Courses Of Chemotherapy Research Articles

Risk stratification in the clinical application of minimal residual disease assessment in acute myeloid leukemia

AbstractBackgroundIn acute myeloid leukemia (AML), further investigation is warranted to integrate measurable residual disease (MRD) with genetic characteristics for formulating a dynamic prognostic system for predicting response and selecting appropriate postremission therapeutic strategies.MethodsThe authors incorporated MRD with genetic risk classification and assessed its impact on transplantation decision making within different risk cohorts, comprising 769 patients with newly diagnosed AML across three clinical trials. Only patients who achieved complete remission (CR) within two courses of chemotherapy were selected.ResultsIn the favorable‐risk and intermediate‐risk groups, patients who underwent transplantation according to the protocol experienced significant 3‐year overall survival (OS) benefits compared with those who did not (favorable‐risk group: hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.73l p = .004; intermediate‐risk group: HR, 0.53; 95% CI, 0.33–0.85; p = .008). In the intermediate‐risk group, early detection of MRD positivity, even after the initial course of chemotherapy, was associated with a significantly elevated cumulative incidence of relapse (47.2% vs. 36.0%; p = .009) and a notable extension of OS with allogeneic hematopoietic stem cell transplantation (HR, 0.47; 95% CI, 0.28–0.79; p = .004). Conversely, patients who achieved MRD negativity at either of the two time points had comparable OS in the favorable‐risk and intermediate‐risk groups, regardless of whether they underwent transplant or not. In the adverse‐risk group, allogeneic hematopoietic stem cell transplantation led to improvements in OS irrespective of MRD status (HR, 0.51; 95% CI, 0.38–0.69; p < .001).ConclusionsEarly clearance of MRD demonstrated significant prognostic value, particularly for patients in the favorable‐risk and intermediate‐risk groups. Positive MRD status after two courses of intensive chemotherapy were associated with a higher relapse rate and inferior OS, necessitating allogeneic hematopoietic stem cell transplantation.

Study protocol: randomized phase III trial of neo-adjuvant and adjuvant chemotherapy vs. immediate surgery and adjuvant chemotherapy for localized soft tissue sarcoma: Japan Clinical Oncology Group study JCOG2102 (NACLESS).

The optimal timing of surgery and the number of courses of perioperative chemotherapy for high-risk soft tissue sarcoma patients are still controversial. Tumour growth during neoadjuvant chemotherapy led to limb amputation in some patients. This study aims to confirm the non-inferiority of surgery and three courses of adjuvant chemotherapy with adriamycin (30mg/m2, days 1 and 2) plus ifosfamide (2g/m2, days 1-5) compared with our standard treatment of three courses of neoadjuvant chemotherapy and surgery followed by two courses of adjuvant chemotherapy with adriamycin plus ifosfamide for localized high-risk soft tissue sarcoma patients. This is a multi-center, two-arm, open-label, randomized phase III trial. The primary aim is to confirm the non-inferiority in overall survival (margin: hazard ratio of 1.61). This is the first randomized controlled trial to compare neoadjuvant chemotherapy and immediate surgery for soft tissue sarcoma. This trial was initiated on 16 November 2022 and registered with the Japan Clinical Trials Registry (jRCTs031220446).

Biomarker Study for Selecting Neoadjuvant Chemotherapy Regimens Based on Prognostic Prediction Using Gastric Cancer Biopsy Specimens from a Phase II Randomized Controlled Trial.

