The Use of Amiloride and Sodium-Glucose Cotransporter 2 Inhibitors in Cisplatin-Induced Hypomagnesemia: A Case Report and Review of the Literature.

Cisplatin, a chemotherapy agent widely used since its FDA approval in 1978 for testicular cancer, is associated with nephrotoxicity and hypomagnesemia. Magnesium supplementation is not only a treatment for hypomagnesemia but also a well-established agent in preventing cisplatin-induced nephrotoxicity (CIN). Considering the challenges associated with intravenous magnesium use and even with the supplementation of oral forms, there is a need for drugs that effectively reduce urinary magnesium excretion. Amiloride and sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) have emerged as potential candidates. Amiloride is a well-known potassium-sparing diuretic that also has a hypomagnesemia effect seen in preclinical data. SGLT2 inhibitors are a drug class initially used in diabetes that was also observed to have positive effects on cardiovascular mortality, diabetic kidney disease, and hypomagnesemia. SGLT2 inhibitors were found to reduce hypomagnesemia in a meta-analysis study of 18 trials. However, these trials were not specifically designed for the evaluation of hypomagnesemia, and their current use in hypomagnesemia is considered off-label.

Overcoming barriers to lung cancer screening using a systemwide approach with additional focus on the non-screened.

BACKGROUND: The lung cancer screening program at St Elizabeth Healthcare (Kentucky, USA) began in 2013. Over 33,000 low-dose computed tomography lung cancer screens have been performed. From 2015 through 2021, 2595 lung cancers were diagnosed systemwide. A Screening Program with Impactful Results from Early Detection, reviews that experience; 342 (13.2%) were diagnosed by screening and 2253 (86.8%) were non-screened. As a secondary objective, the non-screened cohort was queried to determine how many additional individuals could have been screened, identifying barriers and failures to meet eligibility. METHODS: Our QlikSense database extracted the lung cancer patients from the Cancer Patient Data and Management System, and identified and categorized them separately as screened or non-screened populations. Stage distribution was compared in screened and non-screened groups. Those meeting age criteria, with any smoking history, were further queried for screening eligibility, accessing the electronic medical record smoking history and audit trail, and determining if enough information was available to substantiate screening eligibility. The same methodology was applied to CMS 2015 and USPSTF 2021 criteria. RESULTS: The screened and non-screened patients were accounted for in a stage migration chart demonstrating clear shift to early stage among screened lung cancer patients. Additionally, analysis of non-screened individuals is presented. CONCLUSION: Of the St Elizabeth Healthcare eligible patients attributed to primary care providers, 49.6% were screened in 2021. Despite this level of success, this study highlighted a sizeable pool of additional individuals that could have been screened. We are shifting focus to the non-screened pool of patients that meet eligibility, further enhancing the impact on our community.

Tumor Treating Fields therapy with standard systemic therapy versus standard systemic therapy alone in metastatic non-small-cell lung cancer following progression on or after platinum-based therapy (LUNAR): a randomised, open-label, pivotal phase 3 study.

