Oligomonocytic chronic myelomonocytic leukemia (OM-CMML) is defined as those myelodysplastic syndromes (MDSs) or myelodysplastic/myeloproliferative neoplasms, unclassifiable with relative monocytosis (≥10% monocytes) and a monocyte count of 0.5 to <1 × 109/L. These patients show clinical and genomic features similar to those of overt chronic myelomonocytic leukemia (CMML), although most of them are currently categorized as MDS, according to the World Health Organization 2017 classification. We analyzed the clinicopathologic features of 40 patients with OM-CMML with well-annotated immunophenotypic and molecular data and compared them to those of 56 patients with overt CMML. We found similar clinical, morphological, and cytogenetic features. In addition, OM-CMML mirrored the well-known complex molecular profile of CMML, except for the presence of a lower percentage of RAS pathway mutations. In this regard, of the different genes assessed, only CBL was found to be mutated at a significantly lower frequency. Likewise, the OM-CMML immunophenotypic profile, assessed by the presence of >94% classical monocytes (MO1s) and CD56 and/or CD2 positivity in peripheral blood monocytes, was similar to overt CMML. The MO1 percentage >94% method showed high accuracy for predicting CMML diagnosis (sensitivity, 90.7%; specificity, 92.2%), even when considering OM-CMML as a subtype of CMML (sensitivity, 84.9%; specificity, 92.1%) in our series of 233 patients (39 OM-CMML, 54 CMML, 23 MDS, and 15 myeloproliferative neoplasms with monocytosis and 102 reactive monocytosis). These results support the consideration of OM-CMML as a distinctive subtype of CMML.

Genetic studies in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) are essential to establish the correct diagnosis and to optimise their management. Recently, it has been demonstrated that it is possible to detect molecular alterations analysing cell-free DNA (cfDNA) in plasma samples, which is known as liquid biopsy. We have assessed the molecular profile of a cohort of 107 MPN patients [33 polycythaemia vera (PV), 56 essential thrombocythaemia (ET), 14 primary myelofibrosis (PMF) and 4 unclassifiable MPN] by next-generation sequencing (NGS) using cfDNA and paired granulocyte DNA. A high concentration of cfDNA in plasma was observed in patients with high molecular complexity, in MPL-mutated cases, and in PMF patients. Targeted sequencing of cfDNA showed a comparable mutational profile (100% accuracy) to the one obtained in granulocytic DNA and a strong correlation was observed between the variant allele frequency (VAF) of gene mutations in both DNA sources. The median VAF detected in cfDNA (29Á0%; range: 0Á95-91Á73%) was significantly higher than the VAF detected in granulocytes (median 25Á2%; range: 0Á10-95Á5%), especially for MPL mutations (44Á3% vs. 22Á5%). In conclusion, our data support the use of cfDNA as a fast, sensitive and accurate strategy for performing molecular characterisation of MPN patients.

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Oligomonocytic chronic myelomonocytic leukemia (OM-CMML) patients are currently classified into the different categories of the 2017 WHO MDS classification. However recent data support considering OM-CMML as a specific subtype of chronic myelomonocytic leukemia (CMML) given their similar clinical, genomic and immunophenotypic profiles. The main purpose of our study was to provide survival outcome data of a well-annotated series of 42 patients with OM-CMML and to compare them to 162 patients with CMML, 120 with dysplastic type (D-CMML) and 42 with proliferative type (P-CMML). OM-CMML showed significantly longer overall survival (OS) and acute myeloid leukemia-free survival than CMML patients considered as a whole group, and when compared to D-CMML and P-CMML, respectively. Moreover, gene mutations associated with increased proliferation (i.e.: ASXL1 and RAS-pathway mutations) were identified as independent adverse prognostic factors for OS in our series. We found that at a median follow-up of 53.47 months, 29.3% of our OM-CMML patients progressed to D-CMML, and at a median follow-up of 46.03 months, 28.6% of our D-CMML progressed to P-CMML. These data support the existence of an evolutionary continuum among OM-CMML, D-CMML and P-CMML. In this context, we observed that harboring more than 3 mutated genes, ASXL1 mutations and a peripheral blood monocyte percentage above 20% significantly predicted shorter time of progression of OM-CMML into overt CMML. These variables were also detected as independent adverse prognostic factors for OS in OM-CMML. These data support the consideration of OM-CMML as the first evolutionary stage within the proliferative continuum of CMML.

