Revistas
Autores:
Yoshino, T.; Di Bartolomeo, M.; Raghav, K.; et al.
Revista:
NATURE COMMUNICATIONS
ISSN:
2041-1723
Año:
2023
Vol.:
14
N°:
1
Págs.:
3332
DESTINY-CRC01 (NCT03384940) was a multicenter, open-label, phase 2 trial assessing the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-expressing metastatic colorectal cancer (mCRC) that progressed after >= 2 prior regimens; results of the primary analysis are published. Patients received T-DXd 6.4mg/kg every 3 weeks and were assigned to either: cohort A (HER2-positive, immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+), cohort B (IHC 2+/ISH-), or cohort C (IHC 1+). Primary endpoint was objective response rate (ORR) by independent central review in cohort A. Secondary endpoints included ORR (cohorts B and C), duration of response, disease control rate, progression-free survival, overall survival, pharmacokinetics, and safety of T-DXd. 86 patients were enrolled (53 in cohort A, 15 in cohort B, and 18 in cohort C). Results of the primary analysis are published, reporting an ORR of 45.3% in cohort A. Here, we report the final results. No responses occurred in cohorts B or C. Median progression-free survival, overall survival, and duration of response were 6.9, 15.5, and 7.0 months, respectively. Overall serum exposure (cycle 1) of T-DXd, total anti-HER2 antibody, and DXd were similar regardless of HER2 status. Most common grade >= 3 treatment-emergent adverse events were decreased neutrophil count and anemia. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8 patients (9.3%). These findings support the continued exploration of T-DXd in HER2-positive mCRC.
Revista:
CANCERS
ISSN:
2072-6694
Año:
2023
Vol.:
15
N°:
3
Págs.:
733
Simple Summary Radioembolization is a locoregional therapy used in primary liver malignancies with different applications depending on the treatment goal. The aim of this retrospective study was to evaluate postoperative and long-term survival outcomes of patients with unresectable or high biological risk HCC and ICC treated with RE that were finally rescued to liver surgery with curative intent. In a cohort of 34 patients, we assessed that liver resection and transplantation after RE seem safe and feasible with adequate short-term outcomes. Moreover, long-term outcomes after RE and LR were optimal, with a 10-year OS rate greater than 50% for HCC and ICC patients. On the other hand, the 10-year OS rates from RE were also greater than 50% for patients with HCC downstaged or bridged to LT. Radioembolization (RE) may help local control and achieve tumor reduction while hypertrophies healthy liver and provides a test of time. For liver transplant (LT) candidates, it may attain downstaging for initially non-candidates and bridging during the waitlist. Methods: Patients diagnosed with HCC and ICC treated by RE with further liver resection (LR) or LT between 2005-2020 were included. All patients selected were discarded for the upfront surgical approach for not accomplishing oncological or surgical safety criteria after a multidisciplinary team assessment. Data for clinicopathological details, postoperative, and survival outcomes were retrospectively reviewed from a prospectively maintained database. Results: A total of 34 patients underwent surgery following RE (21 LR and 13 LT). Clavien-Dindo grade III-IV complications and mortality rates were 19.0% and 9.5% for LR and 7.7% and 0% for LT, respectively. After RE, for HCC and ICC patients in the LR group, 10-year OS rates were 57% and 60%, and 10-year DFS rates were 43.1% and 60%, respectively. For HCC patients in the LT group, 10-year OS and DFS rates from RE were 51.3% and 43.3%, respectively. Conclusion: Liver resection after RE is safe and feasible with optimal short-term outcomes. Patients diagnosed with unresectable or high biological risk HCC or ICC, treated with RE, and rescued by LR may achieve optimal global and DFS rates. On the other hand, bridging or downstaging strategies to LT with RE in HCC patients show adequate recurrence rates as well as long-term survival.
Revista:
CANCERS
ISSN:
2072-6694
Año:
2023
Vol.:
15
N°:
17
Págs.:
4206
Simple Summary Cancer treatments often have side effects that may impair patients' quality of life. Our research aimed to create a predictive tool able to foresee the likelihood of these severe complications. We used medical data from 267 gastrointestinal cancer patients, applied a particular type of computer model known as a Bayesian network, and evaluated its predictions against real outcomes. The model accurately predicted the risk of developing severe haematological toxicity in 80-85% of cases. This tool, if further validated and refined, may help to identify a vulnerable subset of patients who might benefit from personalized treatment plans.Abstract Purpose: Severe toxicity is reported in about 30% of gastrointestinal cancer patients receiving 5-Fluorouracil (5-FU)-based chemotherapy. To date, limited tools exist to identify at risk patients in this setting. The objective of this study was to address this need by designing a predictive model using a Bayesian network, a probabilistic graphical model offering robust, explainable predictions. Methods: We utilized a dataset of 267 gastrointestinal cancer patients, conducting preprocessing, and splitting it into TRAIN and TEST sets (80%:20% ratio). The RandomForest algorithm assessed variable importance based on MeanDecreaseGini coefficient. The bnlearn R library helped design a Bayesian network model using a 10-fold cross-validation on the TRAIN set and the aic-cg method for network structure optimization. The model's performance was gauged based on accuracy, sensitivity, and specificity, using cross-validation on the TRAIN set and independent validation on the TEST set. Results: The model demonstrated satisfactory performance with an average accuracy of 0.85 (& PLUSMN;0.05) and 0.80 on TRAIN and TEST datasets, respectively. The sensitivity and specificity were 0.82 (& PLUSMN;0.14) and 0.87 (& PLUSMN;0.07) for the TRAIN dataset, and 0.71 and 0.83 for the TEST dataset, respectively. A user-friendly tool was developed for clinical implementation. Conclusions: Despite several limitations, our Bayesian network model demonstrated a high level of accuracy in predicting the risk of developing severe haematological toxicity in gastrointestinal cancer patients receiving 5-FU-based chemotherapy. Future research should aim at model validation in larger cohorts of patients and different clinical settings.
