Assessment of hospitalization rates for immune-related adverse events with immune checkpoint inhibitors.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have become the standard of care in many cancer types. As the number of patients receiving ICIs for various cancers continues to expand, patients and practitioners should be aware of potentially severe immune-related adverse events (irAEs). Despite reports of the incidence of grade 3/4 toxicities, the proportion of patients whose symptoms were clinically severe enough to warrant hospitalization for adverse event management is unknown. METHODS: This single center, retrospective, observational study was designed to determine the impact of irAEs on patients and the hospital. Patients who started ICIs from May 2016 through May 2019 for melanoma or lung cancer were included. The primary outcome was incidence of hospitalization for irAE. Secondary outcomes included median length of hospitalization, time to onset of irAE, rates of hospitalization for irAE per each checkpoint inhibitor regimen, organ system affected, progression free survival, and overall survival. RESULTS: Of 384 patients with melanoma or lung cancer, 27 (7%) were hospitalized at our institution for an irAE. The most common irAE leading to hospitalization was colitis for patients with melanoma and pneumonitis for patients with lung cancer. The median length of stay across all hospitalizations was 10 days. Twenty-five patients required the use of corticosteroids while hospitalized, while eight of these patients required second line irAE treatment. For the total patient population, 34.7% experienced a grade 1/2 irAE and 13.1% experienced a grade 3/4 irAE. CONCLUSION: Our cohort of patients experienced similar rates irAEs as reported in clinical trials and published reports.

Incidence and outcomes of heparin-induced thrombocytopenia in solid malignancy: an analysis of the National Inpatient Sample Database.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction to heparin products characterized by thrombocytopenia with or without thrombosis. This study aimed to determine the incidence, morbidity, mortality and economic burden of HIT in solid-malignancy-related hospitalizations. We analyzed the National Inpatient Sample Database (NIS), the largest public database of hospital admissions in the United States, from January 2012 to September 2015. The primary outcome of the study was the incidence of HIT. Secondary outcomes included incidence of venous thrombosis (acute deep venous thrombosis and pulmonary embolism), arterial thrombosis (thrombotic stroke, myocardial infarctions and other arterial thromboembolism), mortality associated with HIT, length of stay, total hospital charges and disposition. During the study period, 7 437 049 hospitalizations had an associated diagnosis of solid malignancy. Approximately 0·08% (n = 6225) hospitalizations had a secondary diagnosis of HIT in this population. The standardized incidence of total thrombotic events was higher in the solid malignancy with HIT compared to the solid malignancy without HIT group (24·7% vs. 6·8%, P < 0·001). The standardized mortality rate was 4·8% in solid malignancy with HIT compared to 3·4% in the without HIT group (OR, 1·53; 95% CI, 1·25-1·89; P < 0·001). HIT in solid malignancy is a rare condition but associated with increased morbidity and mortality.

Adherence to anti-estrogen therapy in women with hormone receptor-positive breast cancer utilizing bubble packaging: a pilot study.

PURPOSE: This pilot study evaluated adherence to anti-estrogen therapy in women with hormone receptor-positive breast cancer utilizing bubble packaging. METHODS: This was a single-arm prospective investigational pilot study that enrolled 86 patients between August 2012 and April 2014. Descriptive statistics for patient age, race, insurance, stage, duration of treatment, and comorbidities were computed. All patients received routine prescriptions in a "bubble" pack or daily blister pack dispensed by one pharmacy. Participants were considered adherent if they had taken ≥ 80% of the dispensed drug. Disease-free survival (DFS) and overall survival (OS) data were obtained at 78 months. RESULTS: Fifty patients were included in the analysis. The overall adherence rate was 97%. None of the variables examined (race, age, insurance status, and stage) had an impact on adherence rate. Only duration of endocrine therapy had a marginal effect on adherence (p value = 0.06). The late cohort (duration of therapy 37-60 months) was least likely to be compliant at 89.53%. Our 5-year DFS was 94% and 5-year OS was 96%. There was no statistically significant difference in DFS and OS between patients with adherence rate > 90% and < 90%. CONCLUSION: Adherence rate to bubble packaging was higher than that in historical studies. Although this is a single-arm pilot study, these data suggest bubble packaging of anti-estrogen may be a reasonable option to improve adherence in hormone receptor-positive breast cancer patients.

