Tumor Involvement Research Articles

Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma:Pathological Phenotype and Genetic Mutation Analysis of 12 Patients

Introduction: Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (MEITL) is a primary intestinal lymphoma. Previously, it was referred to as Enteropathy Associated T-cell Lymphoma (EATL) type II. However, in the 2016 revision of the WHO classification, MEITL was recognized as a separate entity independent of EATL. EATL is mainly observed in people of Nordic descent and is closely associated with celiac disease, whereas MEITL is more commonly found in Asians and Hispanics without a history of celiac disease. MEITL is an extremely rare condition, accounting for approximately 5% of all Peripheral T-cell Lymphomas (PTCLs). It predominantly affects the small intestine, especially the jejunum. The tumor cells often display an activated cytotoxic T-cell phenotype and express CD8 and CD56. Due to its rarity, there is limited understanding of this disease. Between 2017 and 2022, our center diagnosed only 14 cases of MEITL. We analyzed the clinical characteristics and pathological phenotypes of these patients and further investigated the status of gene somatic mutations using a panel-based genomic exome analysis. Results: Clinical features: From the medical records system, a total of 622 gastrointestinal live tissue biopsy samples were searched from October 2017 to September 2022. Among them, 67 cases (10.8%) were diagnosed as PTCLs, with only 15 cases (2.4%) being identified as MEITL, accounting for 22.3% of all gastrointestinal PTCLs. Out of the 15 MEITL cases, 9 were male, and 6 were female, with a median age of 61 years(figure). Treatment and Efficacy: Seven patients underwent elective surgery due to the involvement of malignant tumors in the gastrointestinal tract, while six patients received emergency surgery for intestinal perforation. Three patients did not undergo chemotherapy, and the remaining 12 patients received a median of 5 (range 1-8) cycles of chemotherapy using the CHOP/CHOP-like regimen. For elderly and frail patients, the dosage was reduced by 20% to 50%. After treatment, one patient achieved complete remission (CR/CRu), three patients had a partial response (PR), six patients had stable disease (SD), and two patients had uncontrolled disease (PD). Pathological Characteristics: The diagnosis of MEITL was confirmed by two hematopathologists. The immunohistochemical staining results are shown in Figure. The results revealed that all patients expressed CD3, CD8, and CD56. Only four cases expressed CD4, including three cases with partial expression. TIA1 was expressed in 11 patients, and granzyme B was expressed in 11 patients, with eight cases showing co-expression of TIA1 and granzyme B. None of the patients expressed CD20, while one case showed weak expression of CD30. Ki67 expression was observed in all cases, with seven cases having Ki67 expression above 80% and all others showing expression above 50%. Gene Mutations: We conducted the Next-Generation Sequencing in 12 patients. The genes include STAT5B (9 cases), SETD2 (7 cases), NRAS (3 cases), KRAS (4 cases), JAK3 (4 cases), BRAF (1 case), BCOR (1 case), CREBBP (4 cases), EZH2 (1 case), EP300 (1 case), JAK1 (1 case), TP53 (3 cases), ATM (1 case), SOCS1 (1 case), CHD2 (1 case), and JAK2 (1 case). All patients showed abnormalities in two or more genes. Survival: Median follow-up time was 4.45 months, and among 15 patients, 14 experienced disease progression. The median progression-free survival (PFS) was 2.9 months (95% CI: 1.7 months to 4.2 months). Up to the follow-up cutoff, 11 patients had died, and the median overall survival (OS) was 4.8 months (95% CI: 3.2 months to 6.4 months). Patients who underwent early elective surgery showed a significant improvement in OS (P=0.012), with a median OS of 18.0 months. Based on gene mutation analysis, mutations in STAT5B and RAS (NRAS or KRAS) (P=0.038, 0.007) were associated with poorer OS, whereas abnormalities in genes like SETD2 did not affect patient OS. Conclusion: Our results show that MEITL is extremely rare, accounting for only 2.4% of all lymphomas involving the intestines. Patients with MEITL have a poor prognosis, with a median OS of less than six months. However, early elective surgery can significantly improve patient survival. MEITL is characterized by a cytotoxic T-cell phenotype, with the majority expressing TIA1 and granzyme B. Commonly occurring gene mutations are found in STAT5B, SETD2, and NRAS or KRAS. Mutations in STAT5B and RAS genes (NRAS or KRAS) often indicate a shorter OS.

A Multicenter Study of CAR-T Cell Therapy for Relapse of B-ALL Post Allogeneic Stem Cell Transplantation

