RESUMEN
BACKGROUND: To investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan-Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots. RESULTS: This study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p < 0.01), and had a higher N2 + N3 stage (11.2% vs 7.24%, 8.69% and 7.48%, p < 0.01). Univariate and multivariate analysis revealed that molecular subtype was the independent risk factor for OS and CSS in patients(p < 0.05). The Kaplan-Meier curves indicated that the HR + /HER-2 + subtype had the highest OS and CSS(p < 0.05). Next, were the HR-/HER-2 + and HR-/HER-2- subtypes, with the HR + /HER-2- group having the lowest OS and CSS(p < 0.05). After propensity score matching, the OS and CSS of patients in the HR + /HER-2 + group remained higher compared to HR + /HER-2- group(p < 0.05). CONCLUSIONS: Patients with invasive ductal carcinoma of different molecular subtypes exhibit varying prognoses after achieving pCR to neoadjuvant chemotherapy. Those in the HR + /HER-2- group are younger, have a higher lymph node stage, and the lowest OS and CSS, whereas patients in the HR + /HER-2 + group have the highest OS and CSS.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Terapia Neoadyuvante , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/mortalidad , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/metabolismo , Persona de Mediana Edad , Tasa de Supervivencia , Pronóstico , Receptor ErbB-2/metabolismo , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Receptores de Progesterona/metabolismo , Programa de VERF , Receptores de Estrógenos/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Quimioterapia Adyuvante/métodos , Estudios RetrospectivosAsunto(s)
Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Terapia Neoadyuvante , Nivolumab , Humanos , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/administración & dosificación , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Atención Perioperativa , Neumonectomía/efectos adversos , Neumonectomía/mortalidad , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/mortalidadRESUMEN
BACKGROUND: The use of surgery in patients with locally advanced pancreatic cancer (LAPC) following induction chemotherapy is increasing. However, most series do not report on the total cohort of patients undergoing surgical exploration; therefore, this single-center study investigates outcomes among all consecutive patients with LAPC who underwent surgical exploration. METHODS: We conducted a retrospective, single-center analysis including all consecutive patients with LAPC (Dutch Pancreatic Cancer Group criteria) who underwent surgical exploration with curative intent (January 2014-June 2023) after induction therapy. Primary outcomes were resection rate and overall survival (OS) from the time of diagnosis. RESULTS: Overall, 127 patients underwent surgical exploration for LAPC, whereby 100 patients (78.7%) underwent resection and 27 patients (21.3%) underwent a non-therapeutic laparotomy due to the extent of vascular involvement (n = 11, 8.7%) or occult metastases (n = 16, 12.6%). The overall in-hospital/30-day mortality rate was 0.8% and major morbidity was 31.3% (in patients after resection: 1.0% and 33.3%, respectively). The overall 90-day mortality rate was 5.5%, which included 3.1% mortality due to disease progression. Resection was associated with longer median OS {29 months (95% confidence interval [CI] 26-43) vs. 17 months (95% CI 11-26); p < 0.001} compared with patients undergoing non-therapeutic laparotomy, with corresponding 5-year OS rates of 28.4% and 7.7%. In Cox proportional hazard regression analysis, only pancreatic body/tail tumors independently predicted OS (hazard ratio 1.788 [95% CI 1.042-3.068]). CONCLUSION: This single-center series found a resection rate of 78.7% in patients with LAPC selected for surgical exploration, with a low risk of mortality and morbidity in all explored patients and a 5-year OS rate after resection of 28.4%.
