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Patients with cancer present a higher risk of rethrombosis and bleeding secondary to anticoagulant treatment than individuals without cancer. Given the lack of specific clinical trials, the decision regarding the optimal duration of treatment must consider multiple factors, including sex. The current study used data from the international, prospective TESEO Registry that includes consecutive patients diagnosed with cancer-associated thrombosis (CAT). Between July 2018 and December 2022, 2,823 patients were included in the TESEO Registry, 1,351 (48%) of whom were female. The most common venous thromboembolic event (VTE) in both sexes was pulmonary embolism (PE), with an incidence of 58.0% among men and 54.3% in women (p=0.045). After a median follow-up of 6.9 months (IQR, 1.9-14.4), the rethrombosis rate at the end of follow up was 10.0% in males and 15.0% in females (p=0.14). The location of the primary tumor in the gastrointestinal tract was associated with a greater risk of rethrombosis, whereas sex had no significant impact. Men presented twice as many major bleeds. Additional risk factors for major bleeding included situations of risk due to tumor site or thrombocytopenia, as well as the presence of active tumor bleeding at the time of VTE diagnosis. Overall survival was higher among women. Given the higher incidence of major bleeding among men, sex should be deemed a relevant factor when deciding on the duration of anticoagulant treatment in cancer patients.

Purpose: This study aimed to develop a set of criteria and indicators to evaluate the quality of care of patients with head and neck cancer (HNC)., Methods: A systematic literature review was conducted to identify valuable criteria/indicators for the assessment of the quality of care in HNC. With the aid of a technical group, a scientific committee of oncologists specialised in HNC used selected criteria to propose indicators that were evaluated with a two-round Delphi method. Indicators on which consensus was achieved were then prioritised by the scientific committee to develop a final set of indicators., Results: We proposed a list of 50 indicators used in the literature or developed by us to be evaluated with a Delphi method. There was consensus on the appropriateness of 47 indicators in the first round; the remaining 3 achieved consensus in the second round. The 50 indicators were scored to prioritise them, leading to a final selection of 29 indicators related to structure (3), process (22), or outcome (4) and covering diagnosis, treatment, follow-up, and health outcomes in patients with HNC. Easy-to-use index cards were developed for each indicator, with their criterion, definition, formula for use in real-world clinical practice, rationale, and acceptable level of attainment., Conclusions: We have developed a set of 29 evidence-based and expert-supported indicators for evaluating the quality of care in HNC, covering diagnosis, treatment, follow-up, and health outcomes., (© 2023. The Author(s).)

High-grade gliomas (HGG) are the most common primary brain malignancies and account for more than half of all malignant primary brain tumors. The new 2021 WHO classification divides adult HGG into four subtypes: grade 3 oligodendroglioma (1p/19 codeleted, IDH-mutant); grade 3 IDH-mutant astrocytoma; grade 4 IDH-mutant astrocytoma, and grade 4 IDH wild-type glioblastoma (GB). Radiotherapy (RT) and chemotherapy (CTX) are the current standard of care for patients with newly diagnosed HGG. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent high-grade gliomas is not well defined and decision-making is usually based on prior strategies, as well as several clinical and radiological factors. Whereas the prognosis for GB is grim (5-year survival rate of 5-10%) outcomes for the other high-grade gliomas are typically better, depending on the molecular features of the tumor. The presence of neurological deficits and seizures can significantly impact quality of life., (© 2023. The Author(s).)

