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  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e11527-e11527
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e11527-e11527
    Abstract: e11527 Background: Breast cancer is a heterogeneous disease with prognostic factors used by the oncologists to decide the treatment. Bcl2 is an antiapoptotic proto-oncogen involved in DNA break process that has been defined historically as a poor prognostic factor. This study was conducted to confirm whether or not bcl-2 is an independent prognostic factor. Methods: In this study, we have reviewed all patients who were diagnosed at our hospital between January 2007 and December 2008 (99 patients). Inclusion criteria were patients diagnosed of breast cancer whose anatomopathological report showed bcl-2 status as well as the rest of the parameters measured. The parameters measured were age, past medical history, menopausal status, TNM, hormone receptors, HER2, p53, Ki67, bcl-2, treatment applied, date of relapse (if any), date of death ( if occurred). All of them characterized by centralization measures. We conducted an analysis of prognostic factor that influenced survival. Results: The average age of diagnosis is 54.6 years (30-94 years). 42.4% were premenopausal. The average tumor size was 2.59 cm ( 0.5-7.5 cm). 81.8% had positive estrogen receptors. 92% were HER2 negative by inmunohistochemistry. 62.6% were p53 negative. Bcl-2 was 84.8% positive. The distribution by stage at diagnosis was: stage I 26.3%; stage II 49.5%; stage III 22.2%. Disease free survival for patients bcl2(+) was 45.6 months versus 22.6 months for patients bcl2 (-) (0.12-22.2; p: 0.00125). Overall survival for the group bcl2(+) was 48 months (41.6-54.3) and bcl2 (-) was 48.24 months (42.48 to 54). Conclusions: We can state that bcl2 is not an independent prognostic factor. Despite the value in other diseases, the determination of bcl-2 by inmunohistochemistry in breast cancer in stages I, II and III at the moment of the diagnosis does not provide any prognostic information.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS3633-TPS3633
    Abstract: TPS3633 Background: Total neoadjuvant therapy (TNT) has recently become a standard therapy for locally advanced rectal cancer (LARC). All nonsurgical interventions, including chemotherapy and concurrent chemoradiotherapy (CRT), are administered before either surgical resection of the rectum or non-operative management (NOM), depending on response to TNT. In the case of NOM, the impact of distant relapse on survival remains to be elucidated and circulating tumor DNA (ctDNA) monitoring has been proposed as a tool for early detection of relapse. Furthermore, predictive biomarkers of response to TNT are warranted for the early identification of patient candidates for NOM. In this regard, stromal contribution to sensitivity to pre-operative CRT is investigated by a transcriptomic signature on baseline tumor samples, as previously proposed by Isella C et al., Nature Genet, 2015. Methods: NO-CUT is a multicenter one-stage phase II trial aimed at assessing if a TNT approach with CAPOX followed by CRT can safely spare demolitive surgery in patients with LARC achieving a clinical complete response without increasing the risk of distant metastatic relapse. A Brookmeyer and Crowley approach was chosen to test the null hypothesis that the true distant relapse-free survival at 2.5 years rate is ≤75% against a one-sided alternative. The NOM cohort of the trial needs to accrue 44 evaluable patients and to be followed for at least 2.5 years. Such design yields a type I error rate of 10% and power of 80% when the true 2.5 years distant RFS proportion is 87%. Since it is assumed that the proportion of patients entering in the NOM cohort of the trial is at least 25%, a total of 180 patients are to be enrolled in NO-CUT study. Patients with medium-low LARC undergo TNT (4 cycles of CAPOX: capecitabine 1000 mg/m 2 bid days 1-14 q 3 weeks; oxaliplatin 130 mg/m 2 day 1 q 3 weeks) and 5 weeks of standard pelvic CT-RT, then restaging with imaging (MRI, CT-scan, and ultrasound endoscopy), and tumor biopsy. According to an algorithm defined for assessing tumor response, patients enter either NOM or surgery cohorts. During the follow-up phase of the trial, the NOM cohort is followed with intensive pelvic imaging and periodic blood samplings for 5 years. Tumor samples and ctDNA are studied at baseline, after TNT, and during follow-up. As of January 2023, 161 of planned 180 patients in 4 centers have been enrolled. Supported by grants from Associazione Italiana Ricerca Cancro (AIRC IG 2017-20685) and Fondazione Oncologia Niguarda. Clinical trial information: EudraCT 2017-003671-60 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 2565-2565
