Racial and regional disparities in deaths in breast cancer.

Breast cancer is the second most diagnosed malignancy in American women with a lifetime occurrence of 1 in 8 women in the United States. There has been a dearth of research focusing on regional differences in breast cancer mortality with respect to race in the US. It is crucial to identify regions that are lagging to uplift the outreach of breast cancer care to certain races. Data for this study were obtained from the 2016-2018 Nationwide Inpatient Sample. In-hospital mortality, race and hospital regions for the patients with the primary diagnosis of Malignant Neoplasms of Breast were studied. Baseline characteristics of participants were summarized using descriptive statistics. The patient population was stratified as per race, hospital region, gender, therapy received and family history. Logistic regression was performed to derive the odds ratio while adjusting for different variables. 99, 543 patients with metastatic breast cancer were identified. African Americans (AAs) were found to have the highest reported deaths at 5.54%, followed by Asians and Pacific Islanders at 4.80% and Caucasians 4.09% (p < 0.0001). The odds of dying were significantly higher in the AA population when compared to Caucasian population (OR 1.391 (1.286-1.504)), and the odds were consistently higher across all regions of the US. In terms of regional disparities with respect to race, AA's had highest mortality in the south whereas all other races had the highest mortality in the west. It was seen that races identifying as "others" had significantly higher odds of dying in the Northeast. It is crucial to identify racial differences in the various regions across the US in order to implement appropriate outreach strategies to tackle these disparities.

Grade 3 Neuroendocrine Tumor (G3NET): An Unusual Tumor With A Histochemical Surprise.

Given the rare occurrence and the indolent course of Neuroendocrine tumors (NETs), few epidemiological studies exist on these cancers. A small but interesting subset of these tumors are G3- Neuroendocrine Tumors. Grade 3 Neuroendocrine tumors (or G3-NETs) are unique in their intermediate prognosis. These grade discordant tumors lie in between high-grade poorly differentiated neuroendocrine carcinomas and grade 2 well-differentiated NETs, which have a worse and better prognosis than this rare entity, respectively. In this case report, we present a case of Grade 3 NET with an unusually high Ki67 index, diagnosed upon biopsy of metastasis visualized on imaging. Additionally, we review existing literature for characteristics, immunohistochemical markers, prognosis, and treatment modalities for the same.

PSMA: a game changer in the diagnosis and treatment of advanced prostate cancer.

Although management of advanced prostate cancer is evolving, a lot of work remains to be done for patients who have exhausted all options. Molecular targeting of prostate specific membrane antigen (PSMA) is valuable not only for diagnostic but also for therapeutic reasons. PSMA is thus considered to be useful in a theranostic approach. PSMA scans are upcoming diagnostic modalities which detect metastatic lesions that are missed by conventional imaging modalities. PSMA ligand therapy is also an upcoming treatment modality that has been proven to be beneficial with minimal toxicity in patients with advanced prostate cancer that have progressed on prior therapy. In this review article, we summarize the current knowledge regarding PSMA diagnostics and PSMA ligand therapies and discuss their implication in the treatment of advanced prostate cancer.

HIV-Associated Anal Cancer.

Anal cancer, despite being a rare malignancy, is increasing in incidence, accounting for 0.5% of all new cancer cases in the United States, with rate of new cases being 1.9 per 100,000 men and women. It is common in immunocompromised individuals, especially those with malignancy, human immunodeficiency virus (HIV) and human papillomavirus (HPV) infection. Despite similar treatment of anal cancer in both HIV-positive and negative patients, guidelines for prevention and treatment of therapy-related side effects are rarely studied. While these patients have a better prognosis on HAART, limited guidelines exist regarding appropriate therapy. There is a common link between HPV and HIV and the transmission of one is associated with increased risk of transmission of the other. HPV vaccine which is known to prevent high-grade cervical intraepithelial neoplasia is thought to also decrease the incidence of anal intraepithelial neoplasia. The association of HPV vaccine in the prevention of anal cancer in high-risk groups with HIV is a scarcely studied subject that requires further research.

Triple-arm androgen blockade for advanced prostate cancer: a review.

