Cancer stem cell assay-guided chemotherapy improves survival of patients with recurrent glioblastoma in a randomized trial.

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors. In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = 0.010) as per interim efficacy analysis. The ChemoID assay-guided group has a significantly lower risk of death (hazard ratio [HR] = 0.44; 95% CI, 0.24-0.81; p = 0.008). Results of this study offer a promising way to provide more affordable treatment for patients with rGBM in lower socioeconomic groups in the US and around the world.

A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors.

INTRODUCTION: Brain metastases (BM) are associated with dismal prognosis, and there is a dearth of effective systemic therapy. In this study, patients with BM from multiple solid tumors were identified from TriNetX databases, their clinicopathological features were evaluated, and the effects of immune checkpoint inhibitor (ICI) therapy were assessed. METHODS: Variables, including median overall survival (OS), Eastern Cooperative Oncology Group (ECOG) performance status, primary diagnosis, and date of diagnosis, were retrieved from TriNetX, a real-world database. Kaplan-Meier plots and log-rank tests were applied to assess significance of differences in survival. Hazard ratio (HR) and 95% confidence interval (CI) values were calculated. All patient data were deidentified. RESULTS: A total of 227,255 patients with BM were identified in the TriNetX database; median OS was 12.3 months from initial cancer diagnosis and 7.1 months from development of BM. OS of BM from nonsmall-cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), melanoma, and renal cell carcinoma (RCC) were 8.7, 14.7, 17.8, and 15.6 months, respectively. After matching patient baseline characteristics, OS of cohorts with or without exposure to ICIs was evaluated. For all types of cancer, median OS durations for the ICI and no-ICI cohorts were 14.0 and 7.9 months, respectively (HR: 0.88; 95% CI: 0.85-0.91). More specifically, OS was remarkably prolonged in patients with NSCLC (14.4 vs. 8.2 months; HR: 0.86; 95% CI: 0.82-0.90), TNBC (23.9 vs. 11.6 months; HR: 0.87; 95% CI: 0.82-0.92), and melanoma (27.6 vs. 16.8 months; HR: 0.80; 95% CI: 0.73-0.88) if patients had exposure to ICIs. In contrast, there was no significant difference in OS of patients with RCC treated with and without ICIs (16.7 vs. 14.0 months; HR: 0.96; 95% CI: 0.86-1.10). CONCLUSIONS: Overall, BM indicates poor patient outcome. Treatment with ICIs improves survival of patients with NSCLC, TNBC, and melanoma and BM; however, no significant improvement was observed in RCC. Investigations to identify prognostic features, oncogenomic profiles, and predictive biomarkers are warranted.

Bone marrow involvement with Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous tumour. Most tumours occur in the head and neck, extremities or torso and 36% of them involve the face. Bone marrow involvement in MCC is rare and to our knowledge only nine cases reported in the English literature. Bone marrow biopsy is not usually performed to stage MCC; thus, the true incidence of bone marrow involvement may be under-reported. The majority of the cases reported in the literature have some form of immunosuppression, which suggests a strong association. We report a case of extensive bone marrow involvement from MCC in an 80-year-old Caucasian woman with a history of rheumatoid arthritis treated with adalimumab, methotrexate and prednisone. It may be prudent to include bone marrow biopsy in the staging of MCC in immune-compromised patients.

Thrombotic thrombocytopenic purpura (TTP) following coronary artery bypass: case series and review of the literature.

We reviewed 10 cases of thrombotic thrombocytopenic purpura (TTP) following cardiac surgery since November 1998. The object of the study was to define the natural history of post-CABG-TTP and to assess response to therapy. All patients underwent CABG; four also underwent aortic valve replacement and six mitral valve replacement. Eight patients had mental status changes and/or unexplained fever. All patients received plasmapheresis ranging from 5 to 24 days and nine required hemodialysis or continuous renal replacement therapy. All had significant improvement in their platelet count, LDH, renal function, and mental status changes at discharge. None of the five surviving patients has relapsed at follow-up ranging from 8 months to 6 years. Early recognition of this syndrome and early institution of plasmapheresis are important for a favorable outcome.

