surgery itself may not lead to negative consequences in terms of fecundity.
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Poliposis Adenomatosa del Colon , Colectomía , Estado Civil , Humanos , Poliposis Adenomatosa del Colon/cirugía , Femenino , Masculino , Adulto , Japón/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Colectomía/efectos adversos , Neoplasias Colorrectales/cirugía , Matrimonio , AncianoRESUMEN
BACKGROUND: FOLFOXIRI plus bevacizumab is a standard first-line chemotherapy for patients with metastatic colorectal cancer (mCRC). However, due to the severe toxicities, this regimen is not widely used. There is limited data on the real-world efficacy and safety. METHODS: We conducted a retrospective analysis of clinical data from mCRC patients who received FOLFOXIRI plus bevacizumab as first-line chemotherapy at 31 institutions. The initial dose was standardized according to the TRIBE regimen. Induction therapy was defined as a combination of oxaliplatin, irinotecan, and fluorouracil. RESULTS: Out of 104 patients who met the criteria, the median age was 58 years (range, 16-72). 81% of patients had an eastern cooperative oncology group performance status (PS) of 0. An initial dose reduction was observed in 63% of patients. The median number of preplanned induction therapy cycles was 12 (range, 4-12). The completion of scheduled induction therapy cycles was observed in 45% of patients, with treatment-related toxicities being the main reason for discontinuation (63%). The median progression-free survival and overall survival were 12.8 months (95% CI, 10.6-15.0) and 27.9 months (95% CI 21.6-34.2), respectively. The objective response rate and disease control rate were 63.7% and 98.9%, respectively. The R0 resection rate was 21.2%. The main grade 3 or higher toxicities were neutropenia (51%), febrile neutropenia (10%), and nausea/vomiting (5%). No treatment-related deaths were observed. CONCLUSION: In a real-world clinical setting, FOLFOXIRI plus bevacizumab demonstrated efficacy and safety comparable to previous clinical trials.
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INTRODUCTION: Bacteroides fragilis (B. fragilis) is considered to act in an anti-inflammatory manner on the intestinal tract. On the contrary, enterotoxigenic B. fragilis (ETBF), a subtype of B. fragilis, produces an enterotoxin (BFT; B. fragilis toxin), leading to asymptomatic chronic infections and colonic tumor formation. However, the impact of B. fragilis and ETBF on the clinical outcome of colorectal cancer (CRC) remains unclear. We aim to assess whether their presence affects the outcome in patients with CRC after curative resection. METHODS: We obtained 197 pairs of matched formalin-fixed paraffin-embedded samples from cancerous and adjacent non-cancerous tissues of patients with pathological stage (pstage) II and III CRC after curative resection. The presence of B. fragilis and ETBF were estimated using real-time polymerase chain reaction, and recurrence-free survival (RFS) and overall survival (OS) of the patients were analyzed. RESULTS: 16S rRNA for B. fragilis and bft DNA were detected in 120 (60.9%) and 12 (6.1%) of the 197 patients, respectively. B. fragilis-positive patients had better RFS than B. fragilis-negative patients, although that was not statistically significant. In subgroup analysis, better outcomes on RFS were observed in the presence of B. fragilis in pstage II and left-sided CRC. The association of B. fragilis positivity on OS was accentuated in the depth of T4 subgroup. No significant differences were observed in RFS and OS between ETBF and non-toxigenic B. fragilis. CONCLUSIONS: Our findings suggest that the presence of B. fragilis is associated with better outcomes in patients with pstage II and III CRC after curative resection.