The randomized phase II COMPASS trial revealed that neither the regimen nor the number of courses of preoperative neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (GC) significantly influence overall survival (OS). However, the impact of NAC regimens on OS may vary from patient to patient. The aim of this study was to identify biomarkers that can predict more appropriate individualized NAC regimens for improved prognosis using biopsy specimens from the COMPASS trial. RNA was extracted from endoscopic biopsy specimens of primary tumors obtained prior to NAC and real-time PCR analysis of 127 genes was conducted to identify those significantly affecting survival in the context of specific NAC regimens. THBS1, MSI1, and IGF2BP3 were identified as significant factors for stratifying survival among different NAC regimens, with statistically significantly interaction p values. Immunohistochemical analysis confirmed that the protein levels of THBS1, MSI1, and IGF2BP3 strongly correlated with their gene expression levels, validating these proteins as reliable biomarkers. This study effectively identified THBS1, MSI1, and IGF2BP3 as promising biomarkers for personalizing NAC regimens in patients with locally advanced GC. By tailoring NAC based on these biomarkers, it is possible to enhance survival outcomes and advance personalized treatment strategies. The findings underscore the potential for incorporating biomarker-guided approaches into clinical trials, aiming to refine and optimize NAC regimens for improved patient-specific treatment efficacy.

The first case of primary malignant melanoma of the esophagus to achieve pathologic complete response after preoperative ipilimumab + nivolumab followed by resection.

Primary malignant melanoma of the esophagus is a rare disease with a poor prognosis. Surgical resection is common, but there is no consensus on perioperative treatment. Studies have reported the efficacy of programmed cell death-1 inhibitors (e.g., nivolumab, pembrolizumab) and anti-cytotoxic T-lymphocyte-associated antigen 4 agents (e.g., ipilimumab) in treating malignant melanoma. Here, we present the first case of primary malignant melanoma of the esophagus with lymph node metastases treated with nivolumab and ipilimumab followed by resection, achieving a pathologic complete response. A 75-year-old man presented with dysphagia. Esophagogastroduodenoscopy revealed a black, elevated lesion in the mid-thoracic esophagus. Biopsy confirmed primary malignant melanoma of the esophagus, showing tumor cells with melanin deposition, positive for HBM45 and S-100 staining. Computed tomography showed enlarged lymph nodes in the subclavian and mediastinum regions, suggesting metastases. After two courses of preoperative chemotherapy with ipilimumab and nivolumab, which significantly shrank the tumor, the patient underwent robot-assisted subtotal esophagectomy and 3-field lymph node dissection. Histopathological examination revealed no tumors or lymph node metastases, confirming a pathologic complete response. Given the rarity and poor prognosis of primary malignant melanoma of the esophagus, this case provides valuable insights for treatment strategies.

Dysphasia: metastatic prostate cancer to the leptomeninges: a case report

BackgroundLeptomeningeal metastasis occurs in 5% of patients with prostate cancer and indicates a very poor prognosis.Case presentationA 60-year-old Caucasian male patient diagnosed with metastatic castration-resistant prostate cancer with sclerotic bone metastases and soft tissue metastases underwent multiple courses of chemotherapy and hormone therapy. The diagnosis of prostate cancer is based on elevated prostate-specific antigen levels and tissue biopsy. He subsequently presented with expressive aphasia. Nonspecific, diffuse irregular dural/pachymeningeal thickening enhancement was noted on magnetic resonance imaging. Upon evaluation by neurology, electroencephalogram was negative for an epileptiform correlate. The workup included a lumbar puncture to rule out infectious etiology. The patient’s neurological status stabilized, and he was discharged home with a plan for continued therapy with abiraterone and prednisone. Due to advanced malignancy, the patient enrolled in hospice and died 3 weeks after hospital discharge.ConclusionsCentral nervous system metastasis occurs very rarely in prostate cancer. With the increase in life expectancy and advances in oncologic therapy for prostate cancer, physicians should be aware of and consider central nervous system metastasis in men aged 50 years and above.

Short- and long-term outcomes of liver resection with hepatic vein reconstruction for liver tumors: A nationwide multicenter survey.

