Difference In Relapse-free Survival Research Articles

Mutations of the PIK3CA gene in patients with breast cancer in the Krasnoyarsk region

Aim. To identify population characteristics of the PIK3CA gene mutation among breast cancer patients in the Krasnoyarsk region.Materials and methods. The study included 140 patients with breast cancer with a certain mutation status of the PIK3CA gene, observed at the Krasnoyarsk Regional Clinical Oncology Center named after A.I. Kryzhanovsky. Determination of PIK3CA gene mutations (exons 2, 5, 8, 10 and 21) was carried out using commercial kits on equipment from Roche (Germany). Statistical processing of the obtained data was carried out using Microsoft Excel and Statistica 12 software products. The assessment of the factor of influence on the relapse-free and overall survival was carried out by constructing and comparing Kaplan–Meier curves. The result was considered statistically significant at a significance level of p <0.05.Results and conclusion. The overall frequency of occurrence of PIK3CA gene mutations is 38.6 %. The most common mutations are H1047X (55.4 %) in exon 21 and E545K (27.8 %) in exon 10. The median age of breast cancer patients with mutation status in the PIK3CA gene was 58.9 [49.0; 67.0] years, median time to relapse or progression was 62.2 [27.0; 84.0] months. There were no statistically significant differences in relapse-free survival between the presence and absence of mutations (p = 0.8). The effect of changes in PIK3CA on a decrease in overall survival rates (p = 0.047) in breast cancer patients was shown.

Description of therapeutic strategies in severe systemic lupus erythematosus-associated immune thrombocytopenia: a retrospective cohort study of response and relapse.

To describe the response and relapse of severe thrombocytopenia in patients with systemic lupus erythematosus (SLE) with different treatments. We performed a retrospective cohort study, which included SLE patients who were hospitalized for thrombocytopenia of less than 30,000/µL platelets, from January 2012 to December 2021. Demographic and clinical information was obtained from clinical records. Kaplan-Meier and logrank test were performed. Forty-seven patients, mostly women (83%) with a median age of 31years, were included in the study. Eight patients (17%) relapsed within a median period of 35.7weeks. Initial acute treatment with prednisone at 1mg/kg/day was as effective as glucocorticoid pulses. However, induction treatment with cyclophosphamide (CYC) had the lowest remission rate (43%, p = 0.034). There was no significant difference in relapse-free survival (RFS) among the acute glucocorticoid treatments. CYC induction was associated with lower RFS compared to rituximab (RTX) (CYC 43.6weeks vs. RTX 51.8weeks, p = 0.040) or azathioprine (AZA) (CYC 43.6weeks vs. AZA 51.2weeks, p = 0.024). Administration of antimalarials was associated with longer RFS (51.6weeks vs. 45.0weeks, p = 0.021). Factors such as antiphospholipid syndrome, IgG anti-β2 glycoprotein I positivity, renal and additional hematologic SLE activity during follow-up significantly reduced RFS. Despite similar response of acute glucocorticoid regimens, induction therapy with AZA or RTX resulted in a longer RFS compared to CYC. Adding an antimalarial also improved RFS. Our study provides evidence that may help develop better treatment strategies for severe thrombocytopenia in SLE patients. Key Points • Induction therapy with azathioprine or rituximab provided longer relapse-free survival in SLE thrombocytopenia compared with cyclophosphamide. • Antimalarial administration was associated with longer relapse-free survival in SLE thrombocytopenia. • Antiphospholipid syndrome, IgG anti-β2 glycoprotein I positivity, as well as renal and additional hematologic SLE activity during follow-up, decreased relapse-free survival.

Beyond diagnosis: exploring the significance of IgG4+ plasma cell count through immunostaining in IgG4-related disease.

To evaluate whether the grade of IgG4+ plasma cell infiltration in biopsies is associated with clinical or serologic outcomes in IgG4-RD. We included 57 patients with biopsy proven IgG4-RD according to the Comprehensive Diagnostic Criteria and/or the 2019 ACR/EULAR Classification Criteria. We collected histological, clinical (disease duration, phenotype, remission and relapses) and serological variables. 29 (50.9%) patients were men, mean age 49.9 years, with a median disease duration of 22 months. The distribution among clinical phenotypes were 14% pancreato-hepato-biliary, 12.3% retroperitoneal/aortic, 29.8% head and neck-limited, 29.8% Mikulicz/systemic and 14% undefined. Thirty-nine patients had a proliferative and 18 a fibrotic phenotype. Most biopsies were from lacrimal gland, lymph node, pancreas, orbit, kidney, retroperitoneum and thyroid gland. Thirty-nine (68.4%) patients had <100 IgG4+ plasma cells/HPF and 18 (31.6%) ≥100 IgG4+ plasma cells/HPF. Patients with ≥100 IgG4+ plasma cells/HPF were more likely to belong to the pancreato-hepato-biliary and the proliferative phenotypes, had fewer relapses and a higher remission rate. On multivariate analysis, the OR for remission at last follow-up was 6.7, 95% CI 1.1-4.42, p=0.03. The log-rank test showed a difference in relapse-free survival between the two groups (HR 2.6, 95% CI 1.2-5.6, p=0.01). According to the ROC analysis, patients with more than 61 IgG4+ plasma cells were less likely to relapse. A count of ≥100 IgG4+ plasma cells/HPF may identify patients with a proliferative phenotype, fewer relapses and a higher remission rate.