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Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia de Inducción , Pancreatectomía , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Tasa de Supervivencia , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pronóstico , Terapia Neoadyuvante/mortalidad , AdultoRESUMEN
RATIONALE: We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up. PATIENTS AND METHODS: This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m2 and CDDP 100 mg/m2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives. RESULTS: From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16-63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3-4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months. CONCLUSION: Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Óseas , Ifosfamida , Osteosarcoma , Humanos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/mortalidad , Osteosarcoma/patología , Adulto , Masculino , Femenino , Persona de Mediana Edad , Adulto Joven , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Ifosfamida/uso terapéutico , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/mortalidad , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Supervivencia sin Enfermedad , Estudios de SeguimientoRESUMEN
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The phase III PRODIGY study demonstrated that neoadjuvant chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 chemotherapy (CSC) improved progression-free survival (PFS) compared with surgery followed by adjuvant S-1 (SC) for patients with resectable locally advanced gastric cancer (LAGC) with clinical T2-3N+ or T4Nany disease. The primary end point was PFS. Overall survival (OS) was the secondary end point. We herein report the long-term follow-up outcomes, including OS, from this trial. A total of 238 and 246 patients were randomly assigned to the CSC and SC arms, respectively, and were treated (full analysis set). As of the data cutoff (September 2022), the median follow-up duration of the surviving patients was 99.5 months. Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (HR, 0.70; stratified log-rank P = .016). In conclusion, neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1. It should be considered one of the standard treatment options for patients with LAGC in Asia.
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Protocolos de Quimioterapia Combinada Antineoplásica , Docetaxel , Combinación de Medicamentos , Terapia Neoadyuvante , Oxaliplatino , Ácido Oxónico , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tegafur/administración & dosificación , Tegafur/uso terapéutico , Docetaxel/administración & dosificación , Docetaxel/uso terapéutico , Oxaliplatino/administración & dosificación , Oxaliplatino/uso terapéutico , Ácido Oxónico/uso terapéutico , Ácido Oxónico/administración & dosificación , Terapia Neoadyuvante/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Quimioterapia Adyuvante , Anciano , Adulto , GastrectomíaRESUMEN
PURPOSE: The aim of study was to screen factors associated with the overall survival of colorectal cancer patients with lymph nodes metastasis who received neoadjuvant therapy and construct a nomogram model. METHODS: All enrolled subjects of the SEER database were randomly assigned to the training and testing group in a ratio of 3:2. The patients of Tangdu Hospital were seemed as validation group. Univariate cox regression analysis, lasso regression and random forest survival were used to screen variables related to the survival of advanced CRC patients received neoadjuvant therapy in the training group. Area under curves were adopted to evaluate the 1,3,5-year prediction value of the optimal model in three cohorts. Calibration curves were drawn to observe the prediction accuracy of the nomogram model. Decision curve analysis was used to assess the potential clinical value of the nomogram model. RESULTS: A total of 1833 subjects were enrolled in this study. After random allocation, 1055 cases of the SEER database served as the training group, 704 cases as the testing group and 74 patients from our center as the external validation group. Variables were screened by univariate cox regression used to construct a nomogram survival prediction model, including M, age, chemotherapy, CEA, perineural invasion, tumor size, LODDS, liver metastasis and radiation. The AUCs of the model for predicting 1-year OS in the training group, testing and validation group were 0.765 (0.703,0.827), 0.772 (0.697,0.847) and 0.742 (0.601,0.883), predicting 3-year OS were 0.761 (0.725,0.780), 0.742 (0.699,0.785), 0.733 (0.560,0.905) and 5-year OS were 0.742 (0.711,0.773), 0.746 (0.709,0.783), 0.838 (0.670,0.980), respectively. The calibration curves showed the difference between prediction probability of the model and the actual survival was not significant in three cohorts and the decision curve analysis revealed the practice clinical application value. And the prediction value of model was better for young CRC than older CRC patients. CONCLUSION: A nomogram model including LODDS for the prognosis of advanced CRC received neoadjuvant therapy was constructed and verified based on the SEER database and single center practice. The accuracy and potential clinical application value of the model performed well, and the model had better predictive value for EOCRC than LOCRC.
