Incidence and Risk of Secondary Malignancy in Patients with Waldenström Macroglobulinemia: A Population-Based Analysis.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma which may predispose individuals to development of secondary malignancies (SMs). The Surveillance, Epidemiology, and End Results (SEER) database is a comprehensive registry of cancer patients in the United States reporting on a wide set of demographic variables. Using the SEER-18 dataset, analyzing patients from 2000 to 2018, we aimed to assess the incidence of SMs in WM patients. Patient characteristics such as gender, age, race, and latency were identified, and respective standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated to compare to the general population. Of the 4,112 eligible WM patients identified, SMs were reported in 699 (17%) patients. The overall risk of developing SM, second primary malignancy, and secondary hematological malignancy was significantly higher in WM patients compared to the general population. Our findings show that WM patients had a 53% higher risk of SMs relative to the general population, and an AER of 102.69 per 10,000. Although the exact mechanism is unclear, the risk of SM development may be due to genetic predisposition, immune dysregulation, or treatment-induced immune suppression.

Redefining Clinical Hyperprogression: The Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) may be associated with hyperprogressive disease (HPD). However, there is currently no standardized definition of HPD, with its risk factors and clinical implications remaining unclear. We investigated HPD in lung cancer patients undergoing immunotherapy, aiming to redefine HPD, identify risk factors, and assess its impact on survival. METHODS: Clinical and radiologic data from 121 non-small cell lung cancer (NSCLC) patients with 136 immunotherapy cases were reviewed retrospectively. Three HPD definitions (Champiat et al., HPDc; Saâda-Bouzid et al., HPDs; and Ferrara et al., HPDf) were employed. Additionally, all new measurable lesions on the post-treatment CT scan were incorporated in measuring the sum of longest diameters (SLD) to define modified HPD (mHPD). RESULTS: Among the 121 patients, 4 (3.3%) had HPDc, 11 (9.1%) had HPDs, and none had HPDf. Adding all new measurable lesions increased HPD incidence by 5%-10% across definitions. Multivariate analysis revealed significantly lower progression-free survival (PFS) and overall survival (OS) for patients with HPDc (HR 5.25, P = .001; HR 3.75, P = .015) and HPDs (HR 3.74, P < .001; HR 3.46, P < .001) compared to those without. Patients with mHPD showed similarly poor survival outcomes as HPD patients. Liver metastasis at diagnosis was associated with HPDs, and a high tumor burden correlated with HPDc. CONCLUSIONS: The incidence and risk factors of HPD varied with different definitions, but mHPD identified more cases with poor outcomes. This comprehensive approach may enhance the identification of at-risk patients and lead to a better understanding of HPD in lung cancer during immunotherapy.

Deep response to a combination of mTOR inhibitor temsirolimus and dual immunotherapy of nivolumab/ipilimumab in poorly differentiated thyroid carcinoma with PTEN mutation: a case report and literature review.

Treating advanced thyroid cancer presents challenges due to its resistance to various treatment modalities, thereby limiting therapeutic options. To our knowledge, this study is the first to report the efficacy of temsirolimus in conjunction with dual immunotherapy of nivolumab/ipilimumab to treat heavily treated advanced PDTC. A 50-year-old female initially presented with a rapidly enlarging mass on her right neck. Subsequent diagnosis revealed poorly differentiated thyroid carcinoma, leading to a total thyroidectomy followed by post-operative radioablation therapy. After four years, an examination for persistent cough revealed a recurrence of the disease within multiple mediastinal nodes. Genetic analysis of blood samples uncovered somatic mutations in the tumor, specifically involving PTEN and TP53. The disease progressed despite palliative radiation, lenvatinib, and nivolumab/ipilimumab therapy. Consequently, temsirolimus, functioning as an mTOR inhibitor, was introduced as an adjunct to the nivolumab/ipilimumab regimen. This combination approach yielded remarkable clinical improvement and disease control for a duration of approximately six months. Temsirolimus likely suppressed the aberrantly activated PI3K/AKT/mTOR signaling pathway, facilitated by the PTEN genetic alteration, thus engendering an effective treatment response. This synergy between targeted agents and immunotherapy presents a promising therapeutic strategy for advanced PDTC patients with limited treatment alternatives. In previous clinical trials, mTOR inhibitors have demonstrated the ability to maintain stable disease (SD) in 65% to 74% for advanced thyroid cancer patients, including those with PDTC. When combined with other targeted therapies, the observed SD or partial response rates range from 80% to 97%. Many of these trials primarily involved differentiated thyroid carcinoma, with diverse genetic mutations. Thyroid cancer patients with alterations in the PI3K/mTOR/Akt appeared to benefit most from mTOR inhibitors. However, no clear association between the efficacy of mTOR inhibitors and specific histologies or genetic mutations has been established. Future studies are warranted to elucidate these associations.

