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1.
Pancreatology ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32222341

RESUMO

BACKGROUND/OBJECTIVES: We sought to identify the reliability of AJCC clinical staging was in comparison to pathologic staging in surgically resected patients with pancreatic cancer. METHODS: We used the National Cancer Database Pancreas from 2004 to 2016 and evaluated patients who underwent resection for PDAC with all documented components of clinical and pathologic stage. We first evaluated the distribution of overall clinical stage and pathologic stage and then evaluated for stage migration by assessing the number of patients who shifted from a clinical stage group to a respective pathologic stage group. To further characterize the migratory pattern, we assessed the distribution of clinical and pathologic T-stage and N-stage. RESULTS: In our cohort of 28,338 patients who underwent resection for PDAC, AJCC clinical staging did not reliably predict pathologic stage. Stage migration after resection was responsible for discrepancies between the distribution of overall clinical stage and pathologic stage. The predominant migration was from patients with clinical stage I disease to pathologic stage II disease. Most patients with clinical T1 and T2 disease were upstaged to pathologic T3 disease and over half of patients with clinical N0 disease were upstaged to pathologic N1 disease after resection. DISCUSSION: Clinical staging appears to overrepresent early T1, T2, and N0 disease, and underrepresent T3 and N1 disease.

2.
Am J Surg ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32107013

RESUMO

OBJECTIVE: We hypothesized that differences in resection rates of colorectal liver metastases exist based on socioeconomic status (SES) inequalities. METHODS: The NCDB was utilized to study patients of different median household income diagnosed with colon adenocarcinoma from 2010 to 2015. RESULTS: A total of 21,258 patients met inclusion criteria, of whom 3,587 (16.9%) underwent metastasectomy. Patients of the highest income quartile were more likely to undergo metastasectomy compared to the lowest quartile (OR 1.20, CI 1.07-1.37, p = 0.003). Overall, patients in the highest income quartile had a median OS of 17.1 months compared with 13.0 months for the lowest quartile (HR 0.85, CI 0.81-0.90, p < 0.001). While metastasectomy was associated with improved OS across all groups, the disparity by income quartile widened (29.2 vs. 22.0 months, respectively; HR 0.51, CI 0.49-0.54, p < 0.001). CONCLUSION: Higher income patients were more likely to undergo metastasectomy compared with lower income patients and were associated with longer OS.

3.
Clin Cancer Res ; 26(8): 1877-1885, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941831

RESUMO

PURPOSE: ctDNA offers a promising, noninvasive approach to monitor therapeutic efficacy in real-time. We explored whether the quantitative percent change in ctDNA early after therapy initiation can predict treatment response and progression-free survival (PFS) in patients with metastatic gastrointestinal cancer. EXPERIMENTAL DESIGN: A total of 138 patients with metastatic gastrointestinal cancers and tumor profiling by next-generation sequencing had serial blood draws pretreatment and at scheduled intervals during therapy. ctDNA was assessed using individualized droplet digital PCR measuring the mutant allele fraction in plasma of mutations identified in tumor biopsies. ctDNA changes were correlated with tumor markers and radiographic response. RESULTS: A total of 138 patients enrolled. A total of 101 patients were evaluable for ctDNA and 68 for tumor markers at 4 weeks. Percent change of ctDNA by 4 weeks predicted partial response (PR, P < 0.0001) and clinical benefit [CB: PR and stable disease (SD), P < 0.0001]. ctDNA decreased by 98% (median) and >30% for all PR patients. ctDNA change at 8 weeks, but not 2 weeks, also predicted CB (P < 0.0001). Four-week change in tumor markers also predicted response (P = 0.0026) and CB (P = 0.022). However, at a clinically relevant specificity threshold of 90%, 4-week ctDNA change more effectively predicted CB versus tumor markers, with a sensitivity of 60% versus 24%, respectively (P = 0.0109). Patients whose 4-week ctDNA decreased beyond this threshold (≥30% decrease) had a median PFS of 175 days versus 59.5 days (HR, 3.29; 95% CI, 1.55-7.00; P < 0.0001). CONCLUSIONS: Serial ctDNA monitoring may provide early indication of response to systemic therapy in patients with metastatic gastrointestinal cancer prior to radiographic assessments and may outperform standard tumor markers, warranting further evaluation.

