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INTRODUCTION: For liver stereotactic body radiation therapy (SBRT), the placement of fiducial markers or retained ethiodized oil by transarterial chemoembolisation (TACE) provides a landmark for consistent target localisation. TACE and fiducial markers are invasive procedures that harbour additional risks. We hypothesise that liver SBRT can be accurately delivered without the use of these invasive surrogate markers. METHODS: We retrospectively identified 50 consecutive patients who underwent liver SBRT with respiratory motion management to a single lesion which exhibited retained ethiodized oil per prior TACE delivery. For each SBRT fraction, two manual rigid image registrations were performed by the treating physician. One using the liver contour as a surrogate for the target and second aligning only to the radio-opaque retained ethiodized oil of the treated lesion. The magnitude of the displacement vector between the two registration methods was used to assess the accuracy of target localisation if ethiodized oil was not present. RESULTS: For the 50 patients, a total of 244 analysable cone-beam CTs (CBCTs) were included (six CBCTs excluded due to poor ethiodized oil visualisation). Respiratory motion management techniques consisted of active breathing control for 13 and abdominal compression for 37 patients. Forty-two patients had peripheral lesions and eight had central lesions (<2 cm from left and right portal veins). The average target localisation offset between the two registration methods (i.e. liver contour vs. retained ethiodized oil alignment) for patients with a single peripheral or central liver lesion was 5.8 and 5.3 mm, respectively. CONCLUSIONS: Across all patients, the average change in target position exceeded 5 mm for image registration methods based on the liver contour alone versus the retained ethiodized oil region. This suggests that margins greater than 5 mm may be required for respiratory motion-managed liver SBRT treatments in patients who do not undergo prior TACE or fiducial placement.
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Neoplasias Hepáticas , Radiocirurgia , Humanos , Óleo Etiodado , Estudos Retrospectivos , Radiocirurgia/efeitos adversos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Marcadores FiduciaisRESUMO
A multitude of blood-based multicancer early detection (MCED) tests assessing cancer-related alterations in circulating genomic analytes and other associated signatures are currently being developed with the potential to disrupt current single-organ screening paradigms. Pathways for clinical implementation of these novel MCED tests have not been delineated, particularly for the patients with signal positive results requiring additional confirmatory testing. In this overview, we highlight early results from prospective clinical studies testing the efficacy of genomic MCED tests in cohorts of patients without known cancer diagnoses. Additionally, we discuss a proposed professional expansion of the oncology practice relating to the diagnostic workup of individuals found to have an MCED signal positive for cancer. As MCED blood tests have the potential to dramatically upend current cancer screening paradigms and downstream cancer therapy, it is imperative for oncologists to be aware of important clinical studies and the multitude of unanswered questions. The current gaps in the clinical implication of these tests may serve as a meaningful and rewarding expansion of oncology practice.
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Neoplasias , Oncologistas , Humanos , Estudos Prospectivos , Neoplasias/diagnóstico , Neoplasias/genética , Oncologia , Detecção Precoce de CâncerRESUMO
Colorectal cancer is the second leading cause of cancer-related deaths in the United States and accounts for an estimated 1 million deaths annually worldwide. The liver is the most common site of metastatic spread from colorectal cancer, significantly driving both morbidity and mortality. Although remarkable advances have been made in recent years in the management for patients with colorectal cancer liver metastases, significant challenges remain in early detection, prevention of progression and recurrence, and in the development of more effective therapeutics. In 2017, our group held a multidisciplinary state-of-the-science symposium to discuss the rapidly evolving clinical and scientific advances in the field of colorectal liver metastases, including novel early detection and prognostic liquid biomarkers, identification of high-risk cohorts, advances in tumor-immune therapy, and different regional and systemic therapeutic strategies. Since that time, there have been scientific discoveries translating into therapeutic innovations addressing the current management challenges. These innovations are currently reshaping the treatment paradigms and spurring further scientific discovery. Herein, we present an updated discussion of both the scientific and clinical advances and future directions in the management of colorectal liver metastases, including adoptive T-cell therapies, novel blood-based biomarkers, and the role of the tumor microbiome. In addition, we provide a comprehensive overview detailing the role of modern multidisciplinary clinical approaches used in the management of patients with colorectal liver metastases, including considerations toward specific molecular tumor profiles identified on next generation sequencing, as well as quality of life implications for these innovative treatments.