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Neoplasias Colorrectales , Terapia Neoadyuvante , Nomogramas , Programa de VERF , Humanos , Masculino , Femenino , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/terapia , Programa de VERF/estadística & datos numéricos , Terapia Neoadyuvante/estadística & datos numéricos , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/mortalidad , Persona de Mediana Edad , Tasa de Supervivencia , Estudios de Seguimiento , Pronóstico , Anciano , Metástasis Linfática , Estadificación de Neoplasias , Adulto , Estudios RetrospectivosRESUMEN
BACKGROUND: Low false negative rates can be achieved with sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with clinical N1 (cN1) disease. We examined changes in axillary management and oncologic outcomes in BC patients with cN1 disease receiving NAC. METHODS: BC patients with biopsy proven cN1 disease treated with NAC were selected from our institutional cancer registry (2014-2017). Patients were grouped by axillary management, axillary lymph node dissection (ALND), SLNB followed by ALND, or SLNB alone. Univariable and multivariable survival analysis for recurrence-free survival (RFS) and overall survival (OS) were performed. RESULTS: 81 patients met inclusion criteria: 31 (38%) underwent ALND, 25 (31%) SLNB + ALND, and 25 (31%) SLNB alone. A SLN was identified in 45/50 (90%) patients who had SLNB. ALND was performed in 25/50 (50%) patients who had SLNB: 18 for a + SLNB, 5 failed SLNB, and 2 insufficient SLNs. 25 patients had SLNB alone, 17 were SLN- and 8 SLN+. In the SLNB alone group, 23/25 (92%) patients received adjuvant radiation (RT). 20 (25%) patients developed BC recurrence: 14 distant (70%), 3 local (15%), 2 regional + distant (10%), and 1 contralateral (5%). In the SLNB alone group, there was 1 axillary recurrence in a patient with a negative SLNB who did not receive RT. Univariable survival analysis showed significant differences in RFS and OS between axillary management groups, ALND/SLNB + ALND vs. SLNB alone (RFS: p = 0.006, OS: p = 0.021). On multivariable survival analysis, worse RFS and OS were observed in patients with TNBC (RFS: HR 3.77, 95% CI 1.70-11.90, p = 0.023; OS: HR 8.10, 95% CI 1.84-35.60, p = 0.006). CONCLUSIONS: SLNB alone and RT after NAC in BC patients with cN1 disease who have negative SLNs at surgery provides long-term regional disease control. This analysis provides support for the practice of axillary downstaging with NAC and SLNB alone.
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Axila , Neoplasias de la Mama , Escisión del Ganglio Linfático , Terapia Neoadyuvante , Biopsia del Ganglio Linfático Centinela , Humanos , Femenino , Terapia Neoadyuvante/mortalidad , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Escisión del Ganglio Linfático/mortalidad , Tasa de Supervivencia , Estudios de Seguimiento , Pronóstico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Quimioterapia Adyuvante/métodos , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Metástasis LinfáticaRESUMEN
BACKGROUND: Immunotherapy is emerging as a promising option for certain locally advanced and metastatic cutaneous malignancies. However, the role of neoadjuvant immunotherapy (NIO) in Merkel cell carcinoma (MCC) with clinically detected regional lymph node metastasis (CDRLNM) has not been fully elucidated. METHODS: For this study, MCC patients with CDRLNM who underwent surgical excision were selected from the National Cancer Database (NCDB). Those who received NIO were propensity-matched with those who did not, and Kaplan-Meier analysis was used to compare overall survival (OS). RESULTS: Of the 1809 selected patients, 356 (19.7%) received NIO followed by wide excision (n = 352, 98.9%) or amputation (n = 4, 1.1%). The rate of complete pathologic response for the primary tumor (ypT0) was 45.2%. Only 223 patents (63.4%) also underwent lymph node dissection (LND). The complete pathologic nodal response (ypN0) rate for these patients was 17.9%. A pathologic complete response of both the primary tumor and the nodal basin (ypT0 ypN0) was seen in 16 of the 223 patients who underwent both primary tumor surgery and LND. Subsequently, 151 pairs were matched between the NIO and no-NIO groups (including only patients with LND). Kaplan-Meier analysis demonstrated a significant OS improvement with NIO (median not reached vs. 35.0 ± 8.0 months; p = 0.025). The 5-year OS was 57% in the NIO group versus 44% in no-NIO group (p = 0.021). CONCLUSION: The study suggests that NIO in MCC with CDRLNM provides improved OS in addition to promising rates of primary complete response, which could change the profile of surgical resection. This supports ongoing clinical trials exploring the use of NIO in MCC.