4.
Surg Endosc ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31844971

RESUMO

BACKGROUND: While the ACOSOG and ALaCaRT trials found that laparoscopic resections for rectal cancer failed to demonstrate non-inferiority of pathologic outcomes when compared with open resections, the COLOR II and COREAN studies demonstrated non-inferiority of clinical outcomes, leading to uncertainty regarding the value of minimally invasive (MIS) techniques in rectal cancer surgery. We analyzed differences in pathologic and clinical outcomes between open versus MIS resections for rectal cancer. METHODS: We identified patients who underwent resection for stage II or III rectal adenocarcinoma from the National Cancer Database (2010-2015). Surgical approach was categorized as open or MIS (laparoscopic or robotic). Logistic regression and Cox proportional hazard analysis were used to assess differences in outcomes and survival. Analysis was performed in an intention-to-treat fashion. RESULTS: A total of 31,190 patients who underwent rectal adenocarcinoma resection were identified, of whom 52.8% underwent open resection and 47.2% underwent MIS resection (31.0% laparoscopic, 16.2% robotic). After adjustment for patient, tumor, and institutional characteristics, MIS approaches were associated with significantly decreased risk of positive circumferential resection margins (OR 0.82, 95% CI 0.72-0.94), increased likelihood of harvesting ≥ 12 lymph nodes (OR 1.12, 95% CI 1.04-1.21), shorter length of stay (OR 0.57, 95% CI 0.53-0.62), and improved overall survival (HR 0.90, 95% CI 0.83-0.98). CONCLUSIONS: MIS approaches to rectal cancer resection were associated with improved pathologic and clinical outcomes when compared to the open approach. In this nationwide, facility-based sample of cancer cases in the United States, our data suggest superiority of MIS techniques for rectal cancer treatment.

5.
Ann Surg Oncol ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31758284

RESUMO

OBJECTIVE: To define short-term and long-term outcomes of IORT for the management of BR/LA PDAC in the era of modern neoadjuvant therapy (NAT). BACKGROUND: In the era of neoadjuvant FOLFIRINOX, many patients with borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC) become candidates for surgical exploration with curative intent. IORT may be used to consolidate treatment for successfully resected patients with close or positive margins or administered in unresectable patients without distant metastases. METHODS: A retrospective review of 158 patients who received IORT in the setting of biopsy-proven BR/LA PDAC following NAT between 2008 and 2017 was performed. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS) of FOLFIRINOX treated patients. RESULTS: Most patients (83%) received FOLFIRINOX, and 95% underwent consolidative chemoradiation therapy (50.4-58.8 Gy). Among FOLFIRINOX-treated patients, 86 underwent combined surgical resection with IORT (10 Gy) while 46 received IORT alone (15-20 Gy). The median PFS and OS were 21.5 and 46.7 months for patients who underwent resection with IORT and 14.7 and 23 months in the IORT alone group. Local progression occurred in 12.7% of patients after resection with IORT, and in 15% of patients who received IORT alone. Major complications occurred in 13% of patients following resection, and 5% of patients after IORT alone, including one death. CONCLUSION: IORT combined with surgical resection appears to be associated with improved survival and minimal morbidity in patients with positive or close margins. IORT is also associated with improved survival in patients with unresectable, non-metastatic disease.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31705172