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Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Qualidade de Vida , Neoplasias Hepáticas/terapia , Biomarcadores , Neoplasias Colorretais/terapiaRESUMO
BACKGROUND: Neoadjuvant treatment with nab-paclitaxel and gemcitabine for potentially operable pancreatic adenocarcinoma has not been well studied in a prospective interventional trial and could down-stage tumors to achieve negative surgical margins. METHODS: A single-arm, open-label phase 2 trial (NCT02427841) enrolled patients with pancreatic adenocarcinoma deemed to be borderline resectable or clinically node-positive from March 17, 2016 to October 5, 2019. Patients received preoperative gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on Days 1, 8, 15, every 28 days for two cycles followed by chemoradiation with 50.4 Gy intensity-modulated radiation over 28 fractions with concurrent fluoropyrimidine chemotherapy. After definitive resection, patients received four additional cycles of gemcitabine and nab-paclitaxel. The primary endpoint was R0 resection rate. Other endpoints included treatment completion rate, resection rate, radiographic response rate, survival, and adverse events. RESULTS: Nineteen patients were enrolled, with the majority having head of pancreas primary tumors, both arterial and venous vasculature involvement, and clinically positive nodes on imaging. Among them, 11 (58%) underwent definitive resection and eight of 19 (42%) achieved R0 resection. Disease progression and functional decline were primary reasons for deferring surgical resection after neoadjuvant treatment. Pathologic near-complete response was observed in two of 11 (18%) resection specimens. Among the 19 patients, the 12-month progression-free survival was 58%, and 12-month overall survival was 79%. Common adverse events were alopecia, nausea, vomiting, fatigue, myalgia, peripheral neuropathy, rash, and neutropenia. CONCLUSION: Gemcitabine and nab-paclitaxel followed by long-course chemoradiation represents a feasible neoadjuvant treatment strategy for borderline resectable or node-positive pancreatic cancer.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neutropenia , Neoplasias Pancreáticas , Humanos , Gencitabina , Neoplasias Pancreáticas/patologia , Adenocarcinoma/tratamento farmacológico , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Albuminas , Paclitaxel , Neutropenia/induzido quimicamente , Terapia Neoadjuvante , Neoplasias PancreáticasRESUMO
PURPOSE: Non-operative management of patients with locally advanced rectal cancer (LARC) is emerging as a popular approach for patients that have no evidence of disease following neoadjuvant therapy. However, high rates of local recurrence or distant metastases have highlighted the urgent need for robust biomarker strategies to aid clinical management of these patients. METHODS: This review summarizes recent advances in the utility of cell-free (cf) and circulating tumor (ct) DNA as potential biomarkers to help guide individualized non-operative management strategies for LARC patients receiving neoadjuvant therapy. RESULTS: Liquid biopsies and the detection of cfDNA/ctDNA is an emerging technology with the potential to provide a non-invasive approach to monitor disease response and improve the identification of patients with LARC that would best benefit from non-operative management. CONCLUSIONS: Substantial work is still needed before cfDNA/ctDNA monitoring can be widely adopted in the clinical setting. Studies reviewed herein highlight several areas of opportunity for improving the effectiveness and utility of cfDNA/ctDNA for managing patients with LARC.