This study clarifies the short- and long-term outcomes of liver resection with hepatic vein (HV) reconstruction for liver tumors and identifies the risk factors for poor outcome. We contacted 263 specialized centers in Japan and collected data on this surgical procedure. Patient characteristics, surgical procedures, and outcomes were then analyzed. A total of 187 patients were enrolled from 36 institutions. Grade C post-hepatectomy liver failure (PHLF) and in-hospital mortality were 3.2% and 1.6%, respectively. The median overall survival (OS) and recurrence-free survival (RFS) were 49.9 and 9.8 months, respectively. Surgical outcomes, OS and RFS did not differ among three types of liver tumors, colorectal liver metastasis (CRLM) (n = 127), hepatocellular carcinoma (n = 27), and intrahepatic cholangiocarcinoma (n = 27). Patients with CRLM and seven or more courses of preoperative chemotherapy had significantly worse OS. Compared with HV reconstruction for securing liver remnant (LR) function (n = 148), reconstruction of the only main HV remaining in the LR (n = 39) had significantly worse short-term outcomes, but did not result in increased mortality, and showed equivalent OS and RFS. Liver resection with HV reconstruction can be achieved safely and contributes to a relatively good long-term outcome for patients with advanced liver malignancies.

Cutaneous Metastasis of Rectal Cancer as a Diagnostic Challenge: A Clinical Case and Literature Review

Background/Objectives: Metastatic colorectal cancer remains a fatal disease, with a 5-year survival rate lower than 15%. The most common metastatic sites are the lungs and the liver, while skin metastases are very rare and often indicate a poor prognosis with a lower survival rate. Methods. Herein, we present the clinical case of a 62-year-old female patient with rectal cancer metastases to the skin of the anogenital and abdominal regions, diagnosed 2 years after completion of treatment of the underlying disease. Results: Histological examination of the skin lesions revealed adenocarcinoma, and expression of the same immunohistochemical markers was also found in the primary tumor and in the cutaneous metastases. However, next-generation sequencing demonstrated differences in the mutational profiles of the primary tumor and metastasis to the skin. Somatic mutations in the APC, TP53, and PTPN11 genes were revealed in primary rectal adenocarcinoma, but another pathogenic TP53 mutation and a frameshift variant in the DYNC1I1 gene were found in cutaneous metastases. The patient underwent several courses of FOLFOX6 chemotherapy in combination with bevacizumab, but the treatment was unsuccessful. An analysis of 50 clinical cases from the literature concerning various manifestations of cutaneous metastases of rectal cancer showed a median survival of 8.5 months from the time of detection of the skin lesions. Conclusions: In this regard, careful skin examination of patients with rectal cancer and timely detection of cutaneous metastases are essential steps in the follow-up of patients who have undergone treatment of the primary tumor.

Can haemodynamic force analysis be used to identify cancer treatment-related cardiac dysfunction? A comparison with strain and ejection fraction.

Abstract Background Haemodynamic Force Analysis (HDF) is an approach to quantification of intraventricular pressure gradients, from routine transthoracic echocardiography. HFA is potentially a sensitive means of assessing LV dysfunction, and has been used for the prediction of LV remodelling, but its use in the detection of subclinical LV dysfunction remains undefined. We sought whether HDF could be used to detect Cancer Treatment-Related Cardiac Dysfunction (CTRCD). Methods From a group of 240 pts undergoing echos at baseline and every 3 months in the course of potentially-cardiotoxic chemotherapy, we matched 28 pts who developed CTRCD with 33 controls. HDF was calculated by tracking the endocardial contour throughout the cardiac cycle (Figure). CTRCD was defined by the development of a 12% relative change in GLS, or an asymptomatic absolute EF change of 10% at 3, 6, 9 and 12 months. Results Of 28 pts developed CTRCD; 17 at 3 months, 5 at 6 months, 3 at 9 months and 3 at 12 months. At the time of developing CTRCD, there was a difference between absolute GLS (p-0.04) and borderline difference in EF (p=0.08). However, although there was a small difference in HDF between groups, the variance of this parameter was large, and the values were not significantly different (Table). There was no difference in total HDF (Table). Conclusions Although absolute levels of systolic HDF were different between pts with CTRCD and controls, the scatter of this parameter was large and no significant difference was documented. HDF may be better for predicting the evolution of abnormal LVs than ion the detection of subclinical dysfunction.

