Abstract Background and Objectives Thymic epithelial tumors often present with autoimmune disorders. While PD-L1–targeting immune checkpoint inhibitors (ICIs) like pembrolizumab offer therapeutic potential, they risk severe myocarditis. We report fatal ICI-induced myocarditis after a single dose, underscoring the need for close monitoring in thymoma patients. Case Presentation A 31-year-old male with type B1/B2 thymoma (pT3, Masaoka stage 3) underwent surgical resection and received adjuvant radiotherapy. After disease relapse, he received six cycles of CAP chemotherapy (cyclophosphamide 500 mg/m 2 , Adriamycin 50 mg/m 2 , cisplatin 50 mg/m 2 ) and showed stable disease. Due to 60% PD-L1 expression, pembrolizumab was initiated. One week post-first dose, he presented with chest pain and dyspnea. Workup revealed elevated troponin, ST-segment elevations, and normal echocardiography, consistent with myocarditis. Despite high-dose steroids and intensive care, he rapidly deteriorated, developing ventricular fibrillation and passed away within 24 h. Conclusion This case underscores the lethal synergy between thymoma’s immunogenic milieu and ICI toxicity, particularly myocarditis. The rapid progression to fatal arrhythmia after a single pembrolizumab dose suggests that thymoma patients may require enhanced cardiac monitoring protocols pre- and post-ICI initiation. Further research is needed to identify risk stratification biomarkers and optimize immunosuppression strategies for this high-risk population.
Abstract Dostarlimab-gxly, a monoclonal anti–PD-1 antibody, has been recognized as being effective for rectal cancer in patients whose tumors are mismatch repair deficient. Even though promising preliminary clinical results have been obtained, further critical appraisal of the efficacy, safety, and use of this drug among the broader spectrum of patients will be required. To bridge this knowledge gap, a systematic review and meta-analysis was conducted involving literature from PubMed, Scopus, and Web of Science from January 2018 to November 2024. The studies that were analyzed based on these primary metrics were complete clinical response (cCR), pathologic complete response (pCR), progression-free survival (PFS), overall survival (OS), and safety profile. The process of screening and filtering of abstracts from PubMed, Scopus, and Web of Science generated 1,246 abstracts, of which 28 were included in the final analysis of dostarlimab-gxly treated patients, who totaled 1,567. Results demonstrated a pooled complete response rate of 32.5%, with notably higher pCR rates in deficient mismatch repair (dMMR) tumors compared to mismatch repair-proficient tumors. Patients who received dostarlimab-gxly with radiotherapy or chemotherapy showed higher response rates but increased risks of toxicity. The most common adverse effects were fatigue, diarrhea, and immune-related colitis. The meta-analysis put emphasis on large improvements in PFS and OS compared to control treatments. Dostarlimab-gxly represents a possible alternative treatment strategy for rectal cancer, predominantly effective in the dMMR context. Given its generally balanced safety profile, it is paramount to remain ever vigilant for potential immune-related adverse events. Future work should concentrate on making combination therapies maximally effective, establishing predictive biomarkers, and performing extensive research to further reinforce these findings.
Abstract Background It is important to be cognizant of the evolving demographics, clinicopathological features, and overall survival (OS) associated with lung carcinoma to devise new strategies for improvement. This study aimed to retrospectively analyze the same at the Regional Cancer Center of Haryana (India). Material and methods A retrospective observational study of carcinoma lung cases registered from January 2015 to December 2020 was conducted analyzing demographics, clinicopathological profile, and OS. Risk factors were compared by log-rank test for univariate analysis. Results A total of 376 patients with a median age of 60 years were evaluated. Male to female ratio was 5.16:1. Out of total patients, 86.9% were smokers with a mean smoking index of 717.09. Non-small cell lung cancer (NSCLC) was diagnosed in 84.31%, small cell lung cancer (SCLC) in 14.89%, and superior vena cava (SVC) syndrome in 0.8% of patients. The most frequent histology among NSCLC patients was squamous cell carcinoma (SCC) (41.49%), followed by adenocarcinoma (31.12%). Performance score was 2 or above in 98.1% of patients. Median OS was 3 months (range 0.3–84 months). Median survival was 3, 2, and 0.4 months in NSCLC, SCLC, and SVC syndrome patients, respectively ( p -value 0.483). Among NSCLC patients, the median OS in stage II patients was 9 months and in stage III and IV patients was 3 months, while in SCLC, the survival was 3 and 2 months in stage III and IV patients, respectively ( p < 0.001). Conclusion Most frequent histopathology was SCC, and smoking was the major risk factor. The study showcased dismal survival in advanced-stage patients. Thus, there is an urgent need to create awareness to seek early medical attention and quick diagnostics.