    Abstract: 2565 Background: The nuclear export protein exportin 1 (XPO1) is overexpressed in many cancers, including GBM. Selinexor is an inhibitor of XPO1 that crosses the blood-brain-barrier and targets cancer cells by sequestering tumor suppressor proteins and oncoprotein mRNAs in the cell nucleus, inducing cancer cell apoptosis. Selinexor is FDA approved for treatment of patients (pts) with refractory multiple myeloma and is under evaluation for GBM. Methods: We previously reported encouraging results from a phase II clinical trial of selinexor for molecularly unselected pts with recurrent GBM (ASCO 2019). On available pre-treatment archival tumor tissue from 57 cases, we performed DNA exome and RNA transcriptome sequencing to use both gene mutations and expressions for exploring molecular correlates of response in selinexor treated pts, in a hypothesis generating, post-hoc, exploratory analysis. Pts with inadequate drug exposure were excluded ( 〈 21 days or 〈 3 doses). We compared OS and PFS between mutated and wild-type patients for genes mutated in at least 5 cases. RNAseq data were used to infer differential protein activities between patients with selinexor sensitive disease (defined as best response of partial or complete response, n = 7) vs. resistant disease (defined as progressive disease as best response, n = 23). Results: Two mutated genes were associated with longer survival in selinexor treated pts: DOCK8 (n = 7; progression free survival [PFS], P = 0.013, hazard ratio [HR] = 3.75 [1.32-10.62]; overall survival, P = 0.009, HR = 15.39 [2.00-118.34] ) and PDX1 (n = 5, PFS, P = 0.014, HR = 4.468 [1.361-14.670]). Other commonly mutated genes in glioma, including IDH1 (n = 9) were observed but not associated with survival. Protein activities inferred from RNA sequencing data were also correlated with response to selinexor. In a machine learning model, ZC3H12A (also called MCPIP-1), a negative regulator of inflammation; RAB43, a member of the RAS family that binds GTP and regulates vesicle trafficking, and SOCS3, a suppressor of cytokine signaling that can antagonize JAK/STAT signaling and repress innate immunity, predicted clinical benefit from selinexor (area under the ROC curve from leave one out cross validation = 0.89, permutation test P 〈 0.04). Conclusions: DOCK8 and PDX1 mutations were favorable prognostic factors in selinexor treated pts. Activity of three proteins (ZC3H12A, RAB43, and SOCS3) predicted clinical benefit from selinexor. Further studies with more pts are required to validate our findings. ClinicalTrials.gov: NCT01986348
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e17503-e17503
    Abstract: e17503 Background: Lung cancer is the leading cause of cancer-related deaths in the Western world. CT and mediastinoscopy are the standard for staging modalities in recent years; PET has emerged as a complement to other techniques. Mediastinal lymph node (MLN) staging is important because it establishes subsequent treatment. The aim of the present study is to analyze the relationship between mediastinal staging by endobronchial ultrasound-guided transbronchial needle aspiration, mediastinoscopy, lymphadenectomy and PET. It also analyzes the patient characteristics like age, sex, histology. Methods: The study prospectively evaluated 42 patients from August 2009 to March 2011. All of them had MLN staging by PET and pathology (tumor resection with systematic lymph node dissection, transbronchial needle aspiration or mediastinoscopy). Univariable date analysis was conducted using Pearson's chi-square test. P values were considered statistically significant if 〈 0.05. Results: The study group comprised 42 patients, 83% men and 17% female, mean age of 66 years. The primary tumor cell type: 45% squamous cell, 33% adenocarcinoma and 19% large cells. 40 patients were smoking. The most frequent location of tumor was upper lobes (58%). The most common stage found after surgery was stage I (42%), stage II (19%), stage III (A: 29%, B: 5%) and stage IV (5%). The kappa statistic for diagnostic agreement between CT and PET was 0.53 (p 〈 0.001). About MLN staging, PET has a sensitivity of 61% and specificity of 53% , positive predictive value 61% and negative 53%. Conclusions: The present study attempts to find the relationship between tumor involvement found in PET and resected tumor specimens obtained from the mediastinum. Our sensitivity and specificity were not concordant with those previously reported; this may be due to the learning curve at our center or the shortness of our series. In contrast we conducted histological examination of all involved MLNs, supporting our data and shows that this confirmation can lead to a change of therapeutic strategy in some cases.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 5
