IgA multiple myeloma-associated mediastinal spinal plasmacytoma presenting as spinal cord compression.

Multiple myeloma associated with extramedullary plasmacytoma at initial presentation is rare. We describe a case of a man in his 30s who initially presented with symptoms of spinal cord compression. Further imaging revealed a mediastinal tumour, with a biopsy confirming plasmacytoma. Immunofixation revealed IgA lambda paraprotein. Bone marrow biopsy demonstrated atypical T-cell cytotoxic proliferation and trilineage hypoplasia. The patient was diagnosed with extramedullary plasmacytoma with active IgA multiple myeloma. The patient received mediastinal radiation to the tumour, followed by anti-myeloma therapy. This diagnosis is critical as managing a solitary plasmacytoma drastically differs from an extramedullary plasmacytoma with active multiple myeloma.

State-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care.

Gastroesophageal cancers (GECs) represent a significant clinical challenge. For early resectable GEC, the integration of immune checkpoint inhibitors into the perioperative chemotherapy and chemoradiation treatment paradigms are being explored and showing promising results. Frontline management of metastatic GEC is exploring the role of targeted therapies beyond PD-1 inhibitors, including anti-human epidermal growth factor receptor 2 agents, Claudin 18.2 inhibitors, and FGFR2 inhibitors, which have shown considerable efficacy in recent trials. Looking ahead, ongoing trials and emerging technologies such as bispecific antibodies, antibody-drug conjugates, and adoptive cell therapies like chimeric antigen receptor T cells are expected to define the future of GEC management. These advancements signify a paradigm shift toward personalized and immunotherapy-based approaches, offering the potential for improved outcomes and reduced toxicity for patients with GEC.

Long-Term Survival Rates and Treatment Trends of Burkitt Lymphoma in Patients with HIV-A National Cancer Database (NCDB) Study.

BACKGROUND: Burkitt lymphoma (BL) accounts for 10-35% of AIDS-defining lymphoma in people with HIV (PWH). Previous research consisting of smaller cohorts has shown decreased survival for HIV-associated BL. This study aims to compare overall mortality in BL patients with and without HIV, while investigating impact of treatment modalities in HIV-associated BL. METHODS: Using the 2004-2019 NCDB, we identified 4312 patients with stage 3 or 4 BL who had a known HIV status and received either chemotherapy alone or chemotherapy and immunotherapy. Time to death was evaluated using Kaplan-Meier survival estimates. Risk of death was evaluated using an extended multivariable Cox model adjusted for multiple factors and with a Heaviside function for HIV status by time period (0-3 month vs. 3-60 month). RESULTS: Of the 4312 patients included, 1514 (35%) had HIV. For months 0-3 from time of diagnosis, HIV status was not associated with a statistically significant increase in risk of death (HR = 1.04, 95% CI: 0.86, 1.26, p = 0.6648). From month 3to 60, positive HIV status was associated with a 55% increase in risk of death compared to those without HIV (95% CI: 1.38, 1.75, p < 0.0001). Further, this difference in hazard rates (0-3 vs. 3-60) was statistically significant (HR = 1.49, 95% CI: 1.22-1.82, p < 0.001). CONCLUSIONS: There is an increased mortality rate from months 3 to 60 in BL patients with HIV compared to patients without HIV. Additionally, risk of death in the first 3 months is significantly decreased by 45% in patients with HIV treated with combination chemotherapy and immunotherapy compared to patients without HIV receiving combination chemotherapy and immunotherapy, providing valuable clinical insight into treatment decision making in the care of HIV-associated BL.

Global inequalities in availability of systemic therapies for cancer care and strategies to address them.

Many Low and middle-income countries face challenges in delivering chemotherapy services due to limitations in infrastructure, inadequate healthcare facilities, and a shortage of trained medical professionals. High-income countries often have well-developed healthcare systems and advanced technology.

Colorectal cancer: Review of signaling pathways and associated therapeutic strategies.