The Role of Bispecific Antibodies in Relapsed Refractory Multiple Myeloma: A Systematic Review.

Multiple myeloma is a heterogeneous clonal malignant plasma cell disorder, which remains incurable despite the therapeutic armamentarium's evolution. Bispecific antibodies (BsAbs) can bind simultaneously to the CD3 T-cell receptor and tumor antigen of myeloma cells, causing cell lysis. This systematic review of phase I/II/III clinical trials aimed to analyze the efficacy and safety of BsAbs in relapsed refractory multiple myeloma (RRMM). A thorough literature search was performed using PubMed, Cochrane Library, EMBASE, and major conference abstracts. A total of 18 phase I/II/III studies, including 1283 patients, met the inclusion criteria. Among the B-cell maturation antigen (BCMA)-targeting agents across 13 studies, the overall response rate (ORR) ranged between 25% and 100%, with complete response/stringent complete response (CR/sCR) between 7 and 38%, very good partial response (VGPR) between 5 and 92%, and partial response (PR) between 5 and 14%. Among the non-BCMA-targeting agents across five studies, the ORR ranged between 60 and 100%, with CR/sCR seen in 19-63%, and VGPR in 21-65%. The common adverse events were cytokine release syndrome (17-82%), anemia (5-52%), neutropenia (12-75%), and thrombocytopenia (14-42%). BsAbs have shown promising efficacy against RRMM cohorts with a good safety profile. Upcoming phase II/III trials are much awaited, along with the study of other agents in concert with BsAbs to gauge response.

Liquid biopsies and minimal residual disease in myeloid malignancies.

Minimal residual disease (MRD) assessment through blood component sampling by liquid biopsies (LBs) is increasingly being investigated in myeloid malignancies. Blood components then undergo molecular analysis by flow cytometry or sequencing techniques and can be used as a powerful tool for prognostic and predictive purposes in myeloid malignancies. There is evidence and more is evolving about the quantification and identification of cell-based and gene-based biomarkers in myeloid malignancies to monitor treatment response. MRD based acute myeloid leukemia protocol and clinical trials are currently incorporating LB testing and preliminary results are encouraging for potential widespread use in clinic in the near future. MRD monitoring using LBs are not standard in myelodysplastic syndrome (MDS) but this is an area of active investigation. In the future, LBs can replace more invasive techniques such as bone marrow biopsies. However, the routine clinical application of these markers continues to be an issue due to lack of standardization and limited number of studies investigating their specificities. Integrating artificial intelligence (AI) could help simplify the complex interpretation of molecular testing and reduce errors related to operator dependency. Though the field is rapidly evolving, the applicability of MRD testing using LB is mostly limited to research setting at this time due to the need for validation, regulatory approval, payer coverage, and cost issues. This review focuses on the types of biomarkers, most recent research exploring MRD and LB in myeloid malignancies, ongoing clinical trials, and the future of LB in the setting of AI.

Outcomes after venetoclax with hypomethylating agents in myelodysplastic syndromes: a systematic review and meta-analysis.