Morphological assessment of angiogenesis factor expression in tumor and microenvironment of breast fibroadenoma and ductal carcinoma: An observational cohort study

Background. Angiogenesis plays a crucial role in the progression of breast cancer. Identifying and investigating the key components of this process, focused on phenotype as well as microenvironment of the tumor, is considered highly relevant for understanding tumor biology. Studies into the expression of angiogenesis-related factors by means of immunohistochemical methods appear valuable for both assessing conventional chemotherapy options and identifying new targets in targeted therapy for breast cancer. Objectives. To investigate angiogenesis in breast ductal carcinoma by assessing the expression of vascular endothelial growth factor, angiopoietin-2, and hypoxia-inducible factor alpha in the context of various therapeutic strategies. Methods. An observational cohort study was conducted using biopsy samples from female patients with confirmed diagnoses of “fibroadenoma” and “ductal carcinoma of the breast,” residents of the Republic of Crimea, who applied to oncological hospitals in Simferopol from January 2021 to January 2023. Examination involved histological sections of breast tumor tissue from 68 patients with verified diagnoses of “ductal carcinoma” and “fibroadenoma” (the mean age of the patients was 65 ± 5). The following cohorts were formed in the study: control group, consisting of patients with breast fibroadenoma (n = 20); two subgroups of patients with ductal carcinoma of the breast (n = 48), including Group I — patients with ductal carcinoma of the breast who had not received chemotherapy (n = 23), Group II — patients with ductal carcinoma of the breast, who underwent surgery following one or more courses of chemotherapy (n = 25). The study involved examining the tumor tissue sections obtained from paraffin blocks, assessing the expression of angiogenesis markers via immunohistochemistry using primary antibodies against vascular endothelial growth factor, angiopoietin 2, and hypoxia-inducible factor alpha. Statistical analysis was carried out using Statistica 10.0 (StatSoft, USA). Differences were considered significant at error probability p ≤ 0.05. The value of p < 0.05 was deemed statistically significant for all types of analysis. Results. The expression of hypoxia-inducible and vascular growth factors differed significantly between both groups with breast ductal carcinoma as well as when compared to the control group. The hypoxia-inducible factor having cytoplasmic localization was detected in the control group with benign processes, whereas the nuclear expression was noted in the breast ductal carcinoma groups. Significant differences in the nuclear expression of hypoxia-inducible factor have been established among groups of patients with confirmed ductal carcinoma of the breast: in Group II, which underwent chemotherapy, expression was notably higher in both the tumor stroma and in the stroma of tumor-free areas. The hypoxia-inducible factor expression was significantly greater at the demarcation zone than that observed in samples from surgically treated women in Group I (p = 0.033; p = 0.034, p < 0.001, respectively). In the tumor epithelium of patients with breast ductal carcinoma, vascular endothelial growth factor was expressed significantly more intensively in the group who did not receive chemotherapy compared to the other group (p < 0.001). Conversely, in the tumor stroma, angiopoietin exhibited significantly higher expression levels among patients who underwent chemotherapy compared to those who received no treatment; this was observed in both the tumor areas due to endothelial cell involvement (p = 0.004) and in conditionally healthy regions of the breast (p < 0.001). In the control group represented by fibroadenoma patients, the expression of the studied factors is more pronounced than in the groups with ductal carcinoma of the breast. Conclusion. The obtained data indicate the activation of angiogenesis processes in the group of patients after chemotherapy, as evidenced by the increased expression of hypoxia-inducible factor, vascular endothelial growth factor, and angiopoietin. This result is associated with the high prevalence of resistant forms of breast ductal carcinoma in Group II. The study of the signaling pathways of angiogenesis and its components provides valuable insights into patterns of occurrence and strategies to overcome chemotherapy resistance in ductal carcinoma of the breast.

How to determine the course of preoperative chemotherapy for spinal tuberculosis: A single-center clinical study.