RESUMO

PURPOSE: Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis with surgical resection offering the best chance for long-term survival and potential cure. However, in up to 36% of patients who undergo surgery, more extensive disease is found at time of operation requiring cancellation of surgery. PET/MR is a novel hybrid technology that might improve local and whole-body staging in ICC patients, potentially influencing clinical management. This study was aimed to investigate the possible management implications of PET/MR, relative to conventional imaging, in patients affected by untreated intrahepatic cholangiocarcinoma. METHODS: Retrospective review of the clinicopathologic features of 37 patients with iCCC, who underwent PET/MR between September 2015 and August 2018, was performed to investigate the management implications that PET/MR had exerted on the affected patients, relative to conventional imaging. RESULTS: Of the 37 patients enrolled, median age 63.5 years, 20 (54%) were female. The same day PET/CT was performed in 26 patients. All patients were iCCC-treatment-naïve. Conventional imaging obtained as part of routine clinical care demonstrated early-stage resectable disease for 15 patients and advanced stage disease beyond the scope of surgical resection for 22. PET/MR modified the clinical management of 11/37 (29.7%) patients: for 5 patients (13.5%), the operation was cancelled due to identification of additional disease, while 4 "inoperable" patients (10.8%) underwent an operation. An additional 2 patients (5.4%) had a significant change in their operative plan based on PET/MR. CONCLUSIONS: When compared with standard imaging, PET/MR significantly influenced the treatment plan in 29.7% of patients with iCCC. TRIAL REGISTRATION: 2018P001334.

8.
Nat Med ; 25(9): 1415-1421, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501609

RESUMO

During cancer therapy, tumor heterogeneity can drive the evolution of multiple tumor subclones harboring unique resistance mechanisms in an individual patient1-3. Previous case reports and small case series have suggested that liquid biopsy (specifically, cell-free DNA (cfDNA)) may better capture the heterogeneity of acquired resistance4-8. However, the effectiveness of cfDNA versus standard single-lesion tumor biopsies has not been directly compared in larger-scale prospective cohorts of patients following progression on targeted therapy. Here, in a prospective cohort of 42 patients with molecularly defined gastrointestinal cancers and acquired resistance to targeted therapy, direct comparison of postprogression cfDNA versus tumor biopsy revealed that cfDNA more frequently identified clinically relevant resistance alterations and multiple resistance mechanisms, detecting resistance alterations not found in the matched tumor biopsy in 78% of cases. Whole-exome sequencing of serial cfDNA, tumor biopsies and rapid autopsy specimens elucidated substantial geographic and evolutionary differences across lesions. Our data suggest that acquired resistance is frequently characterized by profound tumor heterogeneity, and that the emergence of multiple resistance alterations in an individual patient may represent the 'rule' rather than the 'exception'. These findings have profound therapeutic implications and highlight the potential advantages of cfDNA over tissue biopsy in the setting of acquired resistance.


Assuntos
Ácidos Nucleicos Livres/sangue , DNA de Neoplasias/sangue , Neoplasias Gastrointestinais/sangue , Biópsia Líquida , Autopsia , Ácidos Nucleicos Livres/genética , Estudos de Coortes , DNA de Neoplasias/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Heterogeneidade Genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Sequenciamento Completo do Exoma
9.
Ann Surg Oncol ; 26(12): 4091-4099, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31368018

RESUMO

BACKGROUND: Many studies have demonstrated associations between surgical resections at academic centers and improved outcomes, particularly for complex operations. However, few studies have examined this relationship in intrahepatic cholangiocarcinoma (ICC). The hypothesis of this study was that facility type is associated with improved postoperative outcomes and survival for patients with ICC who undergo resection. METHODS: Patients with stages 1 to 3 ICC who underwent hepatectomy were identified using the National Cancer Database (NCDB) (2004-2014). Facilities were categorized as academic or community centers per Commission on Cancer designations. High-volume hospitals were those that performed 11 or more hepatectomies per year. Multilevel logistic mixed-effects models to identify predictors of outcomes and parametric survival-time models were used to determine overall survival (OS). RESULTS: The study identified 2256 patients. Of these patients, 423 (18.8%) were treated at community centers, and 1833 (81.3%) were treated at academic centers. Nearly all high-volume centers were academic facilities (98.5% academic vs. 1.5% community centers), whereas low-volume centers were mixed (65.5% academic vs. 34.5% community centers) (p < 0.001). Surgery performed at an academic center was an independent predictor of decreased positive margins (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.51-0.98; p = 0.04), a lower 90-day mortality rate (OR, 0.62; 95% CI, 0.39-0.97; p = 0.03), and improved OS (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96; p = 0.02). Facility hepatectomy volume was not independently associated with any short- or long-term outcomes. CONCLUSIONS: Treatment at an academic center is associated with fewer positive resection margins, a decreased 90-day mortality rate, and improved OS for patients who undergo ICC resection. Facility surgical volume was not shown to be significantly associated with any postoperative outcomes after adjustment for patient and disease characteristics.

