RESUMEN
Periampullary carcinoma is a malignant gastrointestinal tumor originating from the head of the pancreas, distal bile duct, duodenum, or the ampulla of Vater. Currently, surgery remains the primary treatment option, yet the postoperative recurrence rate remains high. Chemotherapy is the main approach for controlling postoperative recurrence. Histologically, periampullary carcinoma is categorized into two types: intestinal (IN) and pancreaticobiliary (PB) subtype. Each subtype requires different therapeutic approaches, with the PB type primarily treated with gemcitabine and the IN type with 5-FU. Despite these options, patient outcomes are still unsatisfactory. In recent years, the feasibility of immunotherapy in tumor treatment has been increasingly evidenced, although research on its efficacy in periampullary carcinoma treatment is still limited. In this report, we present a case of a periampullary carcinoma patient who experienced recurrence and metastasis after undergoing radical pancreatoduodenectomy and receiving gemcitabine-based chemotherapy post-surgery. Through next-generation sequencing (NGS), we identified high expression levels of programmed cell death-ligand 1 (PD-L1) with a combined positive score (CPS) of 35, high tumor mutation burden (TMB-H), and high microsatellite instability (MSI-H) in this patient. Therefore, we implemented a combination therapy using Tislelizumab and chemotherapy. According to the latest follow-up, the tumors are effectively controlled. Our utilization of immunotherapy combined with chemotherapy holds significant implication for the treatment of periampullary carcinoma.
Asunto(s)
Ampolla Hepatopancreática , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ampolla Hepatopancreática/patología , Masculino , Resultado del Tratamiento , Persona de Mediana Edad , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/terapia , Gemcitabina , Pancreaticoduodenectomía , Femenino , AncianoRESUMEN
Non-pancreatic periampullary tumors have long been neglected, leading to blurred adjuvant treatment strategies. Recent research, like the ISGACA group's study, is uncovering nuances in chemotherapy efficacy for these diverse cancers. Tailored approaches show promise, with artificial intelligence (AI) aiding in personalized treatment plans.
Asunto(s)
Inteligencia Artificial , Humanos , Quimioterapia Adyuvante/métodos , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/patología , Ampolla Hepatopancreática/patologíaAsunto(s)
Adenocarcinoma , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Adenocarcinoma/tratamiento farmacológico , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. PATIENTS AND METHODS: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). RESULTS: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). DISCUSSION: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.
Asunto(s)
Adenocarcinoma , Neoplasias Duodenales , Humanos , Masculino , Femenino , Quimioterapia Adyuvante , Persona de Mediana Edad , Anciano , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Neoplasias Duodenales/tratamiento farmacológico , Neoplasias Duodenales/patología , Neoplasias Duodenales/cirugía , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ampolla Hepatopancreática/patología , Pancreaticoduodenectomía , Estudios de Cohortes , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/cirugía , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Estudios Retrospectivos , Capecitabina/uso terapéutico , Capecitabina/administración & dosificaciónRESUMEN
BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.
Asunto(s)
Adenocarcinoma , Ampolla Hepatopancreática , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Neoplasias del Conducto Colédoco , Oxaliplatino , Humanos , Capecitabina/uso terapéutico , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Masculino , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Ampolla Hepatopancreática/patología , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Adulto , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/mortalidad , Estudios Retrospectivos , Supervivencia sin Progresión , Resultado del TratamientoRESUMEN
Background/Aims: : Palliative chemotherapy (PC) is not standardized for patients with advanced ampulla of Vater adenocarcinoma (AA). This multicenter, retrospective study evaluated first-line PC outcomes in patients with AA. Methods: : Patients diagnosed with AA between January 2010 and December 2020 who underwent PC were enrolled from 10 institutions. Overall survival (OS) and progression-free survival (PFS) according to the chemotherapy regimen were analyzed. Results: : Of 255 patients (mean age, 64.0±10.0 years; male, 57.6%), 14 (5.5%) had locally advanced AA and 241 (94.5%) had metastatic AA. Gemcitabine plus cisplatin (GP) was administered as first-line chemotherapy to 192 patients (75.3%), whereas capecitabine plus oxaliplatin (CAPOX) was administered to 39 patients (15.3%). The median OS of all patients was 19.8 months (95% confidence interval [CI], 17.3 to 22.3), and that of patients who received GP and CAPOX was 20.4 months (95% CI, 17.2 to 23.6) and 16.0 months (95% CI, 11.2 to 20.7), respectively. The median PFS of GP and CAPOX patients were 8.4 months (95% CI, 7.1 to 9.7) and 5.1 months (95% CI, 2.5 to 7.8), respectively. PC for AA demonstrated improved median outcomes in both OS and PFS compared to conventional bile duct cancers that included AA. Conclusions: : While previous studies have shown mixed prognostic outcomes when AA was analyzed together with other biliary tract cancers, our study unveils a distinct clinical prognosis specific to AA on a large scale with systemic anticancer therapy. These findings suggest that AA is a distinct type of tumor, different from other biliary tract cancers, and AA itself could be expected to have a favorable response to PC.