We present a systematic review and meta-analysis to evaluate outcomes after venetoclax (VEN) with hypomethylating agents (HMA) in myelodysplastic syndromes (MDS). We performed a literature search on PubMed, Cochrane Library, EMBASE, and Clinicaltrials.gov. After screening 2004 manuscripts, 16 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed. We analyzed the outcomes of 373 patients from 11 retrospective studies and five phase 1 b clinical trials. Pooled complete response with or without hematological recovery was 60% (95% CI 0.49-0.7, I2= 67%, n = 373). Hematopoietic cell transplantation was performed in 32% of patients (95% CI 0.2-0.46, I2= 62%, n = 187). Overall mortality was 45% (95% CI 0.31-0.59, I2=54%, n = 140). VEN-HMA combination therapy demonstrated promising outcomes in MDS. Prospective randomized data is needed to ascertain the benefit of VEN and its impact in MDS patients.

Intraperitoneal Hematoma After Femoral Catheterization: A Case Report and Literature Review.

Central venous catheters (CVCs) are often crucial in managing severely ill patients, especially those in the intensive care unit. It is estimated that over 5 million CVCs are inserted per year in the United States. The internal jugular, subclavian, or femoral veins are the most used access sites. The catheter is advanced until its tip lies within the proximal third of the superior vena cava, the right atrium, or the inferior vena cava. Unfortunately, the use of CVCs is not without its drawbacks, and multiple immediate and delayed complications have been described. Herein, we report a case of a 70-year-old female with a past medical history significant for chronic obstructive pulmonary disease, coronavirus disease 2019, pneumonia, type 2 diabetes mellitus, and hypertension, who presented to the emergency department from a skilled nursing facility with a two-day history of dyspnea. She was later diagnosed with an intraperitoneal hematoma, an uncommon complication caused by a CVC placement.

Cardiac Amyloidosis: A Rare Cause of Recurrent Chylothorax.

Amyloidosis is caused by the extracellular deposition of fibrils composed of low molecular weight protein subunits. Its two main types are amyloid light chain (AL) amyloidosis and amyloid A (AA) amyloidosis (previously referred to as secondary amyloidosis). Clinical manifestations are dependent upon location, type, and amount of deposit. We report a case of a 72-year-old female who presented to the emergency department for evaluation of cough, fatigue, and shortness of breath. Physical examination was notable for decreased breath sounds bilaterally over the lower lung fields. Computed tomography (CT) of the chest showed a large lobulated right pleural effusion and atelectasis. Two liters of milky, white pleural fluid was removed via thoracocentesis, and pleural fluid analysis was consistent with chylothorax. Over the next 10-day period, there was a reaccumulation of the pleural fluid, which required a pleural catheter placement. The patient underwent video-assisted thoracoscopic surgery with pleural and pericardial tissue biopsy that was consistent with kappa or lambda AL amyloid. Unfortunately, her respiratory status subsequently declined, requiring mechanical ventilation, and eventually leading to cardiac arrest. Cardiac amyloidosis can rarely cause chylous ascites and chylothorax. The absence of electrocardiographic findings of left ventricular hypertrophy combined with apparent left ventricular hypertrophy on echocardiography is strongly suggestive of infiltrative cardiomyopathy such as cardiac amyloidosis. In these cases, cardiac amyloidosis should be considered in the differential diagnosis of chylothorax.

Emerging Role of Antibody-Drug Conjugates and Bispecific Antibodies for the Treatment of Multiple Myeloma.

Multiple myeloma (MM) is characterized by malignant proliferation of malignant plasma cells; it is the second most common hematological malignancy associated with significant morbidity. Genetic intricacy, instability, and diverse clinical presentations remain a barrier to cure. The treatment of MM is modernized with the introduction of newer therapeutics agents, i.e., target-specific monoclonal antibodies. The currently available literature lacks the benefits of newer targeted therapy being developed with an aim to reduce side effects and increase effectiveness, compared to conventional chemotherapy regimens. This article aims to review literature about the current available monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies for the treatment of MM.