Prostate cancer is estimated to be the second most common malignancy in men in the USA in 2020 and represents the second highest mortality from cancer behind lung and bronchial neoplasms. Management of advanced prostate cancer is evolving. Medical androgen deprivation therapy is currently a cornerstone of therapy for prostate cancer; however molecular mechanisms of resistance have emerged leading to castration-resistant prostate cancer that is proliferation of prostate cancer in the setting of low testosterone (< 50 ng/dl). The benefit of double androgen blockade like ADT plus abiraterone acetate or androgen receptor blockers is proven in many clinical trials; however multiple mechanisms of resistance still exist. In theory, another layer of androgen blockade will prevent, or at least slow, prostate cancer proliferation. This direction of thought has recently been explored with multiple clinical trials. In this review article, we summarize the current knowledge regarding androgen resistance, newer androgen inhibition therapies, and the implications of a triple-arm anti-androgen blockade in advanced prostate cancer.

Metastatic squamous cell carcinoma of the colon: a conundrum in colorectal malignancies.

Small-cell carcinoma of the colon is an extremely rare tumour, with poorly understood pathogenesis and unestablished treatment guidelines. The first case was documented in 1919, and only about 100 cases of this condition have been reported to this date. In this case report, we present a case of sigmoid squamous cell carcinoma that eventually led to bowel perforation and was diagnosed on histopathology after emergent surgical intervention. Additionally, we also review the incidence, epidemiology, pathogenesis, immunohistological markers, neogenomics and therapeutic strategies for the same.

PARP inhibitors: shifting the paradigm in the treatment of pancreatic cancer.

Pancreatic cancer, being one of the most fatal cancers, is the 7th leading cause of death globally. Cancer that is resistant to current treatment proves that there is a need for personalized and targeted therapy, based on the tumor and genomic markers. Pembrolizumab and Larotrectinib are examples of current medications used as targeted therapy in pancreatic cancer. Pancreatic cancer has many different molecular subgroups, providing the opportunity for the development of new drugs that can target these groups. Poly (ADP-Ribose) polymerase inhibitors (PARPi) are a group of drugs inhibiting PARP to decrease the stability of the cancer cells. Currently, PARPi are mostly used in ovarian and breast cancer. There are multiple studies that have shown positive effects of PARPi in decreasing the tumor burden in advanced pancreatic cancer. PARPi are the future of pancreatic cancer management, and hence it is important to understand their mechanism, resistance pathways, and their application in the real world.

A Needle in the Haystack: A Rare Case of Spontaneous Tumor Lysis in Newly Diagnosed Chronic Lymphocytic Leukemia Unmasked by Acute Renal Failure.

Tumor lysis syndrome (TLS) is the phenomenon of metabolic derangements that typically follows the initiation of cytotoxic chemotherapy. Metabolic disturbances include hyperphosphatemia, hyperkalemia, hyperuricemia and hypocalcemia. Hematological malignancies are associated with spontaneous TLS (STLS), which is cell lysis in the absence of chemotherapy. STLS is extremely rare in chronic lymphocytic leukemia (CLL). This has been documented only once in the medical literature, making this an extraordinarily uncommon case. We present here a 68-year-old male with a history of benign prostatic hyperplasia (BPH) who is admitted for a two-week history of abdominal pain and three days of anuria, despite adequate fluid intake. Laboratory values yielded a greatly elevated leukocyte count with a lymphocytic predominance and smudge cells. Potassium, phosphorus, and uric acid were also significantly increased. EKG revealed peaked T-waves. Flow cytometry confirmed the presence of an abnormal B-cell population consistent with B-cell chronic lymphocytic leukemia, with the following markers: CD19+, CD20+, CD23+, CD5+, CD10-. He was diagnosed with CLL and treated with aggressive fluid resuscitation, allopurinol and rasburicase. The patient had another similar episode within one month. His CLL fluorescence in-situ hybridization (FISH) showed complex cytogenetics with unmutated IgVH and he was subsequently started on ibrutinib.

The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Extrapulmonary Small Cell Carcinoma.

