Trends in Breast Cancer Incidence and Mortality in the United States From 2004-2018: A Surveillance, Epidemiology, and End Results (SEER)-Based Study.

The incidence and mortality data for patients with breast cancer in the United States are important to healthcare administrators for planning healthcare measures such as screening mammograms. In this study, we examined breast cancer incidence and incidence-based mortality in the United States from 2004-2018 using the Surveillance, Epidemiology, and End Results (SEER) database. We reviewed 915,417 cases of breast cancer diagnosed between 2004 and 2018. Overall, the data showed an increased incidence rate of breast cancer among all races and a decreased mortality rate among all races. Breast cancer incidence rates increased by 0.3% (95% CI, 0.1, 0.4, p<0.001) per year over the study period. Breast cancer incidence rates increased for all age, race, and stage groups except for stage regional, which showed a statistically significant decrease in the incidence of -0.9% (95% CI, -1.1, -0.7, p<0.001). The highest decrease in mortality was observed among white patients, with an overall statistically significant decrease in rates by -14.3% (95% CI, -18.1, -10.4, p <0.001). The highest decrease in rates was observed between 2016 and 2018: -48.6 (95% CI, -52.6, -44.3, p <0.001). In black/African American patients, the overall incidence-based mortality decreased by -11.6% (95% CI -15.9, -7.1 p <.001), with the highest decrease in rates observed between 2016 and 2018 with a decrease of -51.3% (95% CI -56.6, -45.3, p <0.001). In Hispanic Americans, the overall incidence-based mortality decreased by -12.3% (95% CI -16.9, -7.4, p <.001), which is lower than in white Americans.

Coagulation and anticoagulation in COVID-19.

COVID-19 has become a pandemic in the United States and worldwide. COVID-19-induced coagulopathy (CIC) is commonly encountered at presentation manifested by considerable elevation of D-dimer and fibrin split products but with modest or no change in activated partial thromboplastin time and prothrombin time. CIC is a complex process that is distinctly different from conventional sepsis-induced coagulopathy. The cytokine storm induced by COVID-19 infection appears to be more severe in COVID-19, resulting in development of extensive micro- and macrovascular thrombosis and organ failure. Unlike conventional sepsis, anticoagulation plays a key role in the treatment of COVID-19, however without practice guidelines tailored to these patients. We propose a scoring system for COVID-19-coagulopathy (CIC Scoring) and stratification of patients for the purpose of anticoagulation therapy based on risk categories. The proposed scoring system and therapeutic guidelines are likely to undergo revisions in the future as new data become available in this evolving field.

Emergence of overt myeloma in a patient with chronic lymphocytic leukemia on ibrutinib therapy.

Ibrutinib is approved for chronic lymphocytic leukemia (CLL). However, its role in the treatment of multiple myeloma (MM) is not clear and is under investigation. We report a case of CLL that developed MM while on therapy with ibrutinib indicating that this drug may not be active against MM.

Anticoagulants for the treatment of venous thromboembolism in patients with cancer: A comprehensive systematic review, pairwise and network meta-analysis.