10.
Eur J Nucl Med Mol Imaging ; 46(11): 2260-2269, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31359108

RESUMO

PURPOSE: The primary aim of the present study was to evaluate if PET/MR induced management changes versus standard of care imaging (SCI) in treated colorectal cancer patients. The secondary aim was to assess the staging performance of PET/MR and of SCI versus the final oncologic stage. METHODS: Treated CRC patients who underwent PET/MR with 18F-FDG and SCI between January 2016 and October 2018 were enrolled in this retrospective study. Their medical records were evaluated to ascertain if PET/MR had impacted on their clinical management versus SCI. The final oncologic stage, as reported in the electronic medical record, was considered the true stage of disease. RESULTS: A total of 39 patients who underwent 42 PET/MR studies were included, mean age 56.7 years (range 39-75 years), 26 males, and 13 females. PET/MR changed clinical management 15/42 times (35.7%, standard error ± 7.4%); these 15 changes in management were due to upstaging in 9/42 (21.5%) and downstaging in 6/42 (14.2%). The differences in management prompted by SCI versus PET/MR were statistically significant, and PET/MR outperformed SCI (P value < 0.001; odds ratio = 2.8). In relation to the secondary outcome, PET/MR outperformed the SCI in accuracy of oncologic staging (P value = 0.016; odds ratio = 4.6). CONCLUSIONS: PET/MR is a promising imaging tool in the evaluation of treated CRC and might change the management in these patients. However, multicenter prospective studies with larger patient samples are required in order to confirm these preliminary results.

11.
Am J Clin Oncol ; 42(7): 564-572, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31166209

RESUMO

OBJECTIVES: Most localized hepatocellular carcinoma (HCC) patients are not surgically operable or transplantation candidates, increasing the role for nonsurgical therapies. Ablative external beam radiotherapy (XRT) and transarterial radioembolization (TARE) are emerging radiotherapeutic treatments for localized HCC. We sought to evaluate their utilization and efficacy in a large nationwide cohort. MATERIALS AND METHODS: We conducted an observational study of 2685 patients from the National Cancer Database (NCDB) diagnosed with American Joint Committee on Cancer 7th edition clinical stage I to III HCC between 2004 and 2015, treated with definitive-intent XRT delivered in 1 to 15 fractions or TARE. The association between treatment modality (XRT vs. TARE) and overall survival (OS) was defined using propensity score-weighted Kaplan-Meier estimators and propensity score-weighted multivariable Cox regressions. RESULTS: Among 2685 patients, 2007 (74.7%) received TARE and 678 (25.3%) received XRT, with increasing usage for both from 2004 to 2015 (Ptrend<0.001), but with overall greater uptake and absolute usage of TARE. Patients who received TARE were more likely to have elevated alpha fetoprotein and more advanced stage (P<0.05 for all). Median OS was 14.5 months for the entire cohort. XRT was associated with an OS advantage compared with TARE on propensity score-unadjusted analysis (adjusted hazard ratio [AHR], 0.89; 95% confidence interval, 0.79-1.00; P=0.049), but not on propensity score-adjusted analysis (AHR, 0.99; 95% confidence interval, 0.86-1.13; P=0.829). CONCLUSIONS: Our study demonstrates that while both XRT and TARE usage have increased with time, there was greater uptake and absolute use of TARE. We found no difference in survival between XRT and TARE after propensity score adjustment.