Background: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC., Patients and Methods: Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed., Results: Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively., Conclusions: In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC., Competing Interests: Disclosure AP has received research funding from Bristol Myers Squibb, DEMO, KURA Oncology, and Roche and consultant/advisory/honoraria fees from AstraZeneca, Bristol Myers Squibb, HPVtRNA, Merck Serono, MSD, Nanobiotics, and Pfizer companies. JF has served in a consulting or advisory role for Bristol Myers Squibb, Innate Pharma, Merck, Merck Sharp & Dohme, Rakuten, and Roche and has received non-financial support from Bristol Myers Squibb and Merck Sharp & Dohme. KH has received research funding from AstraZeneca, Boehringer Ingelheim, MSD, and Replimune, and consultant/advisory/honoraria fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Codiak, Inzen, Merck Serono, Mersana Therapeutics, MSD, Pfizer, and Replimune. MG has received research funding from Agenus, Bristol Myers Squibb, Cullinan Labs, Genentech, Genocea Biosciences Inc., Kura, LaRoche, NRG, and University of Cincinnati. She has received consulting fees from Amgen Inc., Aspyrian Therapeutics, AstraZeneca Pharmaceuticals, Bayer Healthcare Pharmaceutics, Bicara Therapeutics, Bicara, BioNtech AG, Bristol Myers Squibb, Celgene Corp, Coherus Biosciences, Debiopharm, Eisai Medical Research Inc., EMD Serono, Inc., Genocea Biosciences Inc., Gilead Sciences Inc., Ipsen Biopharmaceuticals Inc., Istari Oncology Inc., iTeos Therapeutics, Kura Oncology, LLX Solutions, LLC, Merck & Co, Mirati Therapeutics, Nektar Therapeutics, NewLink Genetics Corp., OncLive Intellisphere, Roche Diagnostics GmbH, Roche, Seagen, Sensei Biotherapeutics Inc., Shattuck Labs Inc., and TRM Oncology. She received honoraria from OncLive and Roche. She has received support for attending meetings and/or travel from AACR, ASCO, and SITC. She reports an issued patent for NGVL4a-Sig/E7(detox)/HSP70 plasmid DNA for a clinical protocol entitled ‘An open-label phase one study of the safety with stage III or IV HPV16-positive head and neck squamous cell carcinoma’ and pending patents for oral HPV infection detection for oral cancer screening and diagnosis, and for HPV mRNA detection on oral cytology specimens for diagnosis and screening for oral cancer. She reports participation on a data safety monitoring board or advisory board for BioMimetix, Kura, NRG, Seagen, Sensei Biotherapeutics Inc., and SQZBiotech. She reports stock options with Sensei. MJA has received honoraria from AstraZeneca, Bristol Myers Squibb, MSD, ONO, and Roche and is a consultant or advisor for AstraZeneca, Bristol Myers Squibb, Takeda, MSD, Novartis, Roche, and Alpha pharmaceutical. ST reports grants from AstraZeneca, during the conduct of the study; grants and personal fees from Eisai, Novartis, Taiho, MSD, Chugai, Bayer, and Daiichi-Sankyo, outside the submitted work. JW has stock and other ownership interests in Achilles Therapeutics, Nektar Therapeutics, Vesselon, Nuvalent, En Fuego Therapeutics, and Lyell Immunopharma. He has a consulting or advisory role with AstraZeneca, EMD Serono, Genentech, G1 Therapeutics, Jounce Therapeutics, AbbVie, Nanobiotix, Azitra, Eli Lilly, Blueprint Medicines, Pfizer, Saatchi Wellness, Jazz Pharmaceuticals, Boehringer Ingelheim, Regeneron, Genmab, SDP Oncology, and BeiGene. He has received research funding from Mirati Therapeutics, Sumitomo Dainippon Pharma Oncology, Boehringer Ingelheim, and PDS Biotechnology. His institution has received research funding from Amgen, G1 Therapeutics, Immunicum, Inspirna, and Loxo/Lilly. He has had travel, accommodations, or expenses paid by Mirati Therapeutics. JPM is an advisory board member or speaker with honoraria (institution managed) for: Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA, and Nektar Therapeutics. He has accepted travel expenses from: Amgen, Bristol Myers Squibb, Pfizer, and MSD. He is on the data safety monitoring board with honoraria for Psioxus. His institutional conflict of interest (funding to institution for research support) includes all companies. He