Metaplastic Breast Cancer: Characteristics and Survival Outcomes.

Objectives Metaplastic breast cancer (MBC) is a rare neoplasm accounting for <1% of all breast cancer. We evaluated the clinical characteristics and survival outcomes of MBC. Methods Patients diagnosed with pathologically proven MBC were reviewed from the institutional breast cancer database from 2000 to 2017. Results A total of 136 patients diagnosed with MBC were included in the study. The median age of the diagnosis was 60 years, and 60% of patients were stage II at diagnosis, and 22% were stage III. About two-thirds of the patients were triple-negative; 93% had nuclear grade III, and 25% had a lymphovascular invasion. Squamous differentiation (29%) was the most common histologic subtype, followed by the spindle subtype (21%). The most common distant metastases were lung (22%), followed by bone (13%). Moreover, 60% had a mastectomy, 19% had endocrine therapy, 58% had radiation, 51% received anthracycline-based chemotherapy, 26% had non-anthracycline chemotherapy, and 22% received no chemotherapy. In the entire cohort, the two-year overall survival (OS) and five-year OS were 79% and 69%, respectively, and the two-year progression-free survival (PFS) and five-year PFS were 72% and 61%, respectively. On multivariable analysis, the stage of MBC (stage III: hazard ratio (HR), 5.065 (95% confidence interval (CI), 1.02-25.27) (p=0.048)), poor functional status (Eastern Cooperative Oncology Group (ECOG) score, 2; HR, 24.736 (95% CI, 1.92-318.73) (p=0.014)), and distant metastasis to the brain (HR, 8.453 (95% CI, 1.88-38.04) (p=0.005)) and lung (HR, 42.102 (95% CI, 7.20-246.36) (p<0.001)) were significant predictors of decreased OS. Conclusions MBC demonstrated early disease progression and poor overall survival. The stage of MBC, decreased performance status, and metastasis to the lung and brain were independent poor prognostic factors.

Dosage Adjustments for Chemotherapy and Targeted Therapies in Colorectal and Pancreatic Cancer Patients with Hepatic Impairment.

There are many novel chemotherapeutic options and targeted therapies available for the treatment of colorectal and pancreatic cancer. Patients with these cancers often have hepatic impairment either from the metastasis to the liver or from the chemotherapy or targeted therapies used to treat the disease. It is important to describe the effects of these agents in patients with hepatic impairment. This article will review the dosage recommendations for the chemotherapy regimens and targeted therapies in colorectal and pancreatic cancer patients in the setting of hepatic impairment.

Management of Atrial Fibrillation in Patients on Ibrutinib: A Cleveland Clinic Experience.

Background Ibrutinib is a Bruton's tyrosine kinase inhibitor, which is United States Food and Drug Administration (FDA)-approved for chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström's macroglobulinemia. Ibrutinib is associated with atrial fibrillation and bleeding events. Our aim is to determine the management of prior atrial fibrillation when starting ibrutinib, as well as ibrutinib-induced atrial fibrillation. Our focus is on which rate and rhythm control strategies to use and decisions regarding the use of antiplatelet and anticoagulation agents. Materials and Methods We conducted a retrospective descriptive study of case records over a three-year period from February 2014 to February 2017. We reviewed 597 patient charts from the Cleveland Clinic database. Ibrutinib was started in 43 patients. Of those, 10 had atrial fibrillation prior to starting ibrutinib and four developed atrial fibrillation while on ibrutinib. Data was collected for demographic details, co-morbid conditions, CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, prior stroke, transient ischemic attack or thromboembolism, vascular disease, age, and sex category) score, HAS-BLED (hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, and drugs or alcohol) score, and drugs used for antiplatelet effects, for anticoagulation, and for rate and rhythm control. Outcomes for embolic and bleeding events were assessed. Results Of the 43 patients, 14 (32.5%) had or developed atrial fibrillation; 10 (23.26%) had prior atrial fibrillation, and four (9.30%) developed atrial fibrillation after starting ibrutinib. The majority were males (71.42%) and Caucasian (71.42%). The disease breakdown was chronic lymphocytic leukemia (42.86%), mantle cell lymphoma (50%), and Waldenström's macroglobulinemia (7.14%). The mean starting dose of ibrutinib in patients with prior atrial fibrillation was 569 mg and for patients who developed atrial fibrillation was 420 mg. In the 10 patients who had atrial fibrillation prior to ibrutinib, all 10  were on beta blockers, one was on diltiazem, three were on amiodarone, one was on flecainide, one was on digoxin, and one was on Tikosyn® (Pfizer, Inc., New York, NY). The ibrutinib dose was decreased/discontinued in two patients. In patients who developed atrial fibrillation after starting ibrutinib, three were on beta blockers, two on amiodarone, and one on Tikosyn. Ibrutinib was discontinued in one patient. In patients who had prior atrial fibrillation, three were on warfarin, one on enoxaparin, and two on apixaban. In three patients, aspirin and enoxaparin were discontinued. In patients who developed atrial fibrillation after starting ibrutinib, enoxaparin was given to two and apixaban to one. None of the patients had a stroke, transient ischemic attack (TIA), or bleeding events. Conclusions From our study, we concluded that ibrutinib can be safely given in the presence of atrial fibrillation, and when atrial fibrillation was induced, we further concluded that beta blockers were the preferred agents for rate control. Ibrutinib has many drug interactions with other rate and rhythm control agents; hence, their use was lower. When atrial fibrillation was uncontrolled, ibrutinib was temporarily held and then cautiously restarted. The decision to start or adjust anticoagulation depended on the bleeding and stroke risks as assessed by their physicians.