12.
JAMA Oncol ; 5(7): 1020-1027, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31145418

RESUMO

Importance: Patients with locally advanced pancreatic cancer have historically poor outcomes. Evaluation of a total neoadjuvant approach is warranted. Objective: To evaluate the margin-negative (R0) resection rate of neoadjuvant FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) and losartan followed by chemoradiotherapy for locally advanced pancreatic cancer. Design, Setting, and Participants: A single-arm phase 2 clinical trial was conducted at a large academic hospital from August 22, 2013, to May 22, 2018, among 49 patients with previously untreated locally advanced unresectable pancreatic cancer as determined by multidisciplinary review. Patients had Eastern Cooperative Oncology Group performance status 0 or 1 and adequate hematologic, renal, and hepatic function. Median follow-up for the analysis was 17.1 months (range, 5.0-53.7) among 27 patients still alive at study completion. Interventions: Patients received FOLFIRINOX and losartan for 8 cycles. Patients with radiographically resectable tumor after chemotherapy received short-course chemoradiotherapy (5 GyE × 5 with protons) with capecitabine. Patients with persistent vascular involvement received long-course chemoradiotherapy (50.4 Gy with a vascular boost to 58.8 Gy) with fluorouracil or capecitabine. Main Outcomes and Measures: R0 resection rate. Results: Of the 49 patients (26 women and 23 men; median age 63 years [range, 42-78 years]), 39 completed 8 cycles of FOLFIRINOX and losartan; 10 patients had fewer than 8 cycles due to progression (5 patients), losartan intolerance (3 patients), and toxicity (2 patients). Seven patients (16%) had short-course chemoradiotherapy while 38 (84%) had long-course chemoradiotherapy. Forty-two (86%) patients underwent attempted surgery, with R0 resection achieved in 34 of 49 patients (69%; 95% CI, 55%-82%). Overall median progression-free survival was 17.5 months (95% CI: 13.9-22.7) and median overall survival was 31.4 months (95% CI, 18.1-38.5). Among patients who underwent resection, median progression-free survival was 21.3 months (95% CI, 16.6-28.2), and median overall survival was 33.0 months (95% CI, 31.4 to not reached). Conclusions and Relevance: Total neoadjuvant therapy with FOLFIRINOX, losartan, and chemoradiotherapy provides downstaging of locally advanced pancreatic ductal adenocarcinoma and is associated with an R0 resection rate of 61%. Trial Registration: ClinicalTrials.gov identifier: NCT01821729.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia , Losartan/administração & dosagem , Terapia Neoadjuvante , Neoplasias Pancreáticas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Losartan/efeitos adversos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Neoplasias Pancreáticas/patologia , Resultado do Tratamento
13.
Int J Radiat Oncol Biol Phys ; 105(1): 90-95, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31128146

RESUMO

PURPOSE: Definitive chemoradiation with concurrent 5-fluorouracil (5-FU)/mitomycin C (MMC) is an effective treatment for localized anal cancer, but it is associated with significant acute long-term treatment-related toxicity. Pencil beam scanning proton beam (PBS-PT) radiation therapy may potentially reduce this toxicity. This is a multi-institutional pilot study evaluating the feasibility of definitive concurrent chemoradiation with PBS-PT in combination with 5-FU and MMC for carcinoma of the anal canal. METHODS AND MATERIALS: Patients were enrolled on a National Cancer Institute-sponsored, prospective, multi-institutional, single-arm pilot study (NCT01858025). Key eligibility criteria included Eastern Cooperative Oncology Group 0 to 2, age ≥18 years, histologically confirmed invasive squamous cell carcinoma of the anal canal, and clinically staged T1-4, N0-3 disease. Patients were treated with PBS-PT per Radiation Therapy Oncology Group 0529 dose schema and concurrent 5-FU/MMC on day 1 and 29. The primary objective of this study was to determine feasibility of PBS-PT with concurrent 5-FU/MMC, defined as grade 3+ dermatologic toxicity less than 48% (reported grade 3+ dermatologic toxicity from Radiation Therapy Oncology Group 98-11). Secondary objectives were to determine the rates of overall grade 3+ toxicities, clinical complete response rate, and disease outcomes. RESULTS: Between February 2014 and April 2017, we enrolled 25 patients into our study, all of whom were analyzed. Twenty-three patients (92%) completed treatment per protocol, and 2 patients died on treatment. Median time to completion of treatment was 42 days (range, 38-49). The grade 3+ radiation dermatitis rate was 24%. Median follow-up is 27 months (range, 21-50) among the 21 patients still alive. The overall rate of clinical complete response was 88%. The 2-year local failure, colostomy-free survival, progression-free survival, and overall survival are 12%, 72%, 80%, and 84%, respectively. CONCLUSIONS: In our prospective, multi-institutional pilot study of PBS-PT with concurrent 5-FU/MMC, PBS-PT was found to be feasible. A phase 2 study of proton beam radiation therapy is currently underway.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Terapia com Prótons/métodos , Radiodermatite/patologia , Idoso , Canal Anal , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Colostomia , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Projetos Piloto , Intervalo Livre de Progressão , Estudos Prospectivos , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica
14.
Cancer ; 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30913304