Small cell carcinoma is a type of highly aggressive poorly differentiated neuroendocrine tumor that can arise from multiple organs, including but not limited to bronchial tissue, pancreas, gastrointestinal tract, and genitourinary system. The most commonly studied type is small cell lung cancer (SCLC) which carries the worst prognosis among lung cancers. After multiple promising clinical trials, the National Comprehensive Cancer Network has recently added atezolizumab and durvalumab in combination with platinum-based chemotherapy/etoposide to the first-line treatment regimen for extensive-stage SCLC (ES-SCLC). Meanwhile, the recommended treatment for extrapulmonary small cell carcinoma (EPSCC) remains unchanged. In this review, we try to explore the role of immunotherapy in the treatment of EPSCC.

Access to internet, smartphone usage, and acceptability of mobile health technology among cancer patients.

PURPOSE: The use of mobile health (mHealth) technologies to augment patient care enables providers to communicate remotely with patients enhancing the quality of care and patient engagement. Few studies evaluated predictive factors of its acceptance and subsequent implementation, especially in medically underserved populations. METHODS: A cross-sectional study of 151 cancer patients was conducted at an academic medical center in the USA. A trained interviewer performed structured interviews regarding the barriers and facilitators of patients' current and desired use of mHealth technology for healthcare services. RESULTS: Of the 151 participants, 35.8% were male and ages ranged from 21 to 104 years. 73.5% of participants currently have daily access to internet, and 68.2% currently own a smartphone capable of displaying mobile applications. Among all participants, acceptability of a daily mHealth application was significantly higher in patients with a college-level degree (OR 2.78, CI95% 1.25-5.88) and lower in patients > 80 years of age (OR 0.05, CI95% 0.01-0.23). Differences in acceptability when adjusted for current smartphone use and daily access to internet were nonsignificant. Among smartphone users, the desire to increase cancer knowledge was associated with a higher likelihood of utilizing a mHealth application (OR 261.53, CI95% 10.13-6748.71). CONCLUSION: The study suggests that factors such as age, educational achievement, and access to internet are significant predictors of acceptability of a mHealth application among cancer patients. Healthcare organizations should consider these factors when launching patient engagement platforms.

Clinical Advancement and Challenges of ex vivo Expansion of Human Cord Blood Cells.

Apart from peripheral blood stem cell (PBSC), umbilical cord blood (UCB) is now a recognized source of stem cells for transplantation. UCB is an especially important source of stem cells for minority populations, which would otherwise be unable to find appropriately matched adult donors. UCB has fewer mature T lymphocytes compared with peripheral blood, thus making a UCB transplantation (UCBT) with a greater degree of HLA mismatch possible. The limited cell dose per UCB sample is however associated with delayed engraftment and a higher risk of graft failure, especially in adult recipients. This lower cell dose can be optimized by performing double unit UCBT, ex vivo UCB expansion prior to transplant and enhancement of the capabilities of the stem cells to home to the bone marrow. UCB contains naïve and immature T cells, thus posing significant challenges with increased risk of infections, graft versus host diseases (GVHD) and relapse following UCBT. Cell engineering techniques have been developed to circumnavigate the immaturity of the T cells, and include virus-specific cytotoxic T cells (VSTs), T cells transduced with disease-specific chimeric antigen receptor (CAR T cells) and regulatory T cell (Tregs) engineering. In this article, we review the advances in UCB ex vivo expansion and engineering to improve engraftment and reduce complications. As further research continues to find ways to overcome the current challenges, outcomes from UCBT will likely improve.

Current Status and Perspectives of Irradiation-Based Conditioning Regimens for Patients with Acute Leukemia Undergoing Hematopoietic Stem Cell Transplantation.

Acute myeloid leukemia and acute lymphoblastic leukemia are the most common indications for allogeneic hematopoietic stem cell transplantation. Total body irradiation (TBI) is an important part of conditioning regimens. TBI-based regimens offer advantages in sanctuary sites but are associated with significant risks of early and late side effects, including pulmonary toxicity, growth retardation, and second malignancy. TBI is also associated with technical problems, such as dose heterogeneity. With evolving techniques in radiation oncology, it is possible to focus the dose to the entire skeleton while sparing the rest of the body. This technique is called total marrow irradiation (TMI). TMI is able to deliver the same or higher doses to bone marrow while reducing toxicity. With the success of TMI, we are moving toward ultra-personalized conditioning. We review the clinical role of the irradiation-based regimens currently in clinical use, emphasizing on their strengths and limitations. Novel technologies with targeted irradiation accompanied by the modern imaging techniques and increased knowledge of the disease process can help us achieve our goal of maximum response with minimum toxicity.