Abstract PO1-15-03: Spatially resolved analysis of tumor microenvironment in invasive lobular carcinoma

Abstract Background: Invasive lobular carcinoma (ILC) is the second most common histological breast cancer subtype; however, little is known about its tumor microenvironment (TME). Here, we aimed to study ILC TME using spatial transcriptomics (ST). Methods: We performed ST (Visium 10x Genomics) on frozen tumor samples from 43 primary hormone receptor positive (HR+), HER2-negative (HER2-) ILCs. Of note, 9 samples were coming from patients who experienced disease relapse. Relative hematoxylin/eosin (H&amp;E) slides were morphologically annotated (QuPath software). xCell was used to perform cell type enrichment analysis on sample pseudo-bulks. After cross-samples integration, ST spots were clustered using hierarchical clustering (STutility R package). intNMF algorithm was used to perform clustering at the patient-level by combining: RNA sequencing information (relative percentage of spot-level clusters in each sample), morphology and level of colocalization between cancer cells and the other cell types of the tumor microenvironment. METABRIC (HR+, HER2- ILC samples, n = 122) was used as external validation cohort. Survival analyses (univariable and multivariable adjusting for clinicopathological features) were performed using Cox proportional hazard models. Results: The patient-level classification revealed four groups showing different biological characteristics. Differences in terms of morphology (annotation) and pathway enrichment analysis based on marker genes (GSEA) were observed between groups. This information allowed us to annotate our groups as: proliferative (P, n = 12, enriched in tumor cells and proliferation-related pathways), normal-stroma enriched (NSE, n = 10, enriched in fibroblasts and carcinoma in situ), metabolic (M, n = 9, enriched in metabolic-related pathways) and metabolic-immune enriched (MIE, n = 10, enriched in adipose tissue, metabolic and immune-related pathways). Interestingly, a significantly higher presence of macrophages M2 was found in MIE group. Using group-specific gene signatures, we were able to reproduce the same 4 groups in the METABRIC. Of note, we observed significant differences in relapse-free survival (RFS) in METABRIC (p = 0.03), with NSE presenting better outcome, while P, M and MIE presented worse prognosis. Analysing the area of contact between adipocytes and cancer cells typical of MIE group, we noticed an enrichment in metabolic and M2 macrophages-related pathways. In doing so, we derived a 28 gene signature relative to the tumor-adipocytes contact area. Importantly, our signature was highly expressed in M and MIE groups, and it was not correlated with proliferation-related signatures. Interestingly, the adipocytes-related signature was significantly associated with shorter RFS in ILC patients in METABRIC (univariable: HR 1.4, p = 0.023; multivariable: HR 1.6, p = 0.005). Since both proliferation and metabolism showed to be key processes in defining prognosis in ILC, we built a prognostic index by integrating our adipocytes-related signature with genomic grade index (GGI, a proliferation-related signature). Our index outperformed other existing prognostic signatures (e.g., Oncotype DX, MammaPrint, EndoPredict, LobSig) in assessing prognosis (RFS) in ILC in METABRIC (univariable: HR 1.7, p &amp;lt; 0.001; multivariable: HR 1.7, p = 0.002). Conclusions: We identified 4 biologically driven HR+, HER2- ILC groups describing tumor microenvironment heterogeneity. Of note, two of the three groups associated to worse disease outcome were related to metabolism, highlighting the importance of such process in ILC biology and in the future development of new treatment strategies. Moreover, the prognostic power of our index has the potential to refine the assessment of the risk of relapse in ILC. Further validation is warranted. Citation Format: Matteo Serra, Mattia Rediti, Laetitia Collet, Frédéric Lifrange, David Venet, Nicola Occelli, Xiaoxiao Wang, Delphine Vincent, Ghizlane Rouas, Ligia Craciun, Denis Larsimont, Laurence Buisseret, Miikka Vikkula, François Duhoux, Françoise Rothé, Christos Sotiriou. Spatially resolved analysis of tumor microenvironment in invasive lobular carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-03.

RELEVANCE OF OVARIAN PRESERVATION&#x0D; IN YOUNG WOMEN WITH EARLY-STAGE&#x0D; ENDOMETRIAL CANCER AFTER HORMONAL&#x0D; AND SURGICAL TREATMENT:&#x0D; A COMPREHENSIVE LITERATURE REVIEW

Relevance: Ovarian preservation in young women with early-stage endometrial cancer after surgical treatment has been conventionally associated with complications. Nevertheless, recent randomized studies suggest a different perspective.&#x0D; The study aimed to clarify the occurrence of complications, in particular relapses, associated with ovarian preservation in young&#x0D; women after hormonal and surgical treatment for early-stage endometrial cancer.&#x0D; Methods: The analysis included articles published in full text over the past 10 years. We identified relevant observations from studies using a comprehensive search in the following databases: PubMed, Medline, Embase, and Cochrane Library. The search strategy&#x0D; included terms related to endometrial cancer: premenopausal, young woman, endometrial cancer, ovarian conservation. The study&#x0D; followed the PRISMA guidelines for systematic reviews.&#x0D; Results: A total of 178 articles were studied, of which 111 articles (literature reviews and meta-analyses) (62%) described the&#x0D; cases of ovarian preservation. Of these, 84 were excluded for various reasons; 29 eligible articles were included in this analysis.&#x0D; Notably, factors such as younger age (P&lt;0.0001), later year of diagnosis (P=0.03), residence in Central and Southern Europe and&#x0D; the United States (P=0.02), and lower-grade tumors in Asian countries (P&lt;0.002) correlated with the desire of women to preserve&#x0D; their ovaries. The conducted literature review showed that ovarian preservation did not significantly affect cancer-specific survival&#x0D; (risk ratio (HR) =0.78, 95% CI 0.17-2.74) or overall survival (HR=0.78, 95% CI 0.24-1.75).&#x0D; This study’s results remained practically unchanged even after excluding women after radiation and hormone therapy.&#x0D; Conclusion: This literature review revealed no statistically significant difference in relapse-free survival between patients after&#x0D; ovarian preservation at stage IA and partially at stage II com-pared to those after bilateral salpingo-oophorectomy.