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Carcinoma de Células de Merkel , Metástasis Linfática , Terapia Neoadyuvante , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/terapia , Carcinoma de Células de Merkel/patología , Carcinoma de Células de Merkel/cirugía , Terapia Neoadyuvante/mortalidad , Masculino , Femenino , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/mortalidad , Anciano , Tasa de Supervivencia , Estudios de Seguimiento , Pronóstico , Inmunoterapia/métodos , Persona de Mediana Edad , Anciano de 80 o más Años , Estudios Retrospectivos , Escisión del Ganglio LinfáticoRESUMEN
BACKGROUND: In 2023 alone, it's estimated that over 64,000 patients will be diagnosed with PDAC and more than 50,000 patients will die of the disease. Current guidelines recommend neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC, and data is emerging on its role in resectable disease. Neoadjuvant chemotherapy may increase the number of patients able to receive complete chemotherapy regimens, increase the rate of microscopically tumor-free resection (R0) margin, and aide in identifying unfavorable tumor biology. To date, this is the largest study to examine surgical outcomes after long-duration neoadjuvant chemotherapy for PDAC. METHODS: Retrospective analysis of single-institution data. RESULTS: The routine use of long-duration therapy in our study (median cycles: FOLFIRINOX = 10; gemcitabine-based = 7) is unique. The majority (85%) of patients received FOLFIRINOX without radiation therapy; the R0 resection rate was 76%. Median OS was 41 months and did not differ significantly among patients with resectable, borderline-resectable, or locally advanced disease. CONCLUSIONS: This study demonstrates that in patients who undergo surgical resection after receipt of long-duration neoadjuvant FOLFIRINOX therapy alone, survival outcomes are similar regardless of pretreatment resectability status and that favorable surgical outcomes can be attained.
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluorouracilo , Irinotecán , Leucovorina , Terapia Neoadyuvante , Oxaliplatino , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/tratamiento farmacológico , Terapia Neoadyuvante/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Femenino , Estudios Retrospectivos , Leucovorina/administración & dosificación , Irinotecán/administración & dosificación , Fluorouracilo/administración & dosificación , Tasa de Supervivencia , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Anciano , Estudios de Seguimiento , Pronóstico , Pancreatectomía , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/tratamiento farmacológico , AdultoRESUMEN
PURPOSE: This study was designed to investigate the prognostic significance of artificial intelligence (AI)-based quantification of myxoid stroma in patients undergoing esophageal squamous cell carcinoma (ESCC) surgery after neoadjuvant chemotherapy (NAC) and to verify its significance in an independent validation cohort from another hospital. METHODS: We evaluated two datasets of patients with pathological stage II or III ESCC who underwent surgery after NAC. Cohort 1 consisted of 85 patients who underwent R0 surgery for the primary tumor after NAC. Cohort 2, the validation cohort, consisted of 80 patients who received same treatments in another hospital. AI-based myxoid stroma was evaluated in resected specimens, and its area was categorized by using the receiver operating characteristic curve for overall survival (OS) of cohort 1. RESULTS: The F1 scores, which are the degree of agreement between the automatically detected myxoid stroma and manual annotations, were 0.83 and 0.79 for cohorts 1 and 2. The myxoid stroma-high group had a significantly poorer prognosis than the myxoid stroma-low group in terms of OS, disease-specific survival (DSS), and recurrence-free survival (RFS) in cohort 1. Comparable results were observed in cohort 2, where OS, DSS, and RFS were significantly affected by myxoid stroma. Multivariate analysis for RFS revealed that AI-determined myxoid stroma-high was one of the independent prognostic factors in cohort 1 (hazard ratio [HR] 1.97, p = 0.037) and cohort 2 (HR 4.45, p < 0.001). CONCLUSIONS: AI-determined myxoid stroma may be a novel and useful prognostic factor for patients with pathological stage II or III ESCC after NAC.
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Aprendizaje Profundo , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Humanos , Femenino , Terapia Neoadyuvante/mortalidad , Masculino , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/terapia , Persona de Mediana Edad , Tasa de Supervivencia , Pronóstico , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/cirugía , Carcinoma de Células Escamosas de Esófago/terapia , Estudios de Seguimiento , Anciano , Esofagectomía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Quimioterapia Adyuvante , Células del Estroma/patologíaRESUMEN
Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly increasing not only in Western countries but also in East Asia, and it has been attracting the attention of both clinicians and researchers. EGJC has a worse prognosis than gastric cancer (GC) and is characterized by complex lymphatic drainage pathways in the mediastinal and abdominal regions. EGJC was previously treated in the same way as GC or esophageal cancer, but, in recent years, it has been treated as an independent malignant disease, and treatment focusing only on EGJC has been developed. A recent multicenter prospective study revealed the frequency of lymph node metastasis by station and established the optimal extent of lymph node dissection. In perioperative treatment, the combination of multi-drug chemotherapy, radiation therapy, molecular targeted therapy, and immunotherapy is expected to improve the prognosis. In this review, we summarize previous clinical trials and their important evidence on surgical and perioperative treatments for EGJC.