Revista:
PANCREATOLOGY
ISSN:
1424-3903
Año:
2023
Vol.:
23
N°:
4
Págs.:
411 - 419
Background: Despite a potentially curative treatment, the prognosis after upfront surgery and adjuvant chemotherapy for patients with resectable pancreatic ductal adenocarcinoma (PDAC) is poor. Modified FOLFIRINOX (mFOLFIRINOX) is a cornerstone in the systemic treatment of PDAC, including the neoadjuvant setting. Pharmacokinetic-guided (PKG) dosing has demonstrated beneficial effects in other tumors, but scarce data is available in pancreatic cancer.
Methods: Forty-six patients with resected PDAC after mFOLFIRINOX neoadjuvant approach and included in an institutional protocol for anticancer drug monitoring were retrospectively analyzed. 5-Fluorouracil (5-FU) dosage was adjusted throughout neoadjuvant treatment according to pharmacokinetic parameters and Irinotecan (CPT-11) pharmacokinetic variables were retrospectively estimated.
Results: By exploratory univariate analyses, a significantly longer progression-free survival was observed for patients with either 5-FU area under the curve (AUC) above 28 mcg·h/mL or CPT-11 AUC values below 10 mcg·h/mL. In the multivariate analyses adjusted by age, gender, performance status and resectability after stratification according to both pharmacokinetic parameters, the risk of progression was significantly reduced in patients with 5-FU AUC ¿28 mcg·h/mL [HR = 0.251, 95% CI 0.096-0.656; p = 0.005] and CPT-11 AUC <10 mcg·h/mL [HR = 0.189, 95% CI 0.073-0.486, p = 0.001].
Conclusions: Pharmacokinetically-guided dose adjustment of standard chemotherapy treatments might improve survival outcomes in patients with pancreatic ductal adenocarcinoma.
Revista:
BMC MEDICAL EDUCATION
ISSN:
1472-6920
Año:
2023
Vol.:
23
N°:
1
Págs.:
19
Background With university material doubling over time, medical students need to learn how to become successful life-long learners. Overall a Deep Approach (DA) to learning, and Self-Regulation (SR) skills are among the elements with a potential to accelerate learning, and Student Engagement (SE) has been associated with better university outcomes. However, specific recommendations concerning what students should do are lacking. The aim of this study was to identify above-average students' specific attitudes and strategies toward learning. Methods A cross-sectional analysis of the answers to the validated questionnaires Revised Study Process Questionnaire (R-SPQ-2F), SE, and Motivated Strategies for Learning Questionnaire (MSLQ) of 155 s and third-year students included in a prospective interventional study in the University of Navarre in September 2020 was performed. Students were stratified according to their standardized average mean in above-average (mean > 0) and below-average (mean <= 0). Results Overall, 67.1% of students scored higher in DA than in Surface Approach (SA) and had very high Intrinsic Value (IV, median 5.9). A higher proportion of above-average students had DA > SA score (72.7% vs 57.1%, p = 0.05), and showed higher scores in SR (median 4.9 vs 4.3, p = 0.007) compared to below-average, while the latter scored higher in SA (median 24.5 vs 23, p = 0.04), and surface motive (median 11 vs 9, p = 0.007). No differences were found in SE, and both groups had average scores in the cooperative dimension. Differences were rooted to hard work, interest over material and prioritizing understanding over rote-learning motives and aligned strategies. Conclusions Curricula design and assessment should be aligned to promote DA and SR skills among learners. Furthermore, it is paramount that teachers help instill students with interest over material and encourage understanding and hard work, since are traits associated with better results. More studies concerning metacognition and other promising traits for becoming life-long learners and prepared professionals should be made.
Revista:
JOURNAL OF CLINICAL MEDICINE
ISSN:
2077-0383
Año:
2022
Vol.:
11
N°:
12
Págs.:
3472
Background: To analyze the long-term outcomes for advanced cancer patients admitted to an intermediate care unit (ImCU), an analysis of a do not resuscitate orders (DNR) subgroup was made. Methods: A retrospective observational study was conducted from 2006 to January 2019 in a single academic medical center of cancer patients with stage IV disease who suffered acute severe complications. The Simplified Acute Physiology Score 3 (SAPS 3) was used as a prognostic and severity score. In-hospital mortality, 30-day mortality and survival after hospital discharge were calculated. Results: Two hundred and forty patients with stage IV cancer who attended at an ImCU were included. In total, 47.5% of the cohort had DNR orders. The two most frequent reasons for admission were sepsis (32.1%) and acute respiratory failure (excluding sepsis) (38.7%). Mortality in the ImCU was 10.8%. The mean predicted in-hospital mortality according to SAPS 3 was 51.9%. The observed in-hospital mortality was 37.5% (standard mortality ratio of 0.72). Patients discharged from hospital had a median survival of 81 (30.75-391.25) days (patients with DNR orders 46 days (19.5-92.25), patients without DNR orders 162 days (39.5-632)). The observed mortality was higher in patients with DNR orders: 52.6% vs. 23.8%, p 0 < 0.001. By multivariate logistic regression, a worse ECOG performance status (3-4 vs. 0-2), a higher SAPS 3 Score and DNR orders were associated with a higher in-hospital mortality. By multivariate analysis, non-invasive mechanical ventilation, higher bilirubin levels and DNR orders were significantly associated with 30-day mortality. Conclusion: For patients with advanced cancer disease, even those with DNR orders, who suffer from acute complications or require continuous monitoring, an ImCU-centered multidisciplinary management shows encouraging results in terms of observed-to-expected mortality ratios.