Local excision versus radical surgery for anal squamous cell carcinoma: a multicenter study in Japan

BackgroundThe standard treatment for anal squamous cell carcinoma is chemoradiation therapy (CRT), but there is a possibility of over-treatment for early-stage disease. cTisN0 and cT1N0 disease is currently indicated for local excision, but it is unclear whether the indication of local excision can be expanded to cT2N0 disease.Methods126 patients with cTis-T2N0 anal cancer treated at 47 centers in Japan between 1991 and 2015 were included. Patients were first classified into the CRT group and surgical therapy group according to the initial therapy, and the latter was further divided into local excision (LE) and radical surgery (RS) groups. We compared prognoses among the groups, and analyzed risk factors for recurrence after local excision.ResultsThe CRT group (n = 87) and surgical therapy group (n = 39) showed no difference in relapse-free survival (p = 0.29) and overall survival (p = 0.94). Relapse-free survival curves in the LE (n = 23) and RS groups (n = 16) overlapped for the initial 3 years, but the curve for the LE group went lower beyond (p = 0.33). By contrast, there was no difference in overall survival between the two groups (p = 0.98). In the LE group, the majority of recurrences distributed in locoregional areas, which could be managed by salvage treatments. Muscular invasion was associated with recurrence after local excision (hazard ratio: 22.91, p = 0.011).ConclusionLE may be applied to selected patients with anal cancer of cTis-T2N0 stage. Given the high risk of recurrence in cases with muscular invasion, it may be important to consider close surveillance and additional treatment in such patients.

Abstract 6683: The abundance of Fusobacteria nucleatum in tumor tissue is a prognostic factor in patients of right-sided colorectal cancer

Abstract Background: A significant association between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Fusobacteria nucleatum (F. nucleatum) is one of the most famous bacteria associated with colorectal cancer (CRC). It has been reported that the abundance of F. nucleatum is associated with colorectal cancer-specific survival (CSS), however it remains unclear for association with F. nulceatum and relapse-free survival (RFS). If F. nucleatum has a significant involvement in tumor progression of colorectal cancer, the abundance of F. nucleatum should be associated with not only CSS but also RFS in colorectal cancer. In this study, we measured the bacterial mass of F. nucleatum in tumor tissue of CRC patients in Stage II-III to explore the differences in prognosis. Methods: We included patients with CRC in stage II-III who underwent surgical treatment at Nippon Medical School Hospital between January 2017 and December 2020 except patients who received preoperative chemoradiotherapy and had multiple cancers. We measured the absolute of F. nucleatum copy number of the DNA exacted tumor tissues using droplet digital PCR. Results: 253 patients with CRC were included. 128 patients had pathological stage II and 125 patients had pathological stage III. Among 253 patients, 104 patients had right-sided CRC, 89 patients had left-sided, and 60 patients had rectal cancer. F. nucleatum was detected in 166 patients (65.6%), and the median of F. nucleatum copy number was 1.08 (range; 0.00 -2791.3). F. nucleatum copy number was more abundant in right-sided CRC than in left-sided and rectal cancer (p= 0.02, p=0.01). There was no significant difference between stage II CRC and stage III. We categorized patients into two groups based on the median cut point of F. nucleatum copy number: the F. nucleatum-high group and the F. nucleatum-low group for comparison with clinicopathological features and prognosis. Patients with high abundance of F. nucleatum exhibited T4 of tumor depth (p=0.03), right-sided CRC (p=0.01), longer tumor circumference (p &amp;lt;0.001), longer tumor length (p &amp;lt;0.001), and no lymph node metastasis (p=0.024). There was no significant difference in relapse-free survival between the F. nucleatum-high group and F. nucleatum-low group among whole patients (p=0.53). Analyzing divided tumor location, in right-sided CRC high abundance of F. nucleatum was significantly associated with shorter relapse-free survival than low abundance (p=0.02), while in left-sided and rectal cancer there was no significant difference (p=0.61). Conclusion: F. nucleatum was more abundant in right-sided CRC and associated with relapse-free survival only in right-sided CRC. F. nucleatum may make a greater impact on right-sided CRC than on left-sided and rectal cancer. Citation Format: Toshimitsu Miyasaka, Takeshi Yamada, Sho Kuriyama, Akihisa Matsuda, Kay Uehara, Seiichi Shinji, Yasuyuki Yokoyama, Goro Takahashi, Takuma Iwai, Kohki Takeda, Shintaro Kanaka, Hiroshi Yoshida. The abundance of Fusobacteria nucleatum in tumor tissue is a prognostic factor in patients of right-sided colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6683.

Evaluation of Quality of Life and Prognosis of Gastric Cancer Patients After Laparoscopic Subtotal Gastrectomy.