Factors Underlying Racial Disparities in Sepsis Management.

Sepsis, a syndrome characterized by systemic inflammation during infection, continues to be one of the most common causes of patient mortality in hospitals across the United States. While standardized treatment protocols have been implemented, a wide variability in clinical outcomes persists across racial groups. Specifically, black and Hispanic populations are frequently associated with higher rates of morbidity and mortality in sepsis compared to the white population. While this is often attributed to systemic bias against minority groups, a growing body of literature has found patient, community, and hospital-based factors to be driving racial differences. In this article, we provide a focused review on some of the factors driving racial disparities in sepsis. We also suggest potential interventions aimed at reducing health disparities in the prevention, early identification, and clinical management of sepsis.

Multiple Liver Nodules Mimicking Metastatic Disease as Initial Presentation of Multiple Myeloma.

Multiple myeloma is a malignant clonal proliferation of plasma cells in the bone marrow preceded by monoclonal gammopathy of undetermined significance. Initial presentation of multiple myeloma as extramedullary spread in soft tissues particularly in the liver is uncommon. We report a case of a 74-year-old African American female who presented with epigastric pain, hematemesis, elevated alkaline phosphatase, and gamma-glutamyl transferase. Initial impression was peptic ulcer disease; however, ultrasound and CT scan of the abdomen showed multiple liver nodules and perihepatic lymphadenopathy suggestive of metastatic disease. Biopsy of the liver nodules showed CD138 and kappa light chain-restricted positive cells consistent with extramedullary spread of multiple myeloma to the liver. The patient achieved partial response after 6 months of treatment with Velcade, cyclophosphamide, and dexamethasone (VCD). Due to severe neutropenia from cyclophosphamide, regimen was switched to Velcade, Revlimid, and dexamethasone (VRD) which resulted to very good partial response in 1 year which eventually persisted after 4 years. No controlled prospective studies have defined the standard treatment for multiple myeloma with extramedullary spread particularly to the liver. Treatment of multiple myeloma with extramedullary disease follows guidelines for multiple myeloma.

Clinical outcomes of African American patients with advanced or metastatic non-small cell lung cancer on Nivolumab in a single community-based cancer center.

African Americans (AA) have the highest incidence and mortality rates with lung cancer. They are diagnosed at an earlier age with more advanced disease. Programmed cell death protein-1 inhibitor, Nivolumab, was approved as a second-line agent after failure of platinum-based therapy for advanced or metastatic non-small cell lung cancer (NSCLC). The original studies leading to the approval of Nivolumab had insufficient AA patients, thus there is still inadequate knowledge on treatment outcomes among AA patients. Our primary study endpoints were to determine the median overall survival, 1-year overall survival rate, median progression-free survival, and 1-year progression-free survival rate of patients with advanced or metastatic non-small cell lung cancer on Nivolumab. Our secondary study endpoints were to determine the overall tumor response rate, median time to response, median duration of response, and incidence of treatment-related adverse events of grade 3 or 4. In this retrospective study, we reviewed the charts of 38 patients, 29 of which were AA, with advanced or metastatic NSCLC who received Nivolumab from March 1, 2015 until November 30, 2017 from a single community-based cancer center and compared our results with historical data. Adenocarcinoma was the most common histology (71%) among all patients. Seven (18%) continued to use Nivolumab while 21 (55%) discontinued the treatment mainly due to progression of the disease. The median overall survival was 21.4 months (95% CI 13.5-27.4) and 17.6 months (95% CI 11.5-27.6) for all the patients and AA, respectively. Both have statistically significant difference (P < 0.001) compared to the historical studies of Borghaei et al. and Brahmer et al. At 1 year, the overall survival rate was 73% (95% CI 50-86) and 66% (95% CI 40-82) for all patients and AA, respectively. The median progression-free survival was also statistically significant (P < 0.001) between all the patients 6.3 months (95% CI 2.8-8), AA 6.0 months (95% CI 2.3-8.0), and the said historical studies. The 1-year progression-free survival rate was 23% (95% CI 10-39) and 28% (95% CI 12-47) for all patients and AA, respectively. Overall tumor response rate which includes complete and partial responses was 21% (95% CI 10-37) and 24% (95% CI 10-43) for all patients and AA, respectively. The median time to response was 3 and 2.8 months for all patients and AA, respectively. The median duration of response was 3.8 and 4.0 months for all patients and AA, respectively. Treatment-related adverse events of grade 3 or 4 were reported in 8 and 10% in all patients and AA, respectively, similar to the rates previously shown. AA patients with advanced or metastatic NSCLC on Nivolumab had increased overall survival and progression-free survival with similar grade 3 or 4 treatment-related adverse events. Providing adequate access to immunotherapy is indispensable to maximize survival benefit for AA patients.