Asunto(s)
Adenocarcinoma , Ampolla Hepatopancreática , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Conducto Colédoco , Desoxicitidina , Gemcitabina , Oxaliplatino , Cuidados Paliativos , Humanos , Ampolla Hepatopancreática/patología , Masculino , Persona de Mediana Edad , Femenino , Cuidados Paliativos/métodos , Estudios Retrospectivos , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Anciano , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Capecitabina/administración & dosificación , Capecitabina/uso terapéutico , Resultado del Tratamiento , Supervivencia sin ProgresiónRESUMEN
Adenocarcinomas of the ampulla of Vater represent only 0.2% of all gastrointestinal cancers. Due to the low incidence no large clinical trials evaluating efficacy of treatments are available. Adjuvant therapy is often administered in patients with stage IB or higher. Oxaliplatin is considered as an effective and well tolerated therapeutic option. Adverse events associated with this therapy include cardio-, neuro-, nephrotoxicity and myelosuppression. Previously granulomatous pulmonary and liver manifestations have been described in oxaliplatin-based chemotherapy. In this report peritoneal manifestation of granulomatous disease associated with oxaliplatin is described for the first time. Sarcoidlike reactions may be misinterpreted as tumour progression or metastatic disease, and may consequently result in over-treatment.
Asunto(s)
Adenocarcinoma , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Enfermedades Peritoneales , Humanos , Oxaliplatino/efectos adversos , Ampolla Hepatopancreática/patología , Adenocarcinoma/patología , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/etiología , Neoplasias del Conducto Colédoco/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosAsunto(s)
Adenocarcinoma , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Humanos , Ampolla Hepatopancreática/cirugía , Quimioterapia Adyuvante , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/cirugía , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
BACKGROUND: The role of adjuvant chemotherapy (AC) in patients with ampullary adenocarcinoma (AA) remains controversial. This study aimed to determine if AC could improve the prognosis of patients with resected AA. STUDY DESIGN: This study enrolled patients diagnosed with AA at 9 tertiary teaching hospitals. Patients who did and did not receive AC were matched 1:1 using propensity score. The overall survival (OS) and recurrence-free survival (RFS) were compared between the 2 groups. RESULTS: Of the 1,057 patients with AA, 883 underwent curative-intent pancreaticoduodenectomy, and 255 received AC. Because patients with advanced-stage AA received AC more frequently, the no AC group unexpectedly had a longer OS (not reached vs 78.6 months; p < 0.001) and RFS (not reached vs 18.7 months; p < 0.001) than did the AC group in the unmatched cohort. In the propensity score-matched cohort (n = 296), no difference between the 2 groups in terms of OS (95.9 vs 89.8 months, p = 0.303) and RFS (not reached vs 25.5 months; p = 0.069) was found. By subgroup analysis, patients with advanced stage (pT4 or pN1-2) showed longer OS in the AC group than in the no AC group (not reached vs 15.7 months, p = 0.007: 89.8 vs 24.2 months, p = 0.006, respectively). There was no difference in RFS according to AC in the propensity score-matched cohort. CONCLUSIONS: Given its favorable long-term outcomes, AC can be recommended for patients with resected AA, especially those in the advanced stage (pT4 or pN1-2).