The clinical significance of laparoscopic subtotal gastrectomy (LsTG) with a small remnant stomach remains unclear in patients with gastric cancer, including at an advanced stage. The present study assessed postoperative quality of life (QOL) and survival after LsTG compared with laparoscopic total gastrectomy (LTG). We retrospectively analyzed consecutive patients with gastric cancer who underwent LsTG (n=26) or LTG (n=26). Surgical outcome, postoperative nutritional status, QOL, and prognosis were compared between the LsTG and LTG groups. The Postgastrectomy Syndrome Assessment Scale was used to evaluate postoperative QOL. Operating time was significantly shorter (p<0.01) and postoperative morbidity was significantly lower (p=0.04) in the LsTG than in the LTG group. The reduction in body weight after surgery was significantly greater in the LTG than in the LsTG group (p<0.01). The Postgastrectomy Syndrome Assessment Scale revealed that, compared with LTG, LsTG significantly improved postoperative QOL (p<0.05). There was no significant difference in relapse-free survival and cancer-specific survival between the two groups. Three patients in the LTG group died of pneumonia and overall survival was significantly longer in the LsTG group (p=0.01). This study demonstrated the efficacy of LsTG with a small remnant stomach to prevent a decline in postoperative QOL and non-cancer-related death.

CNS Prophylaxis Among Patients with HIV-Associated Diffuse Large B-Cell Lymphoma - a Single Center Retrospective Study

Title: CNS Prophylaxis Among Patients with HIV-Associated Diffuse Large B-Cell Lymphoma - A Single Center Retrospective Study Introduction: Patients with Human Immunodeficiency Virus (HIV) are known to develop Lymphoma at a higher rate compared with the general population, with Diffuse Large B-Cell Lymphoma (DLBCL) being the most common subtype. Historically, before the advent of HIV treatment with antiretroviral therapy (ART), HIV-associated DLBCL was considered a more aggressive type of lymphoma and all patients were treated with central nervous system (CNS) prophylaxis. However, since ART has been widely adopted, there is some data to suggest that HIV-associated DLBCL among those taking ART more closely resembles de-novo DLBCL and may not need to be universally treated with CNS prophylaxis. There are no good prospective trials evaluating which patients who develop HIV-associated DLBCL while on ART should receive CNS prophylaxis. Furthermore, studies that tried to predict which DLBCL patients are at greater risk for CNS relapse explicitly excluded patients with HIV. Despite the absence of data, guidelines have shifted and current NCCN guidelines now recommend that HIV patients with DLBCL should be risk stratified as de-novo DLBCL patients with respect to CNS directed therapy. In this study, patients with HIV-associated DLBCL were retrospectively analyzed to understand the patterns of CNS prophylaxis and effects on relapse free survival. Methods: The Electronic Medical Record was queried at a large academic medical center in New York City for patients with HIV-associated DLBCL between the years of 2012 and 2021 using ICD-10 codes. Other subtypes of Lymphoma such as Burkitt's or Plasmablastic Lymphoma were excluded. Patients who did not receive their entire treatment course within the institution were also excluded. Clinical characteristics at diagnosis, treatment type, CNS prophylaxis, and survival data was collected and analyzed. Results: A total of 38 patients were identified according to the inclusion criteria. 26 patients (68%) underwent screening lumbar punctures (LPs) for CNS disease while 12 patients (32%) did not. The two groups were not statistically different within any categories except for LDH, where the LP group had a median LDH of 492 units/L and the non-LP group had a median LDH of 241 units/L (p-value: 0.031). The two groups were not statistically different in cell of origin subtypes, stage, bone marrow involvement, kidney/adrenal involvement, the use of ART prior to diagnosis, IPI or CNS-IPI scores. In addition, among the group that had an LP done with no CNS involvement (n=25), there was no statistical difference in relapse-free survival among those who received adequate CNS prophylaxis and those who did not (p-value 0.886). Conclusions: Among patients with HIV-associated DLBCL in a large academic medical center in New York City, there is no reliable indicator to predict which were offered screening lumbar punctures and which were not. Clinicians may be using additional measures of aggressiveness not accounted for in standard IPI and CNS-IPI scoring algorithms. Furthermore, there was no clear benefit in relapse free survival among high-risk patients who received adequate CNS prophylaxis versus those who did not in this limited sample size. Further research is needed to determine whether patients with HIV-associated DLBCL should be risk stratified similarly to de-novo DLBCL patients with respect to CNS prophylactic therapy.

Racial and Ethnic Differences in Acuity and Cumulative Frontline Organ Toxicity at the Time of Relapse in Pediatric Acute Myeloid Leukemia