This study aims to explore the clinical efficacy and feasibility of preoperative 1-week chemotherapy for patients with spinal tuberculosis (STB) undergoing complete lesion removal. Clinical data of 76 patients with STB who underwent complete focal debridement in our hospital were collected from June 2020 to September 2023. The patients were divided into 38 cases of preoperative 1-week chemotherapy group (Group A) according to the length of preoperative chemotherapy, and 38 cases of preoperative 2 to 4-week chemotherapy group (Group B). Perioperative related, imaging, and laboratory examination indices as well as postoperative neurological function recovery, postoperative pain recovery, related complications, and clinical efficacy were analyzed to compare the clinical efficacy of the 2 groups. All patients successfully completed the treatment of stage I complete lesion removal combined with bone grafting fusion and internal fixation. The difference in erythrocyte setting rate and C-reactive protein at the same postoperative observation time between the 2 groups was not statistically significant (P > .05). The visual analogue scale scores of patients in the 2 groups decreased significantly with prolonged time, and the difference was statistically significant (P < .05). All patients achieved satisfactory clinical efficacy (P < .05). All patients achieved good clinical outcomes, the difference between the groups was not statistically significant (P > .05). The difference in incision healing rate at 3 months postoperatively and bone graft fusion rate at 6 months postoperatively was not statistically significant between the 2 groups (P > .05). The dissemination and recurrence of Mycobacterium tuberculosis were not statistically significantly different between the 2 groups after surgery (P > .05). In summary, with complete lesion clearance, 1 week of preoperative chemotherapy is feasible in patients with STB with varying degrees of neurological dysfunction.

Prognostic Nutrition Index as a Biomarker for Treatment Sensitivity to Chemotherapy and Nivolumab as the First-Line Treatment in Patients with Unresectable Advanced or Recurrent Gastric Cancer: A Multicenter Study

Introduction: This multicenter study aimed to determine whether the pretreatment prognostic nutrition index (PNI) or a change in the index after two treatment courses could be a biomarker for predicting treatment sensitivity in patients with unresectable advanced or recurrent gastric cancer (GC) treated using chemotherapy and nivolumab as the first-line treatment. Methods: This multicenter retrospective study with 104 patients was conducted at 12 institutions. PNI was calculated before treatment and after two courses of treatment in each case. We also focused on changes in PNI from the pretreatment value. Results: After two courses of chemotherapy plus nivolumab treatment, the high PNI group had significantly better rates of overall survival (OS) (p = 0.0016) and time to treatment failure (p = 0.0060). Low PNI was an independent prognostic factor predicting both therapeutic sensitivity to chemotherapy plus nivolumab treatment and poorer OS. Furthermore, correlation with low pretreatment PNI transitioning to high after two courses of treatment was not noted in any patient in the progressive disease group (p = 0.0075). Conclusions: PNI is a score composed of a patient’s albumin level and lymphocyte count that can be easily assessed in daily clinical practice. Evaluating it is easy for each treatment; thus, when there is a focus on its transition, PNI could be a very powerful biomarker for predicting treatment sensitivity.

Combining a WT1 Vaccine (Galinpepimut-S) with Checkpoint Inhibition (Nivolumab) in Patients with WT1-Expressing Diffuse Pleural Mesothelioma (DPM): A Phase I Study

IntroductionWilms’ tumor suppressor protein (WT1) often presents on the surface of diffuse pleural mesotheliomas (DPMs) and is an ideal therapeutic target. Galinpepimut-S (GPS), a tetravalent, non-HLA restricted, heteroclitic WT1-specific peptide vaccine was safe and effective in early phase clinical trials and upregulates T cell suppressive programmed death-ligand 1 (PD-L1) in the tumor microenvironment of other malignancies. A randomized phase II study of adjuvant GPS in patients with DPM trended toward improved median overall survival. MethodsTo further enhance immunogenicity, we combined GPS with nivolumab, an anti-PD1 monoclonal antibody, in an open-label, single-center phase I study, examining tolerability and immunogenicity in patients with previously treated DPM. We enrolled patients with progressive or recurrent DPM treated with at least one course of pemetrexed-based chemotherapy. Patients received 2 doses of GPS followed by 6 doses of GPS with intravenous nivolumab every 2 weeks, and up to 6 additional cycles until disease progression or unacceptable toxicity. ResultsTen patients were treated; 70% experienced mostly mild treatment-related adverse events; 2 experienced a grade ≥3 adverse event. Three (30%) of 10 patients demonstrated vaccine-specific T-cell responses. There were no partial responses; 3 patients had prolonged stable disease with up to 17% decrease in tumor volume. Median progression-free survival was 3.9 months and the median overall survival was 7.4 months. ConclusionsCoadministration of GPS and nivolumab demonstrated a tolerable toxicity profile and induced immune responses in a subset of patients, but initial response and survival benefit were limited possibly due to the small sample size.