Design and Development of Simple and Low-cost Light Source for Laparoscopic Surgery.

BACKGROUND: The existing medical light source device used in laparoscopy surgery is very costly and is not yet developed in Nepal. This study aimed to build a light source device that is cost-effective and passes all the testing parameters like Light Emitting Diode illumination, color, and heat. METHODS: A method of constructing a light source comprises the steps of designing, assembling the system, and undergoing device testing. The design of the device was done through Sketchup software. The dual switched-mode power supply of 3-4 Voltage to the Light Emitting Diode and 12 Voltage to the rest of the system with cooling technology were used. RESULTS: The Light emitted from the Light Emitting Diode focuses the light directly at the fiber optic cable through the coupler. Moreover, the testing of the device concludes that the increment temperature of the device for 1 hour is 1 degree Celsius whereas the maximum increment temperature was found to be 3 degrees. Additionally, the fiber optic illumination at the port is found to be >50000. Also, the color of the Light Emitting Diode is cool white light having a color temperature of 5700 Kelvin and a color rending index of 92. CONCLUSIONS: The developed device is four times cheaper than a similar device available in the Nepalese market. Also, this device has been developed first of its kind in Nepal.

The Hispanic Paradox in Non-Small Cell Lung Cancer.

OBJECTIVE/BACKGROUND: According to the U.S. Census Bureau, 18% of the total population in the United States identified themselves as Hispanic in 2016 making it the largest minority group. This study aimed to evaluate the effect of Hispanic ethnicity on the overall survival of patients with non-small cell lung cancer (NSCLC) using a large national cancer database. METHODS: We used the National Cancer Database to identify patients diagnosed with NSCLC between 2010 and 2015. The two comparative groups for this study were non-Hispanic Whites (NHWs) and Hispanics. The primary outcome was overall survival. RESULTS: Of the 555,475 patients included in the study, 96.9% and 3.1% were NHWs and Hispanics with a median follow up of 12.6 months (interquartile range 4.1-30.6) and 12.1 months (interquartile range 3.8-29.5), respectively. Hispanics were more likely to be uninsured, and live in areas with lower median household income or education level. In the age-, sex-, and comorbidities-adjusted Cox model, the overall survival was significantly better in Hispanics compared with NHWs (hazard ratio [HR] 0.92, 95% confidence interval 0.90-0.93, p < .001). In a demographic, socioeconomic, clinical, and facility characteristics adjusted Cox model, Hispanics had further improvement in survival (HR 0.79, 95% confidence interval 0.78-0.81, p < .001). The survival advantage was seen in all cancer stages: Stage I-HR 0.76 (0.71-0.80), Stage II-HR 0.85 (0.79-0.92), Stage III-HR 0.81 (0.77-0.85), and Stage IV-HR 0.79 (0.77-0.81). CONCLUSION: Hispanic ethnicity was associated with better survival in NSCLC. This survival advantage is likely the result of complex interactions amongst several physical, social, cultural, genomic, and environmental factors.

Radiotherapy in brain metastases from EGFR-mutated non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) mutations are present in 20-40% of non-small cell lung cancers (NSCLCs). Brain metastasis (BM) is more common in EGFR-mutated NSCLC (25-45%) compared to EGFR wild-type (15-30%). First and second-generation tyrosine kinase inhibitors (TKIs), such as erlotinib and afatinib have proven to be superior to chemotherapy in the front-line treatment of EGFR-mutated NSCLC. Osimertinib, a third-generation EGFR TKI, has demonstrated better blood brain barrier (BBB) penetration, higher rate of intracranial response (66% vs. 43%) and a lower rate of CNS progression when compared to first generation EGFR TKI. Evidence on upfront radiation vs. upfront osimertinib is limited, but rapidly evolving and being tested in ongoing comparative trials. Stereotactic radiation (SRS) is very effective in the control of BMs and has been increasingly used and consequently replacing resection of BMs. SRS also has been increasingly used in the treatment of multiple BMs. Considering the effectiveness of targeted agents such as third generation EGFR inhibitors clinicians now are more frequently faced with the decision, if systemic therapy is safe and effective enough to withhold SRS. Third generation EGFR inhibitors also have fewer adverse events as previous generations. This review discusses the current literature available for management of BM in EGFR-mutated NSCLC.