BACKGROUND: Patients with acute B-cell lymphoblastic leukemia (B-ALL) relapsed after allogeneic stem cell transplantation (allo-HSCT) have very poor prognosis. Chimeric antigen receptor T (CAR-T) cells targeting CD19 have been developed as one of the effective immunotherapies for relapsed/refractory B-ALL. The safety and efficacy of CAR-T cells in patients relapsed after allo-HSCT remain unclear. METHODS: This study analyzed 60 B-ALL patients relapsed after allo-HSCT treated with CAR-T cells between October 2015 and February 2022 from four Chinese centers. Their pre-treatment patient characteristics, treatment regimens, efficacy, adverse effects, and follow-up data were comprehensively analyzed. RESULTS: One patient refused efficacy evaluation. 7 patients died before day 28 after CAR-T infusion. A total of 52 were assessed for efficacy within 28 days after CAR-T infusion.76.92% (40/52) patients achieved complete remission (CR) at Day 28 after CAR-T infusion, including 38 patients who achieved MRD-negative CR. 4 of the 40 patients relapsed at a median follow-up date of 12.1 months. The 1-year OS and EFS of all patients were 52.8% ± 7.0% and 51.5% ± 7.0%, respectively, and the 2-year OS and EFS were 40.1% ± 8.6% and 45.1% ± 8.6%, respectively. Multifactorial analysis showed that patients with severe CRS had worse OS and EFS, and other factors including age, gender, site of CAR-T tumor involvement, type of previous transplantation, previous transplantation type, CAR-T product and CRS grade, etc., did not affect the long-term survival of patients. The incidence of CRS was 80.00%, the incidence of grade ≥3 CRS was 20.83%, and the median time of CRS was 2 days after CAR-T cell infusion (range: 0-34 days). 3 patients (5.00%) died due to multiorgan failure caused by severe CRS, and the rest of the patients' CRS was controlled, and the grade of CRS was related to the proportion of blast cells in the bone marrow prior to CAR-T cell infusion., independent of the type of transplantation and the source of CAR-T cells. The incidence of ICANS was 5.00%. The incidence of aGvHD was 30.00%, and patients who had received prior haploidentical allogeneic HSCT were significantly more likely to develop aGvHD after CAR-T cell infusion than those who had received prior matched allogeneic HSCT. The occurrence of aGvHD after CAR-T treatment was not associated with the occurrence of CRS (p = 1), the presence of aGvHD after prior transplantation (p = 0.3484), the presence of cGvHD after prior transplantation (p = 0.3167), the presence of cGvHD at the time of CAR-T infusion (p = 0.5136), and the presence of prior donor lymphocyte infusion (p = 0.7404), and whether CAR-T cells were from autologous or donor (p = 0.4819). CONCLUSIONS: CAR-T cells are safe and effective in treating B-ALL patients with post-transplant relapse, and donor-derived CAR-T cells do not exacerbate CRS with aGVHD, and there is a high incidence of aGVHD after CAR-T therapy in patients with HLA-haplotype-matched transplantation.

The progress and prospect of sentinel lymph node mapping in endometrial carcinoma

Sentinel lymph node (SLN) refers to the initial site of the lymphatic drainage from a primary tumor area. Identifying the SLN and analyzing tumor involvement can predict the status of the remaining lymph nodes. Accordingly, sentinel lymph node mapping (SLN mapping) has been brought up and widely applied to cancer therapy for its illuminating role in clinical lymph node resection. Sufficient information to guide surgical pathological staging and adjuvant treatment in endometrial cancer can be rendered by SLN mapping, hence minimizing surgery injury and reducing the incidence of complications. Evidence suggests that using SLN mapping does not affect progression-free survival (PFS) and overall survival (OS) of endometrial cancer patients. Furthermore, there is increasing evidence that using SLN mapping has a high detection rate (DR), sensitivity, and negative predictive value (NPV) for patients with early-stage lower-risk endometrial cancer. This review aims to systematically summarize the advances and application prospects of SLN mapping in endometrial cancer, with an expectation of furnishing reference for the clinical application.

Vein Wall Invasion Is a More Reliable Predictor of Oncological Outcomes than Vein-Related Margins after Pancreaticoduodenectomy for Early Stages of Pancreatic Ductal Adenocarcinoma.

Pancreaticoduodenectomy (PD) with vein resection is the only potentially curative option for patients with pancreatic ductal adenocarcinoma (PDAC) with venous involvement. The aim of our study was to assess the oncological prognostic significance of the different variables of venous involvement in patients undergoing PD for resectable and borderline-resectable with venous-only involvement (BR-V) PDAC. We performed a retrospective analysis of prospectively acquired data over a 10-year period. Of the 372 patients included, 105 (28%) required vein resection and vein wall involvement was identified in 37% of those. A multivariable analysis failed to identify the vein-related resection margins as independent predictors for OS, DFS or LR. Vein wall tumour involvement was an independent predictor of OS (risk x1.7-2) and DFS (risk x1.9-2.2) in all models, while it replaced overall surgical margin positivity as the only parameter independently predicting LR during an analysis of separate resection margins (risk x2.4). Vein wall tumour invasion may be a more reliable predictor of oncological outcomes compared to traditionally reported parameters. Future studies should focus on possible pre-operative investigations that could identify these cases and management pathways that could yield a survival benefit, such as the use of neoadjuvant treatments.

Study of lncRNAs in Pediatric Neurological Diseases: Methods, Analysis of the State-of-Art and Possible Therapeutic Implications.

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various cellular processes, and their roles in pediatric neurological diseases are increasingly being explored. This review provides an overview of lncRNA implications in the central nervous system, both in its physiological state and when a pathological condition is present. We describe the role of lncRNAs in neural development, highlighting their significance in processes such as neural stem cell proliferation, differentiation, and synaptogenesis. Dysregulation of specific lncRNAs is associated with multiple pediatric neurological diseases, such as neurodevelopmental or neurodegenerative disorders and brain tumors. The collected evidence indicates that there is a need for further research to uncover the full spectrum of lncRNA involvement in pediatric neurological diseases and brain tumors. While challenges exist, ongoing advancements in technology and our understanding of lncRNA biology offer hope for future breakthroughs in the field of pediatric neurology, leveraging lncRNAs as potential therapeutic targets and biomarkers.

SURG-29. APPROACH SELECTION FOR COMPLEX, MULTI-COMPARTMENTAL PETROCLIVAL MENINGIOMAS: A SYSTEMATIC REVIEW OF ENDOSCOPIC AND TRANSCRANIAL APPROACHES TO AN EXCEEDINGLY DIFFICULT CLASS OF SKULL BASE LESIONS