Introduction: Racial and ethnic disparities in survival outcomes exist in pediatric acute myeloid leukemia (AML), but the role of relapse and its potential contribution to outcome disparities is unknown. We sought to examine differences in relapse-free survival (RFS) and clinical characteristics at the time of relapse by race and ethnicity using a real-world multi-institution cohort of pediatric AML patients. Methods: A retrospective cohort including all pediatric (age &amp;lt;19 years) patients treated for AML from 2011-2019 at 13 institutions in the United States was established and is being actively expanded to include diagnoses through 2023. Data collection was accomplished by detailed chart abstraction performed by trained study personnel. We additionally merged resource utilization data from the Pediatric Health Information System to ascertain patient acuity and cumulative organ toxicity. Analyses were restricted to patients identified in the medical record as Hispanic, non-Hispanic Black (NHB), and non-Hispanic White (NHW) to specifically assess historically marginalized patient populations. Other racial/ethnic groups including multi-racial were excluded due to small numbers. Kaplan-Meier survival curves were generated for RFS by race/ethnicity. Adjusted Cox models compared the hazard of relapse by race/ethnicity. Models adjusted for age at diagnosis, sex, initial risk classification, weight category at diagnosis, and acuity at initial presentation. To assess misspecification of outcome, we performed sensitivity analyses restricted to relapses occurring within 1 year of diagnosis (early RFS). Among the patients who relapsed, descriptive frequencies for clinical and treatment characteristics were reported by race/ethnicity. Results: A total of 437 pediatric patients with AML (28% Hispanic, 18% NHB, median follow-up time 3.0 years) were included in the analytic cohort. There were no statistically significant differences in RFS or early RFS by race/ethnicity (Figure 1). However, among relapsed patients, important qualitative differences were noted at the time of relapse (Table 1). Hispanic and NHB patients were older at relapse than NHW patients. Greater proportions of Hispanic and NHB patients (compared to NHW) experienced cardiovascular, respiratory, and renal failure during frontline therapy. Cumulative prevalence of organ failure in 2 or more systems since initial diagnosis was higher for both Hispanic (50%) and NHB (50%) patients compared to NHW patients (29%). Overweight/obesity at relapse was more prevalent among Hispanic (41%) and NHB (50%) compared to NHW (21%) patients. NHB patients were also more likely to present at relapse with higher acuity, defined as requiring ICU-level resources for 2 or more organ systems within 72 hours of admission, compared to NHW patients (75% vs. 57%). Conclusions: Our data suggest a similar risk of relapse by race and ethnicity. However, differences in cumulative frontline organ toxicity and acuity of presentation may lead to differential treatment at the time of relapse and drive subsequent overall survival disparities for Hispanic and NHB patients with pediatric AML. Future Directions: This was a planned interim analysis, and chart abstraction is ongoing to expand this cohort (anticipated N ~1000). We intend to pursue a series of formal mediation analyses regarding the role of relapse, cumulative organ toxicity during frontline treatment, and selection of salvage regimen on disparities in survival outcomes with the expanded cohort.

Gut microbiota diversity before allogeneic hematopoietic stem cell transplantation as a predictor of mortality in children

AbstractThe correlation existing between gut microbiota diversity and survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has so far been studied in adults. Pediatric studies question whether this association applies to children as well. Stool samples from a multicenter cohort of 90 pediatric allo-HSCT recipients were analyzed using 16S ribosomal RNA amplicon sequencing to profile the gut microbiota and estimate diversity with the Shannon index. A global-to-local networking approach was used to characterize the ecological structure of the gut microbiota. Patients were stratified into higher- and lower-diversity groups at 2 time points: before transplantation and at neutrophil engraftment. The higher-diversity group before transplantation exhibited a higher probability of overall survival (88.9% ± 5.7% standard error [SE] vs 62.7% ± 8.2% SE; P = .011) and lower incidence of grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD). No significant difference in relapse-free survival was observed between the 2 groups (80.0% ± 6.0% SE vs 55.4% ± 10.8% SE; P = .091). The higher-diversity group was characterized by higher relative abundances of potentially health-related microbial families, such as Ruminococcaceae and Oscillospiraceae. In contrast, the lower-diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae. Network analysis detected short-chain fatty acid producers, such as Blautia, Faecalibacterium, Roseburia, and Bacteroides, as keystones in the higher-diversity group. Enterococcus, Escherichia-Shigella, and Enterobacter were instead the keystones detected in the lower-diversity group. These results indicate that gut microbiota diversity and composition before transplantation correlate with survival and with the likelihood of developing aGVHD.

Comparison of clinical features and outcomes of proliferative, fibrotic, and mixed subtypes of IgG4-related disease: A retrospective cohort study.

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients' clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes. We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis. We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils ( P = 0.010), total IgE ( P = 0.006), high-sensitivity C-reactive protein ( P <0.001), erythrocyte sedimentation rate ( P <0.001), complement C4 ( P <0.001), IgG ( P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA ( P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014). Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.

Relationship between histopathological therapeutic effect and prognosis in oral cancer patients after preoperative S-1 chemotherapy followed by surgery.

Preoperative S-1 chemotherapy is administered to prevent tumor proliferation before surgery in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the relationship between the histological therapeutic effect and prognosis in patients with OSCC after pre-operative S-1 chemotherapy. Among 461 OSCC cases, 281 patients who received preoperative S-1 chemotherapy were compared with 180 patients that did not receive chemotherapy to determine the histological therapeutic effect in the resected specimens and the differences in relapse-free survival. The histological chemotherapeutic effect was well correlated with the subsequent prognosis. In an examination of the combined effect of treatment and ypStage, the groups with good S-1 treatment effects had extremely good prognoses, even if the postoperative resection specimens were within the same ypStage. In a stratified search of patients who received S-1 for more than 7days and who had a significantly better prognosis than those who did not receive S-1, it was found that the prognosis was significantly better for patients with tongue cancer according to site; furthermore, tongue cancer, age under 70years of age, male sex, and clinical stage I were factors associated with a significantly better prognosis. Even if the postoperative resection specimens were within the same ypStage, the groups that responded to S-1 treatment were considered to have extremely good prognoses. A good adaptation for S-1 was tongue cancer, and especially tongue cancer with cStage I, male sex, and age less than 70years old.