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e17502-e17502
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e17502-e17502
    Abstract: e17502 Background: Objective: The objective of the study is to indentify the patients diagnosed of stage III non-small cell lung cancer (NSCLC) in Puerta de Hierro Madrid Hospital (Spain) between 2000 and 2008, who had longer overall survival rates (more than 24 months) and longer time to progression after completing initial treatment. Methods: We revised all cases of NSLC seen in our hospital, and of those, selected 147, the ones diagnosed, treated and followed completely in our hospital. We reviewed the age at diagnosis, initial staging, modalities of treatment received in each case, time to progression, site of development of metastasis, time to relapse and overall survival. The time of monitoring was from date of diagnosis until death date or, until transferral to palliative care clinics. Results: We revised 966 histories of patients, of which 147 were diagnosed stage III, treated and followed in our hospital. Most common hystological type were Epidermoid Carcinomas (54.3% versus 21.7% of adenocarcinomas), and were diagnosed at older ages. 45.6% underwent surgery, most of them (41.2%) were treated before with neoadyuvant chemo or radiotherapy, with a median survival of 32.4 months, with an overall survival interval very wide, from 20 days until more than 8 years. Among these patients were the ones who survived more than 24 moths after diagnosis, and those had Ps 0 -1 at diagnosis, less comorbidities and had the same proportion of stage IIIA and IIIB stages. 53% of patients were only treated with cisplatin-based chemotherapy or radiotherapy at 60Gy, and in these cases, the median overall survival was shorter: 9.5 months Conclusions: In our study, neoadyuvant therapies and the protocols used are the most accepted in international guidelines. The patients who underwent chemotherapy and surgery lived much more and they had better Performance Status at diagnosis, so we can conclude that chemotherapy and surgery, if possible, are a good treatment option with longer global survival. Definitive chemotherapy and radiotherapy should be better reserved for those patients who are not candidates for surgery.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e17515-e17515
    Abstract: e17515 Background: The increase in longevity due to a better quality of life in old people makes possible the chemotherapy treatment in the most of patients with Small Cell Lung Cancer. The aim of this research is to evaluate if there are differences in overall survival according to the age (comparing older and younger than 65 years old), in patients treated with the same scheme of chemotherapy. Methods: Patients diagnosed with small cell lung cancer between years 2003 and 2010 and treated in our hospital by the scheme carboplatin 300mg/m 2 IV on day 1, with etoposid 100mg/m 2 per day (iv on day 1 and oral days two to five), were retrospective reviewed to evaluate the overall survival by group of age (older and younger than 65 years old). Results: 96 patients diagnosed of small cell lung cancer were treated in our hospital between 2003 and 2010 with the aforementioned scheme of chemotherapy. 70 of them were on extended stage, and 26 had limited stage; 54 were until 65 years old (56.25%) and 42 were older (43.75%). In extended disease, the elder than 65 presented an overall survival rate one year after the diagnosis of 38.3% (SE 9.3%) and at 18 months 10.2% (SE 6.3%), with a median overall survival of 10 months (Range 1 to 22 months). The younger than sixty five had an overall survival at 12 months of 23.8% (SE 6.6%), and at 18 moths of 5.4 (3.7%), non significant (p:0.437). Their median overall survival was 8.23 months, with a range of 〈 1month to 24 months. In the group with limited stage, the sample older than 65 had a probability of overall survival 1 year after the diagnosis of 46,2% (Standard error (SE), 13.8%), and 23.1% (SE 11.7%) at 18 months, versus a 48.6% (SE 14,8%) at 12 months and 19.4% (SE 12.2%) in younger (p:0.708). The median overall survival in elder than 65 with Limited stage was 11.5 months (6 to 81 months), and for the younger 15 months (range 4 to 25 months). Conclusions: The hybrid scheme carboplatin 300mg/m 2 IV on day 1, with etoposid 100mg/m 2 per day (iv on day 1 and oral days 2 to 5), provides an acceptable overall survival, without significant differences comparing older and younger than 65 years old, both in limited and extended stage.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 7