Abstract INTRODUCTION Petroclival meningiomas are among the most formidable and technically challenging tumors in skull base surgery owing to their deep-seated location and proximity to critical neurovascular structures. Herein, we seek to understand why skull base surgeons preoperatively plan the staged excision of petroclival meningiomas. METHODS Three databases were queried per PRISMA to identify studies describing the indications for staging surgical resection of petroclival meningiomas. RESULTS Fourteen studies describing 187 patients (59.3% female, age range: 5 – 81 years) met inclusion criteria. The most common presenting symptom at diagnosis was headache (24.6%). Other common symptoms included cerebellar signs (16.0%) and gait disturbances (13.4%). Petroclival meningiomas were most commonly observed extending to the cavernous sinus (52.88%) and meckel’s cave (49.04%). With respect to critical neurovasculature, the trigeminal nerve was involved in a majority (54.59%) of petroclival meningiomas, while other relevant cranial nerves with tumor involvement included the facial (16.22%) and vestibulococcular (12.43%). Additionally, the most commonly involve vascular structures were the basilar (2.16%) superior cerebellar arteries (1.62%). Of the 187 patients who underwent surgical resection of petroclival meningioma, 144 (77%) underwent surgery involving a single stage, while 43 (23%) underwent surgery in which a two-stage approach was used. The most common single-stage approaches were the retrosigmoid (n = 35) and transpetrosal (n = 22), while the most common approaches employed in a multi-stage fashion were the subtemporal (n = 6), pterional (n = 5), and suboccipital (n = 4) approaches. To clarify, these approaches were each performed as one half of a two-stage surgery involving a second, separate approach. CONCLUSION Common approaches used in multi-stage procedures included the retrosigmoid, anterior petrosectomy, posterior petrosectomy, orbitozygomatic, translabrynthine, and various combinations thereof. Indications for performing surgery in this manner include coexistence of lesion in both middle and posterior skull base compartments, absence of meaningful hearing function, tumor size, and surgeon preference.

Yttrium-90 Transarterial Radioembolization of Primary Lung Cancer Metastases to the Liver

PurposeTo assess whether yttrium-90 transarterial radioembolization (TARE) is safe and effective in the treatment of primary lung cancer metastases to the liver (LCML). Methods and MethodsThis retrospective study included 57 patients with LCML who were treated with 79 TARE treatments. Histology included non–small cell lung cancer (NSCLC) (n = 27), small cell lung cancer (SCLC) (n = 17), and lung carcinoid (LC) (n = 13). Survival was calculated using Kaplan–Meier method; differences between groups were estimated using log rank test. Cox proportional hazards model was used to determine factors influencing survival. Adverse events were graded using the Society of Interventional Radiology Adverse Events Classification. ResultsMedian overall survival (OS) was as follows: NSCLC, 8.3 months (95% confidence interval [CI], 6.3–16.4 months); SCLC, 4.1 months (95% CI, 1.9–6.6 months); and LC, 43.5 months (95% CI, 7.8–61.4 months). For NSCLC, presence of bilobar vs unilobar disease (hazard ratio [HR], 5.24; 95% CI, 1.64–16.79; P = .002); more tumors, 2–5 vs 1 (HR, 4.88; 95% CI, 1.17–20.37; P = .003) and >5 vs 1 (HR, 3.75; 95% CI, 0.95–6.92; P = .05); and lobar vs segmental treatment (HR, 2.56; 95% CI, 0–NA; P = .002) were negative predictors of OS. For SCLC, receipt of >2 lines of chemotherapy vs ≤2 lines (HR, 3.16; 95% CI, 0.95–10.47; P = .05) was a negative predictor of OS. For LC, tumor involvement of >50% was a negative predictor of OS (HR, 3.77 × 1015; 95% CI, 0–NA; P = .002). There were 11 of 79 severe or life-threatening adverse events within 30 days (abdominal pain, altered mental status, nausea/vomiting, acalculous/aseptic cholecystitis, hyponatremia, pancreatitis, renal failure, and death from pneumonia). ConclusionsTARE has an acceptable safety profile for the treatment of LCML, with survival benefits best seen in LC tumors.

The Reversible BTK Inhibitor Nemtabrutinib Demonstrates Favorable Antitumor Efficacy and Enhances the Function of CAR T Cells in Mantle Cell Lymphoma

Background Covalent Bruton's tyrosine kinase (BTK) inhibitors have revolutionized the therapy of mantle cell lymphoma (MCL). In January 2023, the reversible BTK inhibitor pirtobrutinib was approved by the FDA for the treatment of relapsed or refractory MCL. Nemtabrutinib is another reversible BTK inhibitor which also targets other kinases. The objective of this study was to evaluate the efficacy of nemtabrutinib alone and in combination with anti-CD19 CAR T cells against MCL. Methods Cell viability was measured following a 72-hour treatment with nemtabrutinib in a panel of MCL cell lines using CellTiter-Glo luminescent cell viability assay (Promega). Annexin V/PI staining was utilized to determine whether nemtabrutinib induces cell death through apoptosis. Patient-derived organoids (PDOs) were generated by culturing patient primary cells in 50% Matrigel (Corning) and cultured in cytokine-containing medium. The PDOs were treated for 72 hours, and viability assays were performed. Western blotting was employed to investigate the drug impact on kinase signaling pathways. Nemtabrutinib treated Mino cells were subjected to bulk RNA sequencing to interrogate the transcriptome profiling. The anti-MCL efficacy of nemtabrutinib was tested in an ibrutinib-resistant patient derived xenograft (PDX) mouse model in vivo. Additionally, the potential synergistic effects of nemtabrutinib and anti-CD19 CAR T cells were examined using the luciferase-expressing MCL cells. Results Nemtabrutinib demonstrated comparable growth inhibitory activity to ibrutinib in MCL cell lines with IC 50 values at micromolar concentrations (IC 50 = 0.7-10.1 μM). Remarkably, in the 3D PDO screening system that mimics the tumor microenvironment for MCL, nemtabrutinib displayed superior anti-MCL efficacy compared to ibrutinib (p < 0.01). The apoptotic potential of nemtabrutinib was further investigated using Annexin V/PI staining, revealing a dose-dependent induction of apoptosis, and demonstrated a similar sensitivity profile across cell lines observed with ibrutinib. Western blotting revealed that nemtabrutinib effectively inhibited phosphorylation at both Tyr223 and Tyr551 sites of BTK, and also dramatically suppressed the activation of Src family kinases, Syk and ERK. Bulk RNA-seq was performed to examine the transcriptome profile following nemtabrutinib treatment. 449 genes were identified to be significantly upregulated and 460 genes were downregulated. Gene set enrichment analysis uncovered a significant decrease in TNFα signaling via NF-κB, inflammatory response, and IFNγ response signalings (FDR < 0.05). In an ibrutinib-resistant PDX mouse model, treatment with nemtabrutinib resulted in a significant reduction in tumor burden and effectively attenuated the tumor involvement in spleen, liver and bone marrow. Furthermore, to enhance efficacy, we investigated the combination of nemtabrutinib with anti-CD19 CAR T cells in luciferase-expressing MCL cells. The result demonstrated that nemtabrutinib enhanced the effector function and anti-MCL activity of anti-CD19 CAR T cells. Conclusion Nemtabrutinib demonstrated favorable anti-MCL efficacy in both in vitro and in vivo studies, the promising synergistic effects observed in combination with CAR T cells warrants further investigation in both preclinical and clinical settings.