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Infecciones Bacterianas , Infecciones por Bacteroides , Neoplasias Colorrectales , Humanos , Bacteroides fragilis/genética , Relevancia Clínica , ARN Ribosómico 16S , Pronóstico , Infecciones por Bacteroides/diagnóstico , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Infecciones Bacterianas/complicaciones , Metaloendopeptidasas/genéticaRESUMEN
BACKGROUND: Complex interactions among endogenous and exogenous factors influence the incidence of colorectal cancer (CRC). Germline mutations in mismatch repair (MMR) genes causing Lynch syndrome (LS) are major endogenous factors. The exogenous factor, alcohol consumption, is potentially associated with CRC incidence among patients with LS. However, insufficient data are available to determine whether alcohol consumption influences the time of the first onset of CRC associated with sex, MMR gene mutations, and anatomical tumor site. METHODS: Among 316 patients with LS identified in a Japanese LS cohort, we included 288 with data on age, sex, proband status, alcohol status, smoking status, tumor location, and MMR gene mutations. Multivariable analysis assessed the association of alcohol consumption with earlier onset of the first CRC. RESULTS: Ever drinkers were associated with higher risk of the first onset of CRC than never drinkers (HR 1.54, 95%CI 1.14-2.07, P = 0.004). The association of the first onset of CRC with alcohol consumption was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations (vs those with pathogenic MSH6, PMS2 and EPCAM mutations), and tumors in the proximal colon cancer (vs distal colon and rectal cancer). CONCLUSIONS: Alcohol consumption was associated with earlier onset of the first CRC in Japanese LS cohort. The association was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations, and tumors located in the proximal colon. Our findings illuminate the mechanism of LS-associated carcinogenesis and serve as a recommendation for discontinuing or ceasing alcohol consumption.
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Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Colorrectales , Consumo de Bebidas Alcohólicas/efectos adversos , Estudios de Cohortes , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/complicaciones , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN/genética , Humanos , Masculino , Proteína 2 Homóloga a MutS/genéticaRESUMEN
Background and objectives: In the treatment of the special type of breast cancer (STBC), the choice of chemotherapeutic agents is often based on the characteristic features of the histological type. On the other hand, the surgical strategy is usually determined by the tumor size and presence of lymph node metastasis, and the indication for immediate reconstruction is rarely discussed based on the histological type. The prognoses of STBC and invasive ductal carcinoma of the breast (IDC) patients who underwent subcutaneous mastectomy (SCM) with immediate reconstruction at our institution were compared. Materials and Methods: A total of 254 patients with SCM with immediate reconstruction from 1998 to 2018 were included; their tumor diameter or induration was less than 25 mm, and it was not in close proximity to the skin. Preoperative chemotherapy and non-invasive cancer cases were excluded. Results: The number of patients was 166 for skin-sparing mastectomy (SSM) and 88 for nipple-sparing mastectomy (NSM). The reconstructive techniques were deep inferior epigastric artery perforator flap (DIEP) reconstruction in 43 cases, latissimus dorsi flap reconstruction (LDflap) in 63 cases, tissue expander (TE) in 117 cases, and transverse rectus abdominis myocutaneous flap/vertical rectus abdominis myocutaneous flap (TRAM/VRAM) reconstruction in 31 cases. The histological types of breast cancer were 211 IDC and 43 STBC; 17 were mucinous carcinoma (MUC), 17 were invasive lobular carcinoma (ILC), 6 were apocrine carcinoma, 1 was tubular carcinoma, and 2 were invasive micropapillary carcinoma. There was no difference in local recurrence or disease-free survival (LRFS, DFS) between IDC and STBC, and overall survival (OS) was significantly longer in STBC. OS was better in the STBC group because SCM with immediate reconstruction was performed for STBC, which is a histological type with a relatively good prognosis. Highly malignant histological types, such as squamous cell carcinoma or metaplastic carcinoma, were totally absent in this study. Conclusions: The indications for SCM with immediate reconstruction for relatively common STBCs such as MUC and ILC can be the same as for IDC.