Cancer-associated venous thromboembolism (VTE) is associated with high VTE recurrence and bleeding. We included all randomized clinical trials that evaluated the efficacy and safety of various anticoagulants in cancer-associated VTE. Trial-level data were extracted from 13 trials. Aggregate odds ratios (ORs) were calculated using direct and network meta-analysis. The primary outcome was VTE (pulmonary embolism and/or deep vein thrombosis) recurrence. Secondary outcomes were major bleeding and all-cause mortality. We identified 13 trials with 4869 patient-years of follow-up (6595 total patients; mean age 62.4 ± 12.2; 50.4 % female; 17.7 % hematological malignancies). The most common cancer type was colorectal and 48 % had metastatic cancer at baseline. Compared to vitamin-K-antagonists (VKAs), non-vitamin-K-antagonist-oral-anticoagulants (NOACs) were associated with significantly reduced VTE recurrence (OR, 0.58; 95 % CI, 0.40-0.83) and reduced major bleeding risks (OR, 0.56; 95 % CI, 0.35-0.91). However, no differences were observed in the subgroup analysis of patients with active cancer. Although NOACs were associated with reduced VTE recurrence compared with low-molecular-weight-heparin (LMWHs) (OR, 0.46; 95 % CI, 0.25- 0.85), there was a significant increased major bleeding in high-quality trials. LMWHs were associated with significantly reduced VTE recurrence compared with VKAs (OR, 0.52; 95 % CI, 0.39-0.71) and similar bleeding risks. Conclusions: Among patients with cancer-associated VTE, NOACs were associated with significantly reduced VTE recurrence and bleeding compared with VKAs, however, with similar outcomes in the active cancer population. NOACs were associated with reduced VTE recurrence but higher bleeding risks compared with LMWHs. LMWHs were associated with significantly reduced VTE recurrence and similar bleeding compared with VKAs.

High Ki67 proliferation index but not cell-of-origin subtypes is associated with shorter overall survival in diffuse large B-cell lymphoma.

BACKGROUND: CD10, BCL6, and MUM1 are commonly used immunohistochemical stains for classifying diffuse large B-cell lymphoma (DLBCL), which is useful in predicting outcome. Conflicting reports of the prognostic value of other markers such as BCL2, CD23, and Ki67 proliferation index have been reported. Our objective was to correlate these immunostains and Hans classification with response to therapy and overall survival. MATERIALS AND METHODS: A retrospective study of patients diagnosed with DLBCL from 2008-2014 at a tertiary-care cancer hospital. The slides with the IHC stains were reviewed by two independent pathologists. The clinical outcomes--assessed independently--were response to therapy and overall survival. The treatment response evaluation was based on the new Lugano classification. Statistical analyses were conducted using the Fisher's exact test and Kaplan-Meier survival curves. Significance was set at P < 0.05. RESULTS: Forty-one patients were included in the study with a known Hans classification, available clinical data, and at least 5-year follow-up. CD10 immunostain was reported in all patients, whereas CD23 was the least reported in only four patients. No significant association was observed between CD10, BCL6, MUM1, BCL2, and both Response to therapy and overall survival. Owing to few cases reported CD23 immunostain, further analysis of association is not reported. High Ki67 proliferative index of >80% was statistically significantly associated with shorter overall survival and not statistically significant associated with no response to therapy. Hans classification subtypes were not predictive in regard to therapy response. CONCLUSION: High Ki67 expression (>80%) was associated with shorter overall survival in DLBCL. Hans classification subtypes were not predictive.

Prognostic Utility of Tumor-Infiltrating Lymphocytes in Noncolorectal Gastrointestinal Malignancies.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and mismatch repair gene mutation (MMR) status are emerging biomarkers in immunotherapy. MMR status and TILs have significant clinical implications with regard to treatment with checkpoint inhibitors. We designed a study to determine the frequency and prognostic utility of TILs and MMR in advanced unresectable noncolorectal gastrointestinal (NCGI) malignancies. METHODS: This is a retrospective cohort study of patients who were diagnosed with advanced noncolorectal gastrointestinal tumors. Biopsy specimens were tested for MMR status by immunohistochemistry along with evaluation of TILs. Kaplan-Meier analysis was performed to determine the impact of TILS and MMR on survival. RESULTS: We analyzed 146 patients; the mean age at diagnosis was 66.4 ± 11.2 years. 65.8% patients were male, and 62.3% patients had stage 4 disease. All cases had proficient MMR status. The percentage of patients with TILs >5 was 50.7%. There was no statistically significant difference in median overall survival (OS) by TILs when stratified by stage of tumor. When stratified by type of tumor, median OS by TILs level was significantly different for hepatocellular cancers (⩽5 TILs, 86 days versus >5 TILs 312 days, P = .031). CONCLUSIONS: Our study suggests that MMR-deficient tumors are quite rare in advanced NCGI malignancies. More than 5 TILs per high power field, evaluated simply on a routine hematoxylin and eosin-stained glass slide confer a better prognosis to most noncolorectal gastrointestinal malignancies, especially hepatocellular carcinoma. This has immense clinical utility with regard to eligibility for immunotherapy.