Combination Chemotherapy in Patients with Newly Diagnosed Blastic Plasmacytoid Dendritic Cell Neoplasms (BPDCN): First Results of a Prospective French Trial (LpDessai)

Introduction Blastic plasmacytoid dendritic cell neoplasms (BPDCN) are now well-characterized diseases clearly referenced in the 5 th edition of the World Health Organization (WHO) Classification of Tumors (2022) 1 but treatment remains a real challenge. There is no consensus on the first line treatment even if CD123 targeted therapies are available in the USA and some European countries. Standard chemotherapy remains largely used as first line treatment with better results of leukemia-based regimens despite a high toxicity rate in this frail population 2,3. To establish a reference chemotherapy scheme, we prospectively evaluated the efficacy and toxicity of a combination chemotherapy (idarubicin, methotrexate, L-asparaginase, and dexamethasone) in newly diagnosed BPDCN patients (pts) in France. Patients and methods This single stage phase II study enrolled consecutive adult pts with suspected BPDCN in participating French centers. BPDCN diagnosis was centrally reviewed for cytology and immunophenotype (IF) (Pr Garnache Ottou F, UMR RIGHT BESANCON) and if needed for histology (Dr Petrella T, Montréal, Canada) according to published recommendations 1,4. After giving their informed consent, patients were evaluated for tumoral involvement by PET-scan, systematic lumbar puncture, and the mSWAT score was calculated for skin extension. Patients then received three 21 days-cycles of Ida/Metho/L-asp/Dex combination, before evaluation. Eligible patients with complete response (CR), complete response with incomplete bone marrow recovery (CRi) or partial response (PR) underwent allogeneic hematopoietic stem cell transplantation (HCT). Those not eligible received consolidation chemotherapy with 28 days cycles of Metho/L-asp/Dex (Figure 1). The primary objective was the proportion of patients with CR after 3 cycles of chemotherapy. Secondary objectives were the proportion of patients with an objective response (ORR) defined as CR, CRi or PR, the minimal residual disease (MRD) in responding patients evaluated by the presence of plasmacytoid dendritic cell blast measured by flow cytometry in the bone marrow, the incidence of severe adverse events and overall survival (OS). The competent ethics committee (Comité de Protection des Personnes Île de France 8) approved the study. The Besançon University hospital promoted the trial, financed by a grant of the French National Cancer Institute (INCa-DGOS_11093). Results Twenty-eight pts, originating from 16 centers, were screened between May 2019 and March 2023. Two patients with a misdiagnosis were screen failures. Two patients did not receive the planned chemotherapy due to clinical deterioration; 24 patients (21 male, 3 female) received at least one chemotherapy cycle and 23 are analyzed with a current end-point on June 30, 2023. Median age was 65y (21-79y). ECOG status was 0-1 in 20 cases, and 2 in 3 cases. A cutaneous involvement was identified in 16 pts (70%) and an extra medullary involvement was present in 13 (62%) pts: spleen, n= 6 (25%); lymph nodes, n= 7 (30%). Twenty-three pts (90%) had a bone marrow infiltration (identified only on IF in 4 cases), and 3 cases (14%) a documented central nervous system involvement. Nine pts had to stop planned treatment due to severe adverse events (3 deaths, 4 acute renal failure and 2 grade 4 febrile neutropenia) and in 4 pts, at least one cycle had to be delayed. Among the 15 pts receiving at least 3 cycles, 12 (80% and 50% of the whole cohort) were in ORR (CR = 8, CRi = 2, PR = 2) after the 3rd cycle of chemotherapy, 2 pts did not respond. Eight of ten (80%) CR/CRi pts had a MRD < 10 -4 without any further relapse. Nine of 12 responding patients (75%) received an allogeneic HCT 1-2 months after the end of the 3 rd cycle. Global OS at 6 months for responding or failing pts were 100% and 37% respectively (Figure 2). Conclusion In selected pts, an adapted chemotherapy could offer high CR rate in pts able to follow the planned treatment but remains toxic in frail pts, with only half of the them achieving a 3 rd cycle of chemotherapy. We confirm that pts achieving ORR and receiving HCT obtain prolonged CR. MRD level seems to correlate with OS and could be a useful tool to manage treatment toxicity in BPDCN frail pts.