Lung Cancer Screening Registry Reveals Low-dose CT Screening Remains Heavily Underutilized.

BACKGROUND: Since 2013, the United States Preventive Services Task Force has recommended annual screening for lung cancer in high-risk patients with low-dose computed tomography (LDCT). Current literature has provided estimates of the lung cancer screening rate and only prior to appropriate insurance coverage for LDCTs. The aim of this study was to use newly established registry data to assess the lung cancer screening rate across the United States. MATERIALS AND METHODS: Using data from the Lung Cancer Screening Registry provided by the American College of Radiology in 2016, we collected the total number of LDCT screens performed from all 1962 accredited radiographic screening sites. The 2015 National Health Interview Survey was used to estimate screening eligible smokers per United States Preventive Services Task Force criteria. These data were compared to calculate screening rate. RESULTS: In 2016, 2.0% of 7.6 million eligible smokers were screened. Rates varied by region from 1.1% in the West to 3.9% in the Northeast. The South consisted of 40.4% of eligible smokers and the most accredited screening sites (37%); however, their screening rate was among the lowest (1.7%) in the nation. Smoking cessation counseling was offered to 84% of screened current smokers prior to receiving LDCTs. CONCLUSIONS: Lung cancer screening remains heavily underutilized despite guideline recommendation since 2013, insurance coverage, and its potential to prevent thousands of lung cancer deaths annually.

Treatment Timing in Small Cell Lung Cancer, a National Cancer Database Analysis.

OBJECTIVES: Small cell lung cancer (SCLC) is an aggressive disease treated as soon as possible given its rapid doubling time. Evidence for the appropriate time to chemotherapy initiation (TCI) for SCLC is lacking. This study evaluated TCI in SCLC on a national level. MATERIALS AND METHODS: The National Cancer Database identified 64,491 SCLC patients treated with chemotherapy from 2010 to 2014. Factors associated with TCI were identified with multiple linear regression analyses. TCI was categorized into 4 groups using cutoff points of 7, 14, and 28 days. Using these categories, median overall survival and log-rank test was used for univariate analysis of the survival outcome and the Cox model was used for multivariate analysis. RESULTS: Median TCI was 18 days with 21% treated ≤7 days, 21% in 8 to 14 days, 30% 15 to 28 days, and 28% >28 days from diagnosis. Younger age, white race, no insurance, more comorbidities, and higher stage were associated with shorter TCI. Median overall survival for TCI within 7 days was 8.2 months, 8 to 14 days was 9.2 months, 15 to 28 days was 10.3 months, and > 28 days was 10.8 months (P<0.001). In the multivariate analysis, increased TCI was associated with improved survival across all stages. Among stage IV patients, compared with TCI≤7 days, the hazard ratio (HR) is 0.92 (P<0.001) for 8 to 14 days, HR 0.82 (P<0.001) for 15 to 28 days, and HR 0.77 (P<0.001) for >28 days of TCI. Results were similar for stage III and for stages I+II. CONCLUSIONS: Our results show worse survival with shorter TCI. This provides evidence to inform a discussion regarding appropriate treatment timing and individualizing treatment.

NSCLC patient "migration" for treatment: A retrospective analysis of patient characteristics, travel patterns, and survival differences.