Breast relapse of myeloid sarcoma and SARS-CoV-2 infection following hematopoietic stem cell transplantation in mixed-phenotype acute leukemia: a case report

Abstract Background Mixed-phenotype acute leukemia is a rare, high-risk subtype of acute leukemia. Myeloid sarcoma is a localized tumor formed by the proliferation and infiltration of primitive or immature myeloid cells outside the bone marrow. It is often an extramedullary manifestation of acute myeloid leukemia, and imaging lacks specificity, leading to potential misdiagnosis. Case Presentation A female patient diagnosed with mixed-phenotype acute leukemia achieved complete remission after chemotherapy and allogeneic hematopoietic stem cell transplantation. However, a relapse occurred in the breast after transplantation. The patient achieved local control through mastectomy and removal of the axillary lymph nodes on the affected side. Unfortunately, during the subsequent course of chemotherapy, the patient died of a severe pulmonary infection caused by coronavirus disease 2019. Conclusion Continuous treatment and monitoring of mixed-phenotype acute leukemia patients are essential, especially for those with extramedullary manifestations (such as breast involvement).

Clinical study of immune-targeting combined with attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma

Objective: To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL). Methods: A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×106/L and was 12 (0, 25)×106/L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion: BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.

Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: Insights from the Western Australian Context.

Recent studies have associated total neoadjuvant therapy (TNT) with better treatment adherence, decreased toxicity, improved complete clinical response and anal sphincter preservation rates in patients with locally advanced rectal cancer (LARC). However, real-world experience with TNT in the management of LARC remains limited. This study aimed to evaluate the efficacy and safety outcomes of TNT for LARC in Western Australia. Patients with LARC (cT2-4 and/or cN1-2) who underwent induction chemotherapy followed by neoadjuvant chemoradiotherapy or neoadjuvant chemoradiotherapy followed by consolidation chemotherapy, followed by surgery were recruited from two hospitals in Western Australia. Efficacy outcomes assessed included clinical response (complete, partial, no response), and pathologic complete response (pCR) rate, R0 resection rate, and R1 resection rate were evaluated. Those patients who achieved clinical complete response following TNT were given the option of active surveillance. The safety and tolerability of TNT were assessed. 32 patients with LARC were treated with TNT. In total, 17 patients (53%) received chemoradiotherapy followed by consolidation chemotherapy and 15 patients (47%) received induction chemotherapy followed by chemoradiotherapy. Nine (28%) of the patients with LARC treated with TNT had a complete clinical response, twenty-one (66%) patients had a partial clinical response, and two (6%) patients had no response to TNT. Of the 32 patients, 27 (84%) underwent surgery. There was a 100% R0 resection rate. The pCR rate was 15%. pCR, clinical response, and the R0 resection rate were similar between the two TNT regimens. TNT was well tolerated, with the majority of patients (88%) completing the chemotherapy course with grade 1 and 2 adverse effects. In conclusion, TNT emerges as a promising approach for the management of LARC. However, further research is warranted to refine the optimal TNT protocols, determine its long-term outcomes, and identify patient populations who would benefit the most from this innovative therapeutic strategy.