Autores:
Siena, S.; Di Bartolomeo, M.; Raghav, K.; et al.
Revista:
LANCET ONCOLOGY
ISSN:
1470-2045
Año:
2021
Vol.:
22
N°:
6
Págs.:
779 - 789
Background HER2 amplification has been identified in 2-3% of patients with colorectal cancer, although there are currently no approved HER2-targeted therapies for colorectal cancer. We aimed to study the antitumour activity and safety of tra stuzurnab deruxtecan (an antibody-drug conjugate of humanised a nti-H ER2 antibody with topoisoinerase I inhibitor payloads) in patients with HER2-expressing metastatic colorectal cancer. Methods DESTINY-CRCO1 is an open-label, phase 2 study that recruited patients from 25 clinics and hospitals in Italy, Japan, Spain, the UK, and the USA. Eligible patients had centrally confirmed HER2-expressing inetastatic colorectal cancer that had progressed on two or more previous regimens (HER2-targeted therapies other than trastuzumab denixtecan permitted), were aged 18 years or older (>= 20 years in Japan), had an Eastern Cooperative Oncology Group score of 0 or 1, and had RAS and BRAF(V600E) wild-type tumours. Patients were enrolled into one of three cohorts by HER2 expression level: cohort A (HER2-positive, immunohistochemistry [IHCJ 3+ or IHC2+ and in-situ hybridisation [ISH1-positive), cohort B (IHC2+ and ISH-negative), or cohort C (IHC1+). Patients received 6.4 mg/kg trastuzumab deruxtecan intravenously every 3 weeks until disease progression, unacceptable adverse events, withdrawal of consent, or death. The primary endpoint was confirmed objective response rate in cohort A by independent central review which was assessed in the full analysis set and safety was assessed in the safety analysis set. Both the full analysis set and the safety analysis set included all patients who received one or more doses of trastuzumab denixtecan. This ongoing trial is registered with ClinicalTrials.gov, number NCT03384940. Findings Between Feb 23, 2018, and July 3, 2019, 78 patients were enrolled in the study (53 in cohort A, seven in cohort B, and 18 in cohort C), all of whom received at least one dose of study drug. For the 53 (68%) patients with HER2-positive tumours (cohort A), a confirmed objective response was reported in 24 (45.3%, 95% CI 31.6-59.6) patients after a median follow-up of 27.1 weeks (IQR 19.3-40.1). Grade 3 or worse treatment-emergent adverse events that occurred in at least 10% of all participants were decreased neutrophil count (17 [22%] of 78) and anaemia (11 [14%]). Five patients (6%) had adjudicated interstitial lung disease or pneumonitis (two grade 2; one grade 3; two grade 5, the only treatment-related deaths). Interpretation Trastuzumab deruxtecan showed promising and durable activity in HER2-positive metastatic colorectal cancer refractory to standard treatment, with a safety profile consistent with that reported in previous trastuzumab deruxtecan trials. Interstitial lung disease and prieuinonitis are important risks requiring careful monitoring and prompt intervention. Copyright (C) 2021 Published by Elsevier Ltd. All rights reserved.
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2020
Vol.:
112
N°:
1
Págs.:
16 - 22
Background: the standard treatment for locally advanced rectal cancer is neoadjuvant chemo-radiotherapy, surgery and adjuvant chemotherapy. Only 50% of patients receive the adjuvant treatment due to the surgical complications and toxicity of radiotherapy. Recently, neoadjuvant chemotherapy has been investigated in the locally advanced rectal cancer setting, with the aim of guaranteeing an uninterrupted systemic treatment. The objective of the present study was to assess the safety and efficacy of neoadjuvant chemotherapy in locally advanced rectal cancer.
Methods and patients: patients treated with neoadjuvant chemotherapy and surgery were identified from a prospective database of patients with rectal cancer (cII-III). The primary outcomes were the assessment of the number of R0 resections, the degree of pathologic response, patterns of recurrence and overall and disease-free survival. Treatment schedule: patients received 6-8 cycles of oxaliplatin and fluoropyrimides based chemotherapy.
Results: twenty-seven patients who received neoadjuvant chemotherapy were identified. Twenty-six anterior resections and one Hartmann intervention were performed. An R0 resection was performed in 27 (100%) patients and no involvement of the circumferential margin was observed. Complete pathologic response (ypT0N0) was confirmed in four (14.8%) patients.The median follow-up was 35 months (range: 10-81) and four distant recurrences were recorded. Overall and disease-free survival at five years was 85% and 84.7%, respectively. Twenty-seven (100%) patients received all the cycles of chemotherapy, with a mean of six cycles (range 5-8) per patient.
Conclusions: neoadjuvant chemotherapy is a promising alternative in the locally advanced rectal cancer setting and further phase III clinical trials are clearly warranted.
Revista:
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
ISSN:
1434-6621
Año:
2020
Vol.:
58
N°:
8
Págs.:
1341 - 1348
Background: Genomic alterations studies in cell-free DNA (cfDNA) have increasing clinical use in oncology. Nextgeneration sequencing (NGS) technology provides the most complete mutational analysis, but nowadays limited data are available related to the comparison of results reported by different platforms. Here we compare two NGS panels for cfDNA: OncomineT Pan-Cancer Cell-Free Assay (Thermo Fisher Scientific), suitable for clinical laboratories, and Guardant360 (R) (GuardantHealth), with more genes targeted but only available in an outsourcing laboratory.
Methods: Peripheral blood was obtained from 16 advanced cancer patients in which Guardant360 (R) (G360) was requested as part of their clinical assistance. Blood samples were sent to be analyzed with G360 panel, and an additional blood sample was drawn to obtain and analyze cfDNA with OncomineT Pan-Cancer (OM) panel in an Ion GeneStudio S5T System.
