tbuckley/cabot-search huggingface dataset:
Recurrent vulvar squamous cell carcinoma: Outcomes across the treatment spectrum—Are we making progress?
Authors: Claudia Meloche, Trish Dinh, Johanna Spaans, Tinghua Zhang, Johanne I Weberpals
Journal: Journal of Clinical Oncology (2024)

e17603 Background: No standard treatment exists for recurrent vulvar squamous cell carcinoma (VSCC) and the prognosis is poor. This retrospective study reports on outcomes of recurrent and progressive VSCC patients (pts) across various treatments. Methods: This was a single-center retrospective cohort study conducted at the Ottawa Hospital (Ottawa, Canada). Pts with histologically proven VSCC treated between 2000-2023 were identified, and the study population comprised pts who either recurred or progressed after/during first-line therapy. Clinicopathologic data were collected, and descriptive statistics were performed according to pt demographics, tumor characteristics and treatment modality. Median progression free survival (PFS) and overall survival (OS) were determined by treatment type. The outcomes of unique cases treated with novel therapies are also highlighted. Results: There were 311 pts with a diagnosis of VSCC. Ninety-five pts with recurrent/progressive disease formed the study population with a median age of 72 years and 52% having at least stage III disease at initial diagnosis according to FIGO 2021 staging. The prevailing treatment at time of diagnosis was surgery (74%), with 40% of pts also undergoing radiation, chemotherapy, or a combination of both. Location of disease progression or recurrence was regional 53 (56%), inguinal 31 (33%) and distant 11(12%). There were 60 pts (63)% who had one recurrence, as well as 18 pts (19%) and 3 pts (3%) with two and three recurrences, respectively. Of all patients, 14/95 (15%) showed evidence of early progression following treatment. Treatment for first recurrence included: radiation (18.9%), surgery (16.8%), no treatment (16.8%), chemotherapy (11.6%), chemoradiation (9.4%), surgery with radiation (7.3%) surgery and chemoradiation (2.1%), surgery and chemotherapy (1.1%), and investigational therapy (1.1%). The most common chemotherapy regimen used was cisplatin, while the predominant surgical procedure performed was radical vulvectomy. Two pts received Pembrolizumab for treatment of recurrent disease. One pt received a combination of carboplatinum, paclitaxel and bevacizumab followed by maintenance pembrolizumab for 55 cycles (PFS 27.1 months, mo). A second pt was treated for a second recurrence with carbo-taxol followed by single agent pembrolizumab for 27 cycles with stable disease (PFS 15.7 mo). The mPFS after treatment of first recurrence was 11.6 mo for surgery, 8.7 mo for radiation, 8 mo for chemotherapy, 3.2 mo for chemoradiation, and 2.2 mo for no treatment. Among VSCC pts with recurrent or progressive disease, the median OS from all causes was 21 mo. Conclusions: Pts with recurrent/progressive VSCC who underwent surgery had the most favorable outcomes. Significant promise was shown with pembrolizumab and highlights the need for immunotherapy clinical trials for this rare and fatal woman’s cancer.
Evaluation of body weight and race on pembrolizumab response in patients with endometrial cancer: A case control study.
Authors: Annalyn Welp, Kendall Johnson, Paola A. Gehrig
Journal: Journal of Clinical Oncology (2024)

e17579 Background: Recent studies demonstrate improvement in PFS when pembrolizumab, a humanized monoclonal antibody (mAB) that inhibits the PD-1 receptor, is used with platinum-based regimens for advanced or recurrent endometrial cancer (EC). ASCO recommends studies evaluate the effect of weight on efficacy of anticancer agents to guide dosing. In addition, most studies evaluating the pharmacokinetic effects of mABs typically include only white patients. Pembrolizumab is administered at a flat dose and there are currently no adjustments for weight or race. Therefore, this study was performed to evaluate the impact of weight and race on outcomes in patients with EC treated with pembrolizumab. Methods: This retrospective IRB-approved case-control study included EC patients from 04/2014-12/2022 treated with pembrolizumab. Any patient &gt;18 years with EC who received pembrolizumab was included; carcinosarcoma excluded. Chart review was performed. Response was recorded using RECIST criteria and based on imaging and/or primary oncologist’s determination. Associated toxicities were graded by CTCAE. Statistical testing performed as appropriate. Results: Fifty patients met inclusion criteria, with a mean age of 66.0 years. The majority presented with advanced EC (Stage III or greater) at diagnosis (n=33, 66%). Twenty-eight (56%) had endometroid histology, and 42% (n=21) were MMRd. Most patients received single-agent pembrolizumab (n=26; 52%) or pembrolizumab with lenvatinib (42%), with an average of 8.44 cycles (either 200 mg every 3 weeks or 400 mg every 6 weeks). The table details the objective response rate (ORR) and PFS for patients by race and weight. There was no significant difference in PFS between non-obese (normal weight + overweight) and obese (obese + severely obese) overall. Conclusions: No difference was seen in ORR or PFS between non-obese and obese patients. The study was underpowered to perform tests of statistical significance by race. These data preliminarily suggest pembrolizumab may not need to be adjusted for weight. Larger scale multi-institution trials with a particular emphasis on the recruitment of non-Hispanic Black patients can help clarify whether race-based differences in dosing pembrolizumab may be needed. [Table: see text]
Rate of p53 and MMR IHC assessment accordance between matched D&amp;C and hysterectomy samples in uterine cancer.