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e18522-e18522
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e18522-e18522
    Abstract: e18522 Background: Bone marrow transplant (BMT) has become an increasingly common treatment modality for both malignant and non-malignant conditions. However, BMT requires significant healthcare and financial resources, which can result in allocation disparities across socioeconomic, demographic, and racial/ethnic groups. The data exploring how demographic disparities impact survival after BMT is limited, particularly within the adolescent and young adult (AYA) population, defined as patients between the ages of 15 and 39 years. The goal of this study was to assess overall survival of AYA patients undergoing transplant at our institution and to gain insight into if demographic factors impact the likelihood of mortality after transplantation. Methods: Patients aged 15-39 who underwent transplant at the Wilmot Cancer Institute in Rochester, NY between 2012-2020 were identified. Information regarding demographic characteristics, indication for transplant, and mortality was collected. The primary endpoint was overall survival (OS), defined as the time from transplant to the date of death from any cause or the date of last in-person contact. Survival criteria were estimated using the Kaplan-Meier method and compared using mortality odds ratios. These analyses were stratified by indication for transplant, recorded race/ethnicity, gender, and by age. Results: 169 patients met inclusion criteria, and median OS for the entire cohort was not reached. Of 108 allogenic transplant recipients, median OS was 7.85 years (95% CI [3.3, not estimated]). Median OS for patients receiving transplant for solid tumor pathology was 3 years (95% CI [0.4 years, not estimated] ), compared to other indications for transplant where survival exceeded the median. For allogenic transplant patients, median OS for Black patients was 4.8 years (95% CI [0.7 years, not estimated]), 7.8 years for Caucasian patients (95% CI [3.3 years, not estimated] ), median OS was not reached for Hispanic patients, and 1.1 years for all other minorities (95% CI [0.4 years, not estimated]) (p = 0.28). There was no significant difference in mortality based on insurance type or gender for either type of transplant. There was a significant difference in mortality for allogenic transplant patients based on average median household income when compared at an average income of $60,000/ year (OR 2.6, 95% CI [1.164, 5.6] p = 0.0097). Conclusions: Overall survival for AYA patients who had a transplant for any indication at our institution was better than expected. There were no significant differences for either transplant type based on gender, racial/ethnic background, gender, age, or indication for transplant. There was a significant difference based on median household income. Larger multi-institutional studies are likely needed to accurately identify further demographic disparities.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 8
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e12015-e12015
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e12015-e12015
    Abstract: e12015 Background: Malignacies rank fourth on the leading causes of death in recipients of solid organ transplantation. High-dose immunosuppression, infections with oncogenic viruses and the pre-transplant risk, mainly due to tobacco, make these patients more susceptible for developing cancer. In the present study we reviewed a collective of 50 patients with lung transplantation (LT) and cancer. Methods: Retrospective study of 503 lung transplant patients, performed at the Hospital Universitario Puerta de Hierro during 1993 and 2012. We included the following variables: date of birth, reason and date of transplantation, date of diagnosis of malignancy, histology and response to treatment, date and cause of exitus. The contrasts between proportions were performed using Chi-square test and survival curves using the product-limit method of Kaplan-Meier. Results: The 503 included transplant patients developed a total of 55 post-transplant malignancies in 50 patients. Four patients presented tumors already previous to the transplantation. The main underlying pathologies of the patient collective are idiopathic pulmonary fibrosis (50%), emphysema (30%) and cystic fibrosis (14%). Histology of the 55 post-transplant tumors: 18 skin cancer, 12 lung cancer, 8 gastrointestinal cancer, 6 Non-Hodgkin Lymphomas, 2 bladder cancer, 2 myelodysplastic syndromes, 2 sarcomas and 5 others. The mean age of diagnosis of malignancies is at 59 years (18-68). The mean time from transplantation to tumor diagnosis amounts 4 years (1-15). Of the 21 patients (42%) that have died until data collection, cancer was death cause in 15 (30%) Conclusions: Relying on our data, the majority of malignancies are skin and lung cancer and lymphoproliferative syndromes, attributing complications that should be considered in lung transplantation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e19532-e19532