Results: cfDNA analysis globally rendered 101 mutations. Regarding the 55/101 mutations claimed to be included by manufacturers in both panels, 17 mutations were reported only by G360, 10 only by OM and 28 by both. In those coincident cases, there was a high correlation between the variant allele fractions (VAFs) calculated with each panel (r = 0.979, p < 0.01). Regarding the six actionable mutations with an FDA-approved therapy reported by G360, one was missed with OM. Also, 12 mutations with clinical trials available were reported by G360 but not by OM.
Conclusions: In summary, G360 and OM can produce different mutational profile in the same sample, even in genes included in both panels, which is especially important if these mutations are potentially druggable.
Autores:
Borrero-Palacios, A.; Cebrian, A. (Autor de correspondencia); del Pulgar, M. T. G.; et al.
Revista:
SCIENTIFIC REPORTS
ISSN:
2045-2322
Año:
2019
Vol.:
9
Págs.:
7706
Autores:
Borrero-Palacios, A. ; Cebrian, A. (Autor de correspondencia); del Pulgar, M. T. G.; et al.
Revista:
SCIENTIFIC REPORTS
ISSN:
2045-2322
Año:
2019
Vol.:
9
Págs.:
2589
Cetuximab is a standard-of-care treatment for RAS wild-type metastatic colorectal cancer (mCRC) but not for those harbor a KRAS mutation since MAPK pathway is constitutively activated. Nevertheless, cetuximab also exerts its effect by its immunomodulatory activity despite the presence of RAS mutation. The aim of this study was to determine the impact of polymorphism Fc gamma RIIIaV158F and killer immunoglobulin-like receptor (KIR) genes on the outcome of mCRC patients with KRAS mutations treated with cetuximab. This multicenter Phase II clinical trial included 70 mCRC patients with KRAS mutated. We found KIR2DS4 gene was significantly associated with OS (HR 2.27; 95% CI, 1.08-4.77; P = 0.03). In non-functional receptor homozygotes the median OS was 2.6 months longer than in carriers of one copy of full receptor. Multivariate analysis confirmed KIR2DS4 as a favorable prognostic marker for OS (HR 6.71) in mCRC patients with KRAS mutation treated with cetuximab. These data support the potential therapeutic of cetuximab in KRAS mutated mCRC carrying non-functional receptor KIR2DS4 since these patients significantly prolong their OS even after heavily treatment. KIR2DS4 typing could be used as predictive marker for identifying RAS mutated patients that could benefit from combination approaches of anti-EGFR monoclonal antibodies and other immunotherapies to overcome the resistance mediated by mutation in RAS.
Revista:
PLOS ONE
ISSN:
1932-6203
Año:
2019
Vol.:
14
N°:
5
Págs.:
e0215970
Background Perioperative chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC) has been shown to improve survival compared to an exclusive surgical approach. However, most patients retain a poor prognosis due to important relapse rates. Population pharmacokinetic-pharma-codynamic (PK/PD) modeling may allow identifying at risk-patients. We aimed to develop a mechanistic PK/PD model to characterize the relationship between the type of neoadjuvant therapy, histopathologic response and survival times in locally advanced GC and GEJC patients. Methods Patients with locally advanced GC and GEJC treated with neoadjuvant CT with or without preoperative CRT were analyzed. Clinical response was assessed by CT-scan and EUS. Pathologic response was defined as a reduction on pTNM stage compared to baseline cTNM. Metastasis development risk and overall survival (OS) were described using the population approach with NONMEM 7.3. Model evaluation was performed through predictive checks. Results A low correlation was observed between clinical and pathologic TNM stage for both T (R = 0.32) and N (R = 0.19) categories. A low correlation between clinical and pathologic response was noticed (R = -0.29). The OS model adequately described the observed survival rates. Disease recurrence, cTNM stage >= 3 and linitis plastica absence, were correlated to a higher risk of death. Conclusion Our model adequately described clinical response profiles, though pathologic response could not be predicted. Although the risk of disease recurrence and survival were linked, the identification of alternative approaches aimed to tailor therapeutic strategies to the individual patient risk warrants further research.
Revista:
CANCERS
ISSN:
2072-6694
Año:
2019
Vol.:
11
N°:
5
Págs.:
606
Background: Although surgical resection is the only potentially curative treatment for pancreatic cancer (PC), long-term outcomes of this treatment remain poor. The aim of this study is to describe the feasibility of a neoadjuvant treatment with induction polychemotherapy (IPCT) followed by chemoradiation (CRT) in resectable PC, and to develop a machine-learning algorithm to predict risk of relapse. Methods: Forty patients with resectable PC treated in our institution with IPCT (based on mFOLFOXIRI, GEMOX or GEMOXEL) followed by CRT (50 Gy and concurrent Capecitabine) were retrospectively analyzed. Additionally, clinical, pathological and analytical data were collected in order to perform a 2-year relapse-risk predictive population model using machine-learning techniques. Results: A RO resection was achieved in 90% of the patients. After a median follow-up of 33.5 months, median progression-free survival (PFS) was 18 months and median overall survival (OS) was 39 months. The 3 and 5-year actuarial PFS were 43.8% and 32.3%, respectively. The 3 and 5-year actuarial OS were 51.5% and 34.8%, respectively. Forty-percent of grade 3-4 IPCT toxicity, and 29.7% of grade 3 CRT toxicity were reported. Considering the use of granulocyte colony-stimulating factors, the number of resected lymph nodes, the presence of perineural invasion and the surgical margin status, a logistic regression algorithm predicted the individual 2-year relapse-risk with an accuracy of 0.71 (95% confidence interval [CI] 0.56-0.84, p = 0.005). The model-predicted outcome matched 64% of the observed outcomes in an external dataset. Conclusion: An intensified multimodal neoadjuvant approach (IPCT + CRT) in resectable PC is feasible, with an encouraging long-term outcome. Machine-learning algorithms might be a useful tool to predict individual risk of relapse. A small sample size and therapy heterogeneity remain as potential limitations.