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Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias Retais , Humanos , DNA Tumoral Circulante/uso terapêutico , Terapia Neoadjuvante , Neoplasias Retais/terapia , Neoplasias Retais/tratamento farmacológico , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/uso terapêuticoRESUMO
Cholangiocarcinoma is a lethal malignancy of the biliary epithelium that can arise anywhere along the biliary tract. Surgical resection confers the greatest likelihood of long-term survivability. However, its insidious onset, difficult diagnostics, and resultant advanced presentation render the majority of patients unresectable, highlighting the importance of early detection with novel biomarkers. Developing liver-directed therapies and emerging targeted therapeutics may offer improved survivability for patients with unresectable or advanced disease. In this article, the authors review the current multidisciplinary standards of care in resectable and unresectable cholangiocarcinoma, with an emphasis on novel biomarkers for early detection and nonsurgical locoregional therapy options.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/terapia , Colangiocarcinoma/patologiaRESUMO
Stereotactic body radiotherapy (SBRT) demonstrates excellent local control in early stage lung cancer, however a quarter of patients develop recurrence or distant metastasis. Transforming growth factor-beta (TGF-ß) supports metastasis and treatment resistance, and angiotensin receptor blockade (ARB) indirectly suppresses TGF-ß signaling. This study investigates whether patients taking ARBs while undergoing SBRT for early stage lung cancer exhibited improved overall survival (OS) or recurrence free survival (RFS) compared to patients not taking ARBs. This was a single institution retrospective analysis of 272 patients treated with SBRT for early stage lung cancer between 2009 and 2018. Patient health data was abstracted from the electronic medical record. OS and RFS were assessed using Kaplan-Meier method. Log-rank test was used to compare unadjusted survival between groups. Univariable and multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs). Of 247 patients analyzed, 24 (10%) patients took ARBs for the duration of radiotherapy. There was no difference in mean age, median tumor diameter, or median biologic effective dose between patients taking ARBs or not. Patients taking ARBs exhibited increased OS (ARB = 96.7 mo.; no ARB = 43.3 mo.; HR = 0.25 [95% CI: 0.10 to 0.62, P = .003]) and increased RFS (median RFS, ARB = 64.3 mo.; No ARB = 35.1 mo.; HR = 0.26 [95% CI: 0.10 to 0.63, P = .003]). These effects were not seen in patients taking angiotensin converting enzyme inhibitors (ACEIs) or statins. ARB use while undergoing SBRT for early stage lung cancer may increase OS and RFS, but ACEI use does not show the same effect.
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Produtos Biológicos , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Pulmonares , Radiocirurgia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Produtos Biológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Receptores de Angiotensina/uso terapêutico , Estudos Retrospectivos , Fator de Crescimento Transformador beta , Fatores de Crescimento Transformadores/uso terapêutico , Resultado do TratamentoRESUMO
Cancer remains the second leading cause of death in the United States despite decades of treatment advances. While death rates have fallen for breast, cervical, and colorectal cancers, all of which have population-based screening options, rates remain high for the majority of malignancies, with most diagnosed in the later stages. In addition, adherence to screening recommendations in the United States is low, with high rates of false-positive results. Multi-cancer early detection (MCED) tests detect early cancer signals from as many as 50 or more neoplasms using cell-free DNA and other circulating analytes in blood. They may be more accessible and easier to disseminate than organ-specific tests. However, the impact on cancer-related deaths remains unclear. Other unanswered questions include cost-effectiveness, the impact of false-positive results on patients and costs, the overdiagnosis of more indolent cancers, uptake among patients and clinicians, and the need for protocols covering their use. Research and development of blood-based MCED tests continue.