Vertebral Compression Fracture Post Spine Stereotactic Body Radiotherapy: The Role of Vertebral Endplate

Maintaining hydrostatic pressure -via Pascal's Principle- between vertebral bodies is essential to decrease the chance of vertebral compression fracture (VCF). Vertebral endplates (EP) play an essential role in this matter through maintaining the mechanical environment as well as the proper nutrition of avascular discs. The purpose of this study is to establish the correlation of VCF with disrupted EP by tumor involvement. A retrospective analysis of de novo spine metastases treated with stereotactic body radiotherapy (SBRT) between 2013-2019. Patients (pts) with previous surgical intervention were excluded. VCF defined as new or progression of existing loss of vertebral body height. The vertebral EP region defined in relation to the vertebral body as superior EP vs inferior EP. Kaplan-Meier curves used to analyze the variables. A multivariate proportional hazard model used to assess the risk of all covariates. A total of 111 pts were treated with SBRT with a median dose of 27 Gy (10-35 Gy). Median follow-up was 18 months (1.2-107). The median age was 60 years (24-87) and 59 were males (53%) and 52 were females (47%). The median body mass index (BMI) was 27 kg/m2 (16-47). Almost 9 pts diagnosed with osteoporosis prior radiation. Twelve pts received prolonged steroids. Twenty pts received bisphosphonate and 8 pts received denosumab. The median PTV was 50cc (8-465) and median Conformity Index was 1.05 (0.42-1.4). Almost 75% of pts received >95% of the dose covering 100% of the PTV. The most common histopathologies were renal cell carcinoma (25%), lung (13%) and breast (11%). Most of the pts (77%) had SINS score of 7 or less. 48 pts (43%) had either superior or inferior EP disruption secondary to the tumor at the time of radiation. Twenty pts (18%) had both superiorly and inferiorly disrupted EP. Around 20 pts (18%) developed VCF. The median time to VCF was 5.2 months (1.1-57.4). The one-year cumulative incidence of VCF was 18%. The 1-year cumulative incidence of VCF with either superiorly and/or inferiorly disrupted EP was 29% vs 6%, p value <0.001. The 1-year cumulative incidence of VCF with both superiorly and inferiorly disrupted EP was 57% vs 7% (p value <0.001). The median time to VCF was earlier in pts with both disrupted EP (2.4 months vs 5.7 months, p value <0.05). Other risk factors like SINS score of >7 and local recurrence (LR) associated with higher risk of VCF. On multivariate analysis, LR (HR 8.2 [CI 2.4-28, p- value <0.001]), tumor disrupting the EP (HR 4.5 [CI 1.3-16, p-value<0.018]) and SINS score of seven and above (HR 1.7 [CI 1.3-2.25, p-value <0.001]) correlated with the VCF risk. In this retrospective analysis, tumor disrupting the EP, disease recurrence and high SINS score increased the risk of VCF. Cement augmentation either prophylactically or immediately following SBRT is currently being studied in a prospective trial within our institution.

Outcomes of Watch and Wait Following Total Neoadjuvant Therapy for Rectal Cancer

To evaluate the outcomes of patients with locally advanced rectal cancer who achieved a clinical complete response (cCR) after total neoadjuvant therapy and enrolled in a prospective watch and wait (WW) database. Consecutive patients with locally advanced rectal cancer who achieved cCR following total neoadjuvant therapy (long-course chemoradiotherapy plus systemic chemotherapy) and were enrolled in our institutional WW surveillance protocol from 2014 through 2022 with the intention of organ preservation. Patients with lack of follow up according to our institutional protocol were excluded. Primary outcomes included local tumor regrowth and distant metastatic disease recurrence. Thirty-three consecutive patients (48% male; median age 61 [33-77] years) with the diagnosis of locally advanced rectal adenocarcinoma were managed by a multidisciplinary team. All patients had Eastern Cooperative Oncology Group Performance Status score of 0 or 1 at time of rectal cancer diagnosis. Location of tumor included upper rectum (18%), middle rectum (40%), and lower rectum (42%). On initial staging magnetic resonance imaging, 4 (12%) patients had evidence of extramural venous invasion, 6 (18%) had a threatened mesorectal margin, and 4 (12%) had anal sphincter or levator ani tumor involvement. A majority (61%) received chemotherapy followed by long-course chemoradiotherapy. Only one patient had an unplanned break during radiotherapy. Local tumor regrowth was diagnosed in 4 (12%) patients and all underwent successful salvage surgery without additional local failures at a median follow-up of 19 [12-48] months. Two of these four patients remain disease-free at a median follow-up time of 12.5 months. Mean time to local tumor regrowth as first site of cancer recurrence was 33.5 [18-46] months. Distant metastatic disease as the first site of recurrence occurred two patients (6%). Mean time to distant metastatic disease as first site of recurrence was 27 months. Only one mortality occurred in the entire group at a median follow-up of 49 [8-102] months. Organ preservation after total neoadjuvant therapy for locally advanced rectal cancer yields excellent outcomes with low local and distant relapse rates. Structured surveillance protocols and multidisciplinary care are essential for success.

SCCAg as a Biomarker of Advanced Stage and OS in Limited Resource Setting for Cervical Cancer