Revista:
JOURNAL FOR IMMUNOTHERAPY OF CANCER
ISSN:
2051-1426
Año:
2018
Vol.:
6
Págs.:
96
Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1: 1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival -DFS-) 25.26 months, 95% CI 8. 74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32-18.88).
Revista:
CLINICAL CANCER RESEARCH
ISSN:
1078-0432
Año:
2018
Vol.:
24
N°:
16
Págs.:
3787 - 3789
Although molecular subtype-based stratification and genomic signatures of increasing complexity are becoming a new strategy to guide therapeutic decisions in stage II/III colon cancer, several prognostic factors that can be easily obtained from formalin-fixed paraffin-embedded (FFPE) specimens should be considered to create combined models that better define individual patients' needs. (C) 2018 AACR.
Revista:
CLINICAL AND TRANSLATIONAL ONCOLOGY
ISSN:
1699-048X
Año:
2018
Vol.:
20
N°:
5
Págs.:
658 - 665
Synchronous liver metastases (LM) from gastric (GC) or esophagogastric junction (EGJ) adenocarcinoma are a rare events. Several trials have evaluated the role of liver surgery in this setting, but the impact of preoperative therapy remains undetermined. Patients with synchronous LM from GC/EGJ adenocarcinoma who achieved disease control after induction chemotherapy (ICT) and were subsequently scheduled to chemoradiotherapy (CRT) to the primary tumor and surgery assessment were retrospectively analyzed. Pathological response, patterns of relapse, progression-free survival (PFS), and overall survival (OS) were calculated. From July 2002 to September 2012, 16 patients fulfilling the inclusion criteria were identified. Primary tumor site was GC (nine patients) or EGJ (seven patients). LM were considered technically unresectable in nine patients. Radiological response to the whole neoadjuvant program was achieved in 13 patients. Eight patients underwent surgical resection of the primary tumor; in five of these LM were resected. A complete pathological response in the primary or in the LM was found in four and three patients, respectively. The most frequent site of relapse/progression was systemic (eight patients). Local and liver-only relapses were observed in two patients each. After a median follow-up of 91 months, the median OS and PFS were 23.0 (95% CI 13.2-32.8) and 17.0 months (95% CI 11.7-22.3). 5-year actuarial PFS is 17.6%. Our results suggest that an intensified approach using ICT followed by CRT in synchronous LM from GC/EGJ adenocarcinoma is feasible and may translate into prolonged survival times in selected patients.
Autores:
Maurel, J.; Sanchez-Cabus, S.; Laquente, B.; et al.
Revista:
CANCER CHEMOTHERAPY AND PHARMACOLOGY
ISSN:
0344-5704
Año:
2018
Vol.:
82
N°:
6
Págs.:
935 - 943
BackgroundNeoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC) patients has shown promising results in non-randomized trials. This is a multi-institutional phase II trial of NAT in resectable PDAC patients.MethodsPatients with confirmed resectable PDAC after agreement by two expert radiologists were eligible. Patients received three cycles of GEM (1000mg/m(2)/week) plus daily erlotinib (ERL) (100mg/day). After re-staging, patients without progressive disease underwent 5 weeks of therapy with GEM (300mg/m(2)/week), ERL 100mg/day and concomitant radiotherapy (45Gy). Efficacy was assessed using tumor regression grade (TRG) and resection margin status. Using a single-arm Simon's design, considering the therapy not useful if R0<40% and useful if the R0>70% (alpha 5%, beta 10%), 24 patients needed to be recruited. This trial was registered at ClinicalTrials.gov, number NCT01389440.ResultsTwenty-five patients were enrolled. Adverse effects of NAT were mainly mild gastrointestinal disorders. Resectability rate was 76%, with a R0 rate of 63.1% among the resected patients. Median overall survival (OS) and disease-free survival (DFS) were 23.8 (95% CI 11.4-36.2) and 12.8 months (95% CI 8.6-17.1), respectively. R0 resection patients had better median OS, compared with patients with R1 resection or not resected (65.5 months vs. 15.5 months, p=0.01). N0 rate among the resected patients was 63.1%, and showed a longer median OS (65.5 vs. 15.2 months, p=0.009).ConclusionThe results of this study confirm promising oncologic results with NAT for patients with resectable PDAC. Therefore, the present trial supports the development of phase II randomized trials comparing NAT vs. upfront surgery in resectable pancreatic cancer.
Revista:
HEPATIC ONCOLOGY
ISSN:
2045-0923
Año:
2018
Vol.:
5
N°:
2
Págs.:
HEP09
The hormone secretion in pancreatic neuroendocrine tumors (pNET) causes an important interference in patients' quality of life. We present two cases of pNET metastatic to the liver (a pancreatic endocrine carcinoma with a severe hormonal syndrome and an insulinoma with severe crisis of hypoglycemia and coma) refractory to conventional treatments, which were finally solved with selective internal radiation therapy (SIRT), a nonstandard level 1 therapy. We show two examples of an excellent control of symptoms together with a long survival after treatment with SIRT. The evidence supporting the use of this therapy is level 2. Our case reports strongly support the use of SIRT for the severe clinical syndrome in pNET metastatic to the liver and refractory to somatostatin analogs.
Autores:
Arredondo, J.; Baixauli, J; Pastor, C.; et al.