Role of Venetoclax in the Treatment of Relapsed and Refractory Multiple Myeloma.

Biomarker-driven targeted therapies have been an area of exploration for innovative therapeutic options in oncology. B-cell lymphoma-2 (BCL-2) protein is an anti-apoptotic protein expressed on the clonal plasma cells in patients with multiple myeloma (MM). MM subsets with t (11;14) have overexpression of BCL-2 and can benefit from venetoclax (VEN) when used either alone or in combination with other chemotherapeutic agents with an overall response rate (ORR) ranging from 40% to 100%. The most commonly reported grade ≥ 3 adverse effects include cytopenias and gastrointestinal side effects. This review highlights the meaningful efficacy and tolerable safety of VEN monotherapy and its combination regimens in the treatment of relapsed refractory MM.

Emerging Targets and Cellular Therapy for Relapsed Refractory Multiple Myeloma: A Systematic Review.

Multiple myeloma is the second most common hematologic malignancy and remains incurable. Patients who fail multiple lines of therapy typically have a poor prognosis despite recent advances in myeloma treatment. Chimeric antigen receptor T (CAR T) cell treatment has emerged as a promising therapy for many hematologic malignancies, including recently approved and emerging applications for myeloma treatment. A systematic review of the available clinical trial data for CAR T therapies in multiple myeloma was undertaken. All multiple myeloma trials registered at ClinicalTrials.gov were reviewed and studies mentioning CAR T and studying relapsed/refractory multiple myeloma (R/R MM) were included. PubMed, Google Scholar, and conference proceedings were also reviewed to determine which trials had reported data. Twenty-seven registered clinical trials in humans with published data were identified as of March 10, 2021. The majority of these trials were CAR T cells targeting B-cell maturation antigen (BCMA), and many were Phase I studies. Data demonstrated promising short-term (<12 months) efficacy with low incidence of grade 3 or higher toxicities. CAR T cell therapy in R/R MM remains a promising treatment modality. While one biologic has recently received FDA-approval, the majority of products remain investigational and in early-phase trials. More investigation is needed to determine which CAR T constructs and combination therapies optimize patient outcomes.

Thoracic imaging finding of rheumatic diseases.

In the era of Precision Medicine, diagnostic imaging plays a key role in initial diagnosis and treatment response assessment in thoracic manifestation of various rheumatic disorders; resulting in increased dependency on imaging for treatment planning. Chest radiographs serve as a good initial screening tool for assessment of emergent and urgent thoracic conditions, e.g., pneumothorax, pulmonary edema, consolidation and pleural effusions. Cross-sectional imaging techniques, e.g., computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) are most commonly utilized to evaluate more detailed pulmonary and mediastinal manifestations of rheumatic conditions. Magnetic resonance imaging (MRI) and ultrasound are most commonly used in cardiovascular, neural and musculoskeletal structures. This review article aims to highly key common thoracic imaging findings of rheumatic disorders, highlighting imaging test of choice for the particular disorder.

Advances in maintenance strategy in newly diagnosed multiple myeloma patients eligible for autologous transplantation.

INTRODUCTION: Multiple myeloma (MM) lacks curative therapy. Therefore, researchers continue to conduct studies in an effort to improve progression-free survival (PFS) and overall survival (OS). Maintenance therapy (MT) after autologous stem cell transplant (ASCT) was extensively studied in the last decade and now considered a standard approach. AREAS COVERED: This review evaluated the evidence and updates on various maintenance agents in newly diagnosed multiple myeloma (NDMM) after ASCT. Articles were searched on PubMed and Embase that were published in last 10 years. Both clinical trials and observational studies were evaluated. EXPERT OPINION: Maintenance strategy after ASCT has consistent PFS benefit but lacks conclusive OS improvement. Lenalidomide is superior to thalidomide given reduced neurotoxicity. OS advantage is controversial for both due to inconsistent evidence. Lenalidomide may confer a PFS advantage even at lower doses due to toxicity with higher doses. Bortezomib-based maintenance has some evidence for OS benefit in high-risk MM (HRMM) and renal dysfunction. Ixazomib has preliminary promising results. Two or three drug combinations for MT are potentially safe and more effective, particularly in HRMM although data on this subject is still evolving. Efficacy of various MT regimens in terms of minimal residual disease status needs to be further investigated.