Geographic access and age-related variation in chemotherapy use in elderly with metastatic breast cancer.

Significant age-related variation in chemotherapy use has been observed among elderly patients with metastatic breast cancer (MBC), which may be partly attributable to geographic access factors such as local area physician practice culture and local health care system capacity. The purpose of the paper was to examine how age may modify the effect of geographic access on chemotherapy use in elderly patients with MBC. This was a retrospective cohort study based on the surveillance, epidemiology, and end results-Medicare-linked database of 1992-2002. Chemotherapy use was defined as at least one chemotherapy-related claim within 6-month post-diagnosis. Geographic access to cancer care was measured by four variables: patient travel time to the nearest oncologist practice, local area per capita number of oncologists, local area per capita number of hospices, and local area chemotherapy rate. Using multivariate logistic regression model, both aggregate models with interaction terms and subgroup analyses were conducted. Among 4,533 elderly with MBC, 30.16 % used chemotherapy. Chemotherapy use decreased with age. Both the aggregate model with interaction terms and the subgroup analysis showed that local area chemotherapy rate was positively associated with chemotherapy use (P = .0004 in the whole group; in the subgroup analyses, P < .0001, P = .0006, P = .0006, P = .18, P = .026, respectively). In addition, subgroup analysis showed that, among patients aged 85+ years old, local area oncologist supply was negatively associated with chemotherapy use (P = .028). The impact of geographic access to cancer care is the greatest among the oldest group, for whom the clinical evidence is the least certain.

Cancer incidence in elderly West Virginians.

West Virginia has one of the oldest populations in the nation. Cancer is a common disease among the elderly. With the projected growth of the elderly population (defined as 65 years and older), cancer will become a major public health burden. This article provides a summary of cancer incidence in elderly West Virginians. Incidence data were obtained from the West Virginia Cancer Registry. Approximately 6,262 elderly persons are diagnosed with some form of reportable cancer in West Virginia each year. Among those aged 65 and older, the four leading primary cancer sites in the order of their relative frequency were lung and bronchus cancer (21.8%), prostate cancer (14.6%), colorectal cancer (12.7%), and female breast cancer (9.6%). In general, the burden of cancer was greater in elderly men than in elderly women. Knowledge of the epidemiology of cancer in the elderly can potentially help guide statewide cancer prevention and control efforts and be used for anticipating future health care needs in the state.

Niacin induced coagulopathy as a manifestation of occult liver injury.

Niacin is an effective lipid-lowering agent which occasionally may cause hepatic failure. Liver enzymes are periodically tested during niacin therapy to assess for hepatic injury. We report a case of suppressed synthesis of hepatically derived coagulation factors and other liver proteins in a patient on niacin with no elevation of hepatic aminotransferases. The protein abnormalities reversed rapidly on discontinuation of niacin. It appears that niacin can cause occult liver injury without frank aminotransferase elevations, and may portend severe hepatotoxicity. Periodic assessment of prothrombin time should be considered in addition to aminotransferase levels to screen for liver injury. We believe this is the first reported case of occult hepatic injury due to extended release niacin, presenting as coagulopathy.

The benefit of the neutropenic diet: fact or fiction?

There really should not be a debate about the use of neutropenic diet for cancer patients. Its usefulness has never been scientifically proven. However, neutropenic diets remain in place in many institutions even though their usefulness is controversial. Neutropenic diets were once thought to be important in protecting patients from having to succumb to infection from neutropenia while undergoing chemotherapy. Although food may contain harmful organisms and research has shown that bacterial translocation is possible, recent studies have been unable to obtain significant differences between placebo and intervention groups. The dietetic challenges neutropenic patients struggle with include decreased quality of life, malnutrition, gastrointestinal side effects, food aversion, and impaired cell-mediated immunity from vitamin deficiency. Unanswered questions in regard to the neutropenic diet include the following: (a) which food should be included; (b) which food preparation techniques improve patient compliance; (c) which patient populations benefit most; and (d) when should such a diet be initiated. Without scientific evidence, the best advice for neutropenic patients is to follow food safety guidelines as indicated by government entities.