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Neoplasias de la Mama , Mastectomía Subcutánea , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía , Pronóstico , Colgajos QuirúrgicosRESUMEN
BACKGROUND: The characterisation of desmoplastic reaction (DR) has emerged as a new, independent prognostic determinant in colorectal cancer. Herein, we report the validation of its prognostic value in a randomised controlled study (SACURA trial). METHODS: The study included 991 stage II colon cancer patients. DR was classified by the central review as Mature, Intermediate or Immature based on the presence of hyalinised collagen bundles and myxoid stroma at the desmoplastic front. All clinical and pathological data, including DR characterisations, were prospectively recorded and analysed 5 years after the completion of the registration. RESULTS: The five-year relapse-free survival (RFS) rate was the highest in the Mature group (N = 638), followed by the Intermediate (N = 294) and Immature groups (N = 59). Multivariate analysis revealed that DR classification was an independent prognostic factor, and based on Harrell's C-index, the Cox model for predicting RFS was significantly improved by including DR. In the conditional inference tree analysis, DR categorisation was the first split factor for predicting RFS, followed by T-stage, microsatellite instability status and budding. CONCLUSIONS: Histological categorisation of DR provides important prognostic information that could contribute to the efficient selection of stage II colon cancer patients who would benefit from postoperative adjuvant therapy.
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Neoplasias del Colon/patología , Recurrencia Local de Neoplasia/patología , Células del Estroma/patología , Anciano , Neoplasias del Colon/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recurrencia Local de Neoplasia/terapia , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. METHODS: In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. RESULTS: Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). CONCLUSIONS: The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.
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Ácidos Nucleicos Libres de Células , Neoplasias , Anciano , Biomarcadores de Tumor/genética , Ácidos Nucleicos Libres de Células/genética , Femenino , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Japón , Masculino , Mutación , Neoplasias/genética , Proyectos PilotoRESUMEN
Background and objectives: Our department has been performing primary breast reconstruction for breast cancer surgery, incorporating a transverse rectus abdominis myocutaneous flap (TRAM)/vertical rectus abdominis myocutaneous flap (VRAM) since 1998 and a deep inferior epigastric artery perforator flap (DIEP) since 2008. Currently, most gastrointestinal operations in abdominal surgery are performed laparoscopically or are robot-assisted. Cases in which abdominal surgery was performed after breast reconstruction using an abdominal flap were reviewed. Method: A total of 119 cases of primary breast reconstruction using an abdominal flap performed in our department were reviewed. Result: The reconstructive techniques were DIEP in 69 cases and TRAM/VRAM in 50 cases. After breast surgery, seven abdominal operations were performed in six cases. In DIEP cases, one robotic surgery was performed for uterine cancer, and one laparoscopic surgery was performed for ovarian tumor. In TRAM/VRAM cases, two laparoscopic cholecystectomies, one laparoscopic total gastrectomy, one laparoscopic ileus reduction, and one open total hysterectomy oophorectomy were performed. Six surgeries were completed by laparoscopy or robotic assistance. Conclusion: The survival rate after breast cancer surgery is improving, and the choice of breast reconstruction procedure should take into account the possibility of performing a prophylactic resection of the ovaries due to the genetic background and possibly postoperative abdominal surgery due to other diseases. However, in cases in which laparoscopic surgery was attempted after breast reconstruction using an abdominal flap, the laparoscopic surgery could be completed in all cases.
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Neoplasias de la Mama , Laparoscopía , Mamoplastia , Colgajo Perforante , Neoplasias de la Mama/cirugía , Femenino , Humanos , Ovariectomía , Complicaciones Posoperatorias , Recto del Abdomen/cirugía , Estudios RetrospectivosRESUMEN
The patient is a 67-year-old woman who underwent surgery for left breast cancer in 1990 and right breast cancer in 2003. In 2013, local recurrence of right breast cancer was detected. Then she underwent removal of the local recurrence, axillary lymph node dissection, and post mastectomy irradiation. In 2017 lung metastasis appeared, and she underwent endocrine therapy and chemotherapy. BRCA1/2 analysis showed BRCA1 mutation, so olaparib was started in 2020. The metastatic lesions were reduced markedly, and the skin metastases were crusted over. Although it is necessary to decide when to use olaparib in each case, there is a possibility that olaparib may be effective even in the terminal stage, and it may be considered as one of the treatment options.