New anticoagulants in cancer patient treatments.

Venous thromboembolism (VTE) is a common complication of cancer patients. Initiation of anticoagulant treatment is of vital importance once a diagnosis of VTE has been established. Unfractionated heparin and low-molecular-weight heparins (LMWH) have been the mainstay for in-hospital-based prophylaxis, both postsurgically and on medicine floors, and for the acute management of VTE. The current international guidelines, including American Society of Clinical Oncology, the American College of Chest Physicians, the European Society of Medical Oncology, and the International Society of Thrombosis and Hemostasis, recommend the use of LMWH monotherapy for the long-term management of cancer patients with established acute symptomatic VTE. Although LMWHs have become the preferred treatment for patients with cancer, problems with its use have prompted clinicians to seek newer antithrombotic agents.

Primary Cardiac Sarcoma: 25-Year Cleveland Clinic Experience.

BACKGROUND: Cardiac sarcomas are rare and have a poor prognosis. The median overall survival remains dismal and has been reported ranging from 6 months to a few years. Primary cardiac sarcoma is the most common malignant tumor comprising approximately 95% of all malignant tumors of the heart. METHODS: We conducted a retrospective chart review in a single institution of patients diagnosed between March 1988 and April 2013. A total of 42 patients were identified. The following variables were studied: age at diagnosis, year of diagnosis, sex, stage, site of tumor involvement, tumor histology, grade, treatment modality, type of chemotherapy, and survival outcome. The overall median follow-up time was 49.5 months. RESULTS: The most common histologic type was angiosarcoma. Overall estimated median survival (EMS) was 25 months. Tumors involving the left side of the heart and pericardium demonstrated better survival. Patients who received multimodality treatment (any combination of surgery, radiation therapy, and chemotherapy) had an EMS of 36.5 months compared with 14.1 months for patients treated with surgery, radiation therapy, or chemotherapy only (P=0.05). CONCLUSIONS: Cardiac sarcoma is a lethal tumor with an EMS of 25 months. The tumor histology could be a possible predictor of better survival. Although selection bias may have been present, multimodality therapy (surgery, radiation therapy, and chemotherapy) was associated with improved survival.

Gene expression profiling for early-stage NSCLC.

Lung cancer is the leading cause of cancer-related death in both developed and developing countries with unacceptably high mortality even for early-stage cancers. Present guidelines do not recommend adjuvant chemotherapy for stage I non-small cell lung carcinoma and prompts a search for a prognostic marker that would separate stage I patients into 2 groups, those who would benefit and those who would not benefit from adjuvant treatment. Studies during the last decade showed that the gene expression profiling can be the biomarker being sought. Many gene expression profiling have been found and reported from the analysis of surgical specimens of resected lung cancers during the last decade, and many of them had been shown to have an excellent predictive accuracy. These profiles used in the studies had not only different gene combinations but also different number of genes and methods of identification. Researchers have used microarray assays, RT-quantitative polymerase chain reaction, and more recently microRNA-based techniques to achieve this goal. Unfortunately, most of the profiles were not sufficiently validated and/or were not used in prospective phase III studies. This review focuses on major studies in the field, future prospects, as well as the lessons learned so far. It is shown that the gene expression profiles have a good chance of being implemented in future everyday practice.

Practical recommendations on incorporating new oral anticoagulants into routine practice.