Authors: John Syrios, Anastasios Christidis, Dimitrios Tziortziotis, Antigoni Sourla, Dimitrios Mazis Kourakos, Dimitrios Vlachos, Georgios Vlachos, Kyriakos Mitsakos Barbayiannis
Journal: Journal of Clinical Oncology (2024)

e17587 Background: International guidelines strongly suggest assessment of POLe, MMR, p53 in patients with early stage endometrial cancer. MMR and p53 are commonly assessed with IHC after hysterectomy (+/-BSO). The fixation procedure and the high tumor cellularity of D&amp;C specimens may permit accurate p53 and MMR evaluation. Early knowledge of p53 and MMR status in D&amp;C samples may drive surgical treatment modalities and fertility sparing decision. Methods: In this single center study 73 matched D&amp;C and hysterectomy samples in patients with clinically early stage endometrial cancer were collected and p53 and MMR status was assessed with IHC.Samples were obtained by gynaecologists and gynaecological oncologists and independently assessed by two expert in gynaecological oncology pathologists at REA hospital (Athens-Greece).Immunohistochemistry was performed using Ventana Benchmark Ultra. To determine MMR status, sections were scored visually for loss or intact expression of the proteins MSH6, MSH2, MLH1 and PMS2. Interpretation of immunostaining for each protein was classified as: (i) “retained,” when ≥10% of tumor cells showed a moderate to strong expression; (ii) “loss,” when no evidence of nuclear expression was seen in cancer cells; (iii) “indeterminate,” if IHC staining in tumor cells was less intense compared to the internal control or expression was retained in &lt;10% of neoplastic cells.If, however, the presence of “indeterminate” immunostaining in one or more proteins was coupled with a convincing loss of expression in at least one protein, the tumor was interpreted as “dMMR” tumor.The study was carried out within January 1 st -December 1 st 2023. Results: There was a 100% accordance between p53 assessment in all 73 matched D&amp;C and hysterectomy specimens. Discrepancy in MMR result was observed only in 1 out of the 73 cases, which stained negative for MLH1 in D&amp;C but positive in hysterectomy, yielding an accordance of 98,96% between D&amp;C and hysterectomy specimens. Conclusions: p53 &amp; MMR status can be accurately assessed with IHC in D&amp;C samples. Repeat assessment after hysterectomy may not be necessary. Early knowledge of the molecular imprint of the disease on D&amp;C samples may drive treatment decisions regarding surgical procedures, fertility preservation and further treatment plans. [Table: see text]
Genomic profiling of Chinese patients with endometrial adenocarcinoma (EA).