Tumor profiling and targeted therapy revolutionized the treatment strategies of metastatic colorectal cancer (mCRC) in the last decade. The heterogeneity of CRC tumors plays a critical role in the development of treatment resistance, which underscores the need to understand the molecular mechanism involved in CRC to develop novel targeted therapeutic strategies. This review provides an overview of the signaling pathways driving CRC, the existing targeted agents, their limitations, and future trends.

Immune Checkpoint Inhibitor-Induced Hemophagocytic Lymphohistiocytosis in a Patient With Squamous Cell Carcinoma.

Programmed cell death protein 1 (PD-1) checkpoint inhibitors such as pembrolizumab are novel therapeutics used to treat various advanced malignancies and have been shown to increase patient survival in several studies. However, these drugs have a toxicity profile that ranges from mild side effects such as dermatitis to life-threatening complications. We present a case of pembrolizumab-induced hemophagocytic lymphohistiocytosis (HLH) in an 80-year-old patient with squamous cell carcinoma (SCC) of presumed cutaneous primary. This patient initially presented with weakness and pancytopenia, thought to be immune-related. She developed progressive anemia, after which further workup revealed concern for HLH. She recovered after a course of steroids, tocilizumab, and etoposide. To our knowledge, this patient's course is among a few rare cases of immune checkpoint inhibitor (ICI)-mediated HLH. This case highlights the need for early diagnosis and recognition of HLH as a potential toxicity related to ICI therapy.

Phase 1 trial of carfilzomib in relapsed/refractory peripheral T-cell lymphoma.

Peripheral T-cell lymphomas (PTCL) are a unique subset of lymphomas with a poor prognosis due to limited treatment options. We performed a phase 1 study of carfilzomib in patients with relapsed/refractory PTCL to determine the safety profile and the maximum tolerated dose (MTD) of this agent. The study was a classical 3 + 3 phase 1 design with intra-patient dose escalation allowed beginning on day 8 of cycle 1 and subsequently. Dose-limiting toxicity (DLT) was defined as the occurrence of any grade 3/4 adverse event. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Fifteen patients were enrolled from 3 centers. The median age of patients was 62. The median number of prior therapies for subjects on this trial was five. The MTD of carfilzomib was 36 mg/m2. Dose-limiting toxicities included anemia and sepsis. Serious adverse events were seen in 45% of patients. Single-agent carfilzomib leads to a complete response in one patient and a partial response in one patient. Overall, the drug was reasonably tolerated for a heavily pretreated population, but the limited response rate and short duration of response demonstrate a lack of promise for carfilzomib as a single agent in this patient population.

Impact of Performance Status on Response and Survival Among Patients Receiving Checkpoint Inhibitors for Advanced Solid Tumors.

PURPOSE: Clinical trials, which led to the approval of immune checkpoint inhibitors (ICI), have been almost exclusively performed in patients with good Eastern Cooperative Oncology Group performance status (ECOG PS of 0-1). However, ICI remains an attractive option for patients with advanced tumors and poor PS. We hypothesized that patients with ECOG PS ≥ 2 would have worse outcomes with ICI. METHODS: We retrospectively identified patients with advanced solid tumors who were treated with ICI at our institution. The log-rank test compared the survival among patients with different ECOG PS. We used a proportional hazards model to assess association between ECOG PS and overall survival (OS) with adjustment for covariates including age, sex, malignancy type, time from advance disease diagnosis, and line of therapy. We compared overall response rates between groups with Pearson chi-square exact test. We also analyzed in-hospital mortality and hospice referral rates. RESULTS: We identified 257 patients treated with ICI. One hundred eighty-two patients had ECOG PS 0-1, and 75 had ECOG PS ≥ 2. The median overall survival was 12.6 months for the ECOG PS 0-1 group compared with 3.1 months for the ECOG PS ≥ 2 group (P < .001). The overall response rate for patients with ECOG PS 0-1 was 23% compared with 8% for those with poor PS (P = .005). Patients with poor PS treated with ICI had similar hospice referral rates (67% for ECOG PS ≥ 2 v 61.9% for ECOG PS 0-1, P = .50) but were more likely to have in-hospital death as compared with the good PS group (28.6% v 15.1%, P = .035). CONCLUSION: Despite the appeal of ICI in patients with advanced malignancy and poor PS, outcomes in this cohort were poor. Prospective trials defining the activity and role of ICI in poor PS are urgently needed.