The use of new oral anticoagulants (NOACs) is expected to rise significantly in upcoming years. Therefore, it is important to understand the potential uses, side effects, and management of these agents in routine practice. NOACs have major pharmacologic advantages over warfarin, including a rapid onset and offset of action, fewer drug interactions, and predictable pharmacokinetics. These agents are gaining popularity among both physicians and patients because of their ease of administration and the advantage of eliminating the requirement for regular coagulation monitoring. NOACs work to prevent and treat thrombosis by targeting either thrombin (as with dabigatran) or factor Xa (as with rivaroxaban and apixaban). In this review, we discuss practical recommendations for the use of NOACs and the risks and benefits of incorporating them into routine practice.

A clinical review of small-cell carcinoma of the urinary bladder.

Small-cell carcinoma of the urinary bladder is a rare and aggressive type of bladder cancer that has a poor prognosis. The incidence has been gradually increasing because of the aging population. Owing to its rarity there are no available treatment guidelines. Several retrospective studies and 1 prospective study have provided some insight into therapy for this disease. A multimodal approach that includes chemotherapy, local radiation therapy, and definitive surgery in resectable cases appears to be an optimal management approach.

Immune thrombocytopenia in adults: an update.

Immune thrombocytopenia (ITP) in adults is a chronic disease resulting from increased platelet destruction and impaired platelet production. Splenectomy remains the most effective and durable treatment in cases that are refractory to first-line therapy, but its use has declined because of the availability of alternate medical therapy, the associated risk of infection, and concern for surgery-related complications. Rituximab (Rituxan) may be an effective alternative but carries the risk of immunosuppression.

Targeted therapy for lung cancer.

Lung cancer is considered the number one killer among all cancers. Recent observations have altered the treatment paradigm for non-small-cell lung cancer (NSCLC). The discovery of activating mutations in the epidermal growth factor receptor and anaplastic lymphoma kinase positivity has made personalized treatment for NSCLC more feasible. Both erlotinib and crizotinib have been shown to be effective and safe for subgroup populations, and now personalized treatment for nonsquamous NSCLC has progressed even further. New tyrosine kinase inhibitors are being tested, resistant mutations are being studied, and new detection systems are being incorporated; all these developments will make the detection and treatment of the deadliest cancer more affordable, practical, and effective. The National Comprehensive Cancer Network has already incorporated these new developments into their guidelines for advanced nonsquamous NSCLC.

Hepatitis B reactivation in cancer patients: role of prechemotherapy screening and antiviral prophylaxis.

Hepatitis B virus (HBV) infection is a potentially life-threatening condition that can be effectively prevented by vaccination. In the United States, more than 1.5 million people are infected with HBV, and that number continues to rise with the arrival of immigrants from HBV-endemic countries. Cancer is the second leading cause of death in the United States; 1 in 2 men and women will be diagnosed during their lifetime, and a large proportion of them will require chemotherapy. Chemotherapy-induced immunosuppression can result in HBV reactivation in asymptomatic HBV carriers or patients with resolved HBV infection, causing severe morbidity and mortality. The rate of HBV reactivation depends on several factors, including host and viral factors, and varies from 3-88%. Mortality rates in HBV reactivation range from 23-71%. However, a recent US survey showed that 20% of practicing oncologists never perform any type of HBV screening before the initiation of chemotherapy, and less than 40% perform HBV screening in patients who have high-risk factors for HBV or a history of hepatitis. Given the magnitude of this clinical problem, it is very important to increase awareness among physicians regarding this potentially life-threatening complication. In this article, we review the current understanding of the problem, discuss the existing guidelines from professional societies, and outline a management plan.

Phosphatase inhibitor, sodium stibogluconate, in combination with interferon (IFN) alpha 2b: phase I trials to identify pharmacodynamic and clinical effects.

Since sodium stibogluconate (SSG) inhibited phosphatases including SHP-1 and augmented anti-tumor actions of IFN-α2b in vitro and in mice, two Phase I trials of SSG/IFN-α2b combination were undertaken to evaluate safety and target inhibition. Escalating doses of SSG (200-1200 mg/m2) and fixed doses of IFN-α2b (3x106 units/m2) with or without chemotherapy (dacarbazine, vinblastine, cisplatin) were evaluated for side effects and impact on SHP-1 phospho-substrates and IFNα-stimulated-genes (ISGs) in peripheral blood in 40 patients with metastatic melanoma, soft tissue sarcomas, gastrointestinal stromal tumors, and breast or colorectal carcinomas who did not have other established treatment options. Common adverse events were bone marrow suppression, fatigue, gastrointestinal upset, and asymptomatic lipase elevation (n=13); the latter was dose related and mostly after 10d of SSG/IFN-α2b in combination. Levels of SHP-1 substrates (pSTAT1, pSTAT3, pLck and pSlp76) were increased (up to 3x) in peripheral blood cells following SSG with no potentiation by combination with IFN-α2b. Representative ISGs in peripheral blood were induced after IFN-α2b at 4 and 24 hrs with selective modulations by combination. The median time on trials was 2.3 months (10-281d) with no objective regression of disease. Alive at 1y were 17/40 (43%) patients and after 2y were 8/40 (20%) following treatment initiation. These data demonstrate that SSG impacted signal molecules consistent with PTP inhibition and was tolerated in combination with IFN-α2b. Phase II investigations of SSG could safely utilize doses of up to 1200 mg/m2 of SSG for up to 10d alone or in combination with IFN-α2b with or without chemotherapy.