PURPOSE: Every year a significant population exists of those diagnosed with nonsmall cell lung cancer (NSCLC) who do not receive initial treatment upon diagnosis and then "migrate" to additional hospital before ultimately getting treatment. Migration to different hospitals may play a role in the decision to treat or not-to-treat, and we aimed to evaluate the potential factors that lead to treatment. METHODS: A retrospective review of 6212 patients with NSCLC from 29 Kentucky hospital registries from 2012 to 2014 was performed. Variables collected included hospital accreditation status, age at diagnosis, stage, overall survival (OS), and insurance status. Hospital records were matched to Kentucky Cancer Registry records to determine the number of hospitals visited for treatment. RESULTS: Most patients were treated at their initial hospital (73%). Of the remaining patients, 36% migrated to a different hospital where most received treatment (93%). Migrating to another hospital was associated with Stage I-III disease, younger age (66.4 vs 72.2 years), and longer OS (561 vs 157 days). Notably, migration was also associated with private insurance status and missing treatment modalities at the initial hospital. Treatment after migrating was associated with Stage I-II disease, younger age (65.8 vs 72.8 years), and longer OS (595 vs 153 days). After adjusting for confounders, treated migrating patients lived longer than initially treated patients (591 vs 505 days), especially among those with stage III (563 vs 495 days) and IV (379 vs 300 days) disease. CONCLUSION: This analysis demonstrates a survival benefit for initially untreated patients with advanced disease who migrate to another hospital for treatment. Migration was associated with having private insurance, thus making it noteworthy of the relationship between NSCLC survival benefit and insurance status.

Clinical Outcomes Using Mycophenolate and Tacrolimus for Graft-versus-Host Disease Prophylaxis in Patients Undergoing Allogeneic Stem Cell Transplant: A Single Institution Experience.

For recipients of allogeneic hematopoietic stem cell transplant (HSCT), mycophenolate mofetil (MMF) plus tacrolimus combination is mostly used in reduced-intensity (RIC), and nonmyeloablative conditioning (NMAC) whereas methotrexate and tacrolimus combination is preferred in myeloablative conditioning (MAC). We present single institution outcomes in patients undergoing allogeneic HSCT with both MAC and NMAC/RIC regimen using MMF and tacrolimus for graft-versus-host disease (GVHD) prophylaxis. Data from all adult patients who underwent allogeneic HSCT from 2007 to 2017 was collected from Data Back to Centers web-based application of Center for International Blood and Marrow Transplant Research (CIBMTR). A total of 150 patients were included with the mean age of 46.9 years. For the patients who received MAC (n=109), the cumulative incidence of grade II-IV acute GVHD at day 100 was 37%, grade II-IV acute GVHD at one year was 51%, and chronic GVHD at one year was 38%. For the patients who received NMAC/RIC (n=41), the cumulative incidence of grade II-IV acute GVHD at day 100 was 31%, grade II-IV acute GVHD at one year was 28%, and chronic GVHD at one year was 36%. This institutional analysis shows that the combination of MMF and tacrolimus yields acceptable outcomes for the prevention of acute and chronic GVHD.

Twice-daily intravenous bolus tacrolimus infusion: A safe and effective regimen for graft-versus-host disease prophylaxis.

OBJECTIVE/BACKGROUND: Among patients undergoing allogeneic hematopoietic cell transplant, continuous intravenous (IV) tacrolimus infusion is frequently used for graft-versus-host disease (GvHD) prophylaxis. Twice-daily intermittent IV tacrolimus dosing may confer safety and convenience benefits. METHODS: We performed a retrospective chart review of 66 patients who received twice-daily IV bolus tacrolimus for GvHD prophylaxis. The primary end point of the study was safety, as measured by renal toxicity. The secondary end points included mean tacrolimus serum concentrations, incidence of grades II-IV acute GvHD, electrolyte abnormalities, hyperglycemia, hypertension, and neurologic toxicity. RESULTS: There was acceptable, possibly favorable, incidence of renal toxicity (42%) and no significant difference in grades II-IV GvHD (37%), compared with published data. Mean tacrolimus blood concentrations were not affected by occurrence of renal toxicity. CONCLUSION: We conclude that administration of IV tacrolimus twice daily over 4 h may be safe and effective in preventing GvHD in allogeneic hematopoietic cell transplant.

Performance of community-based lung cancer screening program in a Histoplasma endemic region.