RESUMO

BACKGROUND: Antiangiogenic therapy is a proven therapeutic modality for refractory gastric and gastroesophageal junction adenocarcinoma. This trial assessed whether the addition of a high affinity angiogenesis inhibitor, ziv-aflibercept, could improve the efficacy of first-line mFOLFOX6 (oxaliplatin, leucovorin, and bolus plus infusional 5- fluorouracil) in metastatic esophagogastric adenocarcinoma. METHODS: Patients with treatment-naive metastatic esophagogastric adenocarcinoma were randomly assigned (in a 2:1 ratio) in a multicenter, placebo-controlled, double-blind trial to receive first-line mFOLFOX6 with or without ziv-aflibercept (4 mg/kg) every 2 weeks. The primary endpoint was 6-month progression-free survival (PFS). RESULTS: Sixty-four patients were randomized to receive mFOLFOX6 and ziv-aflibercept (43 patients) or mFOLFOX6 and a placebo (21 patients). There was no difference in the PFS, overall survival, or response rate. Patients treated with mFOLFOX6/ziv-aflibercept tended to be more likely to discontinue study treatment for reasons other than progressive disease (P = .06). The relative dose intensity of oxaliplatin and 5-fluorouracil was lower in the mFOLFOX6/ziv-aflibercept arm during the first 12 and 24 weeks of the trial. There were 2 treatment-related deaths due to cerebral hemorrhage and bowel perforation in the mFOLFOX6/ziv-aflibercept cohort. CONCLUSIONS: Ziv-aflibercept did not increase the anti-tumor activity of first-line mFOLFOX6 in metastatic esophagogastric cancer, potentially because of decreased dose intensity of FOLFOX. Further evaluation of ziv-aflibercept in unselected, chemotherapy-naive patients with metastatic esophagogastric adenocarcinoma is not warranted.

15.
Am J Surg ; 218(5): 959-966, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30871788

RESUMO

BACKGROUND: Administration of adjuvant therapy (AT) in patients with intrahepatic cholangiocarcinoma (ICC) remains inconsistent despite recent trial data. This study investigates predictors of receipt of AT and survival. METHODS: Patients with ICC who underwent resection were identified using the NCDB (2004-2014). Logistic regression and Cox analysis were used to determine predictors of AT and survival, respectively. "High-risk" was defined as positive margins/nodes or stage III/IVa disease. RESULTS: 2813 patients were identified, of whom 42.3% received AT. Patients with positive margins, positive nodes, and higher stage tended to receive AT (p < 0.001). Black patients and patients with Medicare/Medicaid were less likely to receive AT. In "high-risk" patients, AT was associated with lower mortality (HR 0.66, 95% CI 0.56-0.78, p < 0.001). CONCLUSIONS: AT after ICC resection is associated with improved survival in patients with positive margins, positive nodes, and stage III/IVa disease. There are disparities and regional variations in the receipt of AT.

16.
Am J Surg ; 218(1): 157-163, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30635211

RESUMO

BACKGROUND: The most appropriate treatment for early-stage hepatocellular carcinoma (HCC) remains unclear. This study compared the association of resection versus ablation with overall survival (OS) in patients with early-stage HCC. METHODS: Using the National Cancer Database (NCDB), patients diagnosed with stage I/II HCC between 2004 and 2014 were identified. Cox analysis was used to determine predictors of OS. RESULTS: We identified 53,161 patients, of whom 15.9% underwent ablation and 14.5% underwent resection. Patients with fewer comorbidities, larger tumors, and private insurance were more likely to undergo resection. Resection was associated with significantly improved OS compared to ablation (HR 0.58, 95% CI 0.54-0.61, p < 0.001), at all tumor sizes (p < 0.05) and any degree of liver fibrosis (p < 0.05). CONCLUSIONS: Resection of HCC tumors of all sizes and any degree of underlying fibrosis was associated with significantly improved OS compared with ablation. There was pronounced variability in the use of ablation versus resection for early-stage HCC. SUMMARY: This study found that patients with early-stage hepatocellular carcinoma (HCC) have improved overall survival (OS) after surgical resection, compared to ablation, at all tumor sizes and any extent of liver disease. There were also marked variations in treatment patterns for early-stage HCC.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Hepatectomia , Neoplasias Hepáticas/cirurgia , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
17.
Int J Radiat Oncol Biol Phys ; 105(1): 64-72, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30684667