HPV and the Immune System in Head and Neck Cancers: Therapeutic Considerations.

Immunotherapy applications for head and neck squamous cell carcinoma (HNSCC) are rapidly evolving. The progress towards immunotherapy has demonstrated improved outcomes for patients with HNSCC. Human papillomavirus (HPV)-associated HNSCC has a much better prognosis and differs from HPV-negative HNSCC in its genomic and immunologic profile, with strikingly higher immune cell activation and infiltration. Despite an increased incidence of HPV-associated HNSCC, and differences in immune signature based on HPV status, the management does not differ from non-HPV tumors. Clinical trials are ongoing to integrate immunotherapy in the management of early- and late-stage HNSCC, and its current use is limited to the metastatic setting. This article describes the role of immune therapy in HPV-associated HNSCC along with the evidence and perspective behind differing therapeutic considerations.

Targeting the Sanctuary Site: Options when Breast Cancer Metastasizes to the Brain.

Brain metastasis is a poor prognostic factor in breast cancer progression, and traditional treatment options have shown minimal response with overall low median survival rates. The incidence of brain metastasis has been increasing despite and, in part, due to advancements in treatment as a result of prolongation of survival. Targeted therapy such anti-HER2 agents have a lower efficacy in this setting compared to metastases elsewhere; however, novel therapies are emerging in this regard. In this comprehensive review, we discuss risk per subtype, special considerations for therapy selection, current focal and systemic treatments, and recent advancements and potential future targets for success. We present our treatment paradigm and multidisciplinary approach to brain metastases arising from breast cancer based on the available evidence, incorporating molecular characteristics.

Hepatosplenic γ-δ T-Cell Lymphoma: Who Is on Your Speed Dial?

Hepatosplenic γ-δ T-cell lymphoma, an exceptionally uncommon subtype of peripheral T-cell lymphomas, commonly presents with advanced-stage disease manifesting with hepatosplenomegaly, cytopenias, and constitutional symptoms. Management of this subset is challenging as a result of the unique presentation and refractory nature to conventional treatment approaches. There is a lack of consensus guidelines for up-front induction strategies, and the role of consolidative autologous or allogeneic stem-cell transplantation is controversial. Prospective studies are lacking, and treatment is often guided by literature on the basis of case series or single-institution studies, lending to expert opinions influencing treatment paradigms.

The role of targeted therapy in thymic carcinoma.

Thymic carcinoma is a rare entity and can be distinguished from benign thymomas by their aggressive nature and poor prognosis. The National Comprehensive Cancer Network guidelines recommend resection followed by adjuvant platinum-based chemotherapy for resectable tumors. However, the outcomes for metastatic or relapsed thymic carcinomas are poor with no regimen showing a consistent benefit. Moreover, the relative rarity of these tumors makes clinical trials difficult. Molecular analysis of thymomas shows a high incidence of genetic mutations and targeted therapy holds promise. We will briefly outline and review the current role of targeted therapy in thymic cancer.

A 75 year old male with recurrent unilateral pleural effusion and positive ANA.

This case report describes the clinical course and diagnostic challenges arising in a 75 year old man who initially presented with progressive shortness of breath. Imaging revealed a pleural effusion, which was recurrent following thoracentesis. While his initial workup suggested an autoimmune etiology, further diagnostic testing revealed a diagnosis of malignant pleural mesothelioma. Curiously, the patient had no known asbestos exposure, which is classically associated with acquired mesothelioma. There are a small number of similar cases with a possible overlap between positive autoimmune serologies and mesothelioma; however, the underlying pathophysiology remains elusive. It is the authors' goal to contribute this case to the few cases describing such overlap syndromes.