Authors: Guo Huiming, Jin Yuni, Su Liangdi, Liu Yuan, Bao Chan, Li Tian, Zhang Juan, Bei Zhang
Journal: Journal of Clinical Oncology (2024)

e17606 Background: Incidences of endometrial adenocarcinoma are increasing in the Chinese with poor prognosis. Our aim was to explore the genomic profiling of Chinese endometrial adenocarcinoma and whether they could provide potential prognostic and therapeutic implications. Methods: Between January 2019 and August 2023, a total of 204 samples, were obtained from Chinese EA patients at the 3DMed Biobank (Shanghai, China) and The First Affiliated Hospital of Kunming Medical University. Genomic alterations were determined using NGS 733 cancer-related genes panel. TMB-H was defined as above 10 mutation/Mb. Positive PD-L1 expression was defined as ≥1 of CPS. Statistical analyses were performed using R version 3.4.4. Results: A total of 204 patients with EA were included in this study. The median age at diagnosis was 56 (range, 27-92) years old. Among these 204 tissue samples, 178 (87%) were collected from primary lesions. 9.0 %( 12/133) patients exhibited positive PD-L1 CPS status. 19.6% of patients in our cohort exhibited MSI. Median TMB was 6.15 mutation/Mb [0, 473], and 33.8% patients had TMB-H status. In this cohort, a total of 9404 somatic alterations were detected in 96.1% of the patients (196/204), with an average of 46 alterations per patient. The most commonly alternated genes were PTEN (68%), ARID1A (50%), PIK3CA (47%), PIK3R1 (32%), TP53 (31%), ZFHX3 (30%), CTCF (25%), KMT2C (23%), KRAS (22%), CTNNB1 (22%), CHD4 (18%), FAT4 (18%), FAT1 (18%), NCOR2 (17%), ARID1B (17%), AR (16%), BCOR1 (16%), MYC (16%), and NF1 (16%). The hotspot mutations (prevalence higher than 2%) in Chinese EA included PTEN p. R130G, PIK3CA p.R88Q, RNF43 p.G659Vfs*41, PIK3CA p.H1047R, KMT2C p.K2797Rfs*26, CTCF p.T204Nfs*26, KRAS p.G12D, and TEAD2 p.H295Mfs*12. In terms of structural-rearrangements, ten fusions were detected in six genes, with NOTCH2 (n = 4) and RAF1 (n = 2) having the highest number of events. In terms of CNVs, frequently affected genes in Chinese EA included PTEN (249), ARID1A (172), PIK3CA (137), ZFHX3 (110), LRP1B (96), and FAT4 (93). The frequently affected pathways were PI3K (88%), RTK-RAS (72%), and WNT (54%) Furthermore, pathogenic or likely pathogenic germline variants were observed in 33 patients (16.2%). The affected genes included MSH6 (6), MLH1 (4), MSH2 (4), ATM (3), FANCA (3), BRCA2 (3), BRCA1 (2), PMS2 (2), APC (1), BARD1 (1), BLM (1), CDH1 (1), FANCD2 (1), FANCG (1), PALB2 (1), RAD50 (1), RAD54L (1), and RECQL4 (1). Conclusions: In summary, we presented the large-scale genomic profiling of EA in the Chinese population and demonstrated emphasizes the importance of molecular characterization in facilitating clinical decision-making and improving patient outcomes in EA.
Outcomes in patients with anemia hospitalized for endometrial cancer resection: A nationwide analysis.
Authors: Kelly Frasier, Saad Javaid, Vivian Li, Julia Vinagolu-Baur, Nataly Ortega Yaguachi, Evadne Rodriguez, Olivia Del Castillo, Raquel Batista, Kenlee Jonas, Laura Palma
Journal: Journal of Clinical Oncology (2024)

e17585 Background: Endometrial cancer is the most common gynecological malignancy, and It is notably associated with the development of anemia. In light of this, we conducted a retrospective analysis to determine the impact of anemia on patients hospitalized for endometrial cancer resection and other complications during hospitalization. Methods: We conducted a study using the National Inpatient Sample (NIS) data from 2019 and 2020 to identify patients who were admitted with a primary diagnosis of endometrial cancer resection and had a concurrent secondary diagnosis of anemia. Primary outcomes included mortality, and secondary outcomes were the length of stay, total hospitalization charges, and other adverse hospital outcomes. Multivariate logistic regression analysis was used to adjust for confounding variables. Results: A total of 375,109 patients were hospitalized