RESUMO

PURPOSE: Ablative radiation therapy is increasingly being used for hepatocellular carcinoma (HCC) resulting in excellent local control rates; however, patients without evidence of disease progression often die from liver failure. The clinical benefit of proton- over photon-based radiation therapy is unclear. We therefore sought to compare clinical outcomes of proton versus photon ablative radiation therapy in patients with unresectable HCC. METHODS AND MATERIALS: This is a single-institution retrospective study of patients treated during 2008 to 2017 with nonmetastatic, unresectable HCC not previously treated with liver-directed radiation therapy and who did not receive further liver-directed radiation therapy within 12 months after completion of index treatment. The primary outcome, overall survival (OS), was assessed using Cox regression. Secondary endpoints included incidence of non-classic radiation-induced liver disease (defined as increase in baseline Child-Pugh score by ≥2 points at 3 months posttreatment), assessed using logistic regression, and locoregional recurrence, assessed using Fine-Gray regression for competing risks. All outcomes were measured from radiation start date. RESULTS: The median follow-up was 14 months. Of 133 patients with median age 68 years and 75% male, 49 (37%) were treated with proton radiation therapy. Proton radiation therapy was associated with improved OS (adjusted hazard ratio, 0.47; P = .008; 95% confidence interval [CI], 0.27-0.82). The median OS for proton and photon patients was 31 and 14 months, respectively, and the 24-month OS for proton and photon patients was 59.1% and 28.6%, respectively. Proton radiation therapy was also associated with a decreased risk of non-classic radiation-induced liver disease (odds ratio, 0.26; P = .03; 95% CI, 0.08-0.86). Development of nonclassic RILD at 3 months was associated with worse OS (adjusted hazard ratio, 3.83; P < .001; 95% CI, 2.12-6.92). There was no difference in locoregional recurrence, including local failure, between protons and photons. CONCLUSIONS: Proton radiation therapy was associated with improved survival, which may be driven by decreased incidence of posttreatment liver decompensation. Our findings support prospective investigations comparing proton versus photon ablative radiation therapy for HCC.


Assuntos
Carcinoma Hepatocelular/radioterapia , Falência Hepática/epidemiologia , Neoplasias Hepáticas/radioterapia , Fótons/uso terapêutico , Terapia com Prótons/métodos , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Causas de Morte , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Falência Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Fótons/efeitos adversos , Modelos de Riscos Proporcionais , Terapia com Prótons/efeitos adversos , Terapia com Prótons/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
18.
Ann Surg ; 269(4): 733-740, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29227344