Prospects of chimeric antigen receptor T cell therapy in ovarian cancer.

Despite advances in various chemotherapy regimens, current therapeutic options are limited for ovarian cancer patients. Immunotherapy provides a promising and novel treatment option for ovarian cancer. Recently, chimeric antigen receptor (CAR) T cell therapy has shown promising results in hematological tumors and current research is going on in various solid tumors like ovarian cancer. CAR T cells are genetically engineered T cells with major histocompatibility complex-independent, tumor-specific, immune-mediated cytolytic actions against cancer cells. Initial studies of CAR T cell therapy have shown promising results in ovarian cancer, but there are some obstacles like impaired T cell trafficking, lack of antigenic targets, cytokine release syndrome and most important immunosuppressive tumor microenvironment. Optimization of design, improving tumor microenvironment and combinations with other therapies may help us in improving CAR T cell efficacy. In this review article, we highlight the current knowledge regarding CAR T cell therapy in ovarian cancer. We have discussed basic functioning of CAR T cells, their rationale and clinical outcome in ovarian cancer with limitations.

Acute Left Internal Carotid Artery and Right Popliteal Artery Occlusion Related to Cisplatin-Gemcitabine Based Chemotherapy.

OBJECTIVES: The increased risk of thromboembolic complications with active cancer is well known. We present this case to highlight that chemotherapy may increase the risk of thromboembolic events even further in cancer patients. METHODS: We report a case of a 64-year-old male with Diffuse Large B-Cell Non-Hodgkin's Lymphoma who presented with left-sided headache and right calf pain two weeks after starting Rituximab/Gemcitabine/Cisplatin/Dexamethasone chemotherapy. Neurological examination was normal, but there was an absent right dorsalis pedis pulse. He subsequently developed left vision loss. CT angiogram of the head and neck revealed occlusion of his left internal carotid artery and poor opacification of the left ophthalmic artery. An angiogram of the right leg further revealed acute occlusion of the popliteal artery. RESULTS: The patient underwent intra-arterial Tissue Plasminogen Activator injection to his lower limb and was started on Low Molecular Weight Heparin. His vision gradually recovered with time. His chemotherapy regimen was changed to RICE (Rituximab, Ifosfamide, Carboplatin, Etoposide). CONCLUSION: Based on literature review, there are numerous similar presentations of arterial thromboembolism in patients on Cisplatin-based chemotherapy. A high index of suspicion for such events should be maintained for patients on chemotherapy presenting with unusual symptoms.

Prognostic Scoring Systems in Allogeneic Hematopoietic Stem Cell Transplantation: Where Do We Stand?

Allogeneic hematopoietic stem cell transplantation is a potentially curative treatment for many hematologic disorders. Maximizing the benefit of transplantation for disease control while minimizing the risk for associated complications remains the field's leading challenge. This challenge has prompted the development of multiple prognostic scoring systems over the last 2 decades. Prognostic scores can be used for informed decision making, better patient counseling, design of interventional trials, and analysis of prospective and retrospective data. They are also helpful in treatment allocation and personalization according to predicted risk. A better understanding of the molecular and cytogenetic features of the disease, along with the advent of novel therapies, has increased the need for reliable prognostication of which patients will benefit most from transplantation. Here we review the clinical role of the prognostic systems currently in clinical use, examining both their strengths and their limitations.