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Detecção Precoce de Câncer , Neoplasias , Congressos como Assunto , Análise Custo-Benefício , Detecção Precoce de Câncer/métodos , Humanos , Programas de Rastreamento/métodos , Neoplasias/diagnóstico , Estados UnidosRESUMO
Background: The optimal perioperative treatment for adenocarcinoma of gastroesophageal junction (GEJ) tumor remains uncertain. The systematic review aims to assess the best neoadjuvant modality, namely chemotherapy (CT) versus chemoradiotherapy (CRT) based on randomized controlled trials (RCTs) for resectable gastric, esophageal and GEJ tumors. Methods: We performed a comprehensive PubMed database and Cochrane Library search to identify relevant RCTs related to neoadjuvant treatment for resectable GEJ adenocarcinoma. We included all published RCTs (phase 2 or 3) that tested specific neoadjuvant therapies (CT or CRT) if the patient population included GEJ tumors. We applied the Version 2 Cochrane risk-of-bias tool (RoB 2) to all the eligible studies. Outcomes examined included R0 resection and pathological response based on intention-to-treat (ITT) analysis, surgical outcomes, notable adverse events, and overall survival (OS). Each randomized group of every study was noted to be neoadjuvant CRT, CT, or surgery alone in order to compare the outcomes among these treatment approaches. Results: We identified 25 RCTs with 7,855 patients published from 1996 to 2019. Seven studies tested preoperative CT versus surgery alone, 7 tested preoperative radiotherapy (RT) or CRT versus surgery alone, 4 tested preoperative RT or CRT versus preoperative CT, and 7 tested other combinations. The R0 resection ranged 47-100% and the 3-year OS ranged 6-66.1% in all the study arms. In an exploratory analysis, CRT strategies showed a superior R0 resection rate [80.2%; 95% confidence interval (CI): 79.8-80.6%] to surgery alone (60.9%; 95% CI: 60.4-61.3%; P<0.01) and to preoperative CT (63.9%; 95% CI: 63.6-64.2%; P<0.01). When comparing 3- and 5-year OS, improvement was noted when comparing CRT to surgery alone (P<0.01), and perioperative CT to surgery alone (P<0.01), but no definite difference was noted between CRT versus CT. Discussion: Preoperative CRT showed improvement in R0 resection rate to surgery alone and preoperative CT. However, there is no significant difference in OS between CRT and CT. Both neoadjuvant strategies remain clinically meaningful options for patients with resectable GEJ tumors. Lack of patient-level data and inconsistent reporting of key outcomes across studies were the main limitations of our study.
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PURPOSE: External beam radiation therapy (EBRT) is a safe and emerging bridging liver-directed therapy (LDT) to liver transplant (LT) for patients with hepatocellular carcinoma (HCC). The prevalence and clinical characteristics of patients receiving EBRT as an LDT for LT have not been evaluated. Our aim was to describe the utilization of EBRT in patients with HCC evaluated for LT in the United States. METHODS AND MATERIALS: We analyzed United Network for Organ Sharing data from October 2013 to June 2020 and identified patients with HCC who applied for model for end-stage liver disease (MELD) exceptions for LT wait list prioritization. The primary outcome was the period prevalence of EBRT. We examined associations between clinical variables and EBRT and fit survival models with EBRT as a time-varying predictor. RESULTS: We identified 18,543 patients with HCC with MELD exception applications. EBRT was used in 658 patients (3.5%) either alone (1.2%) or combined with other LDT (2.3%). Transarterial chemoembolization was the most used LDT (59.3%), followed by thermal ablation (27.9%) and radioembolization (15.2%). EBRT prevalence rose by an average of 12.2% per year (P = .001). Use of EBRT differed by geographic region, ranging from 2% to 8% (P < .001). EBRT and no EBRT groups had similar initial MELD score, portal vein thrombosis, tumor diameter, number of tumors, bilirubin, and α-fetoprotein (P > .05). Median time-to-transplant from wait list registration for EBRT versus no EBRT groups was 10 months (95% confidence interval, 9.4-10.9) versus 11.9 months (95% confidence interval, 11.7-12.2; P < .001). Evaluated as a time-varying predictor, EBRT increased the risk of LT by 30% (sub-hazard ratio, 1.30; P < .001), while the effect of EBRT on the risk of wait list removal due to clinical deterioration or death (sub-hazard ratio, 1.07; P = .489) was nonsignificant. CONCLUSIONS: In the United States, EBRT is rarely used compared with other LDTs and exhibits geographic variation. Low EBRT utilization highlights a gap in the treatment armamentarium for HCC.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Doença Hepática Terminal , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Doença Hepática Terminal/terapia , Humanos , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Estados Unidos/epidemiologia , Listas de EsperaRESUMO