Factors Affecting Adjuvant Therapy in Stage III Pancreatic Cancer-Analysis of the National Cancer Database.

BACKGROUND: Adjuvant therapy after curative resection is associated with survival benefit in stage III pancreatic cancer. We analyzed the factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer and compared overall survival with different modalities of adjuvant treatment. METHODS: This is a retrospective study of patients with stage III pancreatic cancer listed in the National Cancer Database (NCDB) who were diagnosed between 2004 and 2012. Patients were stratified based on adjuvant therapy they received. Unadjusted Kaplan-Meier and multivariable Cox regression analysis were performed. RESULTS: We analyzed a cohort included 1731 patients who were recipients of adjuvant therapy for stage III pancreatic cancer within the limits of our database. Patients who received adjuvant chemoradiation had the longest postdiagnosis survival time, followed by patients who received adjuvant chemotherapy, and finally patients who received no adjuvant therapy. On multivariate analysis, advancing age and patients with Medicaid had worse survival, whereas Spanish origin and lower Charlson comorbidity score had better survival. CONCLUSIONS: Our study is the largest trial using the NCDB addressing the effects of adjuvant therapy specifically in stage III pancreatic cancer. Within the limits of our study, survival benefit with adjuvant therapy was more apparent with longer duration from date of diagnosis.

Cardiac Arrhythmias Resulting from a Peripherally Inserted Central Catheter: Two Cases and a Review of the Literature.

We present two cases of patients being treated for diabetic ketoacidosis in the intensive care unit who experienced cardiac arrhythmia secondary to peripherally inserted central catheters (PICCs). In one instance, the patient became bradycardic and experienced related loss of consciousness, ultimately requiring cardiopulmonary resuscitation. In the second case, the patient experienced an episode of nonsustained ventricular tachycardia. We explore the various types of arrhythmias that have been reported secondary to central venous catheters, as well as factors that place patients at an increased risk for arrhythmia while undergoing PICC insertion. Furthermore, we look at the literature for methods to improve the insertion of PICC lines by decreasing the risk of catheter over-insertion as well as the effects of training for PICC placement.

Streptococcus Gordonii Empyema: A Case Report and Review of Empyema.

Streptococcus gordonii (S. gordonii) is a pioneer oral bacteria that is recognized as an agent of bacterial endocarditis. However, an extensive review of the literature revealed no reported case of S. gordonii causing empyema. We present a case of a 65-year-old male who presented with respiratory distress. Physical examination revealed several dental caries with decreased breath sounds in the bibasilar regions. A computed tomography (CT) scan of the chest and abdomen demonstrated left-sided pleural effusion and a 4.3 cm x 2.8 cm splenic abscess. He received intravenous (IV) antibiotics, and his blood cultures remained negative. Drainage of the splenic abscess grew S. gordonii. A CT-guided thoracentesis yielded 450 ml of exudative fluid. Pleural fluid cultures grew S. gordonii. A CT scan of the head and neck ruled out an intra-oral abscess. He received six weeks of IV penicillin with a follow-up CT scan showing resolution of both the splenic abscess and the left parapneumonic effusion.

Bent Metal in a Bone: A Rare Complication of an Emergent Procedure or a Deficiency in Skill Set?

Intraosseous (IO) access is an important consideration in patients with difficult intravenous (IV) access in emergent situations. IO access in adults has become more popular due to the ease of placement and high success rates. The most common sites of access include the proximal tibia and the humeral head. The complications associated are rare but can be catastrophic: subsequent amputation of a limb has been described in the literature. We report a 25-year-old female presenting with diabetic ketoacidosis (DKA) in whom emergent IO access was complicated by needle bending inside the humerus. Conventional bedside removal was impossible and required surgical intervention in operating room.