Abstract Introduction and background Anaplastic large cell lymphoma (ALCL) is an atypical clinicopathological entity and its central nervous system (CNS) involvement is rarer still, presenting a diagnostic challenge to physicians. Based on the absence or presence of anaplastic lymphoma kinase (ALK) fusion, it presents as either ALK-negative or ALK-positive subtype, the latter predominantly having a favourable prognosis and presenting in younger patients. The definitive impact of the said ALK protein on the course of the illness is the main area of interest of this study. Methodology The study question was designed using the PICO (participants, interventions, comparisons and outcomes) strategy. We conducted a systematic review in accordance with the PRISMA guidelines and a literature search using PubMed, Google Scholar and Cochrane library using keywords like ‘anaplastic large cell lymphoma’, ‘ALCL’, ‘ALK’ and ‘CNS’. Results We included 30 cases of ALCL in our study, of which 24 cases were ALK positive and the remaining were negative. Eighty-six percent of the former showed 2-year survival when receiving interventions such as methotrexate-based chemotherapy, radiation, non-methotrexate-based chemotherapy and surgery, while none of the ALK-negative patients passed an 8-month survival period. In this study, we assessed the histology, immunochemistry, prognostic factors and treatment methods of disease based on previous records and came to the conclusion that ALCL involving CNS had a better prognosis with a positive ALK protein status and also certain other prognostic factors such as meningeal involvement, T cell as a marker and age less than 18 years.
Abstract Background Endocan is primarily presented as a soluble dermatan sulfate proteoglycan that is expressed in endothelial cells, as well as in serum and plasma. In acute leukemia patients, disease status was found to correlate with endocan levels as it was strongly expressed in untreated patients but decreased after chemotherapy. Furthermore, endocan levels were sensitive to recurrence, as indicated by an increase in levels during relapse. Notably, no significant change in endocan levels was observed before and after chemotherapy in patients who did not achieve remission. Subjects and Methods Our research team conducted a prospective study at Ain Shams University Hospitals, Clinical Hematology, and Stem Cell Transplant Unit. This study included 45 patients diagnosed with de novo acute leukemia. Endocan levels were measured before and at day 28 after chemotherapy induction. Results A high significant statistical correlation was found between the initial and post-induction endocan levels, with higher initial values observed. A nearly significant correlation existed between the initial endocan levels in responders and non-responders (AML) patients, with non-responder patients showing higher values. Furthermore, a significant positive correlation was found between initial endocan and both lactate dehydrogenase and the initial bone marrow evaluation. Conclusion Pre-induction endocan levels are significantly elevated in acute leukemia patients compared to post-induction levels, showing a near significant correlation with remission status in AML, but there was no significant correlation in ALL patients. Endocan level has a potential prognostic significance in acute leukemia.
This narrative review paper examines the use and potential benefits of histone deacetylase inhibitors (HDACis) in pancreatic ductal adenocarcinoma (PDAC) as a combinational therapy. The paper provides a concise overview of the epigenetic events and their effects on gene expression in PDAC, followed by a summary of selected preclinical and clinical studies, demonstrating the efficacy of HDACis as combinatorial treatments. The current therapeutic approach in PDAC includes low-efficacy combination therapies, mainly as a palliative treatment, due to delayed diagnosis, rapid disease progression, and development of metastases. The tumor mutational burden and several epigenetic modifications shape tumor characteristics, regulate the gene expression, and alter the cell cycle. Epigenetic modifications at lysine residues of histones, including acetylation, are mediated by histone acetyltransferases and counteracted by HDACs. HDACis are approved as monotherapy in cutaneous T-cell lymphoma and are potentially effective when administered in combination with other therapies in solid tumors. In particular, combinations of HDACis with tyrosine kinases inhibitors, MEK inhibitors, PI3K inhibitors, 13-cis-retinoic acid, EZH2 inhibitors, and BET inhibitors appear to suppress epithelial–mesenchymal transition, promote apoptosis, and increase overall survival in patients with PDAC.