Purpose: To assess the efficacy and exploratory biomarkers of continuing palbociclib plus endocrine therapy (ET) beyond progression on prior palbociclib-based regimen in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Patients and Methods: The multicenter, open-label, phase II BioPER trial included women who had experienced progressive disease (PD) after having achieved clinical benefit on the immediately prior palbociclib plus ET regimen. Palbociclib (125mg, 100mg, or 75mg daily orally for 3 weeks and 1 week off as per prior palbociclib-based regimen) plus ET of physician's choice were administered in 4-week cycles until PD or unacceptable toxicity. Co-primary endpoints were clinical benefit rate (CBR) and percentage of tumors with baseline loss of retinoblastoma (Rb) protein expression. Additional endpoints included safety and biomarker analysis. Results: Among 33 patients enrolled, CBR was 34.4% (95%CI, 18.6–53.2; P<0.001) and 13.0% of tumors (95%CI, 5.2–27.5) showed loss of Rb protein expression, meeting both co-primary endpoints. Median progression-free survival was 2.6 months (95%CI, 1.8–6.7). No new safety signals were reported. A signature that included baseline mediators of therapeutic resistance to palbociclib and ET (low Rb score, high cyclin E1 score, ESR1 mutation) was independently associated with shorter median progression-free survival (hazard ratio, 22.0; 95%CI, 1.71–282.9; P=0.018). Conclusions: Maintaining palbociclib after progression on prior palbociclib-based regimen seems to be a reasonable, investigational approach for selected patients. A composite biomarker signature predicts a subset of patients who may not derive a greater benefit from palbociclib rechallenge, warranting further validation in larger randomized controlled trials.

To assess the impact of CD133 expression on the prognosis of endometrioid endometrial carcinoma (EEC). We retrospectively assessed CD133 expression in tissue microarray of 116 surgically treated FIGO I-III EEC. Tumors with ≥10% of CD133-expressing cells were considered CD133-positive (CD133+). On the basis of CD133 expression, clinical and pathological parameters, progression-free survival (PFS) and overall survival (OS) were evaluated. Of the EEC studied 85.2% showed CD133-expressing cells. Only 61% (n = 66) of EEC presented ≥10% of CD133 expressing cells and were considered CD133+. The mean OS for CD133+ tumour patients was 161 months (95% CI, 154–168) as compared with 146 months (95% CI, 123–160) for those with CD133- tumors (p = 0.012). The mean PFS for CD133+ tumour was 159 months (95% CI, 149–168) as compared with 147 months (95% CI, 132-161) in those with a CD133-tumour (p = 0.014). CD133+ tumours were less likely to have vascular invasion (p = 0.010) and more likely to be well differentiated (p = 0.034). C133+ tumours predicted favorable OS and PFS of EEC patients, with a Hazard Ratio 4.731 (95% CI, 1.251–17.89; p = 0.022). CD133+ tumor status correlates with favorable prognosis of EEC. Our findings are in agreement with studies addressing brain and colorectal tumours.

Objective: To develop and validate a risk prediction model of 90-day mortality (90DM) using machine learning in a large multicenter cohort of patients undergoing gastric cancer resection with curative intent. Background: The 90DM rate after gastrectomy for cancer is a quality of care indicator in surgical oncology. There is a lack of well-validated instruments for personalized prognosis of gastric cancer. Methods: Consecutive patients with gastric adenocarcinoma who underwent potentially curative gastrectomy between 2014 and 2021 registered in the Spanish EURECCA Esophagogastric Cancer Registry database were included. The 90DM for all causes was the study outcome. Preoperative clinical characteristics were tested in four 90DM predictive models: Cross Validated Elastic regularized logistic regression method (cv-Enet), boosting linear regression (glmboost), random forest, and an ensemble model. Performance was evaluated using the area under the curve by 10-fold cross-validation. Results: A total of 3182 and 260 patients from 39 institutions in 6 regions were included in the development and validation cohorts, respectively. The 90DM rate was 5.6% and 6.2%, respectively. The random forest model showed the best discrimination capacity with a validated area under the curve of 0.844 [95% confidence interval (CI): 0.841-0.848] as compared with cv-Enet (0.796, 95% CI: 0.784-0.808), glmboost (0.797, 95% CI: 0.785-0.809), and ensemble model (0.847, 95% CI: 0.836-0.858) in the development cohort. Similar discriminative capacity was observed in the validation cohort. Conclusions: A robust clinical model for predicting the risk of 90DM after surgery of gastric cancer was developed. Its use may aid patients and surgeons in making informed decisions.

Introduction: Hyperprogressive disease (HPD) as a consequence of immune checkpoint inhibitors in NSCLC has been reported in multiple studies. However, inconsistent results in incidence and survival outcomes within studies, together with different assessment methods, have led to increasing controversy regarding the concept of HPD.Methods: Consecutive patients treated with nivolumab (N ¼ 42) or docetaxel (N ¼ 37) were evaluated. HPD was quantified by applying three different methods (tumor growth rate [TGR], tumor growth kinetics [TGK], and Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]). HPD rates were compared between and within both cohorts using the different methods.Results: Using TGR, TGK, and RECIST 1.1, we identified seven (16.7%), seven (16.7%), and six (14.3%) patients with HPD in the nivolumab cohort and three (8.1%), four (10.8%), and five (13.6%) in the docetaxel cohort, respectively. We observed a higher concordance between TGR and TGK (90.1%) compared with RECIST 1.1 (31.3% and 37.5% with TGR and TGK, respectively). We found no significant differences in the overall survival between patients with progressive disease and HPD in either cohort.Conclusions: TGR and TGK revealed high concordance rates for identifying patients with HPD in NSCLC. The incidence of HPD was numerically higher in patients treated with immune checkpoint inhibitors. Standardization of methods for measuring HPD and its exploration in larger studies are needed to establish its clinical meaning in NSCLC.