Asunto(s)
Adenocarcinoma , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Neoplasias Pancreáticas , Humanos , Quimioterapia Adyuvante , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/cirugía , Estudios de Cohortes , Estudios RetrospectivosRESUMEN
BACKGROUND: Although surgery is the primary treatment for ampullary cancer (AC), the benefit of adjuvant chemotherapy (CTx) has not yet been confirmed. METHODS: AC patients who were administered 5-fluorouracil(FU)/leucovorin(LV)-based CTx after curative intent surgery between 2011 and 2019 were included. Prognosis was compared between the observation (OB) and CTx groups after propensity score matching (PSM) using perioperative variables to control differences in patient characteristics. RESULTS: Before PSM, of 475 patients, those in the CTx group (n = 281) had worse 5-year overall survival (OS) (82.1% vs. 78.5%, p = 0.017) and worse 5-year recurrence-free survival (RFS) (54.9% vs. 75.7%, p < 0.001) than those in the OB group (n = 194). In addition, the CTx group had a higher rate of poor prognostic factors such as a high T stage (p < 0.001), node metastasis (p < 0.001), and poor differentiation (p < 0.001). After PSM, perioperative outcomes were comparable. In addition, there were no significant differences in OS (hazard ratio [HR], 1.085; 95% confidence interval [CI], 0.688-1.710; p = 0.726) or RFS (HR, 0.883; 95% CI, 0.613 1.272; p = 0.505) between the CTx (n = 123) and OB (n = 123) groups even after stratification by TNM stage. Intestinal subtype showed better 5-year OS (83.7% vs 33.2%, p = 0.015) and RFS (46.5% vs 24.9%, p = 0.035) rate compared with pancreatobiliary/mixed subtype. CONCLUSION: Patients who received adjuvant chemotherapy based on 5-FU/LV showed comparable oncologic outcomes to patients in the OB group even after stratification by tumor stage. The patients with intestinal subtype showed oncologic benefit for adjuvant 5-FU/LV CTx compared with pancreatobiliary or mixed subtypes.
Asunto(s)
Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Ampolla Hepatopancreática/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/cirugía , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Estadificación de Neoplasias , Puntaje de PropensiónRESUMEN
INTRODUCTION: The usefulness of adjuvant chemotherapy in biliary tract cancer (BTC) is poorly reported. This study aimed to evaluate the effectiveness and safety of adjuvant gemcitabine plus S-1 (GS) chemotherapy after curative surgical resection for BTC. METHODS: 225 BTC patients who underwent surgical resection between January 2006 and May 2019 were enrolled in this study. Twenty-seven patients received adjuvant chemotherapy with GS (GS group), whereas 67 patients underwent surgery alone (S group). Twenty-three matching pairs were derived through propensity score (PS) matching analysis. Patients received 12 cycles of adjuvant chemotherapy (70 mg/m2 oral S-1 for 7 consecutive days plus intravenous gemcitabine 1,000 mg/m2 on day 7). The primary end point was recurrence-free survival (RFS). The secondary end points were the 1-, 2-, and 3-year RFS and overall survival (OS) rates, tolerability, and frequency of grade 3/4 toxicity. RESULTS: The completion rate was 81.5%; no treatment-related deaths were observed. Grade 3/4 adverse events were seen in 40.7% of the patients. RFS (3-year RFS rate: 59.3% vs. 39.1%, p = 0.049) and OS (3-year OS rate: 71.7% vs. 53.4%, p = 0.008) were significantly better in the GS group than in the S group among PS-matched pairs. DISCUSSION/CONCLUSION: GS chemotherapy after curative surgery was well tolerated, showed better clinical benefit in the adjuvant setting, and can effectively reduce BTC recurrence.
Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Procedimientos Quirúrgicos del Sistema Biliar/métodos , Quimioterapia Adyuvante/efectos adversos , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/cirugía , Desoxicitidina/análogos & derivados , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/cirugía , Tumor de Klatskin/tratamiento farmacológico , Tumor de Klatskin/cirugía , Ácido Oxónico/efectos adversos , Tegafur/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Conducto Colédoco/mortalidad , Desoxicitidina/efectos adversos , Supervivencia sin Enfermedad , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Neoplasias de la Vesícula Biliar/mortalidad , Humanos , Tumor de Klatskin/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Puntaje de Propensión , Tasa de Supervivencia , GemcitabinaRESUMEN
BACKGROUND AND AIMS: Biliary tract cancer (BTC) exhibits diverse molecular characteristics. However, reliable biomarkers that predict therapeutic responses are yet to be discovered. We aimed to identify the molecular features of treatment responses to chemotherapy and immunotherapy in BTCs. APPROACH AND RESULTS: We enrolled 121 advanced BTC patients (68 cholangiocarcinomas [33 intrahepatic, 35 extrahepatic], 41 gallbladder cancers, and 12 Ampulla of Vater cancers) whose specimens were analyzed by clinical sequencing platforms. All patients received first-line palliative chemotherapy; 48 patients underwent programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy after failed chemotherapy. Molecular and histopathological characterization was performed using targeted sequencing and immunohistochemical staining to investigate treatment response-associated biomarkers. Genomic analysis revealed a broad spectrum of mutational profiles according to anatomical location. Favorable responses to chemotherapy were observed in the small-duct type compared with the large-duct type intrahepatic cholangiocarcinoma, with frequent mutations in BRCA1-associated protein-1/isocitrate dehydrogenase 1/2 and KRAS proto-oncogene, GTPase/SMAD family member 4 genes, respectively. The molecular features were further analyzed in BTCs, and transforming growth factor beta and DNA damage response pathway-altered tumors exhibited poor and favorable chemotherapy responses, respectively. In PD-1/PD-L1 blockade-treated patients, KRAS alteration and chromosomal instability tumors were associated with resistance to immunotherapy. The majority of patients (95.0%) with these resistance factors show no clinical benefit to PD-1/PD-L1 blockade and low tumor mutational burdens. Low tumor-infiltrating lymphocyte (TIL) density in tumors with these resistance factors indicated immune-suppressive tumor microenvironments, whereas high intratumoral TIL density was associated with a favorable immunotherapy response. CONCLUSIONS: This study proposes predictive molecular features of chemotherapy and immunotherapy responses in advanced BTCs using clinical sequencing platforms. Our result provides an intuitive framework to guide the treatment of advanced BTCs benefiting from therapeutic agents based on the tumors' molecular features.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática , Antígeno B7-H1/antagonistas & inhibidores , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/genética , Conductos Biliares Extrahepáticos , Conductos Biliares Intrahepáticos , Neoplasias del Sistema Biliar/genética , Carcinoma/genética , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/genética , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/genética , Femenino , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/genética , Humanos , Isocitrato Deshidrogenasa/genética , Linfocitos Infiltrantes de Tumor , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína Smad4/genética , Resultado del Tratamiento , Microambiente Tumoral , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genéticaRESUMEN
BACKGROUND: Outcomes in ampullary cancer (AC) may differ by pathologic subtype. No guidelines exist for the administration of adjuvant therapy (AT). We sought to evaluate the effect of subtype and AT on survival. METHODS: An institutional review of patients undergoing resection for AC from 2008-17 was performed. Recurrence-free (RFS) and overall survival (OS) were assessed by Kaplan-Meier and Cox proportional hazards modeling. RESULTS: Of 53 patients, two-thirds (62%) were stage III. Histologic subtype was evenly split between intestinal and pancreatobiliary (43% and 40%). Half of patients received AT. RFS and OS were 25 (95% CI 16-32) and 41 (CI 22-60) months, respectively, without significant difference by subtype. Stage II/III disease was associated with worse OS (HR 3.7, P = 0.03), which was improved with receipt of AT (HR 0.44, P < 0.05). CONCLUSION: Stage is the primary determinant of survival in AC, which may be improved with AT.
Asunto(s)
Adenocarcinoma/cirugía , Ampolla Hepatopancreática , Quimioterapia Adyuvante/métodos , Neoplasias del Conducto Colédoco/cirugía , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/patología , Ampolla Hepatopancreática/cirugía , Terapia Combinada , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis. METHODS: An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses. RESULTS: Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. CONCLUSION: Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.