This study assesses brain metastases (BM) in non-small cell lung cancer (NSCLC) – its prevalence, risk factors, overall survival, and influencing aspects. A retrospective observational study was conducted at Nghe An Oncology Hospital in Vietnam. We assessed 895 patients diagnosed with NSCLC between June 2019 and June 2023. We used univariate and multivariate logistic regression models to assess the association of BM with factors. We evaluated the overall survival (OS) time using the Kaplan–Meier method and assessed differences using the log-rank test. In addition, we determined the association between OS time and factors using the Cox regression model. The prevalence of BM in NSCLC at the time of diagnosis was 13.1%. BM were associated with non-squamous carcinoma (odds ratio [OR] = 2.04, 95% confidence interval [95% CI]: 1.01–4.14), lymph node stage N3 (OR = 1.77, 95% CI: 1.15–2.72), and serum carcinoembryonic antigen (CEA) ≥5 ng/ml (OR = 1.81, 95% CI: 1.05–3.13). The median OS time for patients with BM was lower than in those without BM (15.3 vs. 18.3 months, p = 0.005). When analyzing multivariable Cox regression, the OS time of patients with BM was associated with positive EGFR/ALK gene mutation status (hazard ratio [HR] = 0.38, 95% CI: 0.20–0.70) and number of brain metastatic in 1–3 lesions (HR = 0.56, 95% CI: 0.33–0.96). The prevalence of BM at the time of diagnosis in NSCLC was 13.1% and was associated with non-squamous carcinoma, node stage, and serum CEA. EGFR/ALK gene mutation status and the number of brain metastatic lesions were independent prognostic factors for OS of BM NSCLC.
Within the nasal cavity and paranasal sinuses, adenocarcinomas comprise 10–20% of all primary malignant neoplasms. A considerable number of them originate from the salivary glands, while some are less well-known and resemble colon adenocarcinomas in their histologic makeup. Adenocarcinoma of the sinonasal region that does not arise from salivary glands is often presented as uncommon growths that are frequently misdiagnosed. Less than 4% of all cancers in this region are of the intestinal type, which shares histologic features with that of colon adenocarcinoma. The main age group affected by this malignancy ranges between 55 and 65 years. Workers in the shoe and hardwood industries frequently develop these tumors, and the risk of acquiring adenocarcinoma is enhanced by about 900 times following wood dust inhalation. Not much has been written about these neoplasms in the oral radiology literature, even though they account for about 4% of the primary neoplasms of the sinonasal tract. We present a case of well-differentiated intestinal-type adenocarcinoma (ITAC) of the sinonasal region with paranasal sinus destruction associated with unusual radiographic appearance.
Conventional treatments for breast cancer use cytotoxic drugs, which cause severe side effects. Researchers are seeking new treatments with fewer side effects and greater efficacy. Probiotics, such as Lactobacillus species, have demonstrated positive effects on various diseases, including cancer. The probiotics Lactobacillus acidophilus and Lactobacillus plantarum were examined using MCF-7 and MCF-10A human breast cancer and normal human breast cell lines, respectively. The cell lines were treated with the supernatant and probiotic pellets, and cell proliferation, viability, apoptosis, and BCL2 gene expression were evaluated. The culture supernatant of L. plantarum significantly inhibited the growth of MCF-7 cell line compared to other groups, including the group treated with both probiotics. The supernatant of L. plantarum increased apoptosis and significantly reduced BCL2 gene expression in MCF-7 cells. No effects were observed in MCF-10A cells. The findings indicated that the supernatant of L. plantarum had a stronger cytotoxic effect on MCF-7 cells. In contrast, the combination of L. plantarum and L. acidophilus showed no synergistic effects. These results suggest that metabolites in the supernatant of L. plantarum contribute to the cytotoxic effects of this probiotic. This probiotic is a promising candidate for breast cancer treatment, and further research is needed to understand its preventive and therapeutic mechanisms.
Deep inspiration breath-hold (DIBH) technique is commonly used in left breast cancer irradiation as it has shown to reduce cardiac and pulmonary doses. DIBH technique has also shown to reduce critical organ doses in right-sided breast cancer patients. This study aimed to demonstrate the single-institution experience of dosimetric benefits of DIBH technique in irradiation of right breast carcinoma patients. Twenty consecutive patients who underwent adjuvant locoregional radiotherapy by DIBH technique for right-sided breast carcinoma were included retrospectively for analysis. Indications for use of DIBH for right-sided disease in our institution included presence of breast implant or need for irradiation of axillary and/or internal mammary nodal basin. For all these patients, planning computed tomography (CT) was obtained in both free breathing (FB) and deep inspiration breath hold (DIBH) using indexed breast board. Treatment was replanned in the FB planning CT slices, and dosimetric endpoints in terms of differences in PTV coverage and doses to lungs, heart, liver, and contralateral breast were compared. Radiation was delivered using either volumetric modulated arc therapy or intensity-modulated radiotherapy technique. There was no significant difference in PTV coverage between FB and DIBH scans showing similar plan qualities. The ipsilateral lung volume showed significant increase with subsequent decrease in the mean dose with DIBH compared to FB (from 14 Gy in the FB plan to 12 Gy with DIBH, p -value 0.01). Technique of DIBH significantly lowered the mean hepatic dose compared to FB technique (3.8 vs. 7.9 Gy, p -value: 0.0001). Contralateral lung mean dose also showed reduction of statistical significance in DIBH. There was significant difference in the mean dose to the heart between the two techniques, as well as in the max dose, which was reduced significantly with DIBH. Contralateral breast mean dose was also reduced with DIBH, though the difference was not statistically significant. DIBH technique showed significant dosimetric benefit in terms of reduced critical organ doses, providing a potential for incorporation into radiotherapy of right-sided breast carcinoma.