SWI/SNF Altered Gastric Carcinoma with Squamous Differentiation in a young patient with aggressive clinical course

Abstract Introduction/Objective Inactivation of SMARCA4 (BRG1) protein subunit of the SWI/SNF complex has been reported in various malignancies affecting multiple organs, often associated with a poor prognosis. We report a rare case of gastric SMARCA4-deficient carcinoma in a young patient, showing squamous differentiation and an aggressive clinical course. Methods/Case Report A 28-year-old male presented with epigastric pain and 15-lb weight loss over 3 months. Evaluation revealed a gastric cardia mass, liver lesion, and gastro-hepatic lymph-node. Biopsy of gastric and liver lesions revealed a poorly differentiated carcinoma. Following a course of neoadjuvant chemotherapy, and immunotherapy, total gastrectomy and distal esophagectomy were performed. Grossly, there was a 13 cm mass involving his gastric cardia and body, extending into his distal esophagus. On microscopy, the transmural tumor was arranged as solid sheets, syncytial aggregates, and nests with a focal pseudoglandular pattern in a lymphoplasmacytic rich stroma. Scattered bizarre giant cells were noted, along with brisk mitosis and focal necrosis. Focally, the tumor showed abundant glassy eosinophilic cytoplasm reminiscent of squamoid cells. Two of forty-two lymph nodes were positive for metastatic carcinoma. IHC showed focal positivity for AE1/3, OSCAR, CAM5.2, along with areas staining for p40 and p63; negative for CK7, CK20, CDX2, SATB2, synaptophysin, INSM1, SOX-10, LCA ERG, and SALL4. Nuclear expression for mismatch repair proteins was retained. HER2 was negative (score 0), and PDL-1 CPS score was 40. EBER in-situ hybridization was negative, with retention of INI-1. There was complete loss of SMARCA4 by IHC and next generation sequencing confirmed frameshift alteration of SMARCA4. Final pathologic diagnosis was SMARCA4 deficient poorly differentiated carcinoma with squamous differentiation (ypT3pN1). The patient received adjuvant therapy with Paclitaxel and Ramucirumab. However, his disease progressed, and he succumbed to his illness five months after surgery. Results (if a Case Study enter NA) N/A Conclusion Our case illustrates that SMARCA4 deficient gastric carcinomas can have heterogeneous morphology, with an aggressive clinical course in young patients. This highlights the importance of early diagnosis and consideration of alternative therapeutic approaches, as these tumors typically do not respond to standard treatments.

Role of Tumor Microenvironment in the Risk of Thromboembolic Complications in Ovarian Cancer

Introduction. Incidence of ovarian cancer remains high in the overall prevalence of oncological pathology. Adjuvant chemotherapy refers to its treatment options. Patients with oncological pathology are faced with a high risk of thrombosis and thromboembolism, with up to 30% lethal outcome within a month of its development. A number of cancer cells are known to induce platelet aggregation, contributing to thrombosis and metastasis as a result of this interaction. Accordingly, the paper is aimed at presenting a clinical case for demonstrating the role of P-selectin expression in the complications in a patient with ovarian cancer. Materials and methods. The present paper evaluates platelet activation marker in a patient undergoing chemotherapy courses after cytoreductive surgery. Following the case conference and in accordance with the clinical recommendations of the Russian Oncology Association (AOR) and Russian Society of Clinical Oncology (RUSSCO), cytoreduction (CC-0), radical hysterectomy, transverse colectomy, left hemicolectomy with rectum resection were performed. The interventions included ascendostomy, pelvic, lateral right-sided and left-sided peritonectomy, pelvic lymphoadenectomy, total omentectomy, Renape-French HIPEC (hyperthermic intraperitoneal chemotherapy), abdominal and pelvic drainage. Expression of P-selectin on the platelet surface was measured as a marker of platelet activation. Results and discussion. At the time of admission, the patient had high CD62 expression activity compared to healthy volunteers (CD62 ADP- — 11.2%, CD62 ADP — 24.7% vs CD62 ADP- — 1.3%, CD62 ADP — 17.2%). During the complex treatment of ovarian cancer, the platelet activation increased (CD62 ADP- — 21.8 %, CD62 ADP+ — 30.1 %). At discharge, CD62 expression values reached the conditional norm, presumably indicating thrombosis development. Conclusion. Tumor microenvironment influences the hemostasis system. Detailed study into this issue obtains a high potential for the prevention of primary and secondary thromboembolic complications in oncologic patients.