ANTECEDENTES: Actualmente se desconoce si la quimioterapia adyuvante ofrece un beneficio en la supervivencia de los pacientes que se someten a resección de un adenocarcinoma ampular. El objetivo de este estudio fue comparar la supervivencia mediante la concordancia estimada por emparejamiento por puntaje de propensión, entre pacientes con y sin quimioterapia adyuvante después de la resección de un adenocarcinoma ampular. MÉTODOS: Se realizó un estudio internacional de cohortes multicéntrico, que incluyó a los pacientes que se sometieron a una duodenopancreatectomía por adenocarcinoma ampular (2006-2017) en 13 centros de seis países. Los puntajes de propensión se usaron para emparejar a los pacientes que recibieron quimioterapia adyuvante con los que no; tanto en la cohorte completa como en dos subgrupos (subtipo pancreaticobiliar / mixto e intestinal). La supervivencia se evaluó utilizando el método de Kaplan-Meier y las regresiones de Cox. RESULTADOS: En total, 1.163 pacientes fueron sometidos a una duodenopancreatectomía por adenocarcinoma ampular. Después de excluir a 179 pacientes, la mediana de supervivencia de los 976 pacientes restantes fue de 67 meses (i.c. del 95%, 56-78), de los cuales un total de 520 pacientes (53%) recibieron quimioterapia adyuvante. En una cohorte de emparejamiento por puntaje de propensión (194 versus 194 pacientes), la mediana de supervivencia fue mejor en los pacientes tratados con quimioterapia adyuvante en comparación con aquellos sin quimioterapia adyuvante (no se alcanzó la mediana de supervivencia versus 60 meses, respectivamente; P = 0,051). En el subtipo pancreaticobiliar/mixto se observó un beneficio en la supervivencia; no se alcanzó la mediana de supervivencia en pacientes que recibieron quimioterapia adyuvante versus 32 meses en el grupo sin quimioterapia, P = 0,020. El subtipo intestinal no mostró beneficio en la supervivencia de la quimioterapia adyuvante. CONCLUSIÓN: Los pacientes con adenocarcinoma ampular resecado pueden beneficiarse de la quimioterapia adyuvante basada en gemcitabina, pero este efecto podría reservarse para aquellos pacientes con subtipo de tumor pancreaticobiliar y/o mixto.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Ampolla Hepatopancreática , Antimetabolitos Antineoplásicos/uso terapéutico , Quimioterapia Adyuvante/métodos , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Ampolla Hepatopancreática/patología , Ampolla Hepatopancreática/cirugía , Quimioterapia Adyuvante/mortalidad , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/cirugía , Desoxicitidina/uso terapéutico , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pancreaticoduodenectomía , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia , GemcitabinaAsunto(s)
Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Erupciones por Medicamentos/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Pirazoles/uso terapéutico , Adenocarcinoma/secundario , Anciano , Ampolla Hepatopancreática , Anticuerpos Monoclonales Humanizados/administración & dosificación , Brazo , Neoplasias del Conducto Colédoco/patología , Erupciones por Medicamentos/etiología , Glucocorticoides/uso terapéutico , Antagonistas de los Receptores Histamínicos/uso terapéutico , Humanos , Neoplasias Hepáticas/secundario , Masculino , Nitrilos , Paclitaxel/administración & dosificación , Prednisolona/uso terapéutico , Pirimidinas , Escroto , Muslo , TorsoRESUMEN
AIM: To improve the outcomes in patients with resectable biliary cancer. MATERIAL AND METHODS: There were 263 procedures for cholangiocellular carcinoma (CCC) for the period 19982017. Adjuvant chemotherapy was performed in 102 (38.8%) patients. Extensiveliver resections (78.9%) prevailed for intrahepatic cholangiocellular carcinoma (n=128), 6 (4.7%) patients required vascular resection. Seventy-seven pancreatoduodenectomies were performed for common bile duct cancer, portal vein resection was done in 8 (10.4%) patients. In case of Klatskin tumor (n=58) liver resection combined with bile duct resection (n=52) prevailed. Portal vein resection was done in 16 (27.6%) patients. RESULTS: Postoperative morbidity in patients with intrahepatic CCC was revealed in 68 (53.1%) cases, mortality in 5 (3.9%) cases. Among patients with Klatskin tumor morbidity was revealed in 51 (87.9%) cases, mortality in 6 (10.3%) cases. In patients with common bile duct cancer morbidity was revealed in 53 (68.8%) cases, mortality in 4 (5.2%) cases. In whole cohort median overall survival was 30 months. R0-resection was associated with better long-term results (median 37 months) compared with R1R2 resection (20 months; p=0.01). Lymph node involvement is associated with significantly worse prognosis (p=0.016), however 5-year survival is observed (25.6%). Adjuvant chemotherapy in R0-resection significantly improved long-term results: median was 46 months (vs. 30 in group without chemotherapy; p=0.02). In intrahepatic CCC patients multiple lesions or mechanical jaundice did not aggravate long-term results. CONCLUSION: R0-resection including lymphadenectomy, resection of adjacent organs and vessels is advisable for CCC. Isolated bile duct resection should be used as an exception. Adjuvant therapy improved long-term results. Multiple lymph node lesion or bile duct infiltration are not contraindications to surgery in intrahepatic CCC patients.