Abstract Background Prostate cancer (PCa) is a significant health concern, with immune cell infiltration playing a crucial role in its pathogenesis. Understanding the immune landscape of prostate tumors compared to healthy tissue is essential for developing novel therapeutic strategies. This study aims to estimate immune cell infiltration in prostate tumors and healthy tissues and investigate the causal relationships between immune phenotypes and PCa using Mendelian randomization. Methods Transcriptomic data from The Cancer Genome Atlas was utilized to compare prostate tumor tissues with healthy controls. Immune cell infiltration was estimated using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts, single-sample Gene Set Enrichment Analysis, and xCell methodologies. Mendelian randomization was employed to explore causal relationships between 731 immune phenotypes and PCa, using five methods including inverse-variance weighting for evaluation. Results with a false discovery rate (FDR)-adjusted P-value <0.05 were considered significant. Sensitivity analyses, including heterogeneity tests, pleiotropy tests, and leave-one-out analyses, were conducted to ensure the robustness of the findings. Results Significant differences in the infiltration of macrophages, neutrophils, and basophils were observed between prostate tumors and healthy tissues. Before FDR correction, 42 immune phenotypes showed a causal relationship with PCa. After FDR correction, CD4 on HLA DR+ CD4+ T cells exhibited a significant causal association with PCa (odds ratio [95% confidence interval] = 0.54 (0.43–0.71), P = 3.86E-06). Sensitivity analyses revealed no abnormalities, confirming the reliability of the results. Conclusions This study highlights the significant differences in immune cell infiltration between PCa and healthy tissues and identifies a causal relationship between specific immune phenotypes and PCa. The findings provide valuable insights for future research and potential therapeutic targets in PCa treatment.
The aim of this study was to assess the thyroid profile in adult acute lymphoblastic leukemia (ALL) and find out the relationship between thyrotropin-releasing hormone (TRH) level and the clinical outcome of the patients. Prospective observational research was conducted from January to June 2024. This study included a sequential sample of 44 newly diagnosed ALL patients aged 15 and above. Each patient underwent full medical history, clinical examination, complete blood count, blood film, bone marrow aspirate, flow cytometry, cytogenetics, karyotyping, and a thyroid profile including T3, T4, thyroid-stimulating hormone (TSH), and TRH. They were evaluated both at the time of diagnosis and after induction chemotherapy. A total of 44 patients were included in the study, 37 males and 7 females. Their ages ranged from 15 to 60 years (mean age 29.56 ± 13.91 years). All initial T3, T4, TSH, and TRH were statistically significantly lower than post-chemotherapy results (with p value = 0.001, 0.007, 0.035, and < 0.00,1 respectively). Initial TSH showed a statistically significant negative correlation with disease-free survival (with r = −033 and p = 0.027). Initial TRH showed a statistically significant negative correlation with overall survival and disease-free survival (with r = −030 and −030 and p = 0.45 and 0.45, respectively). Multiple regression analysis showed that initial TSH was the most significant determining factor of disease-free survival (with = −0.34 and p = 0.029). On the other hand, multiple regression analysis showed that karyotyping was found to be the most significant determining factor of overall survival in multiple regression analysis (with = 0.46 and p = 0.049, respectively). The evaluation of disease-free survival using the Kaplan–Meier curve, based on the initial thyroid profile, indicated the most favorable outcomes in patients with a euthyroid state and euthyroid sick syndrome (ESS). Thyroid hormonal profile is initially affected in some patients with adult ALL. Euthyroid status is most commonly encountered with initial assessment. Abnormalities included ESS, hypothyroidism and hyperthyroidism. Significant improvement in the thyroid profile after the induction phase ensures the role of disease rather than therapy itself. Initial TRH and TSH have a negative prognostic impact on ALL outcomes. Moreover, the euthyroid status and ESS were associated with the best survival of ALL.