Modern problems of bronchial tuberculosis in the world and the Russian Federation: A review

In the Russian Federation there is a positive trend in reducing the incidence of tuberculosis. However, there is a tendency to increase the prevalence of tuberculosis in the bronchi. According to foreign authors, the prevalence of bronchial tuberculosis ranges from 10% to 40%. There are no official statistics on the incidence of bronchial tuberculosis in the Russian Federation. The main contingent of bronchial tuberculosis lesions are young non-smoking women. At the same time, the most common target is the left main bronchus. Currently, no additional methods have been developed in the scheme of specific treatment of patients with pulmonary tuberculosis complicated by bronchial tuberculosis. It is important to understand that the eradication of MBT after an effective course of chemotherapy does not prevent the formation of cicatricial bronchial stenosis. It is also important to note that bacterial excretion in patients with bronchial tuberculosis is much more common than in patients with a comparable process in the lungs, but without bronchial damage. Consequently, tuberculosis of the trachea and bronchi has not only clinical, but also great epidemiological significance.

Primary breast lymphoma mimicking triple-negative breast cancer: a case report with clinical and pathological implications

BackgroundPrimary breast lymphoma (PBL) is a rare type of extranodal lymphoma, the diagnostic process for which presents significant challenges owing to an overlap in clinical and pathological features with those observed in triple-negative breast cancer (TNBC). However, the current literature reveals a paucity of information regarding the ramifications of potential diagnostic errors, particularly in the context of emergent therapeutic strategies for TNBC. Thus, we present a unique report of a case of PBL.Case presentationA 76-year-old female with no past medical or family history presented to the hospital with the chief complaint of a mass in the right breast. Two masses were palpated in the right breast: one 56 mm mass (No. 1) located at 10 o'clock, and a 21 mm large, elastic, hard mass (No. 2) at 4 o'clock. Needle biopsy was performed only on the larger 56 mm mass (No. 1). The results showed invasive carcinoma that was negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. The preoperative diagnosis was right breast cancer (T3N0M0 Stage IIB) of the TNBC subtype. The patient refused the preoperative chemotherapy recommended by the treatment team; therefore, right breast mastectomy and sentinel lymph-node biopsy were performed instead. The histopathological diagnosis of the first mass was diffuse large B-cell lymphoma (DLBCL); that of the second mass (No. 2) was an invasive breast carcinoma of no special type. Postoperative treatment consisted of endocrine therapy (letrozole) for breast cancer, while the DLBCL was treated with chemotherapy and three courses of intrathecal chemotherapy. At the time of this report, the patient is still living, and neither tumor had recurred in the 2 years following surgery.ConclusionsOn rare occasions, PBL can preoperatively mimic TNBC. While this case did not lead to serious consequences, because surgery was eventually selected as the first therapy, clinicians should be aware that the diagnosis of PBL is challenging using only a core-needle biopsy and can often be misdiagnosed as TNBC.

Electrochemotherapy to Treat a Single Thoracic Metastasis in Patient with Breast Cancer

Electrochemotherapy represents one of the therapeutic breakthroughs in the oncology field. In this case report, we describe a woman diagnosed with breast cancer in 2005. The case was treated surgically with right breast mastectomy, with axillary dissection for estrogen receptor positive ductal carcinoma, followed by a course of chemotherapy. Radiotherapy and hormonal adjuvant therapy with aromatase inhibitor were used for 8 years and the treatment plan was completed in 2014. After 17 years from the surgery, a thoracic Hight Resolution Computed Tomography scan showed a single node localized in right intercostal space, treated with a loco-regional treatment without complications. This allowed us to make the patient disease-free again. This case opens a choice in a loco-regional treatment to offer at a patient a new chance.