has an uncompensated advisory role with MSD. SB reports owning stock in Roche Holding AG and is an employee of Verana Health. SCT reports receiving grant or research support from AstraZeneca and Eisai and consultant fees from AstraZeneca. RH is an employee of Dana-Farber Cancer Institute and has a leadership role with NCCN. He is a consultant or advisor for Achilles Therapeutics, AstraZeneca, Bayer, BioNTech AG, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus Biosciences, Eisai, EMD Serono, Genentech, Gilead Sciences, GSK, Immunomic Therapeutics, Loxo, Merck, MIRATI, Pfizer, and Vaccinex. His institution has received research funding from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Genentech, Kura, Merck, and Pfizer. He has other relationships with ISA Pharmaceuticals and Nanobiotix. SK received honoraria from Merck Serono, MSD, Novartis, Bristol Myers Squibb, Amgen, Roche, Sanofi-Aventis, Servier, Incyte, and Lilly; research funding from Merck Serono, Lilly, Bristol Myers Squibb, and Roche. PSM received advisory/lecture honoraria from BMS, KLS Martin Group, and Roche. He has accepted travel expenses from: AstraZeneca, BMS, GSK, KLS Martin Group, MSD, and Roche. VB is a freelance contractor for, and shareholder in, AstraZeneca. PH, BE, SW, RFO, AY, JFK, and NM are or were employees and shareholders of AstraZeneca. SW and NM report published patent WO2021228988A1. TYS has received grants/research funding from AstraZeneca, Bristol Myers Squibb, CUE biopharma, Kura, Merck/MSD, Nanobiotix, Regeneron, and Roche/Genentech, as well as honoraria from Bayer, BioNTech/Syneos, Coherur Biosciences, Cue Biopharma, Innate, KURA, Merck/MSD, Nanobiotix, Sanofi, Vir Biotechnology. All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Venous thromboembolism (VTE) is common in non-small cell lung cancer (NSCLC) patients undergoing systemic chemotherapy. The usefulness of Khorana score (KRS) to predict risk in lung cancer patients is limited, and the identification of patients who would benefit most from thromboprophylaxis is challenging. We aimed to identify variables whose values before chemotherapy helped in predicting VTE occurrence, and build a model to assess VTE risk., Materials and Methods: A cohort of newly diagnosed NSCLC patients to undergo outpatient chemotherapy, not under anticoagulant treatment, was recruited. Pre-chemotherapy demographic, clinical, analytical and tumor-specific variables were collected. Patients were prospectively followed-up for 12 months to record VTE events. Bivariate and multivariate analyses were performed to identify VTE-associated variables, and a prediction model was built and compared with KRS., Results: 90 patients were recruited, 18 of whom had a VTE event during follow-up. High baseline levels of factor VIII (FVIII) and, especially, soluble P-selectin (sP-selectin), were independently associated with VTE risk (hazard ratio [HR] 4.15, 95% confidence interval [CI] 1.17-14.71, and 66.40 [8.70-506.69], respectively). Our so-called Thrombo-NSCLC risk score, which assigns 1 and 3 points to high FVIII and sP-selectin values, respectively, was significantly better than KRS in predicting VTE (area under the curve [AUC] 0.93 vs. 0.55, sensitivity 94.4 vs. 35.0%, specificity 93.1 vs. 60.0%). Our prediction model showed significant discriminating capacity between high risk vs. intermediate/low risk patients, while KRS did not., Conclusions: The Thrombo-NSCLC risk score may be useful to identify those NSCLC patients who would benefit most from thromboprophylaxis., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways., Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2., Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10 -6 ). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance., Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk., Competing Interests: The authors declare that they have no conflict of interest. Ethical approval Study participants were recruited through the CIMBA Initiative, following the approval of the corresponding protocol by the Institutional Review Board or Ethics Committee at each participating center. Written informed consent was obtained from all study participants.

