The neutrophil to albumin ratio as a predictor of pathological complete response in rectal cancer patients following neoadjuvant chemoradiation.

Pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME), in patients with locally advanced rectal cancer, occurs in 15-27% of patients. Because blood cell counts and albumin are a direct indicator of the host environment, a response to nCRT might be predicted by these markers. This study was carried out to determine whether the neutrophil to albumin ratio (NAR) was predictive of pCR in veteran patients. Ninety-eight patients with rectal cancer who underwent standard nCRT, followed by TME were analyzed. Pre-nCRT and post-nCRT hematologic data were collected. Univariate and multivariate analyses were carried out. Kaplan-Meier curves were constructed with our primary endpoint of pCR. Male patients (99%), age 62.4±9.1 years, BMI=27.4±5.9 kg/m, rectal cancer distance from anal verge=7.1±4.5 cm (SD), interval between nCRT and TME=8 weeks, 55% patients=low anterior resection, 95% received 5-fluorouracil, and all patients received radiation, with 15% achieving a pCR. Univariate analysis showed that pre-nCRT carcinoembryonic antigen (15.8±45.1 vs. 3.5±5.3 ng/dl; P=0.002) and the pre-nCRT NAR (16.4±4.8 vs. 14.2±1.6; P=0.002) were associated with pCR. On multivariate analysis, pre-nCRT carcinoembryonic antigen (odds ratio=0.41, 95% confidence interval 0.22-0.77) and pre-nCRT NAR (odds ratio=0.76, 95% confidence interval 0.60-0.97) remained independent predictors of pCR. Overall survival between nonresponders and pCR patients at 1, 5, and 10 years was 96, 62, and 44% versus 93, 85, and 61%, P=0.13, and disease-free survival was 95, 60, and 47% versus 93, 85, and 61%, P=0.17; respectively. Our study shows that the pre-nCRT NAR is an independent predictor of pCR. These findings should be applied to other cohorts to determine its validity and reliability for use as a potential predictor of pCR.

Racial and ethnic disparities in Acute Myeloid Leukemia: 15-year experience at a safety net hospital system.

Despite recent therapeutic advances, ethnic minorities in the U.S. continue to have disproportionately poor outcomes in many hematologic malignancies including AML. We identified 162 adult AML patients treated at a non-transplant safety net hospital from 2007 to 2022 and evaluated differences in disease characteristics, treatment and clinical outcomes based on race and ethnicity. Our cohort consisted of 82 (50.6%) Hispanic, 36 (22.2%) non-Hispanic black and 44 (27.2%) non-Hispanic white and Asian patients. Median age at diagnosis was 42.5, 49.0 and 52.5 years respectively (p=0.025). Hispanics had higher rates of intermediate and high-risk disease (p=0.699) and received high intensity induction and consolidation chemotherapy at lower rates (p=0.962), although differences did not reach statistical significance. Despite this, similar remission rates were achieved. Hispanics with high-risk disease had longer overall survival (OS) than the combined non-Hispanic cohort (mOS 14 m vs 7 m, p=0.030). Multivariate regression analysis showed that OS was negatively associated with age (HR 1.023, p=0.006), intermediate (HR 3.431, p=0.0003) and high-risk disease (HR 4.689, p<0.0001) and positively associated with Hispanic ethnicity (HR 0.614, p=0.026). This report suggests that contrary to other studies, Hispanics, particularly those with high-risk AML, may have improved OS compared to other ethnic groups. These results are unique to our safety net hospital setting where common barriers to medical care and healthcare disparities are largely mitigated.

Small bowel obstruction due to metastatic colon cancer.

Systemic treatment, including monoclonal antibodies against tumor-associated targets, has increased the median survival of patients with metastatic colorectal cancer over 100% in the past few years. The prolonged life-span of these patients has led to the development of new and unusual complications that were typically not seen in the era of 5-fluorouracil and leucovorin. A multidisciplinary approach is now more crucial than ever. In this report, we will discuss a patient who presented with a metastatic lesion nearly obstructing the small bowel three years following the diagnosis of metastatic colon cancer.

Bowel perforation from bevacizumab for the management of colorectal cancer.

Bevacizumab (Avastin) is a recently developed monoclonal antibody, which targets the vascular endothelial growth factor receptor pathway, and is currently used in combination with cytotoxic agents as first-line or second-line therapy for patients with metastatic colon cancer. Common complications from administration of bevacizumab include hypertension, proteinuria, and diarrhea. These complications are typically managed conservatively. More serious complications of bevacizumab administration include venous thromboembolism, bleeding, and bowel perforation. Although these complications are much more infrequent, prompt recognition is imperative for adequate and timely management. In this report, we discuss a patient with bowel perforation from bevacizumab for the treatment of metastatic colorectal cancer.