Variations in the approach to lung metastases in osteosarcoma among pediatric and adult patients.

11528 Background: Osteosarcoma (OS) is most common in the pediatric (ped) and young adult population but can occur at any age. Amongst other factors, older age confers a worse prognosis, and it is uncertain whether this is due to inherent biologic differences or treatment approaches. Lung-only metastases (mets) is common, and metastasectomy is performed frequently to improve overall survival. Little is known about the differences in lung-only metastatic OS and approaches to metastasectomies between ped and adult populations. Methods: A single-institution retrospective chart review using a free-text search engine and keywords “osteosarcoma, “lung mets” and “pulmonary mets”, generated 206 patients(pts) diagnosed from 2006-2021. Eligible pts had a diagnosis of lung-only metastatic disease, resection performed at the institution and at least one year of follow-up data. Data was analyzed in two cohorts based on age at OS diagnosis: ped (age&lt;18) and adult (age &gt; 18 years), as well as with age as a continuous predictor. Results: Fifty pts (27F/23M) with lung only mets were eligible for analysis with a median follow up of 10.4 years. Median age was 23 yrs (range 6-77); 20 pts (40% were ≤18 years old); 31 pts (16 ped, 15 adult) had an extremity primary site. Rates of metachronous (67% vs 60%) and bilateral (50% vs 40%) lung mets were similar in ped vs. adult pts, respectively. The median number of lung mets was 2 (range 1 to &gt; 25) with 50% of patients (35) having 2-6 metastases (8 ped, 20 adult). The median size of lung metastasis was 1.2 cm (range 0.1-4.0 cm). 15 ped pts (75%) underwent metastasectomy, compared to 19 adult (63.3%) (OR 1.74, p = 0.39). Probability of metastasectomy decreased with age when used as a continuous predictor (p = 0.11). Ped pts were more likely to have an open procedure as compared to thoracoscopic (OR 12.75, p &lt; 0.01). There was no significant difference in relapse-free survival between ped and adult pts who underwent metastatectomy (p = 0.84). Median overall survival following lung metastasis detection was 5.8 years for ped pts compared to 3 years for adult pts (p = 0.15 from Cox model). Conclusions: Multiple tumor and patient-specific factors affect the decision to undergo metastatectomy in lung-only OS. In our single-center study we learned that timing, pattern, and number of lung mets in ped vs. adult pts were similar, but younger pts were more likely to undergo an open procedure. Our data trended towards a lower chance of undergoing metastatectomy with older age. Larger studies are required to further understand decision-making and therapeutic outcome and a randomized study of open vs. thoracoscopic metastatecomy for lung-only OS mets is underway. In this small study, many patients with lung-only metastatic OS had long-term survival. We showed that relapse-free survival post-metastatecomy was similar in ped and adult patients.

Galectin-3 and matrix metalloproteinases 2 and 9 in peripheral blood of gastric cancer patients

Background: High incidence of gastric cancer (GC), its aggressive clinical course, rapid tumor dissemination, low sensitivity to chemotherapy and lack of reliable laboratory diagnostic criteria urgently require a search for the most informative markers associated with key biologic properties of the tumors.&#x0D; Aim: Comparative analysis of galectin-3, matrix metalloproteinase (MMP)-2, and MMP-9 levels in peripheral blood of GC patients and healthy donors, assessment of association of these markers with clinical morphological characteristics of the disease, and prognosis of overall and relapse-free survival.&#x0D; Materials and methods: Sixty (60) primary treatment-nave GC patients (38 men, 22 women) aged 29 to 81 years and 90 healthy donors compatible with their age and sex were included into the study. Galectin-3 was measured in EDTA plasma, MMP-2 and MMP-9 in serum with standard direct enzyme immunoassay kits "Human MMP-2 (total)", "Human MMP-9 (total)", "Human Galectin-3" (RD Systems, USA).&#x0D; Results: Plasma galectin-3 concentration in the GC patients was significantly higher than in the healthy controls (median 12.9 and 10.6 ng/ml, respectively; p 0.0001). No difference in serum MMP-9 levels between GC patients and control subjects were found, while MMP-2 level in the control group was significantly higher, than in the GC patients (p = 0.039). No association between galectin-3, MMP-2, and MMP-9 blood levels in the GC patients could be identified. In contrast to GC patients, there was a positive correlation of plasma galectin-3 with age in the control group (rs = 0.51, p 0.005). No associations between the biomarkers levels in blood and clinical and morphological characteristics of GC were established, except MMP-9 being higher at Т4а invasion depth as compared to the earlier Т2 level. Marked differences in the overall survival depending on plasma galectin-3 levels were found, with the cut-off level of 12.9 ng/ml: the 5-year overall survival in the patients with low galectin-3 was better, than in those with its higher level (50 and 43%, respectively; however, the difference was non-significant, р 0.1). Both overall and relapse-free survival of the GC patients was higher in those with low ( 212 ng/ml) serum MMP-2: the 5-year overall survival in this group comprised 60% versus 23% in the patients with higher MMP-2 (p = 0.018). The difference in relapse-free survival was non-significant. Serum MMP-9 levels had no significant impact on the survival of GC patients.&#x0D; Conclusion: The ambiguous data on the clinical role of galectin-3, MMP-2, MMP-9 in GC obtained in this study indicate the necessity of further investigation of their possible utility for the diagnostics and prognosis of treatment results.