RESUMO

OBJECTIVE: The aim of this study was to determine (1) whether preoperative factors can predict resectability of borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant FOLFIRINOX, (2) which patients might benefit from adjuvant therapy, and (3) survival differences between resected BR/LA patients who received neoadjuvant FOLFIRINOX and upfront resected patients. BACKGROUND: Patients with BR/LA PDAC are often treated with FOLFIRINOX to obtain a margin-negative resection, yet selection of patients for resection remains challenging. METHODS: Clinicopathologic data of PDAC patients surgically explored between 04/2011-11/2016 in a single institution were retrospectively collected. RESULTS: Following neoadjuvant FOLFIRINOX, 141 patients were surgically explored (BR: 49%, LA: 51%) and 110 (78%) were resected. Resected patients had lower preoperative CA 19-9 levels (21 vs 40 U/mL, P = 0.03) and smaller tumors on preoperative computed tomography (CT) scan (2.3 vs 3.0 cm, P = 0.03), but no predictors of resectability were identified. Median overall survival (OS) was 34.2 months from diagnosis for all FOLFIRINOX patients and 37.7 months for resected patients. Among resected patients, preoperative CA 19-9 >100 U/mL and >8 months between diagnosis and surgery predicted a shorter postoperative disease-free survival (DFS); Charlson comorbidity index >1, preoperative CA 19-9 >100 U/mL and tumor size (>3.0 cm on CT or >2.5 cm on pathology) predicted decreased OS. DFS and OS were significantly better for BR/LA PDAC patients treated with neoadjuvant FOLFIRINOX compared with upfront resected patients (DFS: 29.1 vs 13.7, P < 0.001; OS: 37.7 vs 25.1 months from diagnosis, P = 0.01). CONCLUSION: BR/LA PDAC patients with no progression on neoadjuvant FOLFIRINOX should be offered surgical exploration. Except size, traditional pathological parameters fail to predict survival among resected FOLFIRINOX patients. Resected FOLFIRINOX patients have survival that appears to be superior than that of resectable patients who go directly to surgery.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Idoso , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
19.
Pract Radiat Oncol ; 8(6): 414-421, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29937235

RESUMO

PURPOSE: This study aimed to assess the safety and efficacy of administering liver reirradiation to patients with primary liver tumors or liver metastasis. METHODS AND MATERIALS: A total of 49 patients (with 64 individual tumors) who received liver reirradiation at our institution between June 2008 and December 2016 were identified for retrospective review. Patients were treated to the same, different, or a combination of previously treated liver tumors for recurrent primary (53%) or metastatic (47%) disease using photons or protons. Clinical and treatment-related factors were compiled and patients were monitored for toxicity and evidence of classic or nonclassic radiation-induced liver disease. Survival was estimated with the Kaplan-Meier method and cumulative incidence of local failure (LF) was used to estimate LF using the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: The median age at the time of reirradiation was 72 years and the median interval between radiation courses was 9 months. At a median follow-up of 10.5 months, 36 patients (73%) had died, 9 patients (18%) were alive, and 4 patients (8%) were lost to follow-up. The median survival for the cohort was 14 months. The overall 1-year estimate of LF was 46.4%. The 1-year estimates of LF for liver metastases and hepatocellular carcinoma were 61.0% and 32.5%, respectively. The average prescription dose was similar between the reirradiation and initial courses (equivalent dose in 2 Gy fractions EQD2: 65.0 vs 64.3 Gyα/ß = 10, respectively) but the average dose to the untreated liver was lower at the time of reirradiation (EQD2: 10.5 vs 13.9 Gyα/ß = 3, respectively, P = .01). Among patients with hepatocellular carcinoma, the average normal liver dose was significantly larger for patients who exhibited a worsening of Child-Pugh score after reirradiation compared with those who did not (1210 cGy vs 759 cGy, P = .04). With regard to toxicity, 85.7% of patients experienced grade 1 to 2 toxicity, 4.1% developed grade 3, and only 2 patients (4.1%) met the criteria for radiation-induced liver disease after reirradiation. CONCLUSIONS: Liver reirradiation may be an effective and safe option for select patients; however, further prospective study is necessary to establish treatment guidelines and recommended dosing.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Reirradiação , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Taxa de Sobrevida
20.
J Natl Compr Canc Netw ; 16(6): 693-702, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29891520

RESUMO

The NCCN Guidelines for Neuroendocrine and Adrenal Tumors provide recommendations for the management of adult patients with neuroendocrine tumors (NETs), adrenal gland tumors, pheochromocytomas, and paragangliomas. Management of NETs relies heavily on the site of the primary NET. These NCCN Guidelines Insights summarize the management options and the 2018 updates to the guidelines for locoregional advanced disease, and/or distant metastasis originating from gastrointestinal tract, bronchopulmonary, and thymus primary NETs.


Assuntos
Neoplasias das Glândulas Suprarrenais/terapia , Prestação Integrada de Cuidados de Saúde/normas , Oncologia/normas , Tumores Neuroendócrinos/terapia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Humanos , Tumores Neuroendócrinos/diagnóstico , Sociedades Médicas/normas , Estados Unidos
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