Coronary artery bypass grafting (CABG) in patients with immune thrombocytopenia (ITP): a community hospital experience and review of the literature.

We reviewed the records of 51 patients with Immune Thrombocytopenia (ITP) who underwent Coronary Artery Bypass Grafting (CABG) at Charleston Area Medical Center between June 1992 and September 2005. There were 41 males and 10 females with a median age of 68 years (range 49-87). Four patients had a previous splenectomy, one of whom had it performed concomitantly with the CABG. Three patients were on chronic corticosteroids on admission. The median pump time was 114 minutes (range: 42-244 minutes). The median cross-clamp time was 62 minutes (range 22-192 minutes). The median total chest tube drainage postoperatively was 1,346 cc (range: 265-9875cc). The mean preoperative and 24 hour postoperative platelet count was 126,000 (range 58,000-323,000) and 99,000/mm3 (range: 27,000-194,000), respectively. Twenty-one (40%) patients received platelet transfusions. Platelets were given intraoperatively or postoperatively in all but two of those patients. The median number of units of platelets given was 10 (range: 6-52). Twenty-seven (53%) received packed red cells intraoperatively or postoperatively. The median number of red cells given was 2 (range: 1-34). Other hemostatic agents given intraoperatively/ postoperatively included aprotinin (8 patients), aminocaproic acid (10 patients), DDAVP (5 patients), and intravenous gammaglobulin (IgG) in 3 patients. Thirteen patients were given corticosteroids preoperatively with little improvement in platelet count. CABG may be successfully performed in ITP patients with moderate thrombocytopenia (> or = 50,000/mm3) using conventional therapies (e.g., transfusions, IV IgG, hematinics) without the need for preoperative splenectomy or prolongation of hospital stay. However, a prospective study on the ideal management of ITP patients undergoing CABG would be beneficial.

Endometrial carcinoma diagnosed by scapular biopsy: A case report.

► Endometrial cancer diagnosed by scapular biopsy. ► Advanced cancer may present with metastatic disease to the bone.

Building a statewide clinical trials network for cancer care in West Virginia.

In the United States, mortality rates have been declining for certain tumors, For the majority of advanced stage cancer types, cure is unattainable but treatment is still evolving. Advances in the treatment of cancer can be achieved by enrolling patients in cancer clinical trials. Presently, less than 3% of adult cancer patients participate on clinical trials in the United States. Providing cancer care and access to clinical trials are a challenge in a rural state, with a dispersed population base, such as West Virginia. Building upon recognition of barriers to clinical trials awareness and access, oncology leaders in the state are in the formative stages of developing a statewide cancer clinical trials network. Realization of this network will have an enormous impact on cancer care in our state and perhaps can serve as a model for other community and physician teams for other diseases.

Use of radiation after breast conserving surgery (BCS) for DCIS and early invasive breast cancer at Charleston Area Medical Center (CAMC). A study of compliance with National Comprehensive Cancer Network (NCCN) guidelines.

The National Comprehensive Cancer Network (NCCN) recommends that patients with ductal carcinoma in situ (DCIS) and stage I/II invasive breast cancer receive radiation therapy following breast conserving surgery (BCS). The purpose for our study was to determine 1) the percentage of patients with DCIS and stage I/II breast cancer who received radiation therapy following BCS and 2) the clinical factors associated with the use of radiation. We retrospectively studied 606 patients treated between 2000 and 2007 with BCS for DCIS (n=104) and stage I/II breast cancer (n=502). Overall 93 percent of patients in our study received radiation therapy. We found that almost 85 percent and 95 percent of patients with DCIS and stage I/II breast cancer respectively received radiation therapy. Patients with invasive breast cancer who were less than 70 years of age and who received adjuvant systemic therapy were significantly more likely to receive radiation. The data from our study indicate that the use of radiation following BCS is high at our institution. Periodic review of treatment practices at local hospitals is valuable in assessing compliance with national guidelines and in improving quality of care.

Triple-negative breast cancer in West Virginia.