Autoimmune Hepatitis: A Risk Factor for Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a very aggressive and lethal tumor, which arises from the epithelial cells of bile ducts. CCA comprises about 3% of all gastrointestinal malignancies and its incidence is on the rise in the recent years. Anatomically, it is classified into intrahepatic, perihilar, or extrahepatic (distal) CCA. There are a number of risk factors associated with CCA including primary sclerosing cholangitis, fibropolycystic liver disease, parasitic infection, viral hepatitis, chronic liver disease, and genetic disorders like Lynch syndrome. Autoimmune hepatitis is also recently reported to have an association with development of CCA. We report an interesting case of perihilar CCA in the setting of autoimmune hepatitis along with a literature review. This case highlights the importance of early treatment and close clinical follow-up of patients with autoimmune hepatitis for development of CCA.

Thrombotic thrombocytopenic purpura presenting as acute coronary syndrome.

In patients presenting with thrombotic thrombocytopenia purpura and non-ST elevation myocardial infarction, prompt initiation of plasma exchange takes precedence over other invasive diagnostic procedures for coronary artery disease. Such procedures should be delayed until clinical condition and laboratory parameters have been stabilized.

Safety and efficacy of radioimmunotherapy (RIT) in treatment of non-Hodgkin's lymphoma in the community setting.

INTRODUCTION: Radioimmunotherapy (RIT) is a unique therapeutic modality that combines biologic and radiolytic mechanisms to induce tumor kill. RIT is underutilized in the community outpatient setting. METHODS: This is an institutional review of patients treated with RIT at St. John Hospital and Medical Center (SJH&MC) 2003-2011. RIT agents were dosed according to recommended guidelines. Response was assessed using the Revised Response Criteria for Malignant Lymphoma and toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events. The primary aim was to assess overall response rate (ORR) and overall survival (OS). The secondary aim was to assess the impact of variable host and disease factors on the ORR to RIT and OS. RESULTS: Forty-eight patients were treated with RIT within the specified period at SJH&MC; of which 52% with follicular lymphoma (FL) and 46% with diffuse large B cell lymphoma (DLBCL). The majority of patients had relapsed or refractory disease (98%). Median duration of follow-up was 17 months. The ORR was 73% with 44% complete remission (CR) rate and OS of 48 months. The ORR was 79% with 58% CR rate and OS of 82 months among FL patients. Among DLBCL patients, the ORR was 65% with 30% CR rate and OS of 39 months. Response to last therapy before RIT was the only significant predictor of response to RIT and a significant predictor of OS in multivariate analyses. Prior exposure to EBRT did not predict response or survival in multivariate analyses. Toxicity was manageable and predominantly hematologic. CONCLUSIONS: RIT is effective and feasible for use in the community outpatient setting. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Patients with B-cell NHL can safely receive RIT close to home. With some coordination of effort, it is not difficult for community-based cancer centers to implement this treatment modality.

Primary Cardiac Lymphoma: Lessons Learned from a Long Survivor.

Primary cardiac lymphoma (PCL) is a rare neoplasm that involves the heart, pericardium, or both. Patients with PCL have median survival of approximately 7 months. We report a 63-year-old woman with PCL treated with chemoimmunotherapy but relapsed 7 years later. She received automated implantable cardioverter-defibrillator (AICD) prophylactically shortly after the diagnosis. She presented with a breast recidive 7 years after initial diagnosis and died of relapsed small cell lung cancer. As many patients with PCL die early in the disease course due to life-threatening arrhythmias, preemptive implantation of AICD may improve mortality and prevent early death. Chemoimmunotherapy is effective in inducing remission in patients with PCL. Late and unusual pattern of relapse may be more frequent in patients with PCL and should be explored further. This case presents one of the longest surviving patients with PCL reported in the literature.