Elevated serum squamous cell antigen (SCCAg) has been previously correlated with poor survival, extensive tumor involvement, and recurrence for cervical cancer. Failure of serum SCCAg to normalize after treatment completion has also been studied as a poor prognostic indicator. This is the first study describing the association of SCCAg with stage and outcomes in patients diagnosed with cervical cancer in Botswana, in a population with a majority of women who are living with HIV (WLWH). Patients with histologically confirmed cervical cancer were enrolled in a prospective observational study between August 2016 and April 2020 in Botswana. Among all patients undergoing definitive chemoradiation, serum SCCAg was determined at pre-treatment baseline, end of treatment (EOT), and 3-month follow-up (normal reference range 0.3 -1.9 ng/ml). Normalization of SCCAg was defined as return to the reference range after treatment (SCCAg response), and was measured first at EOT; if EOT values were not available, 3-month values were utilized. Patients were staged according to FIGO 2009 criteria, early stage was defined as Stage I-II; while advanced stage was defined as Stage III-IV. Median follow-up was 44 months. A significant cut-off point for baseline and SCCAg response correlated with overall survival (OS) was calculated utilizing a log-rank test RESULTS: Among 234 patients who were diagnosed with histologically confirmed cervical cancer, 73.5% were WLWH (mean CD4 count 466 cells/mL). 92.9% of all cancers were squamous cell carcinoma. 68.8% of patients had elevated SCCAg at time of diagnosis. There was no significant difference in mean baseline SCCAg between WLWH (13.3 ng/mL) and women living without HIV (9.07 ng/mL), p = 0.1052. There was a significant difference seen in mean SCCAg between early (7.9 ng/mL ± SD 13.4) and advanced (18.9 ng/mL, ± SD 29.8) stage disease at diagnosis, p < 0.0001. Baseline SCCAg > 7.9 ng/mL was found to be associated with worse OS (p < 0.001). 5-year OS was significantly different among patients with SCCAg response < = 2.8 (5-year OS 66.2%), vs. SCCAg >2.8 ng/mL (5-year OS 42.4%). There was no significant difference in average SCCAg values between EOT (p = 0.68) and 3-month follow-up (p = 0.24). There was no difference in the proportion of patients who experienced normalized SCCAg by HIV status (p = 0.67). There was no significant difference in SCCAg among WLWH and women living without HIV. Among patients with elevated SCCAg above normal at baseline, SCCAg was associated with early vs. advanced stage disease. Additionally, there was a significant difference seen in overall survival by two measurement points: baseline SCCAg >7.9 ng/mL and response SCCAg >2.8 ng/mL. SCCAg may be utilized as a biomarker in low-resource settings to refine prognosis. Further studies will be needed to determine utility and validation in predicting recurrence risk and/or lymph node metastases.

Incidence and Prognostic Factors of Painful Vertebral Compression Fracture Caused by Spine Stereotactic Body Radiotherapy

Most studies of vertebral compression fracture (VCF) caused by stereotactic body radiotherapy (SBRT) do not mention the symptoms. We aimed herein to determine the rate and prognostic factors of painful VCF caused by SBRT for spinal metastasis. Between August 2013 and December 2021, spinal segments with VCF were retrospectively identified in patients treated with spine SBRT. Iatrogenic VCFs, excluding pathological fractures, were classified into a modified group and graded using CTCAE v5.0 as grade 1 (painless), grade 2 (mildly painful), or grade 3 (intensely painful, requiring hospitalization or surgery). The primary endpoint was the rate of painful VCF (grades 2-3). Moreover, various factors specific to the patient, tumor, and treatment were evaluated to determine their value in predicting the rate of painful VCF. In total, 934 spinal segments in 387 patients were analyzed. The median follow-up after SBRT was 14 (range: 0-107) months. Sixty iatrogenic fractures (6.4%) comprising 31 de novo fractures and 29 existing VCF progressions were identified. The patients' median age was 68 (range: 38-79) years, and 31 (52%) spinal segments had a history of radiotherapy. Grade 1, 2, and 3 VCFs were confirmed in 41, four, and 15 segments, respectively. The rate of grade 3 VCF was 2.0% (19 / 934) of the spinal segments treated with SBRT. Eight (0.9%) VCFs required surgery for stabilization or decompression of spinal canal stenosis. None of the 17 VCFs treated with posterior decompression and fixation before SBRT developed into a painful VCF. On univariate analysis, the painful VCF rate was significantly higher in patients with no posterolateral tumor involvement than in those with bilateral or unilateral involvement (56.3% vs 22.7%; p = 0.026). Other spinal instability neoplastic score (SINS) components (Location, Pain, Bone lesion, Alignment, Vertebral body collapse), SINS (Stable/ Potentially unstable vs Unstable), age, number of spinal levels, radiation history, existing VCF, and interval between SBRT and VCF showed no significant correlation with painful VCF. Although VCF is a known adverse effect of spine SBRT, 68% of the cases examined were painless (grade 1). Intensely painful VCFs (grade 3) were confirmed in only 1.6% of all the treated spinal segments. The absence of posterolateral tumor involvement was significantly associated with painful VCF.

Survival prognosis model for elderly women with epithelial ovarian cancer based on the SEER database.

We aimed to analyze the risk factors of elderly women with epithelial ovarian cancer (EOC) using data on the SEER database, and to generate a nomogram model their 1-, 3-, and 5-year prognoses. The resulting nomogram model should be useful for clinical diagnoses and treatment. We collected clinical data of women older than 70 years with epithelial ovarian cancer (diagnosed on the basis of surgical pathology) from the SEER database including datasets between 2010 and 2019. We randomly grouped the data into two groups (7:3 ratio) using the R language software. We divided the independent prognostic factors obtained by univariate and multi-factor Cox regression analyses into training and validation sets, and we plotted the same independent prognostic factors in a nomogram model of overall survival (OS) at 1, 3, and 5 years. We used the C-index, calibration curve, and area under the curve to validate the nomograms. We further evaluated the model and its clinical applicability using decision curve analyses. We identified age, race, marital status, histological type, AJCC staging, differentiation degree, unilateral and bilateral tumor involvement, number of positive lymph nodes, chemotherapy, surgery, sequence of systemic treatment versus surgery, and time from diagnosis to treatment as independent prognostic factors for elderly women with EOC (P < 0.5). The C-indexes were 0.749 and 0.735 in the training and validation sets, respectively; the ROC curves showed that the AUC of each prognostic factor was greater than 0.7; and, the AUC values predicted by the line plot were similar in the training and validation sets. The decision curves suggest that this line plot model has a high clinical value for predicting overall survivals at 1, 3, and 5 years in elderly women with EOC. The nomogram model in this study can provide an accurate assessment of the overall survival of women older than 70 years with EOC at the time of the first treatment, and it provides a basis for individualized clinical treatment.