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Neoplasias Esofágicas , Esofagectomía , Unión Esofagogástrica , Humanos , Unión Esofagogástrica/cirugía , Unión Esofagogástrica/patología , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/terapia , Resultado del Tratamiento , Esofagectomía/efectos adversos , Esofagectomía/mortalidad , Gastrectomía/mortalidad , Gastrectomía/efectos adversos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/terapia , Escisión del Ganglio Linfático , Quimioterapia Adyuvante , Metástasis Linfática , Factores de Riesgo , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/mortalidadRESUMEN
BACKGROUND AND OBJECTIVES: Given increased utilization of neoadjuvant therapy (NAT) for gastric adenocarcinoma, practice patterns deviating from standard of care (upfront resection) remain unknown. We sought to identify factors associated with NAT use and survival outcomes among early-stage gastric cancers. METHODS: The National Cancer Database identified patients with early-stage (T1N0M0) gastric cancer (2010-2020). Multivariable logistic regression assessed characteristics associated with NAT utilization compared to upfront surgery. After 1:1 propensity score matching, Kaplan-Meier methods and Cox regression assessed overall survival (OS). RESULTS: Of 6452 patients with early-stage gastric cancer, 626 (9.7%) received NAT. Patients who received NAT were more likely treated at community hospitals, had moderate to poorly differentiated disease, and tumors located in the cardia (all p < 0.05). After propensity score matching, 1,248 patients remained. Median OS for NAT was 37.1 months (IQR 20.2-64.0) versus 45.6 months (IQR 22.5-72.8) for resection (p < 0.001). Treatment with NAT remained independently predictive of worse OS on Cox regression (hazard ratio 1.19; 95% confidence interval 1.05-1.34). CONCLUSIONS: Although patients who received NAT had more aggressive prognostic features, NAT was associated with worse OS despite accounting for this selection bias. These results highlight the importance of adhering to guidelines, regardless of differing disease characteristics, which has significant implications on outcomes.
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Terapia Neoadyuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/terapia , Neoplasias Gástricas/cirugía , Femenino , Masculino , Terapia Neoadyuvante/mortalidad , Persona de Mediana Edad , Anciano , Tasa de Supervivencia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/terapia , Adenocarcinoma/cirugía , Gastrectomía/mortalidad , Estadificación de Neoplasias , Quimioterapia Adyuvante/mortalidad , Pronóstico , Estudios Retrospectivos , Estudios de Seguimiento , Puntaje de PropensiónRESUMEN
PURPOSE: For operable triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), clinical prognostication and postoperative decision-making relies exclusively on whether a pathologic complete response (pCR) is achieved or not. We evaluated whether extent of disease at presentation further influenced overall survival (OS) among patients with pCR or with residual disease (RD) following NAC. METHODS: Patients with stage I-III TNBC who underwent NAC were identified from the National Cancer Database from 2010 to 2019. Overall survival was assessed by disease extent using the Kaplan-Meier method and Cox proportional hazards regression for univariate and multivariable analysis. RESULTS: A total of 35,598 patients met inclusion criteria, and 11,967 achieved pCR. Ten-year OS was 88.5% and varied by cT and cN category at presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (90.9%) and was worst in those with cT3-4, cN2-3 disease (72.0%). A total of 23,631 patients had RD. Ten-year OS was 60.1% and varied by cT and cN category at presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (73.0%) and was worst in those with cT3-4, cN2-3 disease (36.3%). Notably, OS was significantly poorer for patients with cT3-4, cN2-3 disease at diagnosis and pCR versus those with cT1-2 cN0 and RD (aHR 1.30, 95% confidence interval 1.03-1.63, p = 0.03). CONCLUSIONS: Among patients with TNBC, extent of disease at presentation was prognostic for OS independently of response to NAC. Patients with advanced stage at presentation had poorer OS even in the context of pCR. Further investigation is needed to evaluate whether additional adjuvant therapy strategies should be considered for these patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/mortalidad , Femenino , Terapia Neoadyuvante/mortalidad , Persona de Mediana Edad , Tasa de Supervivencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Seguimiento , Pronóstico , Anciano , Quimioterapia Adyuvante , Adulto , Estudios Retrospectivos , Neoplasia ResidualRESUMEN