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Neoplasias de la Mama , Actividades Cotidianas , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/cirugía , Ftalazinas , PiperazinasRESUMEN
Accumulating evidence suggests that dysregulation of transcriptional enhancers plays a significant role in cancer pathogenesis. Herein, we performed a genome-wide discovery of enhancer elements in colorectal cancer (CRC). We identified PVT1 locus as a previously unrecognized transcriptional regulator in CRC with a significantly high enhancer activity, which ultimately was responsible for regulating the expression of MYC oncogene. High expression of the PVT1 long-non-coding RNA (lncRNA) transcribed from the PVT1 locus was associated with poor survival among patients with stage II and III CRCs (p < 0.05). Aberrant methylation of the PVT1 locus inversely correlated with the reduced expression of the corresponding the PVT1 lncRNA, as well as MYC gene expression. Bioinformatic analyses of CRC-transcriptomes revealed that the PVT1 locus may also broadly impact the expression and function of other key genes within two key CRC-associated signaling pathways - the TGFß/SMAD and Wnt/ß-Catenin pathways. We conclude that the PVT1 is a novel oncogenic enhancer of MYC and its activity is controlled through epigenetic regulation mediated through aberrant methylation in CRC. Our findings also suggest that the PVT1 lncRNA expression is a promising prognostic biomarker and a potential therapeutic target in CRC.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales/patología , Elementos de Facilitación Genéticos , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Proteínas Proto-Oncogénicas c-myc/genética , ARN Largo no Codificante/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/genética , Humanos , Pronóstico , Proteínas Proto-Oncogénicas c-myc/metabolismo , Tasa de SupervivenciaRESUMEN
Risk stratification in Stage II and III colorectal cancer (CRC) patients is critical, as it allows patient selection for adjuvant chemotherapy. In view of the inadequacy of current clinicopathological features for risk-stratification, we undertook a systematic and comprehensive biomarker discovery effort to develop a risk-assessment signature in CRC patients. The biomarker discovery phase examined 853 CRC patients, and identified a gene signature for predicting recurrence-free survival (RFS). This signature was validated in a meta-analysis of 1212 patients from nine independent datasets, and its performance was compared against established prognostic signatures and consensus molecular subtypes (CMS). In addition, a risk-prediction model was trained (n = 142), and subsequently validated in an independent clinical cohort (n = 286). As a result, this mesenchymal-associated transcriptomic signature (MATS) identified high-risk CRC patients with poor RFS in the discovery (hazard ratio [HR]: 1.79), and nine validation cohorts (HR: 1.86). In multivariate analysis, MATS was the most significant predictor of RFS compared to established prognostic signatures and CMS subtypes. Intriguingly, MATS robustly identified CMS4-subtype in multiple CRC cohorts (AUC = 0.92-0.99). In the two clinical cohorts, MATS stratified low and high-risk groups with a 5-year RFS in the training (HR: 4.11) and validation cohorts (HR: 2.55), as well as predicted response to adjuvant therapy in Stage II and III CRC patients. We report a novel prognostic and predictive biomarker signature in CRC, which is superior to currently used approaches and have the potential for clinical translation in near future.
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Biomarcadores de Tumor/genética , Quimioterapia Adyuvante/métodos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Perfilación de la Expresión Génica/métodos , Mesodermo/química , Neoplasias Colorrectales/patología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Inestabilidad de Microsatélites , Estadificación de Neoplasias , Cuidados Paliativos , Pronóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Although regorafenib or trifluridine/tipiracil (FTD/TPI) has been recognized as a later-line standard treatment in patients with metastatic colorectal cancer (mCRC), not all patients have beneficial outcomes. This study aimed to develop a prognostic scoring system for evaluating the overall survival (OS) benefit. METHODS: Patients included in the REGOTAS study, which comprised 489 patients (regorafenib group: 199; FTD/TPI group: 290 patients), were evaluated. OS was analyzed using multivariate Cox proportional model. The prognostic score was calculated using the worst four individual factors weighted by hazard ratio, and the total scores were categorized as low-, moderate-, and high-OS benefit. RESULTS: The worst four factors in the regorafenib group were AST > 40 IU/dL (point, + 3), CRP ≥ 1.0 mg/dL (+ 2), number of metastatic organ site ≥ 3 (+ 2), and duration from initiation of 1st-line chemotherapy < 18 months (+ 2), while they were AST (+ 2), CRP (+ 2), CA19-9 > 37.0 U/mL (+ 2), and ECOG PS ≥ 1 (+ 2) in the FTD/TPI group. These corresponded to a total prognostic score of > 5, 2-4, and 0 points in the regorafenib group and 8, 2-6, and 0 points in the FTD/TPI group. The median OS in the low, moderate, and high OS benefit group was 3.3 (95% CI 3.0-3.7), 8.1 (95% CI 6.4-9.7), and 12.6 months (95% CI 10.6-14.6) in the regorafenib group and 2.8 (95% CI 2.0-3.5), 7.5 (95% CI 6.6-8.3), and 15.4 months (95% CI 9.7-21.2) in the FTD/TPI group. CONCLUSION: These prognostic scores are useful for identifying patients with mCRC who will obtain survival benefits from these drugs.