Asunto(s)
Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/cirugía , Colangiocarcinoma/cirugía , Neoplasias del Conducto Colédoco/cirugía , Antineoplásicos/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Quimioterapia Adyuvante , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/patología , Hepatectomía , Humanos , Escisión del Ganglio Linfático , Pancreaticoduodenectomía , Vena Porta/patología , Vena Porta/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: Attempts have been made to revise the nodal stage due to simplicity of current N staging system in ampullary adenocarcinoma. However, because of the disease rarity, there have only been a few studies assessing the prognostic impact of lymph node (LN) parameters. METHODS: We retrospectively analyzed 120 patients who underwent radical resection followed by adjuvant chemoradiotherapy for ampullary adenocarcinoma. The effect of LN parameters (number of total harvest LNs, number of metastatic LN (MLN), lymph node ratio (LNR), and log odds of positive LNs (LODDS)) on overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival were evaluated. Cutoff points of MLN, LNR and LODDs were determined using maximal χ2 method. RESULTS: Fifty-seven patients (48%) were staged as pN1 and their survival was not significantly decreased compared with pN0 patients. There was also no significant difference between patients with MLN 0 vs. 1. In univariate analyses, MLN (0-1 vs. ≥2), LNR (≤17% vs. >17%) and perineural invasion were common prognosticators for OS and LRFS. Distant metastasis-free survival was not influenced by LN status. In addition, multivariate analysis revealed that among the LN parameters, LNR was able to independently predict both OS and LRFS. CONCLUSIONS: LNR performs better than other LN related parameters for predicting survival. After radical resection followed by adjuvant treatment, survival of patients with one positive LN does not seem to differ from patients without LN metastasis.
Asunto(s)
Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/cirugía , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Adenocarcinoma/tratamiento farmacológico , Adulto , Anciano , Fuga Anastomótica/etiología , Quimioradioterapia Adyuvante/efectos adversos , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Supervivencia sin Enfermedad , Femenino , Humanos , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Nervios Periféricos/patología , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Periampullary cancers are uncommon malignancies, often amenable to surgery. Several studies have suggested a role for adjuvant chemotherapy and chemoradiotherapy in improving survival of patients with periampullary cancers, with variable results. The aim of this meta-analysis was to determine the survival benefit of adjuvant therapy for periampullary cancers. METHODS: A systematic review was undertaken of literature published between 1 January 2000 and 31 December 2015 to elicit and analyse the pooled overall survival associated with the use of either adjuvant chemotherapy or chemoradiotherapy versus observation in the treatment of surgically resected periampullary cancer. Included articles were also screened for information regarding stage, prognostic factors and toxicity-related events. RESULTS: A total of 704 titles were screened, of which 93 full-text articles were retrieved. Fourteen full-text articles were included in the study, six of which were RCTs. A total of 1671 patients (904 in the control group and 767 who received adjuvant therapy) were included. The median 5-year overall survival rate was 37·5 per cent in the control group, compared with 40·0 per cent in the adjuvant group (hazard ratio 1·08, 95 per cent c.i. 0·91 to 1·28; P = 0·067). In 32·2 per cent of patients who had adjuvant therapy, one or more WHO grade 3 or 4 toxicity-related events were noted. Advanced T category was associated worse survival (regression coefficient -0·14, P = 0·040), whereas nodal status and grade of differentiation were not. CONCLUSION: This systematic review found no associated survival benefit for adjuvant chemotherapy or chemoradiotherapy in the treatment of periampullary cancer.