OBJECTIVES: Lung cancer screening with low dose computed-tomography (LDCT) is currently recommended for high-risk populations based on mortality benefit shown in the National Lung Screening Trial (NLST). This study evaluated performance of a community-based lung cancer screening program in a Histoplasma endemic region. MATERIALS AND METHODS: Demographic and clinical information was collected through retrospective review of patients in the Lung Cancer Screening program of a Kentucky (Histoplasma endemic region) health system from 2016 and 2017. A positive LDCT screen is defined as Lung-RADS version 1.0 assessment categories 3 or 4. Patients characteristics, initial screening results and follow up were analyzed and compared to NLST results. RESULTS: A total of 4500 LDCT screens were performed in 2016 (39%) and 2017 (61%) with 43% adherence rate to repeat annual screen in 2017. Mean age of patients was 64 years, with majority being females (54%) and current smokers (69%) with average 52-pack year smoking history. The rate of positive LDCT was 13.3% (600) varying based on baseline (14.6%) and annual (9.5%) screen. A total of 70 lung cancers were diagnosed among all positive LDCT screens (11.7%) with a false positive rate of 12%. CONCLUSIONS: Baseline positive screens in our study are similar to NLST data with Lung-RADS criteria implementation (14.6% vs 13.6%, p = 0.15) despite being a Histoplasma endemic region. Our study shows a successful performance of a community-based lung cancer screening program in a Histoplasma endemic region.

Timing of treatment in small-cell lung cancer.

Small-cell lung cancer (SCLC) is an aggressive disease with poor survival and rapid doubling time. Current practice is to treat SCLC as soon as possible but evidence on appropriate timing of treatment from diagnosis (TTD) is lacking. This is a retrospective analysis of SCLC patients from the 2012 to 2015 Kentucky Cancer Registry. Data collected included age at diagnosis, stage, gender, race, insurance and treatment. Factors and survival associated with TTD were identified with logistic regression analyses and Cox proportional hazards models. Among the 2992 SCLC patients, 2371 (79%) of SCLC patients were treated with one or more treatment modalities. Among treated patients, 93% received chemotherapy ± radiation with the mean TTD of 18 days. Most patients (80%) have TTD of ≤ 4 weeks with 33% treated within 1 week, 20% 1-2 weeks, and 27% 2-4 weeks from diagnosis. Delay in treatment (TTD > 4 weeks) was less in stage III and IV disease (odds ratio: 0.33 and 0.27 respectively, p < 0.01) but not significantly associated with age, race, gender, and insurance. One and two-year survival of patients with TTD ≤ 4 weeks was significantly worse when compared to > 4 weeks (hazard ratio = 1.43, 95% CI 1.2-1.6, p < 0.01; HR = 1.45, 95% CI 1.3-1.6, p < 0.01 respectively). These results show a trend toward better survival with late treatment of SCLC. Therefore, a general urgency to treat SCLC needs to be re-evaluated with consideration of patients needing more optimization before treatment. Further studies are needed to better clarify the appropriate timing of treatment from diagnosis in SCLC and who will benefit from early versus late treatment.

Correction to: Outcomes of hypercalcemia of malignancy in patients with solid cancer: a national inpatient analysis.

In the original publication the last column of the table 2 is aligned incorrectly. The correct version of table 2 is given below.

Outcomes of hypercalcemia of malignancy in patients with solid cancer: a national inpatient analysis.