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Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéutico , Pirrolidinas/uso terapéutico , Trifluridina/uso terapéutico , Uracilo/análogos & derivados , Anciano , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Timina , Resultado del Tratamiento , Uracilo/uso terapéuticoRESUMEN
Perioperative chemotherapies are expected to improve prognosis of patients with colorectal liver metastasis(CRLM). In patients with a resectable CRLM, the adjuvant chemotherapy with 5-FU/LV effectively prolongs DFS or RFS. In patients with unresectable CRLM, a neoadjuvant chemotherapy with high response rate and high liver resection rate, such as FOLFOX(or CAPOX, SOX)plus bevacizumab, FOLFOX/FOLFIRI plus cetuximab, or FOLFOXIRI plus bevacizumab, could be an optimal regimen for the conversion therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales , Neoplasias Hepáticas , Bevacizumab , Neoplasias Colorrectales/tratamiento farmacológico , Terapia Combinada , Fluorouracilo , Humanos , Leucovorina , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Compuestos Organoplatinos , OxaliplatinoRESUMEN
The treatment for desmoid-type fibromatosis involves surgical resection and medication therapy, but the standard treatment has not yet been established. In the West, the usefulness of radiation therapy has been reported. We encountered a patient with desmoid-type fibromatosis in the pelvis who was treated by radiation and medication therapies and achieved a good tumor reduction effect. The patient was a 70-year-old man. He had a 6-year history of pain in the right leg and had a palpable mass on the right side of the anus; he was admitted to our department. CT showed a 12×7×12 cm mass in the pelvis, and CT-guided needle biopsy revealed a desmoid-type fibromatosis. Because tumor exclusion resulted in obstruction of the rectum, radiation therapy(60 Gy in 30 Fr)was started after performing transverse colon colostomy; simultaneous medication therapy with a COX-2 inhibitor and the anti-allergic agent tranilast was administered. Cystic degeneration was observed 5 months after the end of radiation therapy, and after 12 months, the tumor volume had halved. Around 28 months after the end of radiation therapy, medication treatment has been continued with slow contraction.
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Fibromatosis Agresiva , Anciano , Terapia Combinada , Fibromatosis Agresiva/terapia , Humanos , Masculino , Pelvis , Tomografía Computarizada por Rayos X , Carga TumoralRESUMEN
The current histopathological risk-stratification criteria in colorectal cancer (CRC) patients following a curative surgery remain inadequate. In this study, we undertook a systematic, genomewide, biomarker discovery approach to identify and validate key EMT-associated genes that may facilitate recurrence prediction in CRC. Genomewide RNA expression profiling results from two datasets (GSE17538; N = 173 and GSE41258; N = 307) were used for biomarker discovery. These results were independently validated in two, large, clinical cohorts (testing cohort; N = 201 and validation cohort; N = 468). We performed Gene Set Enrichment Analysis (GSEA) for understanding the function of the candidate markers, and evaluated their correlation with the mesenchymal CMS4 subtype. We identified integrin subunit beta like 1 (ITGBL1) as a promising candidate biomarker, and its high expression associated with poor overall survival (OS) in stage I-IV patients and relapse-free survival (RFS) in stage I-III patients. Subgroup validation in multiple independent patient cohorts confirmed these findings, and demonstrated that high ITGBL1 expression correlated with shorter RFS in stage II patients. We developed a RFS prediction model which robustly predicted RFS (the area under the receiver operating curve (AUROC): 0.74; hazard ratio (HR): 2.72) in CRC patients. ITGBL1 is a promising EMT-associated biomarker for recurrence prediction in CRC patients, which may contribute to improved risk-stratification in CRC.