What to report in sellar tumor MRI? A nationwide survey among German pituitary surgeons, radiation oncologists, and endocrinologists

PurposeWhile MRI has become the imaging modality of choice in the diagnosis of sellar tumors, no systematic attempt has yet been made to align radiological reporting of findings with the information needed by the various medical disciplines dealing with these patients. Therefore, we aimed to determine the prevailing preferences in this regard through a nationwide expert survey.MethodsFirst, an interdisciplinary literature-based catalog of potential reporting elements for sellar tumor MRI examinations was created. Subsequently, a web-based survey regarding the clinical relevance of these items was conducted among board certified members of the German Society of Neurosurgery, German Society of Radiation Oncology, and the Pituitary Working Group of the German Society of Endocrinology.ResultsA total of 95 experts (40 neurosurgeons, 28 radiation oncologists, and 27 endocrinologists) completed the survey. The description of the exact tumor location, size, and involvement of the anatomic structures adjacent to the sella turcica (optic chiasm, cavernous sinus, and skull base), occlusive hydrocephalus, relationship to the pituitary gland and infundibulum, and certain structural characteristics of the mass (cyst formation, hemorrhage, and necrosis) was rated most important (> 75% agreement). In contrast, the characterization of anatomic features of the nasal cavity and sphenoid sinus as well as the findings of advanced MRI techniques (e.g., perfusion and diffusion imaging) was considered relevant by less than 50% of respondents.ConclusionTo optimally address the information needs of the interdisciplinary treatment team, MRI reports of sellar masses should primarily focus on the accurate description of tumor location, size, internal structure, and involvement of adjacent anatomic compartments.

Risk factors for early and late cholecystitis after covered metal stent placement for distal biliary obstruction.

Cholecystitis is a major adverse event after self-expandable metallic stent placement for distal biliary obstruction (DBO). Covered self-expandable metallic stent (CSEMS) is being increasingly used, but few studies have investigated risk factors for cholecystitis limited to CSEMS. The present study aimed to identify risk factors for cholecystitis after CSEMS. Patients who underwent initial CSEMS placement for DBO between November 2014 and September 2021 were enrolled and followed-up until death, recurrent biliary obstruction, cholecystitis, or until March 2022. Cholecystitis within 30 days of CSEMS was defined as early cholecystitis and after 30 days as late cholecystitis. Cholecystitis occurred in 51 of 339 patients (15%) after CSEMS. Forty-one patients (80.4%) had early cholecystitis, and 10 (19.6%) had late cholecystitis. Multivariate logistic regression analysis revealed that the maximum diameter of the common bile duct (CBD) (per 1 mm increase) (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.76-1.00; p = .044), gallbladder stones (OR: 3.63; 95% CI: 1.62-8.10; p = .002), and tumor involvement in the cystic duct (CD) (OR: 4.87; 95% CI: 2.16-11.00; p < .001) were significant independent risk factors associated with early cholecystitis. No significant risk factors were identified for late cholecystitis. A smaller CBD diameter, gallbladder stones, and tumor involvement in the CD were identified as risk factors for early cholecystitis development after CSEMS.

Bone marrow composition features and possibilities of tumor involvement diagnosing in patients with classic Hodgkin’s lymphoma

Background. Classical Hodgkin’s lymphoma is a B-cell lymphoproliferative disease, the tumor substrate of which is Berezovsky–Reed–Sternberg cells, characterized by CD30, PAX-5, CD15 expression and the absence of CD3, CD45. In some cases, tumor cells express CD20. modern anticancer therapy has increased the survival probability for most patients, not only with early but also with advanced stages of classical Hodgkin’s lymphoma. Such successes are mainly due to the distribution of patients into prognostic groups and the choice of an appropriate treatment regimen. tumor infiltration of the bone marrow suggests assigning patients to the advanced stages group, followed by the choice of an intensive therapy program. Aim. To determine the bone marrow involvement frequency according to positron emission tomography combined with computed tomography (PET/CT), with 18F-fluorodeoxyglucose (FDG) and bone marrow trephine biopsy (bmtb), to compare the results obtained with primary tumor immunophenotype and bone marrow cellular composition, and to identify of prognostic risk factors. Materials and methods. The study included 107 patients with newly diagnosed classical Hodgkin’s lymphoma, who underwent a diagnostic examination at the moscow research institute of oncology named after P. A. Herzen – a branch of the National Medical Research Center for Radiology and the “Lapino” clinical Hospital from 2015 to 2022, followed by anticancer therapy and further follow-up. Morphology of the primary tumor biopsy specimen in all patients and immunohistochemical (IHC) study using a wide panel of monoclonal antibodies (CD15, CD30, CD3, CD45, CD20, PAX-5 anti-gens; in some cases epstein–barr virus proteins expression) in most cases were performed. All patients underwent a morphological and / or IHC study of BMTB and the majority underwent aspiration biopsy and PET/CT with 18F-FDG. Results. The most common histological variant of classical Hodgkin’s lymphoma was nodular sclerosis (86.9 %). The majority of patients (51.4 %) were assigned to the advanced stage prognostic group. bone marrow tumor infiltration was statistically significantly more frequently diagnosed during PET/CT with 18F-FDG compared with the results of the BMTB – in 27.1 % and 12.1 % of cases, respectively (p &lt; 0.05). when comparing the results of both diagnostic methods, it was found that in 17.1 % of cases, bone marrow infiltration, detected during PET/CT, was not confirmed by IHC examination of the trephine biopsy. In addition, it was found that the majority of cases with CD20+/± and CD15+/± expression in the primary tumor were observed in the group of patients without bone marrow involvement. when assessing the cellular composition of bone marrow aspirates, it was revealed that in patients with bone marrow tumor infiltration, an increase in cellularity and megakaryocytes number along with a decrease in the plasma cells number is observed. Conclusion. The results suggest further study of bone marrow immunomorphological features in order to identify prognostic factors and search for new therapeutic targets. a more extended analysis of bone marrow aspirate immunomor-phological characteristics using new modern diagnostic methods, minimal residual disease status as a surrogate marker seems to be relevant and necessary to confirm the depth of the antitumor response achieved. Detection of CD20+/±- and cd15+/±-Berezovsky–Reed–Sternberg cells according to primary tumor IHC analysis indicates a low probability of bone marrow tumor infiltration, but further analysis is required on a large clinical and laboratory material.