Medullary carcinoma (MC) of the colon is one of the rarest types of colon adenocarcinoma with distinct phenotype and clinical outcomes. Annual incidence is noted to be around five to eight out of 10,000 cases of colon cancer, which is partly can be attributed to lack of understanding of these tumors for many years that has resulted in incorrect diagnosis. Comprehensive pathological examination is important along with immunohistochemical staining for accurate diagnosis of MC of the colon. It is usually diagnosed at stage 2 or 3, where surgery is the mainstay of treatment. Given the rarity of the tumor, there are no specific guidelines to direct adjuvant treatments. Most of the recommendations are inherited from colon adenocarcinoma guidelines. Here, we report a case report of elderly gentleman with early-stage medullary carcinoma of the colon and its prognosis, pathological findings, and treatment implications.
Primary breast adenocarcinoma arising in ectopic breast tissue within the vulva is an exceedingly rare occurrence, posing significant diagnostic challenges due to its unusual presentation. Differentiating it from other vulvar neoplasms is crucial for prompt and appropriate management. We present the case of a 55-year-old female with a history of negative medical and family history, presenting with an atypical vulvar lesion with extensive bone metastasis. Even though normal findings were obtained on mammogram and breast ultrasound, biopsy revealed undifferentiated carcinoma. Further immunohistochemical analysis supported a diagnosis of mammary carcinoma originating from malignant accessory breast tissue. Treatment involved paclitaxel and carboplatin chemotherapy along with zoledronic acid infusions and pelvic bone radiotherapy, which resulted in an initial complete response. However, a subsequent vulvar lesion recurrence necessitated hormonal therapy, leading to another complete response. This case highlights the diagnostic complexity and therapeutic challenges associated with primary breast adenocarcinoma in vulvar ectopic breast tissue. Comparison with similar cases underscores the importance of meticulous evaluation, precise immunohistochemistry, and interdisciplinary collaboration for accurate diagnosis and tailored treatment.
Immune checkpoint inhibitors (ICIs), while revolutionizing cancer treatment, can lead to a spectrum of side effects due to their broad impact on the immune system. Common side effects include fatigue, skin reactions and gastrointestinal issues. However, ICIs can also induce immune-related adverse events (irAEs), affecting various organs, such as the lungs, liver and endocrine system. Severe irAEs, though infrequent, can include myocarditis, colitis and neurologic complications such as neuropathy and myasthenia gravis. Vigilant monitoring and collaborative management by healthcare providers are essential to balance the anti-tumour effects of ICIs with the potential autoimmune consequences. We describe a case of ICI-induced myasthenia gravis, myocarditis, myositis and hepatitis that was recognized and managed in the broader context of myasthenia gravis. It is essential that patients on ICIs to be regularly monitored for irAEs during treatment for their malignancies due to the risk of potentially fatal complications.
The purpose of this research is to analyze the neutrophil-to-lymphocyte ratio (NLR) to define prognostic factors in patients with breast cancer and to analyze the NLR values among stages, grades, and fractions.
The global burden of cancer continues to rise, with projections indicating a 47% increase in new cases by 2040. The integration of oncology and palliative care has emerged as a vital approach to address the complex needs of cancer patients. This position paper, endorsed by the Palliative Care Working Group of the Hellenic Society of Medical Oncology (HeSMO), emphasizes the significance of early integration of palliative care with cancer-directed therapies. It highlights the benefits of this approach, including improved quality of life, symptom control, emotional well-being, and enhanced survival rates for patients. The paper also addresses the challenges of palliative care provision in Greece and advocates for comprehensive education for health-care professionals, especially oncologists and nurses, to effectively manage palliative care needs. The importance of multidisciplinary teams (MDTs), survivorship care plans (SCPs), home-based palliative care, and end-of-life care discussions is underscored. By aligning with international guidelines and recommendations, HeSMO strives to establish a supportive health-care system in Greece that offers equitable access to high-quality palliative care for all cancer patients, thus ensuring their well-being throughout their cancer journey.
Various molecular cancer variables, including K-RAS, B-RAF, and HER2/neu, are essential in the growth and advancement of tumors. Matrix metalloproteinase-9 (MMP-9) is suggested as a biomarker that is excessively produced in different types of malignancies and plays a critical role in chemotherapy resistance that leads to tumor progression and metastasis.