Bevacizumab-associated hypertension: etiology, incidence, and management.

Bevacizumab (Avastin) is a recently developed monoclonal antibody, which targets the vascular endothelial growth factor signaling pathway, and is currently used in combination with cytotoxic agents as first-line or second-line therapy for patients with metastatic colon cancer. Hypertension is a known risk factor associated with the use of bevacizumab. In this report, we describe the incidence, etiology, and management of patients with this complication.

Decreasing Inappropriate Use of Rasburicase to Promote Cost-Effective Care.

BACKGROUND: Rasburicase is a recommended treatment of tumor lysis syndrome and patients at high-risk for developing tumor lysis syndrome. Unfortunately, it is expensive, and unnecessary use raises costs of care. METHODS: Plan, Do, Study, Act methodology was used to decrease the inappropriate use of rasburicase. In the Plan phase, a multidisciplinary quality improvement team reviewed the rasburicase ordering process and its prescription patterns at Parkland Health and Hospital System between October 2015 and September 2017 to determine appropriate interventions for improvement. In the Do phase, interventions were deployed to improve rasburicase prescriptions. In the Study phase, the team reviewed the rasburicase orders and appropriateness from February 2018 to October 2018. During the Act phase, the interventions were found to be successful, and the process changes were solidified. RESULTS: At baseline, 65 doses of rasburicase were administered during the 2-year baseline period, 21 of these (32.3%) were inappropriate. Review of the ordering process identified pitfalls: one-click ready-to-sign order, fixed default dose, no hard-stop alert requiring physicians to review and confirm appropriate indications, and lack of secondary pharmacy review. We aimed to reduce the percentage of inappropriate rasburicase orders from a baseline of 32.3% to 10% over 3 months. In February 2018, we implemented the interventions, which resulted in reduction in inappropriate rasburicase use, with only a single inappropriate order placed in 7 months postintervention. CONCLUSION: A multidisciplinary approach and classic quality improvement methodology enabled us to reduce inappropriate rasburicase use. Straightforward electronic medical record interventions and secondary pharmacy review are effective in addressing overuse.

Reducing Hospitalizations: Institution of Outpatient Infusional EPOCH-Based Chemotherapy at a Safety Net Hospital.

PURPOSE: EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) -based chemotherapy is traditionally administered inpatient because of its complex 96-hour protocol and number of involved medications. These routine admissions are costly, disruptive, and isolating to patients. Here, we describe our experience transitioning from inpatient to outpatient ambulatory EPOCH-based chemotherapy in a safety-net hospital, associated cost savings, and patient perceptions. METHODS AND MATERIALS: Guidelines for chemotherapy administration and educational materials were developed by a multidisciplinary team of physicians, nurses, and pharmacists. Data were collected via chart review and costs via the finance department. Patient satisfaction with chemotherapy at home compared with hospitalization was measured on a Likert-type scale via direct-to-patient survey. RESULTS: From January 30, 2017, through January 30, 2018, 87 cycles of EPOCH-based chemotherapy were administered to 23 patients. Sixty-one ambulatory cycles (70%) were administered to 18 patients. Of 26 cycles administered in the hospital, 18 (69%) were the first cycle of treatment. Rates of inappropriate prophylactic antimicrobial prescription and laboratory testing were lower in the outpatient setting. Eight of nine patients surveyed preferred home chemotherapy to inpatient chemotherapy. Per-cycle drug costs were 57.6% lower in outpatients as a result of differences in the acquisition cost in the outpatient setting. In total, the transition to ambulatory EPOCH-based chemotherapy yielded 1-year savings of $502,030 and an estimated 336 days of avoided hospital confinement. CONCLUSION: Multiday ambulatory EPOCH-based regimens were successfully and safely administered in our safety-net hospital. Outpatient therapy was associated with significant savings through avoided hospitalizations and reductions in drug acquisition cost and improved patient satisfaction.

Use of platelet and erythroid growth factors during induction chemotherapy for acute lymphoblastic leukaemia in a Jehovah's Witness.

We present a 21-year-old woman diagnosed with Philadelphia (Ph) chromosome-like CD20 positive B-cell acute lymphoblastic leukaemia (ALL). She was a Jehovah's Witness (JW) and declined all blood product transfusion support. She was initiated on the CALGB 10403 chemotherapy protocol for her ALL. She received darbepoetin alfa and romiplostim as supportive therapies for her disease/chemotherapy-associated anaemia and thrombocytopaenia. A complete remission was achieved with negative minimal residual disease and she remains in remission 18 months after diagnosis. This case report describes the successful treatment of an adult JW with Ph-like CD20 +B cell ALL, in the absence of blood product transfusions, using growth factor support.