Revista:
CLINICAL AND TRANSLATIONAL ONCOLOGY
ISSN:
1699-048X
Año:
2017
Vol.:
19
N°:
3
Págs.:
379 - 385
Neoadjuvant chemotherapy is being actively tested as an emerging alternative for the treatment of locally advanced colon cancer (LACC) patients, resembling its use in other gastrointestinal tumors. This study assesses the mid-term oncologic outcome of LACC patients treated with oxaliplatin and fluoropyrimidines-based preoperative chemotherapy followed by surgery. Patients with radiologically resectable LACC treated with neoadjuvant therapy between 2009 and 2014 were retrospectively analyzed. Radiological, metabolic, and pathological tumor response was assessed. Both postoperative complications, relapse-free survival (RFS), and overall survival (OS) were studied. Sixty-five LACC patients who received treatment were included. Planned treatment was completed by 93.8 % of patients. All patients underwent surgery without delay. The median time between the start of chemotherapy and surgery was 71 days (65-82). No progressive disease was observed during preoperative treatment. A statistically significant tumor volume reduction of 62.5 % was achieved by CT scan (39.8-79.8) (p < 0.001). It was also observed a median reduction of 40.5 % (24.2-63.7 %) (p < 0.005) of SUVmax (Standard Uptake Value) by PET-CT scan. Complete pathologic response was achieved in 4.6 % of patients. Postoperative complications were observed in 15.4 % of patients, with no cases of mortality. After a median follow-up of 40.1 months, (p (25)-p (75): 27.3-57.8) 3-5 year actuarial RFS was 88.9-85.6 %, respectively. Five-year actuarial OS was 95.3 %. Preoperative chemotherapy in LACC patients is safe and able to induce major tumor regression. Survival times are encouraging, and further research seems warranted.
Revista:
CLINICAL AND TRANSLATIONAL ONCOLOGY
ISSN:
1699-048X
Año:
2016
Vol.:
18
N°:
9
Págs.:
909-914
Combined treatment for LARC obtains a 5-year OS rounding 90 %. Follow-up based on thoracic-abdominal CT scan allows an early diagnosis of metastatic lesions. Surgical resection of metastases, regardless of their location, greatly increases the patient's survival rate.
Revista:
BRITISH JOURNAL OF CANCER
ISSN:
0007-0920
Año:
2016
Vol.:
115
N°:
6
Págs.:
655 - 663
Background: The degree of histopathological response after neoadjuvant therapy in locally advanced gastric cancer (GC) is a key determinant of patients' long-term outcome. We aimed to assess the pattern of histopathological regression after two neoadjuvant approaches and its impact on survival times.
Methods: Regression grade of the primary tumour (Becker criteria) and the degree of nodal response by a 4-point scale (grades A-D) were assessed. Grade A-true negative lymph nodes (LNs); grade B and C-infiltrated LNs with any or little evidence of nodal response; and grade D-complete pathological response in a previously infiltrated LN. A favourable pathological response was defined as Becker Ia-b and grade D.
Results: From 2004 to 2014, 80 patients with GC (cT3-4/N + by CT-scan/EUS) were treated with either preoperative chemotherapy (ChT, n = 34) or chemoradiation (CRT, n = 46). Patients in the CRT group had a higher likelihood of achieving a Becker Ia-b response (58 vs 32%, P = 0.001), a grade D nodal regression (30 vs 6%, P = 0.009) and a favourable pathological response (23 vs 3%; P = 0.019). Patients with a grade D nodal response had a longer 5-year PFS and OS compared with those with a grade B or C response. Patients with a baseline negative LN status had similar outcomes irrespective of the preoperative therapy received (5-year OS; ChT vs CRT, 58 vs 51%, P = 0.92).
Conclusions: Preoperative chemoradiation increases the likelihood of achieving favourable ...
Revista:
MINERVA CHIRURGICA
ISSN:
1827-1626
Año:
2015
Vol.:
70
N°:
6
Págs.:
495 - 498
Revista:
NEURO-ONCOLOGY
ISSN:
1522-8517
Año:
2014
Vol.:
16
N°:
4
Págs.:
520 - 527
ackground: Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is contraindicated or biopsy results are inconclusive. Recent findings show that GBM cells release microvesicles that contain a select subset of cellular proteins and RNA. The aim of this hypothesis-generating study was to assess the diagnostic potential of miRNAs found in microvesicles isolated from the serum of GBM patients.
Methods: To control disease heterogeneity, we used patients with newly diagnosed GBM. In the discovery stage, PCR-based TaqMan Low Density Arrays followed by individual quantitative reverse transcriptase polymerase chain reaction were used to test the differences in the miRNA expression levels of serum microvesicles among 25 GBM patients and healthy controls paired by age and sex. The detected noncoding RNAs were then validated in another 50 GBM patients.
Results: We found that the expression levels of 1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p) were significantly associated with a GBM diagnosis. In addition, RNU6-1 was consistently an independent predictor of a GBM diagnosis.
Conclusions: Altogether our results uncovered a small noncoding RNA signature in microvesicles isolated from GBM patient serum that could be used as a fast and reliable differential diagnostic biomarker.
Revista:
JOURNAL OF GASTROINTESTINAL ONCOLOGY
ISSN:
2078-6891
Año:
2014
Vol.:
5
N°:
2
Págs.:
148-153
Neoadjuvant chemotherapy as a systemic treatment for stage IV colon cancer does not indicate surgery contraindication nor increases postoperative morbimortality by a significant amount.
Revista:
JOURNAL OF GASTROINTESTINAL ONCOLOGY
ISSN:
2078-6891
Año:
2014
Vol.:
5
N°:
2
Págs.:
104-111
Oxaliplatin/fluorpyrimidine neoadjuvant chemotherapy induces major tumour shrinkage at both the pathological and radiological levels. The CT scan shows a high accuracy and a low overstaged rate in LACC patients treated by means of a neoadjuvant approach.