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Neoplasias Colorrectales/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Integrina beta1/genética , Recurrencia Local de Neoplasia/genética , Transcriptoma , Anciano , Estudios de Cohortes , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Conjuntos de Datos como Asunto , Femenino , Perfilación de la Expresión Génica , Humanos , Integrina beta1/metabolismo , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Transducción de SeñalRESUMEN
BACKGROUND: FoundationOne CDx is a cancer genome profiling test that has already been approved by the FDA, but its clinical utility in Japanese patients is unknown. In this study, we examined the clinical utility of FoundationOne CDx. METHODS: 46 samples from 43 Japanese pretreated patients with advanced solid tumors were tested with FoundationOne CDx between September 2018-January 2019. RESULTS: The median age of 43 patients was 63 years(ranged 18 to 82 years), and among them 24 were males and 19 females. Major cancer types were hepato-biliary and pancreatic(8 cases)and other digestive organs(8 cases). All 27 cases in which genome cancer board had been completed by January 17, 2019 were analyzable, and the number of detected gene mutations(except VUS)was an average of 4.3(ranged 0 to 14)per case. Of the 27 cases, one or more mutations were found in 26 cases(96%), and in all such 26 cases actionable mutations with candidates for therapeutic agents were found. In 4(15%)of them, the treatment corresponding to the gene mutation was performed. Among the cases in which target disease matched and clinical trials of the drug were being conducted in Japan, only one case participated in the trial. The most common reason for not participating in the trial was disease deterioration and PS reduction (33%). CONCLUSIONS: The FoundationOne CDx test showed that it can detect gene mutations in various cancer types in Japanese patients.
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Neoplasias , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Mutación , Adulto JovenRESUMEN
BACKGROUND: This study compared the efficacy of regorafenib and trifluridine/tipiracil (TFTD) in patients with metastatic colorectal cancer (mCRC) who are refractory to standard chemotherapy, because despite their clinical approval, it still remains unclear which of these two drugs should be used as initial treatment. MATERIALS AND METHODS: The clinical data of patients with mCRC who were treated with regorafenib or TFTD and those of drug-naive patients, between June 2014 and September 2015, were retrospectively collected from 24 institutions in Japan. Overall survival (OS) was evaluated using the Cox's proportional hazard models based on propensity score adjustment for baseline characteristics. RESULTS: A total of 550 patients (223 patients in the regorafenib group and 327 patients in the TFTD group) met all criteria. The median OS was 7.9 months (95% confidence interval [CI], 6.8-9.2) in the regorafenib group and 7.4 months (95% CI, 6.6-8.3) in the TFTD group. The propensity score adjusted analysis showed that OS was similar between the two groups (adjusted hazard ratio [HR], 0.96; 95% CI, 0.78-1.18). In the subgroup analysis, a significant interaction with age was observed. Regorafenib showed favorable survival in patients aged <65 years (HR, 1.29; 95% CI, 0.98-1.69), whereas TFTD was favored in patients aged ≥65 years (HR, 0.78; 95% CI, 0.59-1.03). CONCLUSION: No significant difference in OS between regorafenib and TFTD was observed in patients with mCRC. Although the choice of the drug by age might affect survival, a clearly predictive biomarker to distinguish the two drugs should be identified in further studies. IMPLICATIONS FOR PRACTICE: Previous studies of patients with metastatic colorectal cancer refractory to standard chemotherapy had demonstrated that both regorafenib and trifluridine/tipiracil could result in increased overall survival compared with placebo, but there are no head-to-head trials. This large, multicenter, observational study retrospectively compared the efficacy of regorafenib and trifluridine/tipiracil in 550 patients with metastatic colorectal cancer refractory to standard chemotherapy who had access to both drugs. Although no difference in overall survival was found between the two drugs in adjusted analysis using propensity score, regorafenib showed favorable survival in patients aged <65 years, whereas trifluridine/tipiracil was favored in patients aged ≥65 years in the subgroup analysis.