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers., Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided., Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10(-) (6)) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10(-3)). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed., Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes., Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach., Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments., Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers., Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies., (©2014 American Association for Cancer Research.)

Purpose: The current incidence of cancer in the world is 14 million cases in 2012, with a mortality rate of 8.2 million in that year. The incidence of cancer in Spain exceeds 215,000 cases a year, and survival rates are the highest when compared to those of our neighbouring countries. Among the reasons for the steady decrease in cancer mortality rates in Spain, two causes must be highlighted: the increasing efficacy of treatment and prevention measures. It is important evaluate the opportunity of early detection and prevention in these tumors., Methods: We have reviewed the evidence published in the most prevalent tumors. The evidence levels described in this paper are based on the GRADE system., Results: We show the recommendations about primary and secondary prevention in breast cancer, cervical cancer, colorectal cancer, prostate cancer and lung cancer., Conclusion: The diffusion of these preventive tools can reduce the incidence of cancer and increase the number of early diagnostics in the most prevalent tumors.

Epidermal growth factor receptor gene (EGFR) alteration is a common feature in most of glioblastoma multiforme (GBM). Robust response of anti-EGFR treatments has been mostly associated with the EGFR deletion mutant variant III (EGFRvIII) and expression of PTEN. We have performed a prospective trial in order to confirm the efficacy of erlotinib treatment in patients with relapsed GBM who expressed EGFRvIII and PTEN. All patients included in the trial were required to be PTEN (+++), EGFR (+++) and EGFRvIII (+++) positives by immunohistochemistry. This new phase II trial enrolled 40 patients and was design to be stopped in case of fewer than two responses in the first 13 patients. Patient eligibility included histopathology criteria, radiological progression, more than 18 years old, Karnofsky performed status, KPS > 50, and adequate bone marrow and organ function. There was no limit to the number of prior treatments for relapses. No enzyme-inducing antiepileptic drugs were allowed. The primary endpoints were response and progression-free survival at 6 months (PFS6). Thirteen patients (6 men, 7 women) with recurrent GBM received erlotinib 150 mg/day. Median age was 53 years, median KPS was 80, and median prior treatments for relapses were 2. There was one partial response and three stable diseases (one at 18 months). PFS at 6 months was 20 %. Dose reduction for toxicity was not needed in any patient. Dermatitis was the main treatment-related toxicity, grade 1 in 8 patients and grade 2 in 5 patients. No grade 3 toxicity was observed. Median survival was 7 months (95 % IC 1.41-4.7). As conclusion, monotherapy with erlotinib in GBM relapses patients with high protein expression for PTEN (+++), EGFR (+++), and EGFRvlII (+++) showed low toxicity but minimal efficacy and the trial stopped.

Pancreatic carcinoma (PC) represents the fourth leading cause of cancer death in Spain with a death rate of 2,400 males and 2,000 females per year. Poor outcome related to its silent nature and the lack of reliable secondary prevention measures translate into advanced-stage diagnosis, 75 % of deaths within the first year of diagnosis and 5-year survival rate of <5 %. Family history was first recognized as a risk factor for PC. Further population-based and case-control studies subsequently found that 7.8 % of patients with PC have a family history of the same tumor and individuals with a first-degree relative with PC have a 3.2-fold increased risk of developing PC. Overall, it is estimated that up to 10 % of PC have a familial component. However, known genetic syndromes account for <20 % of the observed familial aggregation of PC. We review the most important aspects in epidemiology, molecular biology and clinical management of familial PC.

There is a current unmet medical need for treatment of leptomeningeal metastases (LMD). To analyze the efficacy and safety of systemic temozolomide (TMZ) for first-line treatment of patients with LMD associated with solid tumors, a phase II, non-randomized, multicenter, prospective study was conducted. The planned duration of treatment was a maximum of six cycles (24 weeks) or until unacceptable toxicity was reported. One cycle of oral TMZ (100 mg/m(2) daily) consisted of one week on treatment/one week off treatment for four weeks. The study was stopped early because of poor accrual. Nineteen patients (median age 51(33-72); 32 % male) were enrolled. The LMD source was breast cancer (53 %) and non-small-cell lung cancer (37 %). Previous treatment was chemotherapy (100 %), surgery 74 %, radiotherapy 79 %, and hormone therapy 42 %. The average last dose of TMZ received by patients was 171 mg and only one patient required dose reduction. Three of 19 patients (15.8 %) had clinical benefit and 16 of 19 patients (84.2 %) progressed. Of the two patients completing the study (six cycles, 24 weeks), one had a partial response and the other stable disease. Median survival was 43 days (95 % CI 28.7-57.3); there were 18 deaths. Median TTP was 28 days (95 % CI 14-42). The most common adverse event was vomiting (52.6 %); nine patients (47.4 %) reported at least one serious adverse event but only one episode of thrombocytopenia was drug related. Median Karnofsky score remained at or above 70 % throughout the study, and was 75 % at the end of the study. First-line TMZ was well tolerated, and did not adversely affect the quality of life of patients with LMD. Future studies are needed to verify the efficacy results of this pilot trial.

Aim: To investigate the prevalence and penetrance of hMSH6 mutations in Spanish HNPCC families that was negative for mutation in hMLH1 or hMSH2., Methods: We used PCR-based DGGE assay and direct sequencing to screen for hMSH6 gene in 91 HNPCC families., Results: we have identified 10 families with germ-line mutations in the DNA sequence. These mutations included two intronic variation, three missense mutation, one nonsense mutation, and four silent mutations. Among the 10 germ-line mutations identified in the Spanish cohort, 8 were novel, perhaps, suggesting different mutational spectra in the Spanish population. Detailed pedigrees were constructed for the three families with a possible pathogenic hMSH6 mutation. The two silent mutations H388H and L758L, detected in a person affected of colorectal cancer at age 29, produce loss of the wild-type allele in the tumor sample. Immunohistochemical analysis showed that expression of MSH6 protein was lost only in the tumors from the carriers of V878A and Q263X mutations., Conclusion: Altogether, our results indicate that disease-causing germ-line mutations of hMSH6 are very less frequent in Spanish HNPCC families.