Revista:
JOURNAL OF NEURO-ONCOLOGY
ISSN:
1573-7373
Año:
2013
Vol.:
115
N°:
3
Págs.:
429 - 435
Interesting neurological and cytological response rates after intrathecal (i.t) liposomal cytarabine have been observed in patients with leptomeningeal carcinomatosis (LMC) from solid tumors. However, the potential use of those responses as early predictors of time-to-progression (TTP) and overall survival (OS) is unexplored. 27 consecutive patients with LMC treated with 50 mg i.t liposomal cytarabine under compassionate drug use were retrospectively studied. All patients received i.t treatment every 2 weeks during induction and every 4 weeks during maintenance periods. Neurological and cytological responses were assessed before every liposomal cytarabine cycle. Most of the patients were female (17/27) diagnosed with breast cancer (15/27). A complete neurological response was seen among 11 % of the patients; partial response in 22 % of the patients; stable disease in 30 % of the patients and progressive disease in 37 % of them. Cytological assessment was available in 11/27 patients showing a 26 % complete response rate. The median time to neurological and cytological response was 15 days and 14 days, respectively. Patients showing a combined neurological and cytological response showed a significantly longer median TTP (122 vs. 3 days; p = 0.001) and OS (141 vs. 3 days; p = 0.002) compared to those showing both neurological and cytological progression. No grade 4 toxicities were recorded. According to these preliminary results, early neurological and cytological responses may be further studied as early predictors of TTP and OS in patients receiving i.t liposomal cytarabine for LMC.
Revista:
COLORECTAL DISEASE
ISSN:
1462-8910
Año:
2013
Vol.:
15
N°:
5
Págs.:
552-27
Neoadjuvant chemotherapy followed by surgery and chemotherapy for LACC is safe without apparent increase of early and medium-term complications
Revista:
DISEASES OF THE COLON AND RECTUM
ISSN:
0012-3706
Año:
2013
Vol.:
56
N°:
4
Págs.:
416-421
Patients with low third locally advanced rectal cancer with a poor response to neoadjuvant chemoradiotherapy (high y-pathological stage or low tumor regression grade) are at high risk of recurrence. Intense surveillance and the design of alternative therapeutic approaches aimed to lower the distant failure rate seem warranted.
Revista:
Hepatology
ISSN:
0270-9139
Año:
2013
Vol.:
57
N°:
3
Págs.:
1078 - 1087
Radioembolization (RE)-induced liver disease (REILD) has been defined as jaundice and ascites appearing 1 to 2 months after RE in the absence of tumor progression or bile duct occlusion. Our aims were to study the incidence of REILD in a large cohort of patients and the impact of a series of changes introduced in the processes of treatment design, activity calculation, and the routine use of ursodeoxycholic acid and low-dose steroids (modified protocol). Between 2003 and 2011, 260 patients with liver tumors treated by RE were studied (standard protocol: 75, modified protocol: 185). REILD appeared only in patients with cirrhosis or in noncirrhosis patients exposed to systemic chemotherapy prior to RE. Globally, the incidence of REILD was reduced in the modified protocol group from 22.7% to 5.4% and the incidence of severe REILD from 13.3% to 2.2% (P < 0.0001). Treatment efficacy was not jeopardized since 3-month disease control rates were virtually identical in both groups (66.7% and 67.2%, P = 0.93). Exposure to chemotherapy in the 2-month period following RE and being treated by the standard protocol were independent predictors of REILD among noncirrhosis patients. In cirrhosis, the presence of a small liver (total volume <1.5 L), an abnormal bilirubin (>1.2 mg/dL), and treatment in a selective fashion were independently associated with REILD. Conclusion: REILD is an uncommon but relevant complication that appears when liver tissue primed by cirrhosis or prior and subsequent chemotherapy is exposed to the radiation delivered by radioactive microspheres. We designed a comprehensive treatment protocol that reduces the frequency and the severity of REILD. (HEPATOLOGY 2013)
Revista:
EUROPEAN JOURNAL OF CANCER
ISSN:
0959-8049
Año:
2012
Vol.:
48
N°:
12
Págs.:
1774-1780
Background: The immunoglobulin G1 (IgG(1)) monoclonal antibody (MoAb) Cetuximab is active in metastatic colorectal cancer (mCRC) as first or subsequent lines of therapy. Efficacy seems restricted to KRAS wild-type tumours. IgG(1) may also induce antibody dependent cell mediated citotoxicity (ADCC) by recruitment of immune effector cells. ADCC is influenced by Fc gamma receptor (Fc gamma R) polymorphisms. We investigated the association of Fc gamma R polymorphisms and disease control rate (DCR) in mCRC patients treated with chemotherapy plus Cetuximab. Patients and methods: Tumour tissues from 106 patients were screened for KRAS codon 12 and 13 mutations using a sensitive multiplex assay (DxS, Manchester, United Kingdom). NRAS (codons: 12, 13 and 61), PI3K (exon 20) and BRAF (exon 15) were analysed by direct sequencing. Fc gamma RIIa and Fc gamma RIIIa polymorphisms were genotyped by TaqMan assays. Results: DCR was significantly higher in KRAS wild-type tumours (61% versus 39%, p - 0.049). In epidermal growth factor receptor (EGFR) downstream-mutated mCRC patients, those harbouring an Fc gamma RIIa H/H genotype had a higher DCR than alternative genotypes (67% versus 33%, p = 0.017). By multivariate analysis, Fc gamma RIIa-131H/H remained significantly correlated with DCR (p = 0.008). Conclusion: Fc gamma R polymorphisms may play a role in the clinical efficacy of Cetuximab in EGFR downstream mutated mCRC patients. Further research into Cetuximab immune-based mechanisms in KRAS-mutated patients seems warranted. (C) 2012 Elsevier Ltd. All rights reserved.