for resection of Endometrial cancer, among whom 55,345 had concurrent anemia. After adjusting for confounding factors, no difference in mortality between the two groups was observed(OR=1.37, 0.91-2.07; p=0.127). However, patients with anemia had a longer length of stay (4.11 days without and 6.05 days with anemia, p&lt;0.001) and a higher total cost of hospitalization ($ 81,112 without and $ 108,436 with anemia, p&lt;0.001). Patients with anemia were at a higher risk of developing sepsis (OR=3.15, 2.60-3.82, p&lt;0.001), acute respiratory failure (OR= 2.64, 2.19-3.19; p&lt;0.001), ICU admission (OR= 2.30, 1.95-2.72; p&lt;0.001), acute coronary syndrome (OR= 2.17, 1.06-4.43; p=0.032), acute kidney injury (OR= 2.78, 2.50-3.09; p&lt;0.001), constipation (OR =1.51, 1.33-1.71; p&lt;0.001), diarrhea (OR= 2.11, 1.61-2.76; p&lt;0.001), pneumonia (OR =2.20, 1.70-2.84; p&lt;0.001), red blood cell transfusion (OR= 9.45, 8.39-10.64; p&lt;0.001), platelet transfusions (OR= 4.43, 3.19-6.16; p&lt;0.001), venous thromboembolism (OR= 2.50, 2.07-3.03; p&lt;0.001), enteral feeding (OR= 6.96, 1.59-30.43; p=0.01), parenteral feeding (OR= 2.91, 2.19-3.85; p&lt;0.001), urinary tract infection (OR =2.08, 1.77-2.43; p&lt;0.001), and the involvement of palliative care (OR= 1.59, 1.18-2.13; p&lt;0.001). There was no difference in having chemotherapy in both groups (OR 0.79, 95% CI 0.29-2.12, p=0.652). Conclusions: Anemia is associated with increased healthcare resource utilization and adverse in-hospital outcomes in patients undergoing resection of Endometrial cancer. Anemia might not be the only predictor of mortality, but identifying and treating it before any interventions can decrease the risk of adverse outcomes and improve quality of life. [Table: see text]
ERS statement on transition of care in childhood interstitial lung diseases
Authors: Petr Pohunek, Effrosyni Manali, Susanne Vijverberg, Julia Carlens, Felix Chua, Ralph Epaud, Carlee Gilbert, Matthias Griese, Bulent Karadag, Eitan Kerem, Václav Koucký, Nadia Nathan, Spyridon Papiris, Suzanne Terheggen-Lagro, Lukáš Plch, Alba Torrent Vernetta, Andrew Bush
Journal: European Respiratory Journal (2024)

Interstitial lung diseases (ILD) are a heterogeneous group of rare diffuse diseases affecting the lung parenchyma in children and adults. Childhood interstitial lung diseases (chILD) are often diagnosed at very young age, affect the developing lung, and can have different presentations and prognosis compared to adult forms of these diseases. In addition, chILD in many cases may apparently remit, and have a better response to therapy and better prognosis than adult ILD. Many affected children will reach adulthood with minimal activity or clinical remission of the disease. They need continuing care and follow-up from childhood to adulthood if the disease persists and progresses over time, but also if they are asymptomatic and in full remission. Therefore, for every chILD patient an active transition process from paediatric to adult care should be guaranteed. This European Respiratory Society (ERS) statement provides a review of the literature and current practice concerning transition of care in chILD. It draws on work in existing transition care programmes in other chronic respiratory diseases, disease-overarching transition-of-care programmes, evidence on the impact of these programmes on clinical outcomes, current evidence regarding long-term remission of chILD as well as the lack of harmonisation between the current adult ILD and chILD classifications impacting on transition of care. While the transition system is well established in several chronic diseases, such as cystic fibrosis or diabetes mellitus, we could not find sufficient published evidence on transition systems in chILD. This statement summarises current knowledge, but cannot yet provide evidence-based recommendations for clinical practice.
Neoadjuvant immune checkpoint blockade in mismatch repair deficient endometrial cancer: An update on recurrence-free survival and correlative biomarkers.