BACKGROUND: Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC. METHODS: A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022. Multivariable regression analysis was performed to assess risk factors associated with ROMD. Kaplan-Meier curves with log-rank analyses were generated to estimate time-to-event end points. RESULTS: The study enrolled 366 patients. Upfront and borderline resectable anatomic staging comprised 80% of the cohort, whereas 20% had locally advanced disease. The most common NAC regimen was FOLFIRINOX (n = 274, 75%). For 55 patients (15%) who harbored ROMD, the most common site was liver-only metastases (n = 33, 60%). The independent risk factors for ROMD were increasing CA19-9 levels during NAC (odds ratio [OR], 7.01; confidence interval [CI], 1.97-24.96; p = 0.008), indeterminate liver lesions (OR, 2.19; CI, 1.09-4.39; p = 0.028), and enlarged para-aortic lymph nodes (OR, 6.87; CI, 2.07-22.74; p = 0.002) on preoperative cross-sectional imaging. Receipt of palliative chemotherapy (p < 0.001) and eventual formal pancreatectomy (p = 0.04) were associated with survival benefit in the log-rank analysis. The median overall survival (OS) of the patients with ROMD was nearly 15 months from the initial diagnosis, with radiologic evidence of metastases occurring after a median of 2 months. CONCLUSIONS: Radiologic occult metastatic disease remains a clinical challenge associated with poor outcomes for patients who have PDAC treated with multi-agent NAC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático , Terapia Neoadyuvante , Pancreatectomía , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Masculino , Femenino , Terapia Neoadyuvante/mortalidad , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Factores de Riesgo , Anciano , Tasa de Supervivencia , Carcinoma Ductal Pancreático/secundario , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/mortalidad , Estudios de Seguimiento , Pronóstico , Fluorouracilo/administración & dosificación , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Oxaliplatino/administración & dosificación , Leucovorina/administración & dosificación , Adulto , Estudios Prospectivos , Irinotecán/administración & dosificación , Metástasis LinfáticaRESUMEN
BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NAC) is becoming favored for all pancreatic adenocarcinoma (PDAC). Patients with seemingly resectable disease infrequently still display vascular involvement intraoperatively. Outcomes following NAC versus upfront surgery in patients undergoing pancreaticoduodenectomy (PD) with vascular resection are unknown. METHODS: We performed a retrospective cohort study of PDAC patients who underwent PD with vascular resection between January 1, 2013, to December 31, 2020, within a single academic center. Clinicopathologic characteristics and disease-free survival (DFS) were compared between NAC versus upfront surgery cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. RESULTS: Eighty-one patients who underwent PD with vascular resection for PDAC were included. Forty-six patients (56%) received NAC. The NAC cohort more often had pathologic N0 status (47.8% vs. 8.6%, p < 0.001), had decreased vascular invasion (11% vs. 40%, p = 0.002), and completed chemotherapy (80% vs. 40%, p < 0.01). The NAC cohort demonstrated improved DFS (40.5 vs. 14.3 months, p = 0.007). In multivariable analysis, NAC remained independently associated with increased DFS (HR = 0.48, p = 0.02). CONCLUSIONS: NAC was associated with improved clinicopathologic outcomes and DFS in PD with vascular resection. These findings demonstrate the advantage of NAC in PDAC patients undergoing PD with vascular resection.