There has been a staggering increase in the incidence of rectal cancer, drawing our attention to early detection and optimization of its medical and surgical treatment. With this review we highlight all the major trials that revolutionized rectal cancer management and improved oncologic outcomes. We present the origins of the trimodal therapy and the studies that supported the sequence of treatment. We describe the evolution in surgical management with total mesorectal excision as the standard of care, and we review the most impactful short- vs. long-course long-course radiation therapy trials. Today, the current standard of care for non-metastatic locally advanced rectal cancer includes preoperative chemoradiation with either induction or consolidation chemotherapy, total mesorectal excision and adjuvant therapy. We discuss the advent of the "watch and wait" strategy for patients who have a complete clinical response after total neoadjuvant treatment, as well as possible future directions in the treatment of locoregional disease.
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BACKGROUND AND OBJECTIVES: Colorectal liver metastasis (CRLM) is a leading cause of morbidity and mortality in patients with colorectal cancer. Hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve survival in patients with resected CRLM and to facilitate conversion of technically unresectable disease. METHODS: Between 2016 and 2018, n = 22 HAI pumps were placed for CRLM. All patients received systemic chemotherapy concurrently with HAI floxuridine/dexamethasone. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. RESULTS: HAI pumps were placed in seven patients with completely resected CRLM and 15 patients with unresectable disease. Twenty-one patients received HAI floxuridine with a median of 5 total HAI cycles (interquartile range: 4-7). Biliary sclerosis was the most common HAI-related complication (n = 5, 24%). Of the 13 patients treated to convert unresectable CRLM, 3 (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10). For all HAI patients, the mean OS was 26.7 months from CRLM diagnosis, while the median PFS and hepatic PFS from pump placement were 9 and 13 months, respectively. CONCLUSION: Concomitant HAI and systemic therapy can be utilized at multidisciplinary programs for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease.
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Neoplasias Colorretais , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/patologia , Floxuridina , Fluoruracila , Artéria Hepática/patologia , Humanos , Bombas de Infusão , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgiaRESUMO
BACKGROUND: Non-operative management of early-stage polypectomy-identified colorectal cancer (CRC) may be a safe alternative, but limited data exist. METHODS: We compared outcomes between adults with post-polypectomy CRC who did and did not ultimately undergo resection from 2003 to 2018. Overall (OS) and recurrence-free (RFS) survival were calculated via log rank analysis using the Mantel-Cox method and plotted on Kaplan-Meier curves with significance evaluated at P < 0.05. RESULTS: N = 78 patients were included, most commonly with rectal/rectosigmoid CRC (45%). Almost half (47%) had resections, and the remaining 41 patients (53%) underwent organ-sparing techniques. Chemoradiation was administered to 5 of these 41 patients (12%), all with rectal cancer. At median follow-up of 52 months, 5-year OS and RFS were 78% and 100% with no significant differences when compared to resection (all P > 0.1). DISCUSSION: Using evidence-based patient selection and adjuvant therapy, organ-sparing management provides equal survival when compared to resection for post-polypectomy CRC.
