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Patrones de tratamiento y resultados clínicos en pacientes con leucemia mieloide aguda no elegibles para quimioterapia de inducción intensiva: estudio de vida real en América Latina
No full textIntroduction. There is a knowledge gap concerning patients with acute myeloid leukemia (AML) who are not eligible for intensive induction chemothera-py; this, together with a recent increase in the incidence in Latin America, encloses a need. Through real-world evidence, we describe and compare the results of the different treatment strategies within this context. Methodology. This is a longitu-dinal, descriptive, retrospective study of a cohort of Latin American patients with AML not eligible for intensive induction chemotherapy, treated with low-intensity chemotherapy or with the best supportive care alone between January 1, 2015, to December 31, 2018. Results. Of a total of 125 patients (median age 74.8 years), the majority received low-intensity chemotherapy (78.4%). The median time in months of overall survival (9.2), progression-free survival (4.8), and time to treatment failure (3.8) were longer in patients receiving hypomethylating agents. Additionally, better results were observed with low-intensity chemotherapy (complete response 11.2% and stable disease 17.3%) compared to the best supportive care alone. Conclu-sion. We deliver a real-world standpoint of Latin American patients with AML who are not eligible for intensive induction chemotherapy. Our findings pave the first steps of the way to describe, understand, and support informed decision-making processes in our region
Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial
No full textBackground: PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma. Methods: KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every 3 weeks for up to 35 cycles. All participants received investigator's choice of fluorouracil (intravenous, 800 mg/m2 per day) administered continuously on days 1-5 of each 3-week cycle plus cisplatin (intravenous, 80 mg/m2) administered on day 1 of each 3-week cycle or capecitabine (oral, 1000 mg/m2) administered twice daily on days 1-14 of each 3-week cycle plus oxaliplatin (intravenous, 130 mg/m2) administered on day 1 of each 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, PD-L1 status, and chemotherapy in permuted block sizes of four. The primary endpoint was overall survival, assessed in the intention-to-treat (ITT) population, and the populations with a PD-L1 combined positive score (CPS) of 1 or higher, and PD-L1 CPS of 10 or higher. Safety was assessed in the as-treated population, which included all randomly assigned participants who received at least one dose of study intervention. Here, we report the results of the interim analysis. This study is registered with ClinicalTrials.gov, NCT03675737, and recruitment is complete. Findings: Between Nov 8, 2018, and June 11, 2021, 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789). Most participants were male (527 [67%] of 790 participants in the pembrolizumab plus chemotherapy group; 544 [69%] of 789 participants in the placebo plus chemotherapy group) and White (426 [54%]; 435 [55%]). Median follow-up at the data cutoff was 31·0 months (IQR 23·0-38·3). Median overall survival was longer in the pembrolizumab group than in the placebo group in the ITT population (12·9 months [95% CI 11·9-14·0] vs 11·5 months [10·6-12·1]; hazard ratio [HR] 0·78 [95% CI 0·70-0·87]; p<0·0001), in participants with a PD-L1 CPS of 1 or higher (13·0 months [11·6-14·2] vs 11·4 months [10·5-12·0]; 0·74 [0·65-0·84]; p<0·0001), and in participants with a PD-L1 CPS of 10 or higher (15·7 months [13·8-19·3] vs 11·8 months [10·3-12·7]; 0·65 [0·53-0·79]; p<0·0001). The most common grade 3-5 adverse events of any cause were anaemia (95 [12%] of 785 participants in the pembrolizumab group vs 76 [10%] of 787 participants in the placebo group) and decreased neutrophil count (77 [10%] vs 64 [8%]). Serious treatment-related adverse events occurred in 184 (23%) participants in the pembrolizumab group and 146 (19%) participants in the placebo group. Treatment-related deaths occurred in eight (1%) participants in the pembrolizumab group and 16 (2%) participants in the placebo group. No new safety signals were identified. Interpretation: Participants in the pembrolizumab plus chemotherapy group had a significant and clinically meaningful improvement in overall survival with manageable toxicity compared with participants in the placebo plus chemotherapy group. Therefore, pembrolizumab with chemotherapy might be a first-line treatment option for patients with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma
Clinical Features and Outcomes of Triple-Negative Breast Cancer Among Latin American Adolescents and Young Adults Compared to Middle-Aged and Elder Females: A Cohort Analysis Over 15 Years