Asunto(s)
Terapia Neoadyuvante , Neoplasias Pancreáticas , Pancreaticoduodenectomía , Humanos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Femenino , Masculino , Estudios Retrospectivos , Terapia Neoadyuvante/mortalidad , Anciano , Persona de Mediana Edad , Tasa de Supervivencia , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Estudios de Seguimiento , Procedimientos Quirúrgicos Vasculares/mortalidad , Procedimientos Quirúrgicos Vasculares/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , PronósticoRESUMEN
BACKGROUND: The benefit of adjuvant therapy (AT) remains unclear in pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and surgical resection. METHODS: The 2019 National Cancer Database was queried for patients with non-metastatic PDAC who received NAT followed by pancreaticoduodenectomy. Only patients with data regarding receipt of AT were included. Patients were classified if they had nodal down-staging specifically, or any downstaging (Tumor, Nodal, or overall). Propensity score matching (PSM) adjusted for pretreatment covariate imbalance between groups. The weighted Kaplan-Meier method and log-rank test were used to estimate the cumulative survival. RESULTS: After exclusion criteria and PSM, a total of 2784 patients remained; 1689 (60.7%) received AT and 1095 (39.3%) did not receive AT. Among all, those with additional AT had a significantly improved overall survival (OS) (p < 0.001). Upon evaluation of patients without downstaging after NAT, those who received AT had improved OS (no nodal downstaging or any downstaging; p = 0.002; p = 0.001). When evaluating patients with downstaging after NAT, those receiving AT did not have improved OS (nodal downstaging or any downstaging: p = 0.352; p = 0.99). CONCLUSION: Response to NAT appears to correlate with the benefit of AT following pancreaticoduodenectomy; patients who have a favorable response to NAT may not benefit from AT.
Asunto(s)
Carcinoma Ductal Pancreático , Terapia Neoadyuvante , Neoplasias Pancreáticas , Pancreaticoduodenectomía , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/tratamiento farmacológico , Masculino , Femenino , Terapia Neoadyuvante/mortalidad , Quimioterapia Adyuvante , Anciano , Persona de Mediana Edad , Tasa de Supervivencia , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adenocarcinoma/tratamiento farmacológico , Estudios Retrospectivos , Estudios de Seguimiento , PronósticoRESUMEN
BACKGROUND: According to current international guidelines, stage cT2N0M0 gastric adenocarcinoma warrants preoperative chemotherapy followed by surgery. However, upfront surgery is often preferred in clinical practice, depending on patient clinical status and local treatment preferences. OBJECTIVE: The aim of the present study was to assess the impact of neoadjuvant chemotherapy in overall survival (OS) and disease-free survival (DFS) of cT2N0M0 patients. METHODS: A retrospective analysis was performed among 32 centers, including gastric adenocarcinoma patients operated between January 2007 and December 2017. Patients with cT2N0M0 stage were divided into upfront surgery (S) and neoadjuvant chemotherapy followed by surgery (CS) groups. Inverse probability of treatment weighting (IPTW) was used to compensate for baseline differences between the groups. RESULTS: Among the 202 patients diagnosed with cT2N0M0 stage, 68 (33.7%) were in the CS group and 134 (66.3%) were in the S group. CS patients were younger (mean age 62.7 ± 12.8 vs. 69.8 ± 12.1 years for S patients; p < 0.001) and had a better health status (World Health Organization performance status = 0 in 60.3% of CS patients vs. 34.5% of S patients; p = 0.006). During follow-up, recurrence occurred in 27.2% and 19.6% of CS and S patients, respectively, after IPTW (p = 0.32). Five-year OS was similar between CS and S patients (78.9% vs. 68.3%; p = 0.42), as was 5-year DFS (70.4% vs. 68.5%; p = 0.96). Neoadjuvant chemotherapy was associated with neither OS nor DFS in multivariable analysis after IPTW. CONCLUSIONS: Patients with cT2N0M0 gastric adenocarcinoma did not present a survival or recurrence benefit if treated with perioperative chemotherapy followed by surgery as opposed to surgery alone.
Asunto(s)
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadyuvante , Puntaje de Propensión , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Masculino , Femenino , Terapia Neoadyuvante/mortalidad , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Adenocarcinoma/terapia , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Tasa de Supervivencia , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/mortalidad , Pronóstico , Estadificación de Neoplasias , Gastrectomía/mortalidadRESUMEN
BACKGROUND: Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting. METHODS: This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45-50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup. RESULTS: Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37-0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44-0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors. CONCLUSION: After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors.