Modulation of deoxycytidine kinase (dCK) and glycogen synthase kinase (GSK-3ß) by anti-CD20 (rituximab) and 2-chlorodeoxyadenosine (2-CdA) in human lymphoid malignancies.

BACKGROUND: The combination of rituximab and 2-CdA is an effective therapy for B-cell tumors. However, the molecular mechanisms and enzymatic pathways involved in the interaction between the two agents are not fully understood. In this study, we provide molecular evidence for positive interaction between these two agents with resultant therapeutic benefit. METHODS: Efficacy of the R-2CdA regimen was evaluated in thirteen patients with B-cell tumors (9 CLL; 3 WM and 1 FL), in vitro against 3 lymphoma cell lines and in a xenograft mouse model. Treatment-induced changes involving phenotype, kinase activity and protein expression were assessed in vitro and in the mouse xenograft tumors. The interaction between RTX and 2-CdA was analyzed using the multiple comparison method, Tukey's honestly significant difference (HSD). For the clinical and animal data, survival functions were estimated using the Kaplan-Meier method and compared by the log-rank test. P-values <0.05 were considered statistically significant. All statistical analyses were evaluated using GraphPad Prism 4 (San Diego, CA). RESULTS: 9 of 12 (75%) evaluable patients responded to the R-2-CdA regimen with median duration of response of 34 months. Median survival of patients from diagnosis and from completion of R-2-CdA treatment was 13.3 and 7.9 years, respectively. In vitro, the combination was effective in all 3 cell lines of lymphomas but with higher sensitivity in the follicular lymphoma cell line. The combination was also effective in the WSU-WM-SCID xenograft model with dose-dependent response and synergistic benefit. All animals were tumor-free for up to 120 days post 2 cycles of this regimen. Rituximab induced activation of deoxycytidine kinase (dCK), p38 mitogen activated protein kinase (p38MAPK) and glycogen synthase kinase-3ß (GSK-3ß) in the xenograft WSU-WM tumors. Chemical inhibition of p38MAPK led to inhibition of the GSK-3ß phosphorylation suggesting that GSK-3ß is regulated by p38MAPK in this model. CONCLUSION: Collectively, our studies show concordance between the activity of R-2-CdA in vitro, in human and in WSU-WM xenograft model attesting to the validity of this model in predicting clinical response. Modulation of dCK and GSK-3ß by rituximab may contribute to the positive therapeutic interaction between rituximab and 2-CdA.

Phase II Study of Gemcitabine and Docetaxel Combination in Patients with Previously Treated Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck.

Purpose. To explore the safety and efficacy of gemcitabine and docetaxel (GEMDOC) in previously treated patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods. Patients with advanced SCCHN previously pretreated with one or two lines of palliative chemotherapy were treated with gemcitabine and docetaxel until disease progression. Results. Thirty-six patients were enrolled, and 29 were response evaluable. 16 (55%) experienced clinical benefit (response or stable disease). Six (21%) patients achieved partial response (PR), none achieved complete response (CR), and the overall response rate (ORR) was 21% (95% CI: 0.10-0.38). Ten (28%) patients had stable disease. The median response duration (RD) for the 6 PR patients was 3.2 months (80% CI: 2.0-6.1 months). Median overall survival was 4.2 months (95% CI: 2.4-7.0 months). Among the 33 treated patients: 13 (39%) patients had grade 3-4 anemia, 10 (30%) had grade 3-4 neutropenia. Conclusion. The study drugs were relatively safe, and the clinical benefit (PR + SD) rate was 55%. However, the efficacy objective for this regimen was not met. Given the good safety profile, further investigation of this regimen with the addition of a targeted agent may lead to better efficacy.