No full textPurpose: Outcomes of females with triple-negative breast cancer (TNBC) are rarely explored in adolescents and young adults (AYAs). We compared clinical and survival outcomes of Latin American AYAs (p39 years) with middle-aged (40–59 years) and older (q60 years) females with TNBC by cancer stage. Methods: We performed a single-center retrospective cohort study among treated females with cancer stages I–III diagnosed from 2000 to 2014 in Peru. We evaluated overall survival (OS) and event-free survival (EFS). Time-to-event methods were used for analyses. Results: Of 1582 females with TNBC, 350 (22%) were AYAs, 887 (56%) were middle-aged, and 345 (22%) were older women. Tumor size >5 cm, histological grade III, and brain metastasis were more common features in AYAs. AYAs were treated more frequently with neoadjuvant chemotherapy. With a median follow-up of 102 months, the 5-year OS/EFS for AYAs was 55%/53%, similar to middle-aged (54%/49%) and older females (56%/51%). AYAs were not at higher risk for decreased OS or EFS in the multivariable Cox analysis. Our findings remained consistent by cancer stage. Conclusion: Although Latin American AYAs with TNBC have more aggressive clinical features at diagnosis, survival outcomes were comparable with middle-aged and older women with TNBC, suggesting that age is not a risk factor for worse survival outcomes if treatment is given according to cancer stage. Our findings should be interpreted with caution given the lack of information on certain covariates such as comorbidities. Strategies for early detection in primary care and prompt referral for treatment initiation should be developed. ª Mary Ann Liebert, Inc
Metabotyping of Andean pseudocereals and characterization of emerging mycotoxins
No full textPseudocereals are best known for three crops derived from the Andes: quinoa (Chenopodium quinoa), canihua (C. pallidicaule), and kiwicha (Amaranthus caudatus). Their grains are recognized for their nutritional benefits; however, there is a higher level of polyphenism. Meanwhile, the chemical food safety of pseudocereals remains poorly documented. Here, we applied untargeted and targeted metabolomics approaches by LC-MS to achieve both: i) a comprehensive chemical mapping of pseudocereal samples collected in the Andes; and ii) a quantification of their contents in emerging mycotoxins. An inventory of the fungal community was also realized to better know the fungi present in these grains. Metabotyping permitted to add new insights into the chemotaxonomy of pseudocereals, confirming the previously established phylotranscriptomic clades. Sixteen samples from Peru (out of 27) and one from France (out of one) were contaminated with Beauvericin, an emerging mycotoxin. Several mycotoxigenic fungi were detected, including Aspergillus sp., Penicillium sp., and Alternaria sp. © 2022 Elsevier Lt
Prognostic factors of pediatric ependymomas at a National Cancer Reference Center in Peru
No full textBackground: Ependymomas are central nervous system tumors that significantly impact the quality of life and carry a high mortality rate. Both the disease itself and its treatment cause significant morbidity. At a national level in Peru, there are no reports on clinical characteristics of the disease. Methods: This retrospective study captured patient aged less than 19 years with a diagnosis of ependymoma from 2012 to 2022 at a tertiary center in Lima. Results: 85 patients were included with a median follow-up time was 51.6 months. The 5-year overall survival and progression-free survival were 55.89% (95% CI: 44.28 – 65.99) and 37.71% (95% CI: 26,21-49,16) respectively. The main prognostic factors identified were completed treatment (p=0.019), adjuvant chemotherapy (p=0.048), presence of metastasis (p=0.012), and disease recurrence (p=0.02). Conclusions: The survival of patients with ependymoma is below that reported in high-income countries. Incomplete treatment and treatment abandonment are factors that negatively impact the prognosis. Further studies are needed to identify barriers in the referral and treatment process for patients with ependymoma
A Spectrum of Metastases to the Breast: Radiologic-Pathologic Correlation
No full textMetastases to the breast from non-mammary origin are rare. The majority of these lesions appear as secondary manifestations of melanoma and lymphoma, followed by lung carcinomas, gynecological carcinomas, and sarcomas. There has been a steady trend of an increase in diagnosis of intramammary metastases owing to the current advances in imaging technology. Imaging features depend on the type of primary neoplasm and route of dissemination, some of which resemble primary breast cancer and benign breast entities. There are certain imaging features that raise the level of suspicion for metastases in the correct clinical context. However, imaging manifestations of intramammary metastases do not always comply with the known classic patterns. The aim of this review is to clarify these features, emphasizing radiologic-pathologic correlation and a multidisciplinary approach, since most cases are found in patients with advanced disease. © 2023 Society of Breast Imaging. All rights reserved
Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial
No full textBackground: In the KEYNOTE-826 study, the addition of the anti-PD-1 monoclonal antibody pembrolizumab to chemotherapy with or without bevacizumab improved overall survival and progression-free survival (primary endpoints) versus placebo plus chemotherapy with or without bevacizumab, with manageable toxicity, in patients with persistent, recurrent, or metastatic cervical cancer. In this Article, we report patient-reported outcomes (PROs) from KEYNOTE-826. Methods: KEYNOTE-826 is a multicentre, randomised, phase 3 trial in 151 cancer treatment centres in 19 countries. Eligible patients were aged 18 years or older with persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemotherapy (previous radiosensitising chemotherapy was allowed) and not amenable to curative treatment and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) centrally by means of an interactive voice response system in a double-blind manner to receive either pembrolizumab 200 mg or placebo every 3 weeks intravenously for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m2 plus cisplatin 50 mg/m2 or carboplatin area under the curve 5 mg/mL per min, intravenously) with or without bevacizumab 15 mg/kg every 3 weeks intravenously. Randomisation (block size of 4) was stratified by metastatic disease at diagnosis, planned bevacizumab use, and PD-L1 combined positive score. Patients, investigators, and other study personnel involved in study treatment administration or clinical evaluation of patients were unaware of treatment group assignments. PRO instruments were the EORTC Quality-of-Life-Core 30 (QLQ-C30), the EORTC cervical cancer module (QLQ-CX24), and the EuroQol-5 dimension-5 level (EQ-5D-5L) visual analogue scale, each collected before treatment at cycles 1–14 and every other cycle thereafter. Primary endpoints were overall survival and progression-free survival per RECIST version 1.1 by investigator review. Change from baseline in QLQ-C30 global health status (GHS)–quality of life (QoL) was a prespecified secondary endpoint and was assessed in the PRO full analysis population (all patients who received at least one dose of study treatment and completed at least one post-baseline PRO assessment). Other PRO analyses were protocol-specified exploratory endpoints. The study is registered with ClinicalTrials.gov, NCT03635567, and is ongoing. Findings: Between Nov 20, 2018, and Jan 31, 2020, of 883 patients screened, 617 were randomly assigned (pembrolizumab group, n=308; placebo group, n=309). 587 (95%) of 617 patients received at least one dose of study treatment and completed at least one post-baseline PRO assessment and were therefore included in the PRO analyses (pembrolizumab group, n=290; placebo group, n=297). Median follow-up was 22·0 months (IQR 19·1–24·4). At week 30, QLQ-C30 completion was 199 (69%) of 290 patients in the pembrolizumab group and 168 (57%) of 297 patients in the placebo group; compliance was 199 (94%) of 211 and 168 (90%) of 186, respectively. The least squares mean change in QLQ-C30 GHS–QoL score from baseline to week 30 was −0·3 points (95% CI −3·1 to 2·6) in the pembrolizumab group and −1·3 points (−4·2 to 1·7) in the placebo group, with a between-group difference in least squares mean change of 1·0 point (95% CI −2·7 to 4·7). Median time to true deterioration in GHS–QoL was not reached (NR; 95% CI 13·4 months–NR) in the pembrolizumab group and 12·9 months (6·6–NR) in the placebo group (hazard ratio 0·84 [95% CI 0·65–1·09]). 122 (42%) of 290 patients in the pembrolizumab group versus 85 (29%) of 297 in the placebo group had improved GHS–QoL at any time during the study (p=0·0003). Interpretation: Addition of pembrolizumab to chemotherapy with or without bevacizumab did not negatively affect health-related quality of life. Along with the efficacy and safety results already reported from KEYNOTE-826, these data support the benefit of pembrolizumab and the value of immunotherapy in patients with recurrent, persistent, or metastatic cervical cancer. Funding: Merck Sharp & Dohme
Leveling Up the Access to Radiation Therapy in Latin America: Economic Analysis of Investment, Equity, and Inclusion Opportunities Up to 2030