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases

BackgroundTertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver...

Comparative analysis of the effectiveness of neoadjuvant systemic therapy and primary surgical treatment of patients with &lt;i&gt;BRCA&lt;i/&gt;-associated triple-negative T1 breast cancer

BACKGROUND: BRCA-associated triple-negative breast cancer does not only have a better overall survival rate, but also a longer recurrence-free period in compatison to patients with sporadic breast cancer. BRCA-associated triple-negative breast cancer shows high sensitivity to chemotherapeutic agents, but the benefit of systemic neoadjuvant therapy for patients with tumor size T1 in triple-negative breast cancer is unclear.&#x0D; AIM: The aim of the study is to determine the recurrence rate in the patients with BRCA-associated triple-negative breast cancer and to determine the recurrence rate for the group of patients with tumor size T1, depending on the initial treatment.&#x0D; MATERIALS AND METHODS: The study includes the data of 129 patients diagnosed with BRCA-associated triple-negative breast cancer treated in the period from 2010 to 2022 at the Department of Breast Tumors of the N.N. Petrov National Medical Research Center of Oncology. All the patients have been divided into two groups depending on the initial treatment. Group I included 93 (72.1%) patients whose treatment was started with systemic neoadjuvant therapy, group II, whose initial treatment involved surgery, included 36 (27.9%) patients.&#x0D; RESULTS: In group I, the number of recurrences was 22 (23.6%), and in group II 6 (16.6%). Depending on the pathomorphological response to systemic neoadjuvant therapy, the patients of group I have been separated: in the group of patients with a complete pathomorphological response, the number of relapses was 6 (13.3%), and in the group of patients with a partial pathomorphological response 16 (33.3%). A comparative analysis of 2 groups with tumor size T1 has shown that in group I the number of patients with tumor size T1 was 11 (11.8%) cases, and in group II 16 (44.4%). Subgroup comparative analysis in group I, taking into account tumor size T1, has shown that recurrence has not been observed when a complete pathomorphological response was achieved in 8 (17.7%) patients, and in the group with partial pathomorphological response in 3 (6.25%) patients with tumor size T1. A relapse has been observed in 1 (2%) case. With clinical tumor size T1 (n = 16), there was no recurrence in group II.&#x0D; CONCLUSIONS: Patients diagnosed with BRCA-associated triple-negative breast cancer remain at a high risk of recurrence at a later stage of the disease, but this does not apply to patients with a tumor size T1 since the difference in relapse-free survival [AP1] between patients, whose treatment was started with neoadjuvant systemic therapy and patients, whose initial treatment involved surgery % with a clinical tumor size T1, is not confirmed.

Optimal choice of drug antitumor treatment in patients with Fibrolamellar liver carcinoma

Introduction. Fibrolamellar hepatocellular carcinoma (FlC) is a rare subtype of hepatocellular carcinoma (HCC). Drug antitumor treatment of FlC has not been studied sufficiently due to the rarity of the pathology and requires further research to choose an effective treatment.Aim. The choice of effective drug antitumor treatment in patients with fibrolamellar liver carcinoma.Materials and methods. The retrospective study included 31 patients with FlC who received drug antitumor therapy at the N.N. Blokhin National Research Center of Oncology of the Ministry of Health of the Russian Federation in the period from 2005 to 2020. The patients were divided into comparison groups: “targeted therapy” (mainly sorafenib), “chemotherapy” (mainly gemcitabine + cisplatin). A comparative intergroup analysis of the effectiveness of drug antitumor treatment in the 1st and 2nd lines of therapy was carried out. Adjuvant chemotherapy was evaluated for time without progression. The correlation of the number of treatment lines in the anamnesis with the prognosis of the disease was also evaluated.Results. Analysis of the effect of adjuvant therapy on relapse-free survival did not prove significant differences between the comparison groups (p = 0.112; log-rank test). Therapy with multikinase inhibitors (mainly sorafenib) allows to achieve a better time without progression compared to chemotherapy (mainly gemcitabine + cisplatin / oxaliplatin) (p = 0.000; log-rank test) in patients in the 1st line of FlC treatment. OS did not significantly differ between the groups (p = 0.417; log-rank test). In line 2, time without progression in patients receiving targeted therapy (p = 0.042; log-rank test) is higher compared to patients receiving chemotherapy in line 2. A longer duration of OV was recorded in the groups of patients who underwent 2 lines of drug antitumor treatment and in the group of 3 or more lines compared with the use of only 1st line of treatment (p = 0.024) and (p = 0.003), respectively.Conclusion. The results of the work demonstrate an advantage in the appointment of targeted therapy as the 1st and 2nd lines of drug antitumor treatment, while the appointment of chemotherapy remains a less prognostically favorable option. Adjuvant therapy administration did not demonstrate a statistically significant difference in relapse-free survival.