In 2007, the American Cancer Society ranked West Virginia 43rd in breast cancer incidence rates for individual states. Despite our improvements in medical care, the advanced pathological characteristics of breast cancer at diagnosis receive little attention. Consequently, we compared the changing pattern of early breast cancer in several cohort studies conducted at regional medical centers in West Virginia. The data used in this analysis was derived from 320 women presenting at West Virginia University Hospital (WVUH) in Morgantown between 1999 and 2004, with a diagnosis of invasive breast cancer. Details of age, tumor size and axillary lymph node status were compared with tumor registry information published from a cohort study of 191 patients from the Charleston Area Medical Center (CAMC) between 1990 and 1991. Only histologically documented adenocarcinomas of the breast were included. Tumor size was characterized using the TNM system and staged according to AJCC criteria. For comparative purposes, details from the two regional centers were compared with tumor characteristics from a large longitudinal cohort of 2,484 breast cancers from the Women's Health Initiative (WHI) study. Baseline median age at diagnosis of women screened at WVUH was younger than patients at CAMC (52 vs. 60). Women diagnosed with triple-negative breast cancer at WVUH and CAMC had similar age distributions. Within the triple-negative patients at WVUH, 44% of patients were less than 50 years of age and 20% were less than 40 years of age. At CAMC, 35% were less than 50 years of age and 7% were less than 40 years of age. For women at WVUH, 61.5% presented with T1 tumors compared to 65.5% at CAMC. These figures were lower than the WHI average of 80.3%. In contrast, more women presented with larger T2 tumors at our medical centers compared with the national study, 32.6% versus 17.4% respectively. At WVUH, 2.3% of women had T3 tumors (> or =5 cm) compared with 1% at CAMC. Similar to the WHI study, 35-42% of women at WVUH and CAMC were diagnosed at the T1c stage. Approximately, 30% were diagnosed with positive lymph nodes, compared to 23% in the national study. Combined breast cancer data from our medical centers show an increase in more advanced tumors and positive regional lymph node involvement at the time of diagnosis compared to national reports. Other factors such as obesity, diabetes, poverty and access to mammography screening could be influencing the poorer outcomes for women with breast cancer in West Virginia.

Does sex make a difference in survival of patients undergoing resection for early stage non-small cell lung cancer (NSCLC)?

OBJECTIVE: To determine if sex associated differences exist in presentation and survival of patients undergoing resection for early stage nonsmall cell lung cancer (NSCLC). PATIENTS AND METHODS: Retrospective review of 2207 patients with Surveillance, Epidemiology, and End Results (SEER) Summary Stage I, II or III (local or regional disease) patients eligible for surgery, nonsmall cell lung cancer diagnosed and treated in WV between 1993 and 2000, which underwent surgery as a first course of treatment. Data set obtained from the West Virginia Cancer Registry. RESULTS: 1332 male cases and 875 female cases were reviewed. No statistically significant difference was found with mean age of diagnosis (men 66.5 years; women 67.2 years). A greater proportion of women had adenocarcinoma (p < 0.0001), lower grade (p = 0.002), and lower SEER summary stage (p = 0.009). There was no difference in laterality of tumor, 30-day post surgery survival or surgical procedure between men and women. Regression analysis showed a higher hazard ratio was associated with a increasing stage, grade, and those > or =65 years of age while lower hazard ratio was associated with adenocarcinoma. CONCLUSIONS: This study found that stage, grade, age, and histology, but not sex was the significant prognostic indicators of death in five years.

Pharmacological thromboembolic prophylaxis for medical patients in a tertiary care, teaching community hospital: room for improvement.

Venous Thrombembolism (VTE) is a potentially lethal complication in hospitalized patients. Studies indicate that pharmacological prophylaxis may reduce the incidence of VTE. However, the use of VTE prophylaxis remains unclear. We aimed to retrospectively assess whether medically ill hospitalized patients with established risk factors receive pharmacological VTE prophylaxis in our 912-bed community-based tertiary care teaching hospital between 1997 and 2003. We randomly selected a sample of 350 medically ill (non surgical) hospitalized patients with risk factors for VTE. A total of 164 of 321 patients (51.1%) received pharmacological VTE prophylaxis. Patients with a platelet count of greater than or equal to 278 K/cu mm, a weight of 146 to 184 lbs, or a weight > or = 185 lbs were found more likely to receive prophylaxis. Patients with cancer as well as other diagnoses (compared to MI patients) were less likely to receive prophylaxis. We conclude that there continues to be a significant underutilization of VTE prophylaxis in this patient population. Strategies for identifying patients at risk for VTE and implementing appropriate protocols to ensure that these patients receive prophylaxis are necessary.