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Terapia Recuperativa , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/secundario , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Japón , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Compuestos de Fenilurea/administración & dosificación , Pronóstico , Puntaje de Propensión , Piridinas/administración & dosificación , Pirrolidinas , Estudios Retrospectivos , Tasa de Supervivencia , Timina , Trifluridina/administración & dosificación , Uracilo/análogos & derivadosRESUMEN
Treatment of rectal cancer with postoperative pelvic recurrence may complicate infection and may be difficult to treat. We experienced 2 cases complicated with sepsis due to infection in the pelvic local recurrence in which radiation therapy was performed and they were shifted to outpatient molecular-targeted drug therapy. Case 1 involved a 58-year-old woman. In December 2011, colostomy and chemotherapy were performed for locally advanced rectal cancer. In June 2012, we performed low anterior resection. In January 2014, chemotherapy was started for pelvic recurrence. She discontinued treatment for 4 months due to personal circumstances. Recurrence was worsened, and infection caused sepsis and she was admitted to the hospital in February 2017. Infection was not improved with antibiotic drugs, and radiation therapy(60 Gy/30 times)was performed. Infection was improved, and panitumumab monotherapy was started and she was discharged. Case 2 involved a 61-year-old man. In February 2014, a lower anterior resection for rectal cancer was performed. In September 2015, chemotherapy was started for pelvic recurrence. In November 2016, chemotherapy was discontinued due to esophageal variceal rupture. Recurrence was worsened, and infection caused sepsis and he was admitted to the hospital in May 2017. Radiation therapy(50 Gy/20 times)was performed after colostomy. Infection was improved, and cetuximab monotherapy was started and he was discharged.
Asunto(s)
Neoplasias del Recto , Sepsis , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pelvis , Neoplasias del Recto/complicaciones , Neoplasias del Recto/cirugía , Sepsis/complicacionesRESUMEN
PURPOSE: Sarcopenia is reported to be associated with complications after surgery. However, there is no established optimal parameter to determine sarcopenia affecting surgical outcome. This study investigated whether morphologic change of the psoas muscle (MPM) reflects sarcopenia and could be a predictor of complications after colorectal cancer surgery. METHODS: Colorectal cancer patients who underwent primary tumor resection with anastomosis between 2015 and 2016 were analyzed. MPM score was evaluated as the ratio of the short-to-long axis of the psoas muscle in CT images at the L3 vertebrae and classified into five MPM grades. Then, the impact of MPM grade on development of postoperative complications was investigated. RESULTS: A total of 133 patients were studied. MPM score was significantly correlated to the sectional areas of the psoas muscle at the L3 vertebrae which was evaluated by manual tracing. 21.1% of the subjects were classified into severe MPM (defined as MPM grade 3-4). Overall and infectious complications were noted in 37 (27.8%) and 16 (12.0%) patients. Severe MPM (odds ratio [OR] 2.71, 95% confidence interval [CI] 1.09-6.73), longer operative time (OR 1.01, 95%CI 1.001-1.01), and open surgery (OR 2.73, 95%CI 1.17-6.35) were identified as independent risk factors of overall complications. Severe MPM (OR 4.26,95%CI 1.38-13.10) and open surgery (OR 3.42, 95%CI 1.11-10.48) were identified as independent factors associated with infectious complications. CONCLUSIONS: MPM grade may be used as a simple and convenient marker of sarcopenia and to identify patients at increased risk of complications after colorectal cancer surgery.