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Pólipos do Colo , Neoplasias Colorretais , Neoplasias Retais , Adulto , Pólipos do Colo/cirurgia , Neoplasias Colorretais/patologia , Terapia Combinada , Tratamento Conservador , Humanos , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/cirurgia , Estudos RetrospectivosRESUMO
The role of neoadjuvant chemoradiotherapy and/or chemotherapy (neoCHT) in patients with pancreatic ductal adenocarcinoma (PDAC) is poorly defined. We hypothesized that patients who underwent neoadjuvant therapy (NAT) would have improved systemic therapy delivery, as well as comparable perioperative complications, compared to patients undergoing upfront resection. This is an IRB-approved retrospective study of potentially resectable PDAC patients treated within an academic quaternary referral center between 2011 and 2018. Data were abstracted from the electronic medical record using an institutional cancer registry and the National Surgical Quality Improvement Program. Three hundred and fourteen patients were eligible for analysis and eighty-one patients received NAT. The median overall survival (OS) was significantly improved in patients who received NAT (28.6 vs. 20.1 months, p = 0.014). Patients receiving neoCHT had an overall increased mean duration of systemic therapy (p < 0.001), and the median OS improved with each month of chemotherapy delivered (HR = 0.81 per month CHT, 95% CI (0.76-0.86), p < 0.001). NAT was not associated with increases in early severe post-operative complications (p = 0.47), late leaks (p = 0.23), or 30-90 day readmissions (p = 0.084). Our results show improved OS in patients who received NAT, driven largely by improved chemotherapy delivery, without an apparent increase in early or late perioperative complications compared to patients undergoing upfront resection.
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BACKGROUND: The definition of early recurrence (ER) in rectal cancer is unclear, and the association of ER with post-recurrence survival (PRS) is poorly described. We therefore sought to identify if time to recurrence (TTR) is associated with PRS. METHODS: We reviewed all curative-intent resections of nonmetastatic rectal cancer from 2003 to 2018 in our institutional registry within an NCI-Designated Comprehensive Cancer Center. Clinicopathologic data at diagnosis and first recurrence were collected and analyzed. ER was pre-specified at < 24 months and late recurrence (LR) at ≥ 24 months. PRS was evaluated by the Kaplan-Meier method and Cox proportional hazards modeling. RESULTS: At a median follow-up of 53 months, 61 out of 548 (11.1%) patients undergoing resection experienced recurrence. Median TTR was 14 months (IQR 10-18) with 45 of 61 patients (74%) classified as ER. There were no significant baseline differences between patients with ER and LR. Most recurrences were isolated to the liver (26%) or lung (31%), and 16% were locoregional. ER was not associated with worse PRS compared to LR (P > 0.99). On multivariable analysis, detection of recurrence via workup for symptoms, CEA > 10 ng/mL at recurrence, and site of recurrence were independently associated with PRS. CONCLUSION: ER is not associated with PRS in patients with resected rectal cancer. Symptomatic recurrences and those accompanied by CEA elevations are associated with worse PRS, while metastatic disease confined to the liver or lung is associated with improved PRS. Attention should be directed away from TTR and instead toward determining therapy for patients with treatable oligometastatic disease.