Evidence-based supportive care in multiple myeloma.

Multiple myeloma (MM) is a hematological malignancy characterized by an abnormal clone of plasma cells in the bone marrow. MM and its therapy increase the risk of complications like anemia, osteolytic lesions, pain, infections, and renal abnormalities in MM patients. Supportive care for MM patients improves the quality of life. Treatment with bisphosphonates decreases skeletal-related events. Vertebroplasty and kyphoplasty are done in cases of vertebral compression fractures. Prophylactic antibiotics and antivirals can decrease infections related to morbidity. Plasmapheresis in patients with renal dysfunctions decreases dialysis dependency and improve quality of life.

Interventions to Reduce Stigma Related to Mental Illnesses in Educational Institutes: a Systematic Review.

This investigation reviews the effectiveness of anti-stigma interventions employed at educational institutes; to improve knowledge, attitude and beliefs regarding mental health disorders among students. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist guidelines were followed and protocol was registered in PROSPERO (CRD42018114535). Forty four randomized controlled trials were considered eligible after screening of 104 full-text articles against inclusion and exclusion criteria.Several interventions have been employed to tackle stigma toward psychiatric illnesses, including education through lectures and case scenarios, contact-based interventions, and role-plays as strategies to address stigma towards mental illnesses. A high proportion of trials noted that there was a significant improvement for stigma (19/25, 76%), attitude (8/11, 72%), helping-seeking (8/11, 72%), knowledge of mental health including recognition of depression (11/14, 78%), and social distance (4/7, 57%). These interventions also helped in reducing both public and self-stigma. Majority of the studies showed that the anti-stigma interventions were successful in improving mental health literacy, attitude and beliefs towards mental health illnesses.

Retraction: Small Intestinal Tumors: A Rare Case of Tubulovillous Adenoma in Duodenum.

[This retracts the article DOI: 10.7759/cureus.4671.].

Small Intestinal Tumors: A Rare Case of Tubulovillous Adenoma in Duodenum.

The small intestine is a relatively privileged organ; primary tumors are uncommon among malignancies of the gastrointestinal tract, with an average annual incidence rate of 9.9 per million people. Among these uncommon tumors, duodenal tumors are even rarer with an average incidence rate of 0.4% only. Histopathological examination mostly shows villous type. Tubulovillous histology is extremely rare with an incidence of less than 1% of all duodenal tumors. These tumors are either found incidentally or during screening for familial disorders such as familial adenomatous polyposis or Gardner's syndrome. Patients usually have symptoms such as diarrhea and abdominal pain along with weight loss over a period of months. Itching over the whole body and progressive yellow discoloration of sclera and skin (jaundice) can also be present when tumor compresses the common bile duct (CBD) and causes obstruction, especially in the region of ampulla of Vater. Examination of the abdomen may or may not reveal a mass lesion. Abdominal radiography and ultrasound show intra- and extra-hepatic biliary dilatation along with distention of CBD and growth at the lower end of CBD. Endoscopic retrograde cholangiopancreatography (ERCP) is, however, the investigation of choice as it not only allows direct visualization of a biliary tree but biopsy specimens can also be taken. Palliative procedures like placing a stent in the common bile duct to relieve obstruction can be done or a drain can be placed to drain bile. The definitive treatment is the Whipple procedure involving gastrojejunostomy, choledochojejunostomy, and cholecystectomy. Our case is unique as the patient had duodenal tubulovillous adenoma, a very rare tumor among the already uncommon duodenal tumors. The patient underwent Whipple procedure, T tube was placed, and feeding jejunostomy was done. An uneventful recovery occurred.