Haematuria as an uncommon initial presenting symptom of metastatic squamous cell carcinoma (SCC) to kidney.

A 47-year-old female presented with a 2-week history of painless haematuria. Urine dipstick showed moderate leucocytes. Blood and urine cultures were negative and cytology was negative for malignant cells. Flexible cystoscopy was negative for any bladder pathology. An ultrasonogram of the abdomen showed a mass in the left kidney. CT showed a mass-like lesion within the left kidney suspicious for renal carcinoma, and cavitary lesions in both lungs. Biopsy of the lung showed clusters of atypical cells suspicious for squamous cell carcinoma (SCC), and left kidney lesion showed malignant cells derived from SCC. A whole body positron emission tomography/CT showed lesions in the lungs, left kidney and skeleton. Complete clinical examination, laboratory and imaging studies did not reveal any site of primary tumour in any part of the body. Haematuria is a very unusual initial presentation of metastatic tumour to kidney.

BOOP as a rare complication of gemcitabine therapy.

Gemcitabine is commonly used in combination with carboplatin in patients with advanced non-small-cell lung cancer (NSCLC). Gemcitabine has good clinical activity against NSCLC and is well tolerated by the patients. Myelosuppression is its dose-limiting toxicity. A potential side effect of gemcitabine is pulmonary toxicity. Among pulmonary toxicities, pneumonia, bronchospasm, acute respiratory distress syndrome, pleural effusion and interstitial pneumonitis are well documented, but bronchiolitis obliterans organising pneumonia (BOOP) is a rarely observed adverse effect of gemcitabine therapy. The authors report a female patient who presented with progressively worsening shortness of breath, low-grade fever and non-productive cough 10 days after completion of gemcitabine therapy for poorly differentiated invasive squamous cell carcinoma of lung with bone metastases. Histopathology of a transbronchial biopsy established the diagnosis of BOOP. Treatment with intravenous steroids resulted in prompt clinical improvement, but the patient later died of progression of her lung cancer.

Pulmonary toxicities of tyrosine kinase inhibitors.

The incidence of pulmonary toxicities with the use of tyrosine kinase inhibitors (TKIs) is not very high; however, various case reports and studies continue to show significant variability in the incidence of these adverse events, ranging from 0.2% to 10.9%. Gefitinib and erlotinib are orally active, small-molecule inhibitors of the epidermal growth factor receptor tyrosine kinase that are mainly used to treat non-small cell lung cancer. Imatinib is an inhibitor of BCR-ABL tyrosine kinase that is used to treat various leukemias, gastrointestinal stromal tumors, and other cancers. In this article, we review data to identify the very rare but fatal pulmonary toxicities (mostly interstitial lung disease) caused by these drugs.

Pulmonary toxicities of biologics: a review.

With the advancement of research in cancer treatment more and more drugs are being introduced for the treatment of cancer. In this review study, we have tried to look at some of the relatively newly introduced drugs, commonly referred to as biologics. The aim of this study was to review the very rare but fatal pulmonary toxicities (mostly interstitial lung disease) caused by these drugs. The drugs that were reviewed are rituximab, cetuximab, bevacizumab, alemtuzumab, and trastuzumab. This review basically aims at presenting a basic introduction (mechanism of action and indications of use) of these drugs followed by a summary of the incidence, various clinical presentations, diagnosis, treatment options, and outcome of patients around the world who presented with pulmonary toxicities caused by these drugs.

A renal mass in a patient with melanoma.

A 61-year-old man presented to the emergency room with significant weight loss. Laboratory analysis revealed elevations in blood urea nitrogen, creatinine, and white blood cell count. Computed tomography imaging showed a large, infiltrative mass in the right renal vein, with metastasis to the brain. Biopsy of soft tissue mass and kidney revealed positive staining for malignant melanoma. Malignant melanoma to the kidney is extremely rare, and imaging modalities alone cannot differentiate neoplasms in the kidney. It is therefore necessary to use specific immunocytochemical staining along with imaging modalities to make a specific diagnosis when the primary origin of the tumor is unknown.