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Recidiva Local de Neoplasia , Neoplasias Retais , Humanos , Prognóstico , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a rare cancer. Patients in rural areas may face reduced access to advanced treatments often only available at referral centers. We evaluated the association of referral center treatment with treatment patterns, outcomes, and geography in patients with ICC. METHODS: We queried the Oregon State Cancer Registry for ICC between 1997 and 2016, collecting clinicopathologic, demographic, and oncologic data. Patients were classified by treatment at a referral center or non-referral center. 'Crowfly' distance to the nearest referral center (DRC) was calculated. Outcomes were evaluated using Kaplan-Meier, Cox proportional hazards modeling, and logistic regression. RESULTS: Over 20 years, 740 patients with ICC had a median age of 66 years. Slightly more than half (n = 424, 57%) were non-referral center treated and 316 (43%) were referral center treated. Referral center treatment increased over time (odds ratio [OR] 1.03/year, p < 0.05). Referral center-treated patients had improved overall survival in all patients (median 9 vs. 4 months, p < 0.001), in the non-metastatic group (median 13 vs. 6 months, p < 0.001), and in patients not receiving liver resection (median 6 vs. 3 months, p < 0.05). On multivariable analysis, referral center-treated patients more often underwent chemotherapy, resection, or radiation (all p < 0.05). Increasing DRC (OR 0.98/20 km, p < 0.05) was independently associated with non-referral center treatment. CONCLUSION: Patients with ICC who are evaluated at a referral center are more likely to receive treatments associated with better oncologic outcomes, including patients who are not managed with hepatic resection. Increasing the DRC is associated with treatment at a non-referral center; interventions to facilitate referral, such as telemedicine, may lead to improved outcomes for patients with ICC in rural states.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Idoso , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/terapia , Hepatectomia , Humanos , Encaminhamento e ConsultaRESUMO
BACKGROUND: Gallbladder cancer (GBC) is often incidentally diagnosed after cholecystectomy. Intra-operative biliary tract violations (BTV) have been recently associated with development of peritoneal disease (PD). The degree of BTV may be associated with PD risk, but has not been previously investigated. METHODS: We reviewed patients with initially non-metastatic GBC treated at our institution from 2003 to 2018. Patients were grouped based on degree of BTV during their treatment: major (e.g., cholecystotomy with bile spillage, n = 27, 29%), minor (e.g., intra-operative cholangiogram, n = 18, 19%), and no violations (n = 48, 55%). Overall survival (OS) and peritoneal disease-free survival (PDFS) were evaluated with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: Ninety-three patients were identified; the median age was 64 years (range 31-87 years). Seventy-six (82%) were incidentally diagnosed. The median follow-up was 23 months; 20 (22%) patients developed PD. The 3-year PDFS for patients with major, minor, and no BTV was 52%, 83%, and 98%, respectively (major vs. none: p < 0.001; minor vs. none: p < 0.01). BTV was not associated with 5-year OS (HR 1.53, p = 0.16). CONCLUSION: Increasing degree of BTV is associated with higher risk of peritoneal carcinomatosis in patients with GBC and should be considered during preoperative risk stratification. Reporting biliary tract violations during cholecystectomy is encouraged.
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Adenocarcinoma/cirurgia , Sistema Biliar/patologia , Colecistectomia/efeitos adversos , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias Peritoneais/patologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/etiologia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n = 3) and rectal cancer (n = 2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the Dual-Index Degenerate Adaptor-Sequencing (DIDA-Seq) error-correction method, we serially interrogated plasma cell-free DNA at 28-41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient- and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.
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BACKGROUND: Determination of the comparative efficacy of one therapy over another for hepatocellular carcinoma (HCC) can be challenging. Application of a recognized value framework to published studies could objectively compare the potential benefit across available therapies. MATERIALS AND METHODS: An umbrella review of phase III trials for HCC therapies was performed. ASCO Value Framework Net Health Benefit Score version 2 (ASCO-NHB v2) scores, the primary analysis, and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 scores, the secondary analysis, were computed using selected drug registration trials. Both scores were compared between drugs that were Food and Drug Administration (FDA)-approved by 2020 and those that were not. RESULTS: Of the 22 studies identified, nine were FDA-approved and 13 were not. Across 22 trials, the median overall survival (OS) was 9.2 months (range, 1.9-16.4 months), with a median gain of 0.35 month (range, 2.3-3.3 months). HCC therapies that were FDA-approved showed longer OS (median 10.7 v 7.9 months, P < .01) and higher ASCO NHB scores (+18.4 v -5.7 scores, P < .01). The median gain in OS was 2.2 months in the approved treatments compared with -0.3 months in the unapproved group, with no difference in progression-free survival between the two groups. CONCLUSION: The nine FDA-approved therapies for HCC have higher mean NHB score than those that were not FDA-approved. The application of ASCO-NHB v2 and other proposed value frameworks could examine data of future therapies for HCC through a patient-oriented approach.