No full textPurpose: Latin America faces a shortage in radiation therapy (RT) units and qualified personnel for timely and high-quality treatment of patients with cancer. Investing in equitable and inclusive access to RT over the next decade would prevent thousands of deaths. Measuring the investment gap and payoff is necessary for stakeholder discussions and capacity planning efforts. Methods and Materials: Data were collected from the International Atomic Energy Agency's Directory of Radiotherapy Centers, industry stakeholders, and individual surveys sent to national scientific societies. Nationwide data on available devices and personnel were compiled. The 10 most common cancers in 2020 with RT indication and their respective incidence rates were considered for gap calculations. The gross 2-year financial return on investment was calculated based on an average monthly salary across Latin America. A 10-year cost projection was calculated according to the estimated population dynamics for the period until 2030. Results: Eleven countries were included in the study, accounting for 557,213,447 people in 2020 and 561 RT facilities. Approximately 1,065,684 new cancer cases were diagnosed, and a mean density of 768,469 (standard deviation ±392,778) people per available unit was found. By projecting the currently available treatment fractions to determine those required in 2030, it was found that 62.3% and 130.8% increases in external beam RT and brachytherapy units are needed from the baseline, respectively. An overall regional investment of approximately United States (US) 872,889,949 will be necessary by 2030, with the expectation of a 2-year posttreatment gross return on investment of more than US $2.1 billion from patients treated in 2030 only. Conclusions: Investment in RT services is lagging in Latin America in terms of the population's needs. An accelerated outlay could save additional lives during the next decade, create a self-sustaining system, and reduce region-wide inequities in cancer care access. Cash flow analyses are warranted to tailor precise national-level intervention strategies
Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials
No full textClinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The combined analysis of SOFT-TEXT compared outcomes in 4,690 premenopausal women with estrogen/progesterone receptor-positive (ER/PgR+) early breast cancer randomly assigned to 5 years of exemestane + ovarian function suppression (OFS) versus tamoxifen + OFS. After a median follow-up of 9 years, exemestane + OFS significantly improved disease-free survival (DFS) and distant recurrence-free interval (DRFI), but not overall survival, compared with tamoxifen + OFS. We now report DFS, DRFI, and overall survival after a median follow-up of 13 years. In the intention-to-treat (ITT) population, the 12-year DFS (4.6% absolute improvement, hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.90; P 2 cm (4.5%) or grade 3 tumors (5.5%). These sustained reductions of the risk of recurrence with adjuvant exemestane + OFS, compared with tamoxifen + OFS, provide guidance for selecting patients for whom exemestane should be preferred over tamoxifen in the setting of OFS
End-of-neoadjuvant treatment circulating microRNAs and HER2-positive breast cancer patient prognosis: An exploratory analysis from NeoALTTO
No full textBackground: The absence of breast cancer cells in surgical specimens, i.e., pathological complete response (pCR), is widely recognized as a favorable prognostic factor after neoadjuvant therapy. In contrast, the presence of disease at surgery characterizes a prognostically heterogeneous group of patients. Here, we challenged circulating microRNAs (miRNAs) at the end of neoadjuvant therapy as potential prognostic biomarkers in the NeoALTTO study. Methods: Patients treated within the trastuzumab arm (i.e., pre-operative weekly trastuzumab for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks; post-operative FEC for 3 cycles followed by trastuzumab up to complete 1 year of treatment) were randomized into a training (n= 54) and testing (n= 72) set. RT-PCR-based high-throughput miRNA profile was performed on plasma samples collected at the end of neoadjuvant treatment of both sets. After normalization, circulating miRNAs associated with event free survival (EFS) were identified by univariate and multivariate Cox regression model. Results: Starting from 23 circulating miRNAs associated with EFS in the training set, we generated a 3-circulating miRNA prognostic signature consisting of miR-185-5p, miR-146a-5p, miR-22-3p, which was confirmed in the testing set. The 3-circulating miRNA signature showed a C-statistic of 0.62 (95% confidence interval [95%CI] 0.53-0.71) in the entire study cohort. By resorting to a multivariate Cox regression model we found a statistical significant interaction between the expression values of miR-194-5p and pCR status (p.interaction =0.005) with an estimate Hazard Ratio (HR) of 1.83 (95%CI 1.14- 2.95) in patients with pCR, and 0.87 (95%CI 0.69-1.10) in those without pCR. Notably, the model including this interaction along with the abovementioned 3-circulating miRNA signature provided the highest discriminatory capability with a C-statistic of 0.67 (95%CI 0.58-0.76). Conclusions: Circulating miRNAs are informative to identify patients with different prognosis among those with heterogeneous response after trastuzumab-based neoadjuvant treatment, and may be an exploitable tool to select candidates for salvage adjuvant therapy. Copyright © 2023 Di Cosimo, Ciniselli, Pizzamiglio, Cappelletti, Silvestri, El-Abed, Izquierdo, Bajji, Nuciforo, Huober, Cameron, Chia, Gomez, Iorio, Vingiani, Pruneri and Verderio