Clinical and ultrasound features of pseudomyxoma peritonei and its histopathological subtypes among women seen at a Philippine tertiary hospital: A 10-year review

OBJECTIVES: Pseudomyxoma peritonei (PMP) in women arises from an appendiceal or ovarian pathology and presents either of two histological subtypes of differing prognosis, disseminated peritoneal adenomucinosis (DPAM), or peritoneal mucinous carcinomatosis (PMCA). This study aimed to evaluate the demographic, clinical, and sonographic features among affected women and the differences between the two histological subtypes. METHODS: A retrospective study was conducted involving 36 women with histopathological diagnosis of PMP who had preoperative ultrasound and underwent surgery at the department of obstetrics and gynecology in a tertiary hospital. Demographic and clinical data, ultrasound images and reports, and final histopathology were reviewed. To compare the subtypes, one-way analysis of variance for continuous data and Chi-square/Fisher exact test for categorical data were used, with P &lt; 0.05 indicating statistical significance. RESULTS: Patients were mostly &gt;50 years of age, multigravid, and presented with abdominal distention. Ultrasound examinations consistently showed amorphous, mixed echo or echogenic ascites, peritoneal thickening, and omental caking. Adnexal/ovarian masses were detected in 66.7% of cases. Omental caking was significantly more prevalent in PMCA (83.3%; P = 0.0002), whereas larger ovarian tumors (&gt;20 cm) and papillarities were more common in DPAM (both 92.9%; P = 0.0005). Most patients underwent gynecologic surgery (n = 31; 86.1%), and 14 (38.9%) required readmission due to recurrence. The final histopathology revealed largest tumor involvement of the appendix (n = 13; 36.1%), the ovaries (n = 11; 30.5%), or undetermined (n = 12; 33.3%). CONCLUSIONS: Preoperative diagnosis of PMP is possible based on its clinical and ultrasound features. Although the subtypes are similar in most of these features, certain ultrasound findings may aid in distinguishing them.

Meme Koruyucu Cerrahide İntraoperatif Ultrason ve Frozen Patoloji Kullanımının Güvenli Cerrahi Sınır Üzerindeki Etkinliği

Background: Breast cancer is the most common cancer in women over the age of 40. The lifetime risk is around 12%. Today, breast cancer patients are diagnosed at an early stage thanks to screening programs, and thus mortality has decreased to around 25-30%. The positivity or closeness of surgical margins in breast conserving surgery varies between 5-60%. Negativity of surgical margins is very important to prevent future recurrent breast cancer, to pre-vent recurrent surgeries, and to prevent additional treatments. In this study, we aimed to investigate the efficacy of intraoperative ultrasonography and frozen section use in breast cancers treated with breast conserving surgery in obtaining safe surgical margins and in postoperative cosmetic terms. Materials and Methods: This study includes 150 patients diagnosed with breast cancer and treated with breast con-serving surgery in between January 2015 and January 2019. The presence of distant metastases and multifocal or centrally located tumor involvement in the breasts were investigated. The localization of the tumor was marked anatomically by preoperative ultrasonography in all patients. The operation was started 15 minutes after the injec-tion. The tumor was completely excised, leaving at least 1 cm of intact tissue around the tumor, including the skin, on the preoperatively marked area, including the underlying muscle fascia. Medial and superior borders were marked with string. This excised tissue block was examined with intraoperative ultrasonography. Results: The mean age of the patients was 48,3± 9.7 years. While the tumor was located in the right breast in 83 (55.3%) of the patients, it was located in the left breast in 67 (44.7%) patients. The tumor was located in the upper outer quadrant in 67 (44.7%) patients, in the upper inner quadrant in 53 (35.3%) patients, and in the lower outer quadrant in 30 (20%) patients. Axillary dissection was performed in 21 (14 %) of the patients because sentinel lymph node was positive. In histological typing, 141 (94 %) patients were ductal carcinoma and 9 (6 %) patients were lobular carcinoma. Conclusions: As a result of our study and literature review, we think that frozen examination together with intraope-rative ultrasonography is a simple, easily applicable and cosmetically good method to determine the safe surgical margin in breast conserving surgery.

Spare the Nipple: A Systematic Review of Tumor Nipple-Distance and Oncologic Outcomes in Nipple-Sparing Mastectomy.

Preserving the nipple-areolar complex (NAC) in breast cancer surgery improves patient satisfaction and quality of life. The oncologic safety of NSM in tumors < 2cm from the nipple remains in question. We conducted a systematic review to determine whether TND < 2cm was associated with increased risk of LRR in patients undergoing NSM. We included studies of invasive or in situ breast cancer < 2cm from NAC undergoing NSM which reported LRR rates. LRR rates were stratified by TND and culminated across studies. Cohort study quality was assessed using Newcastle-Ottawa Criteria. Meta-analysis was not possible due to heterogeneity in reporting survival outcomes. We identified seven retrospective cohort studies with 2295 patients and 18 case series with 3507 patients. Direct tumor involvement of NAC was considered an absolute contraindication to NSM in all studies. In cohort studies, median follow-up was 31-112 (range 14-204) months. Cohorts with TND < 2cm did not have a significantly higher rate of LRR. Amongst case series, 275 patients had TND < 2cm. Combined LRR in case series was 2.6%, with median follow-up 10.4-71 (range 0-158) months. Our systematic review did not identify TND < 2cm as a significant risk factor for LRR. NSM appears oncologically safe in select patients with TND < 2cm. Given the improved quality of life associated with NSM compared to skin-sparing mastectomy, we suggest NSM as the procedure of choice in appropriately selected patients.