Clinical and Molecular Profiling of AML Patients with Chromosome 7 or 7q Deletions Incontext of TP53 Alterations and Venetoclax Treatment

Background Deletions in chromosome 7 (del(7)) or its long arm (del(7q)) constitute the most common adverse cytogenetic events, seen in approximately 20-30% of newly diagnosed AML and portend worse outcomes (Grimwade et al., 1998). These deletions often co-occur in the context of complex karyotype and TP53 alterations (Rücker et al., 2012). The European Leukemia Network (ELN) 2017 classification in adult AML patients (Döhner et al., 2017) considers AML patients with del7q as an intermediate risk. However, del(7) was classified as adverse risk. Yet, for the purpose of clinical studies and therapeutic decisions, AML with del(7) and del(7q) are often consolidated as one cytogenetic group and able patients are generally recommended to undergo stem cell transplantation in first remission to mitigate the risk of relapse (DiNardo et al., 2020; Kalwinsky et al., 1990). However, in-depth clinical and molecular characterization comparing AML patients with del(7) versus del(7q) have been limited to small patient cohorts (Poiré et al., 2019). We herein aimed at conducting in-depth clinical and molecular characterization of AML patients with del(7) or del(7q) in the context of venetoclax therapy and TP53 mutations. Methods We retrospectively analyzed 243 treatment-naive patients with AML and del(7) (168/243; 69%) or del(7q) (75/243; 31%) who did not receive any myeloid-directed therapy prior to AML diagnosis. Fifty-one percent of patients had targeted next-generation genomic sequencing, while another 46% had at least one other myeloid-related gene sequenced. The mutation profile yielded 374 mutations in 40 genes, and 169/243 (69.5%) patients had ≥1 mutation (Figure 1). Patients were stratified based on co-occuring TP53 alterations and venetoclax therapy. Results Patients with del(7q) had similar demographic and molecular profiles compared to patients with del(7). The median OS duration for AML patients with del(7) compared to del(7q) was 7.4 vs 8.4 months respectively (p=0.20) and the median remission duration was 5.3 vs 6.2 months respectively (p=0.16). These data suggest that AML patients with chromosome 7 and 7q have similar clinical features and outcomes. Since mutations in TP53 were the most common in our AML cohort, we investigated the significance of TP53 alterations on the outcomes of AML patients with del(7) or del(7q). Except for higher rate of complex cytogenetics in AML patients with TP53 alterations (p<0.0001), the clinical and demographic characteristics were similar among patients with del(7) or del(7q) with or without TP53 alterations. However, patients with del(7) or del(7q) who harbored TP53 alterations had significantly worse OS (5.5 vs 10.5 months p < 0.0001) and remission duration (4.7 vs 6.8 months p=0.0035) but not RFS (3.5 vs 3.4 months p=0.16) compared to those with TP53 wildtype. We next investigated the clinical outcomes of patients with del(7) and del(7q) treated with venetoclax-based therapies. A total of 39/243 (16%) of patients received VEN-based therapy as part of their frontline therapy (31/168 (18%) in del(7) versus 8/75 (11%) in del(7q), p= 0.13). Remarkably, AML patients with del(7) who received VEN-based therapy (Rx + Ven) had significantly worst outcomes than patients treated without VEN-based (Rx) regimens with or without TP53 mutation. Specifically, the median OS, RFS and remission duration for del(7) Rx + Ven were the shortest at 5.8 months (p=0.47), 0.1 months (p<0.0001) and 2.2 months (p=0.0015), respectively, compared to the other treatment groups (Figure 2). Among patients with TP53 alterations in del(7) and del(7q) subgroups, the addition of venetoclax did not improve clinical outcomes. The median OS for del(7) TP53-alt Rx vs del(7) TP53-alt Rx+Ven was 5.2 months vs 4.5 months, respectively (p = 0.6). The median OS for del(7q) TP53-alt Rx vs del(7q) TP53-alt Rx+Ven was 6.4 months vs 7.9 months respectively (p = 0.69). Conclusion We conducted a comprehensive clinical and molecular analysis of AML patients with del(7) and del(7q) revealing differences in relapse-free survival in these patients, but not in OS or remission duration. This suggests that del(7q) should also be considered an adverse event. The co-occurrence of TP53 alterations conferred worse outcomes in del(7) and del(7q) patients, while addition of venetoclax did not improve outcomes. There is an unmet need to identify therapies that would improve outcomes in AML patients with del(7) or del(7q). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Is Total Omentectomy Mandatory in T3 and T4a Gastric Cancer for Laparoscopic Distal Gastrectomy?

Despite the lack of strong evidence, total omentectomy (TO) remains the recommended procedure for gastric cancer (GC) for T3 or deeper tumors. Partial omentectomy (PO) has recently become a preferred procedure owing to its simplicity during laparoscopic distal gastrectomy (LDG); however, the oncological role of PO needs to be elucidated. Overall, 341 patients with T3 or T4a GC who had undergone LDG between 2009 and 2016 were divided into TO (n = 167) and PO (n = 174) groups. Propensity matching was performed with respect to covariance age, sex, T and N stage, tumor size, and degree of tumor differentiation. Clinicopathological characteristics and long-term follow-up data were analyzed for both groups. After successful propensity matching, both groups included 107 patients. In a matched cohort, no significant difference in clinicopathologic features and short-term surgical outcomes was observed between the two groups. Furthermore, no significant difference in relapse-free survival (RFS; p = 0.201) and peritoneal seeding-free survival (PSFS; p = 0.094) was observed. However, tumor recurrence as peritoneal metastasis occurred in 5 (4.7%) patients in the PO group and 13 (12.1%) patients in the TO group. In Cox proportional hazards analysis, omentectomy was not identified as a significant factor for RFS, PSFS, and overall survival; however, advanced N and T4a stage were considered significant factors for RFS and PSFS, respectively. PO may be adopted during the LDG of T3 or T4a GC without definite gross serosal exposure. More large-scale evidence or prospective study is recommended.