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Ampolla Hepatopancreática/cirugía , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/cirugía , Neoplasias Duodenales/tratamiento farmacológico , Neoplasias Duodenales/cirugía , Adenocarcinoma/mortalidad , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias Duodenales/mortalidad , Humanos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Capecitabine with oxaliplatin (CAPOX) has previously demonstrated clinical activity in patients with small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Herein, the authors conducted a phase 2 trial to evaluate the benefit of adding bevacizumab to CAPOX. METHODS: In this phase 2, single-arm, single-center, open-label study, patients aged ≥18 years with untreated, advanced SBA or AAC were recruited. Patients received capecitabine at a dose of 750 mg/m2 orally twice daily on days 1 to 14, oxaliplatin at a dose of 130 mg/m2 intravenously on day 1, and bevacizumab at a dose of 7.5 mg/kg intravenously on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary objectives included response rate, overall PFS, overall survival, and toxicity. RESULTS: Between August 2011 and November 2014, a total of 30 patients were enrolled into the study (male/female ratio of 13/17; median age of 63 years [range, 33-78 years]; and 7 patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 0, 20 patients with an ECOG PS of 1, and 3 patients with an ECOG PS of 2). Of the 30 patients, 23 (77%) had SBA (18 of duodenal origin and 5 of jejunal/ileal origin) and 7 patients (23%) had AAC (5 of pancreaticobiliary subtype, 1 of mixed subtype, and 1 of intestinal subtype). The most common grade 3 toxicities observed were fatigue and hypertension (7 patients each [23%]), neutropenia (6 patients [20%]), and diarrhea (3 patients [10%]) (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The probability of PFS at 6 months was 68% (95% confidence interval [95% CI], 52% to 88%). The response rate was 48.3%, with 1 complete response and 13 partial responses; 10 patients achieved stable disease. At a median follow-up of 25.9 months, the median PFS was 8.7 months (95% CI, 4.9-10.5 months) and the median overall survival was 12.9 months (95% CI, 9.2-19.7 months). CONCLUSIONS: The results of the current study indicate that CAPOX with bevacizumab is an active and well-tolerated regimen for patients with SBA and AAC. These findings support the need for further investigation into the clinical benefit of targeting angiogenesis in patients with SBA and AAC. Cancer 2017;123:1011-17. © 2016 American Cancer Society.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Ampolla Hepatopancreática/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias Intestinales/tratamiento farmacológico , Intestino Delgado/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Bevacizumab/administración & dosificación , Capecitabina/administración & dosificación , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Comorbilidad , Femenino , Humanos , Neoplasias Intestinales/mortalidad , Neoplasias Intestinales/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Resultado del TratamientoRESUMEN
PURPOSE: Combination chemotherapy with gemcitabine and cisplatin is a standard treatment for patients with advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of gemcitabine- and cisplatin-based concurrent chemoradiotherapy in patients with unresectable biliary tract cancer. METHODS: Patients with pathologically proven, unresectable, non-metastatic biliary tract cancer were enrolled. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1, 8, and 15. Cisplatin was administered intravenously at a dose of 70 mg/m(2) on day 1. All the patients underwent concurrent radiotherapy with 45 Gy in 1.8-Gy daily fractions. After treatment completion, tumor response was evaluated by using computed tomography. RESULTS: Eighteen patients were enrolled between June 2007 and October 2011. Their median age was 61 years (range, 38-72 years). Eight patients (44.5 %) were diagnosed with gallbladder cancer, six (33.3 %) with Klatskin's tumor, and four (22.2 %) with distal common bile duct cancer. After treatment completion, partial response was achieved in five patients (27.8 %) and stable disease in 13 patients (72.2 %). The overall response rate was 27.8 %, and the disease stabilization rate was 100 %. No grade 4 adverse events or treatment-related deaths occurred. The most common grade 3 adverse events were thrombocytopenia (33.3 %) and anemia (11.1 %). The median progression-free and overall survival times were 6.8 months (range, 4.5-19.8 months) and 9.6 months (5.4-30.4 months), respectively. CONCLUSIONS: This study shows that gemcitabine- and cisplatin-based concurrent chemoradiotherapy is feasible and tolerable in patients with unresectable and non-metastatic biliary tract cancer.