Asunto(s)
Adenocarcinoma , Terapia Neoadyuvante , Pancreatectomía , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/mortalidad , Masculino , Femenino , Terapia Neoadyuvante/mortalidad , Anciano , Persona de Mediana Edad , Tasa de Supervivencia , Quimioterapia Adyuvante , Estudios de Seguimiento , Adenocarcinoma/terapia , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pronóstico , Radioterapia Adyuvante , Estudios RetrospectivosRESUMEN
BACKGROUND: Novel neoadjuvant chemoimmunotherapy treatments are being investigated for locally advanced non-small-cell lung cancer (NSCLC), but real-world outcomes for neoadjuvant treatments are poorly understood. This study examined neoadjuvant treatment patterns, real-world event-free survival (rwEFS) and overall survival (OS) in patients with resected, stage II-III NSCLC in the United States (US). METHODS: This retrospective study identified patients in the SEER-Medicare database (2007-2019) with newly diagnosed stage II, IIIA, and IIIB (N2) NSCLC (AJCC 8th edition) treated with neoadjuvant chemo/chemoradiotherapy and resection (index date: neoadjuvant therapy initiation). Neoadjuvant treatment regimens were described. rwEFS (time from index to first recurrence or death, whichever occurred first) and OS (time from index to death) were summarized by Kaplan-Meier analysis for overall population, by disease stage at diagnosis, and by neoadjuvant treatment modality. RESULTS: 221 patients (stage II, N=70; stage III, N=151) met eligibility criteria. The median follow-up from index was 32.7 months. All patients received neoadjuvant chemotherapy (51%) or chemoradiotherapy (49%) prior to surgery; 97% of patients received platinum-based regimens, among which carboplatin+paclitaxel was the most frequent (45%). In all patients, median rwEFS was 17.6 months and 5-year rwEFS was 20.9%; median OS was 48.5 months and 5-year OS was 44.9%. 71% of patients had disease recurrence during follow-up; among them, 28% developed locoregional recurrence as the first recurrence event. CONCLUSIONS: Patients with resected, stage II-III NSCLC who received neoadjuvant chemo/chemoradiotherapy have high rates of disease recurrence and poor survival outcomes, highlighting need for more effective treatments to improve survival rates.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Terapia Neoadyuvante , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidad , Terapia Neoadyuvante/mortalidad , Terapia Neoadyuvante/métodos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Tasa de Supervivencia , Estadificación de Neoplasias , Estados Unidos , Neumonectomía , Resultado del Tratamiento , Programa de VERF , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: A pathological complete response (pCR) following chemoradiation (CRT) or short-course radiotherapy (scRT) leads to a favourable prognosis in patients with rectal cancer. Total neo-adjuvant therapy (TNT) doubles the pCR rate, but it is unknown whether oncological outcomes remain favourable and whether the same characteristics are associated with pCR as after CRT. METHODS: Comparison between patients with pCR in the RAPIDO trial in the experimental [EXP] (scRT, chemotherapy, surgery, as TNT) and standard-of-care treatment [STD] (CRT, surgery, postoperative chemotherapy depending on hospital policy) groups. Primary and secondary outcomes were time-to-recurrence (TTR), overall survival (OS) and association between patient, tumour, and treatment characteristics and pCR. RESULTS: Among patients with a resection within six months after preoperative treatment, 120/423 (28%) [EXP] and 57/398 (14%) [STD] achieved a pCR. Following pCR, 5-year cumulative TTR and OS rates in the EXP and STD arms were 8% vs. 7% (hazard ratio 1.04, 95%CI 0.32-3.38) and 94% vs. 93% (hazard ratio 1.41, 95%CI 0.51-3.92), respectively. Besides the EXP treatment (odds ratio 2.70, 95%CI 1.83-3.97), pre-treatment carcinoembryonic antigen (CEA) <5, pre-treatment tumour size <40 mm and cT2 were associated with pCR. Distance from the anal verge was the only characteristic with a statistically significant difference in association with pCR between the EXP and STD treatment (Pinteraction=0.042). pCR rates did not increase with prolonged treatment time. CONCLUSIONS: The doubled pCR rate of TNT compared to CRT results in similar oncological outcomes. Characteristics associated with pCR are the EXP treatment, normal CEA, and small tumour size.