Authors: Marco de Bruyn, Anneke L. Eerkens, Koen Brummel, Annegé Vledder, Sterre T. Paijens, Marta Requesens, Dominik Loiero, Nienke van Rooij, Annechien Plat, Floris-Jan R. Haan, Patty Klok, David Church, René Wardenaar, Floris Foijer, Viktor Koelzer, Tjalling Bosse, Jos Bart, Mathilde Jalving, An K.L Reyners, Hans Nijman
Journal: Journal of Clinical Oncology (2024)

e17593 Background: We recently reported 37.5% radiologic and 50% pathologic response rates in a phase I feasibility study of neoadjuvant pembrolizumab in 10 mismatch repair deficient (MMRd) endometrial cancer (EC). Based on the safety data and promising responses, a phase II study with extended neo-adjuvant treatment has been initiated. Here, we provide an update on the recurrence-free survival (RFS), and unique correlative clinicopathologic, genomic and immunologic biomarkers from the phase I trial. Methods: Tumor differentiation, (germline) mismatch repair status, immune cell distribution, presence of tertiary lymphoid structures (TLSs), T cell receptor (TCR) diversity and common driver mutations (TSO500) were analyzed. Patients were stratified by radiologic or major pathologic responses. RFS was determined from time of surgery. Results: Two recurrences have been observed in non-responding patients, with a median and longest disease-free survival of 17 and 26 months, respectively. Responding patients were characterized by dedifferentiated histology (grade 3), somatic MMRd, and a monoclonal T cell expansion, which was evaluable in the interim biopsy. Neither common driver mutations, nor variants of unknown significance from the TSO500 panel were related to response. Pre- and post-treatment T cell and B cell densities were not correlated with response, nor was the presence of TLS. Pembrolizumab-responsive T cell clones could be detected in peripheral blood prior to initiation of treatment, remained constant throughout treatment duration and were detected in post-treatment tumor-draining lymph nodes (TDLN). Conclusions: Neoadjuvant pembrolizumab is associated with monoclonal T cell expansion in responding patients, which can be evaluated using pipelle biopsy. Repeat assessment of TCR clonality during extended neoadjuvant treatment is currently being evaluated. Clinical trial information: NCT04262089 .
Pole mutated endometrial carcinoma: Clinical and genomic characteristics from a real-world UK cohort.
Authors: Narda Chaabouni, Katherine Vroobel, Ayoma Attygalle, Paula Proszek, Liam Johnson, Michaela Smalley, Ridwan Shaikh, Susan Lalondrelle, Alexandra Taylor, Angela Joy George
Journal: Journal of Clinical Oncology (2024)

e17600 Background: Pathogenic mutations within the DNA polymerase epsilon (POLE) exonuclease domain characterise the POLE/ultra-mutated molecular subgroup as defined by the Cancer Genome Atlas (TCGA) Research Network. Our study aimed to evaluate clinical and genomic characteristics of POLE mutated endometrial carcinoma (EC) from a real-world cohort. Methods: 246 tumour samples from patients diagnosed with primary endometrial cancer (EC) between September 2007 and June 2022 were sequenced using the Royal Marsden RMH200 Solid panel which includes 233 genes and evaluates microsatellite instability (MSI) and tumour mutational burden (TMB). Droplet Digital PCR (ddPCR) was used for MLH1 promoter methylation status in each case. Mismatch repair proteins (MMR) and P53 were tested by immunohistochemistry (IHC). Patients’ characteristics were documented from our electronic records. Results: POLE mutations were identified in 21 patients (8.5%). Mean age at diagnosis was 63 years old (52-92). Mean BMI was 28.5 (21.1-48) and 38.1% of patients had hypertension (n=8). 20 cases were stage I (95%) and 1 case was stage III (5%). Predominant histological subtype was endometrioid in 17 cases (81%). The other histological subtypes comprised clear cell (n=1), mixed (n=1) and carcinosarcoma (n=2). All patients had surgery and 15 (71.4%) received adjuvant therapy which included chemotherapy in 4 (19%) cases. Mean TMB was 125.11 mut/Mb (25.77-345.82). 8 (38%) cases demonstrated MMR deficiency with MLH1 promoter hypermethylation detected in 7/8 cases. P53 was wild type (WT) in 17 (81%) and subclonal mutant in 4 (19%) of cases. 13 (61.9%) cases were microsatellite stable and 8 (38.1%) MSI-high. Recognised pathogenic POLE variants were identified in 16 (76.2%) cases: V411L* c.1231G (n=7), P286R c.857C&gt;G (n=4), A456P c.1366G&gt;C (n=2), A465V c.1394C&gt;T (n=1), P436R c.1307C&gt;G (n=1), M444K c.1331T&gt;A (n=1).After a median follow-up of 21 months, one patient developed distant recurrence and died of progressive brain metastases following surgery for stage IA grade 1 endometrioid carcinoma, however recurrence was not biopsied. Conclusions: In this real-world cohort, POLE mutated EC cases were associated with a favourable prognosis. One distant recurrence was observed in initially uterine-confined case but was not histologically proven. Further research is needed to prognosticate POLE mutated EC and define appropriate adjuvant treatment recommendation.