Hypercalcemia of malignancy (HCM) is present in one-third of cancer patients and is associated with a significant mortality risk of 50% within 1 month of diagnosis. We aimed to study the impact and outcomes of HCM in hospitalized patients with solid cancer. We analyzed data captured in the National Inpatient Sample database of the Agency of Healthcare Research and Quality. The study included all hospitalizations in adult solid cancer patients between January 2012 and September 2015 with hypercalcemia. All encounters associated with HCM were identified using the ICD-9 code (275.42) for hypercalcemia. Encounters with other known causes of hypercalcemia were excluded. The co-primary outcomes were incidence of HCM and inpatient mortality. During the study period, 7,501,209 hospitalizations met our inclusion criteria. Approximately 1.7% (n = 126,875) of these hospitalizations were related to HCM. This corresponds to approximately 1 in 59 solid malignancy associated hospitalizations. The mean age of patients with HCM was 65.7 years; 49% were females; 69% were Caucasians; 73% had metastatic disease and 22% received a palliative care consult. When compared to those without HCM, those hospitalized with HCM had a significantly longer mean hospital length of stay (7.3 days vs. 5.6 days, p < 0.001), higher inpatient mortality (12.3% vs. 5.5%, adjusted OR 1.76 (95% CI 1.69-1.84), p < 0·0001), and a greater likelihood of discharge to other facilities (27.4% vs. 16.2%, p < 0.0001). Although HCM accounts for < 2% of all hospitalizations in patients with solid cancer, those with HCM display higher mortality than those without HCM.

Management of immunotherapy toxicities in older adults.

Advanced age is a risk factor for cancer and is attributed to dysregulation of the immune system. Historically, treatment of advanced cancer has primarily involved systemic chemotherapy that is associated with high treatment related toxicity especially in older adults. Immune checkpoint inhibitors (ICIs) provide an exciting treatment option for older adults in terms of efficacy and safety as compared to systemic chemotherapy. Given the pace of approval of ICIs for multiple cancers, there is an increase in both the use of ICIs and the associated immune-related adverse events. In this article, we address how to approach immunotherapy related toxicities in older adults given the availability of limited data.

"Lost to Follow-up" Among Adult Cancer Survivors.

BACKGROUND: Follow-up cancer care is important for patients who have received IV chemotherapy but some patients discontinue their care and are lost to follow-up (LFU) at the cancer center where they were treated. The purpose of this study was to determine what proportion of cancer survivors are LFU at 5 years after treatment, the timing of LFU, and the characteristics of those who do not continue survivorship care. METHODS: Adult patients with cancer who were treated with chemotherapy at a large community teaching hospital in 2006 and 2007 were identified and linked with State tumor registry data. Hospital medical records were reviewed to obtain information on demographics, diagnosis, treatment, and date of last follow-up visit. Characteristics of patients with ≥5 years of follow-up care were compared with those who were LFU. RESULTS: In total, 487 patients received chemotherapy and 304 died (62%) during the 5-year follow-up period. Among the 183 cancer patients who were known to be alive at 5 years, 92 (50%) were LFU and 50% (46/92) of this LFU group were LFU within 1 year of diagnosis. At 5 years, follow-up care was continuing for 55% of women, compared with 39% of men. The highest proportion of follow-up was observed among lung cancer patients (84%), followed by patients with breast cancers (63%) and gastrointestinal cancers (40%). Patients with hematological cancers had the lowest follow-up proportion at 5 years (29%) (P<0.05). Follow-up was not significantly associated with age (P=0.48), insurance status(P=0.29), and race(P=0.06). CONCLUSIONS: It is estimated that 65% of the cancer survivors in the United States are ≥5 years beyond their diagnosis but there is little data on oncology follow-up rates. In our retrospective study of 183 patients who were treated with chemotherapy only 49.7% continue to follow-up at their treatment center. LFU has important implications in planning long-term care strategies for cancer survivors and in survivorship research.

Bilateral adrenal hemorrhage in polycythemia vera.

Bilateral adrenal hemorrhage (BAH) is a rare complication typically seen in critically ill patients, which can lead to acute adrenal insufficiency and death unless it is recognized promptly and treated appropriately. We describe the case of a 64-year-old man with polycythemia vera found to be unresponsive with fever, hypotension, tachycardia, and hypoglycemia. Electrocardiogram showed ST-elevation with elevated troponin, hemoglobin, prothrombin time, and partial thromboplastin time. He required aggressive ventilator and vasopressor support. Despite primary coronary intervention, he remained hypotensive. Random cortisol level was low. He received stress dose hydrocortisone with immediate hemodynamic stability. BAH was highly suspected and was confirmed by non-contrast abdominal computed tomography. Prompt recognition and timely initiated treatment remain crucial to impact the mortality associated with acute adrenal insufficiency.