Revista:
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN:
0360-3016
Año:
2012
Vol.:
83
N°:
2
Págs.:
587-593
PURPOSE:
To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer.
METHODS AND MATERIALS:
Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m(2) b.i.d., Monday to Friday) and oxaliplatin (60 mg/m(2) on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed.
RESULTS:
A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively.
CONCLUSIONS:
Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible
Revista:
STEM CELLS
ISSN:
1066-5099
Año:
2011
Vol.:
29
N°:
11
Págs.:
1661 - 1671
Revista:
JOURNAL OF SURGICAL ONCOLOGY
ISSN:
0022-4790
Año:
2011
Vol.:
104
N°:
2
Págs.:
124-129
Background: Significant tumor downstaging has been achieved in patients with localized gastric adenocarcinoma by preoperative chemoradiotherapy (ChRT) or induction chemotherapy (Ch). However the influence of ChRT and Ch on postoperative outcomes has not yet been clarified, with very few studies examining this issue. We retrospectively analyzed the efficacy in terms of pathological response and early postoperative complications of two protocols of preoperative ChRT and Ch for locally advanced gastric cancer. Methods: Between 2000 and 2008, 72 patients with operable locally advanced gastric cancer (cT3-4/N+) were treated with preoperative treatment: 1-patients receiving induction Ch or 2-neoadjuvant Ch followed by concurrent ChRT. Postoperative histopathological regression and surgical complications were investigated including variables related to patients, surgical variables, preoperative treatment, and tumor. Results: There were no differences in the incidence of complications between the ChRT and Ch groups (30.9% vs. 33.3%). The most frequent complications were nonspecific surgical complications (pneumonia [12.5%] and infection from intravenous catheters [9.7%]). Risk factors for complications were high-body mass index (BMI > 25 kg/m(2)) and extension of surgery to the pancreas and spleen. A major pathological response was observed in 33.3% of patients, being more frequent in the ChRT group (47.6% vs. 13.3%; chi(2), P = 0.0024).
Revista:
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN:
0360-3016
Año:
2011
Vol.:
80
N°:
3
Págs.:
698-704
PURPOSE:
To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution.
METHODS AND MATERIALS:
From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment.
RESULTS:
Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%.
CONCLUSIONS:
The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.
Revista:
The Journal of Immunology
ISSN:
0022-1767
Año:
2011
Vol.:
187
N°:
11
Págs.:
6130 - 6142
Twenty-four patients with metastatic cancer received two cycles of four daily immunizations with monocyte-derived dendritic cells (DC). DC were incubated with preheated autologous tumor lysate and subsequently with IFN-alpha, TNF-alpha, and polyinosinic:polycytidylic acid to attain type 1 maturation. One DC dose was delivered intranodally, under ultrasound control, and the rest intradermally in the opposite thigh. Cyclophosphamide (day -7), GM-CSF (days 1-4), and pegIFN alpha-2a (days 1 and 8) completed each treatment cycle. Pretreatment with cyclophosphamide decreased regulatory T cells to levels observed in healthy subjects both in terms of percentage and in absolute counts in peripheral blood. Treatment induced sustained elevations of IL-12 in serum that correlated with the output of IL-12p70 from cultured DC from each individual. NK activity in peripheral blood was increased and also correlated with the serum concentration of IL-12p70 in each patient. Circulating endothelial cells decreased in 17 of 18 patients, and circulating tumor cells markedly dropped in 6 of 19 cases. IFN-gamma-ELISPOT responses to DC plus tumor lysate were observed in 4 of 11 evaluated cases. Tracing DC migration with [(111)In] scintigraphy showed that intranodal injections reached deeper lymphatic chains in 61% of patients, whereas with intradermal injections a small fraction of injected DC was almost constantly shown to reach draining inguinal lymph nodes. Five patients experienced disease stabilization, but no objective responses were documented. This combinatorial immunotherapy strategy is safe and feasible, and its immunobiological effects suggest potential activity in patients with minimal residual disease. A randomized trial exploring this hypothesis is currently ongoing.
Revista:
CLINICAL AND TRANSLATIONAL ONCOLOGY
ISSN:
1699-048X
Año:
2011
Vol.:
13
N°:
12
Págs.:
899-903
OBJECTIVES Analysis of the results on the treatment of esophageal cancer by transthoracic esophagectomy by a multidisciplinary team of surgeons and oncologists. METHODS Between January 1990 and December 2009, 100 consecutive patients underwent transthoracic esophagectomy. Data were collected prospectively and clinical, pathological and histological features of the tumors were analyzed as well as the results of postoperative morbidity and mortality. RESULTS The average patient age was 55 years (range 31- 83 years). In 59 cases the tumor was located in the lower third and in 41 cases in the middle third. Forty-six patients had adenocarcinoma and 54 squamous cell carcinoma. In 54 cases radio-chemotherapy was planned preoperatively. Classifi cation according to pathological tumor stage was: stage 0 in 21 patients, stage I in 10 patients, stage IIa in 28, stage IIb in 9, stage III in 21 and stage IV in 11. The mean number of lymph nodes examined was 14 (range 0-28). Hospital mortality occurred in 4 cases and postoperative complications in 29 patients (33%). The most frequent postoperative complication was pulmonary complications in 17 cases. The average hospital stay was 15.2 days (range 10-40 days) CONCLUSIONS The results of esophageal cancer have been improved in recent years due to the formation of multidisciplinary teams in this pathology. In our study we have shown that the results obtained with the transthoracic technique for cancer of the esophagus are within the ranges rep
Revista:
Cardiovascular and Interventional Radiology
ISSN:
0174-1551
Año:
2010
Vol.:
33
N°:
3
Págs.:
523 - 531