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e19532-e19532
    Abstract: e19532 Background: The aim of this study was to evaluate the characteristics of patients older and younger than 70 years diagnosed with follicular lymphoma (FL). Methods: A review of the clinical database of 131 patients with LF treated in our hospital between May 1980 and January 2013 was performed. Clinical, treatment, and following items were obtained. Results: 34 patients were 70 years of age or older (70.6 to 83.9 years) and 98 were younger (23-69.3 years), without significant differences with respect to gender, histology grade, stage and Performance Status. The extranodal involvement sites in the younger group were more frequent in spleen (17.1%), liver (17.1%), bowel (14.3%) and head and neck (11.4%), meanwhile in the eldest were in lung (35.7%), bone (21.4%) and pleura (14.3%), with significant differences (p=0.007). The median Overall Survival (OS) was 8.1 years (1.2-31.4) in the younger group and 4.3 years (1.2-7.2) in the older group. The median of probability of Free Progression Survival (FPS) was 3.2 years (0.1-31.4) in younger patients and 1.7 years (0.1-5.5) in older patients. It exists significant differences in the probability of OS and FPS (both p 〈 0.001), with worse results in older patients. The analysis of the causes of death (FL, second tumour or other causes) does not demonstrate significant differences between both groups. Differences were not found between the age groups when CHOP versus CVP was used. Not using rituximab in addition to CHOP scheme implies a relative risk of relapse of 3.3 (95% IC 1.5-6.9 p 〈 0.001). Conclusions: It should be noted a worse OS and FPS in the older population. Nevertheless, the different extranodal involvement suggests a different biologic behaviour in both groups. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS4155-TPS4155
    Abstract: TPS4155 Background: GC represents a worldwide problem; radical surgery remaining the gold standard of curative treatment. In the West, even with peri-operative chemotherapy, 5-year survival rate is approximately 40%. GC is a heterogeneous disease, well characterized by different molecular classifications, all having in common the role of the immune system and a T-cell inflamed phenotype across all subtypes. The anti-PD-L1 Av antibody has demonstrated efficacy in GC with response rates of around 10% in the refractory setting. The addition of other immune checkpoint inhibitors to chemotherapy have demonstrated efficacy in the metastatic setting. The combination of Av to perioperative chemotherapy may increase pathological responses by a synergistic effect, and then improving the survival (OS). Methods: The MONEO is an open-label, non-randomized, multicentric, phase II study that explores the combination of Av plus peri-operative FLOT (docetaxel, oxaliplatin, fluorouracil/leucovorin) in resectable GC pts. EudraCT 2019-000782-21; ClinicalTrials NCT03979131. Main inclusion criteria require pts with histologically proven GC, stage Ib (T1N1 only) - IIIC (7th AJCC Ed), available paraffin block from diagnosis and surgery, evaluable disease (RECIST 1.1) amenable to radical surgery. Significant comorbidities and active autoimmune diseases are excluded. Treatment consists of surgery with 4 peri-operatory cycles of FLOT + Av, followed by Av up to one year. The primary objective is the pathological complete response (pCR) rate, compared to historical data. Secondary objectives include OS, disease-free survival, R0 resection rate, tolerability and biomarker analysis. Key point is the comprehensive biomarker analysis from tissue and blood samples (pathological immune response, TCR clonality, immune contexture characterization, immunodynamic monitoring). Statistics for an estimated 33% pCR (historical 16%), 82% power, 0.1 one-side type I error. 37 pts will be recruited from 10 Spanish centers. The sponsor is Vall d'Hebron Institute of Oncology (VHIO), principal investigators Dr. Melero and Dr. Alsina. In compliance with the Helsinki Declaration. At a data cut-off day of 5 th of February 2021, 38 patients have been enrolled, 27 of them have had the surgery. Although the difficulties during the COVID19 pandemia, only two patients had been withdrawn from the study. Clinical trial information: NCT03979131.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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