Primary cutaneous follicle center lymphoma of the arm with a novel chromosomal translocation t(12;21)(q13;q22): a case report.

We report a reciprocal translocation between the long arms of chromosomes 12 and 21, t(12;21)(q13;q22), in a patient with primary cutaneous follicle center lymphoma. Follicle center lymphoma of the skin and follicle center cell lymphoma of the lymph node are morphologically and immunophenotypically very similar. However, the clinical behavior and prognosis of these tumors are different due to the molecular basis of these malignancies. Follicle center cell lymphoma of the lymph node is determined by the presence of a unique translocation between chromosomes 14 and 18, t(14;18)(q32;q21), BCL-2-JH gene rearrangement, that is not present in primary cutaneous follicle center lymphomas. Chromosomal translocations in the primary skin lymphomas have not been previously reported. We hope that our discovery of a new translocation t(12:21)(q13q22) will encourage further investigation into the molecular basis of this translocation and other cytogenetic abnormalities in primary cutaneous B-cell lymphomas.

Gefitinib (IRESSA, ZD 1839) as a salvage treatment for patients with advanced non-small cell lung cancer.

This study assessed the anti-tumor activity and tolerability of gefitinib (IRESSA, ZD 1839) in a series of patients with previously treated advanced non-small cell lung cancer (NSCLC) seen at Charleston Area Medical Center in Charleston, W.Va. All patients were required to have proven advanced or metastatic NSCLC, along with meeting other study criteria. In 41 patients, the partial response rate was 7%, and 10% of patients achieved stable disease. Symptom improvement (dyspnea, anorexia) was reported in 44%. Mean survival for the entire group was 6.7 months (10.3 months for females, 3.7 months for males), with a 6-month survival rate of 33%. Adverse events were generally mild (grade I or II) and reversible and consisted mostly of diarrhea, rash, and anorexia. Although the major response rate was low, gefitinib (IRESSA, ZD 1839) demonstrated clinically meaningful anti-tumor activity with significant improvement in symptoms in this heavily pretreated group of patients with advanced NSCLC.

The prevalence of viral hepatitis and HIV infections in patients with congenital bleeding disorders.

Patients with clotting disorders, including hemophilias A and B, and von Willebrand Disease generally receive pooled human blood products, and are at high risk for HIV-1 and hepatitis A, B and C viral infection. This retrospective study describes patients receiving treatment at a federally funded Hemophilia Treatment Center (HTC) from 1998 - 2002 and assesses the prevalence of viral infection. In addition, current rates of viral infection are compared to 1984-1996 rates.

Prognostic indicators for stage II (Dukes' stage B) adenocarcinoma of the colon.

To determine the prognostic indicators that are associated with lower disease free survival (DFS) and overall survival (OS) in stage II colon cancer patients, the tumor registry records were reviewed for all patients diagnosed with stage II and III adenocarcinoma of the colon at Charleston Area Medical Center from 1986 to 1994. The prognostic indicators of 174 stage II patients who had not undergone treatment were assessed for DFS and OS. The results demonstrated that the 5-year OS was reduced for those patients with the following prognostic indicators: male, obstruction at time of presentation, need for blood transfusion, and those who had < 7 LNR (lymph nodes removed). In addition, DFS and OS curves for stage II patients with < 7 LNR were not significantly different from survival curves for stage III patients. Treatment decisions are made based primarily on stage, and stage II patients are not routinely offered adjuvant therapy. Placing patients on a randomized clinical trial, until a standardized treatment is agreed upon, is one alternative. If patients are ineligible for, or refuse a clinical trial, then patients with poor prognostic indicators should be considered for adjuvant treatment.