Reducing Wait Time Between Admission and Chemotherapy Initiation.

PURPOSE: Reducing the length of stay is a high-priority objective for all health care institutions. Delays in chemotherapy initiation for planned preadmissions lead to patient dissatisfaction and prolonged length of stay. PATIENTS AND METHODS: A multidisciplinary team was formed as part of the ASCO Quality Training Program. We aimed to reduce the time to initiation of chemotherapy from patient arrival at Parkland Hospital from a median of 6.2 hours at baseline to 4 hours over a 6-month period (35% reduction). The team identified inconsistency in blood work requirements, poor communication, and nonstandard patient arrival times as key causes of delay in the process. Plan-Do-Study-Act (PDSA) cycles were implemented based on identified improvement opportunities. The outcome measure was time from arrival to chemotherapy start. Data were obtained from time stamps in the electronic health record. RESULTS: The first PDSA cycle included patient reminders to arrive at specific times, improved communication using a smartphone secure messaging application, and preadmission notes by oncology fellows detailing whether fresh blood work were needed on admission. Baseline data from 36 patients and postimplementation data from 28 patients were analyzed. Median time from admission to chemotherapy initiation preprocess change was 6.2 hours; it was 3.2 hours postchange. A sustained shift in the process was apparent on a control chart. CONCLUSION: Delays in initiation of chemotherapy can be prevented using classic quality improvement methodology and a multidisciplinary team. We aim to further refine our PDSA cycles and ensure sustainability of change.

Gemcitabine and platinum-based chemotherapy in metastatic breast cancer.

Although anthracyclines and the taxanes comprise the most active first-line cytotoxic treatments in patients with hormone-insensitive or life-threatening metastatic breast cancer, many patients progress and require other chemotherapeutic agents. Development of new combinations and/or agents is thus needed. Gemcitabine (Gemzar) and platinum compounds have been employed as single agents, and the addition of gemcitabine to the platinums results in significant clinical benefit and response rates. Correlative biologic studies are expected from several already-reported trials and may help elucidate predictive factors for both response and toxicity when combining gemcitabine and the platinums. Trials incorporating these doublets in earlier stages of breast cancer or in the neoadjuvant setting may further elucidate their role in breast cancer treatment.

KIF14 promotes AKT phosphorylation and contributes to chemoresistance in triple-negative breast cancer.

Despite evidence that kinesin family member 14 (KIF14) can serve as a prognostic biomarker in various solid tumors, how it contributes to tumorigenesis remains unclear. We observed that experimental decrease in KIF14 expression increases docetaxel chemosensitivity in estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative, "triple-negative" breast cancers (TNBC). To investigate the oncogenic role of KIF14, we used noncancerous human mammary epithelial cells and ectopically expressed KIF14 and found increased proliferative capacity, increased anchorage-independent grown in vitro, and increased resistance to docetaxel but not to doxorubicin, carboplatin, or gemcitabine. Seventeen benign breast biopsies of BRCA1 or BRCA2 mutation carriers showed increased KIF14 mRNA expression by fluorescence in situ hybridization compared to controls with no known mutations in BRCA1 or BRCA2, suggesting increased KIF14 expression as a biomarker of high-risk breast tissue. Evaluation of 34 cases of locally advanced TNBC showed that KIF14 expression significantly correlates with chemotherapy-resistant breast cancer. KIF14 knockdown also correlates with decreased AKT phosphorylation and activity. Live-cell imaging confirmed an insulin-induced temporal colocalization of KIF14 and AKT at the plasma membrane, suggesting a potential role of KIF14 in promoting activation of AKT. An experimental small-molecule inhibitor of KIF14 was then used to evaluate the potential anticancer benefits of downregulating KIF14 activity. Inhibition of KIF14 shows a chemosensitizing effect and correlates with decreasing activation of AKT. Together, these findings show an early and critical role for KIF14 in the tumorigenic potential of TNBC, and therapeutic targeting of KIF14 is feasible and effective for TNBC.

Metastatic rectal cancer to the breast.

Rectal cancer metastatic to the breast is an exceedingly rare event with around 15 cases reported in the literature. A metastatic breast deposit from the rectum signifies diffuse disseminated disease or a highly aggressive tumor such that surgical intervention other than palliation has a limited role. In the present report, we discuss a patient who presented with rectal cancer and developed a breast metastatic deposit. She soon developed progressive metastatic involvement of the lungs and the soft tissues and succumbed to the malignant course of this disease 12 months after the diagnosis of the primary rectal tumor.