BACKGROUND: Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell survival, leading to immunogenic cell death and enhanced antitumour immune response. In preclinical models of non-small-cell lung cancer, TTFields amplified the effects of chemotherapy and immune checkpoint inhibitors. We report primary results from a pivotal study of TTFields therapy in metastatic non-small-cell lung cancer. METHODS: This randomised, open-label, pivotal phase 3 study recruited patients at 130 sites in 19 countries. Participants were aged 22 years or older with metastatic non-small-cell lung cancer progressing on or after platinum-based therapy, with squamous or non-squamous histology and ECOG performance status of 2 or less. Previous platinum-based therapy was required, but no restriction was placed on the number or type of previous lines of systemic therapy. Participants were randomly assigned (1:1) to TTFields therapy and standard systemic therapy (investigator's choice of immune checkpoint inhibitor [nivolumab, pembrolizumab, or atezolizumab] or docetaxel) or standard therapy alone. Randomisation was performed centrally using variable blocked randomisation and an interactive voice-web response system, and was stratified by tumour histology, treatment, and region. Systemic therapies were dosed according to local practice guidelines. TTFields therapy (150 kHz) was delivered continuously to the thoracic region with the recommendation to achieve an average of at least 18 h/day device usage. The primary endpoint was overall survival in the intention-to-treat population. The safety population included all patients who received any study therapy and were analysed according to the actual treatment received. The study is registered with ClinicalTrials.gov, NCT02973789. FINDINGS: Between Feb 13, 2017, and Nov 19, 2021, 276 patients were enrolled and randomly assigned to receive TTFields therapy with standard therapy (n=137) or standard therapy alone (n=139). The median age was 64 years (IQR 59-70), 178 (64%) were male and 98 (36%) were female, 156 (57%) had non-squamous non-small-cell lung cancer, and 87 (32%) had received a previous immune checkpoint inhibitor. Median follow-up was 10·6 months (IQR 6·1-33·7) for patients receiving TTFields therapy with standard therapy, and 9·5 months (0·1-32·1) for patients receiving standard therapy. Overall survival was significantly longer with TTFields therapy and standard therapy than with standard therapy alone (median 13·2 months [95% CI 10·3-15·5] vs 9·9 months [8·1-11·5]; hazard ratio [HR] 0·74 [95% CI 0·56-0·98]; p=0·035). In the safety population (n=267), serious adverse events of any cause were reported in 70 (53%) of 133 patients receiving TTFields therapy plus standard therapy and 51 (38%) of 134 patients receiving standard therapy alone. The most frequent grade 3-4 adverse events were leukopenia (37 [14%] of 267), pneumonia (28 [10%]), and anaemia (21 [8%]). TTFields therapy-related adverse events were reported in 95 (71%) of 133 patients; these were mostly (81 [85%]) grade 1-2 skin and subcutaneous tissue disorders. There were three deaths related to standard therapy (two due to infections and one due to pulmonary haemorrhage) and no deaths related to TTFields therapy. INTERPRETATION: TTFields therapy added to standard therapy significantly improved overall survival compared with standard therapy alone in metastatic non-small-cell lung cancer after progression on platinum-based therapy without exacerbating systemic toxicities. These data suggest that TTFields therapy is efficacious in metastatic non-small-cell lung cancer and should be considered as a treatment option to manage the disease in this setting. FUNDING: Novocure.

Cellular Therapy for Lung Cancer: Focusing on Chimeric Antigen Receptor T (CAR T) Cells and Tumor-Infiltrating Lymphocyte (TIL) Therapy.

Lung cancer is a leading cause of morbidity and mortality in the United States and worldwide. The introduction of immune checkpoint inhibitors has led to a marked improvement in the outcomes of lung cancer patients. Despite these advances, there is a huge unmet need for therapeutic options in patients who are not candidates for targeted or immunotherapy or those who progress after first-line treatment. With its high mutational burden, lung cancer appears to be an attractive target for novel personalized treatment approaches. In this review, we provide an overview of two adoptive cell therapy approaches-chimeric antigen receptors (CAR) T-cell therapy and Tumor-infiltrating lymphocytes (TILs) in lung cancer with an emphasis on current challenges and future perspectives. While both these therapies are still in the early phases of development in lung cancer and need more refinement, they harbor the potential to be effective treatment options for this group of patients with otherwise poor prognoses.

Social Distancing to Avoid SARS-CoV-2 Infection in Cancer and Noncancer Patients.

BACKGROUND: Social distancing has been recommended by the Centers for Disease Control and Prevention to avoid exposure to SARS-CoV-2 ( Epidemiol Prev 2020;44:353-362).Cancer patients on or after active therapy seem to be more prone to COVID being symptomatic and life-threatening. When evaluating cancer patients' risk of acquiring COVID, it is essential to know the behavior of cancer patients that will affect their risk of exposure. However, it is not known to what degree social distancing is practiced by cancer patients compared with noncancer patients and what factors lead to the decision to distance oneself. METHOD: After a pilot phase using patients' MyChart messaging, links to the electronic questionnaires were texted to patients using Twillio. Responses were stored on REDCap (Vanderbilt University, Nashville, TN). Six questions about their social distancing behavior and mask wearing were posed and responses were compared between cancer and noncancer patients. Demographics, comorbidities, and a questionnaire about anxiety (Generalized Anxiety Disorder 7-item scale) were recorded. To assess differences between cancer and noncancer groups, Bonferroni-corrected χ 2 tests and proportions confidence intervals were used. RESULTS: The pilot survey was sent in mid-2020 and the full survey followed in January 2021 during a high community COVID incidence. Three hundred eighty-seven cancer patients (32.4% responded) and 503 noncancer patients (22.9% responded) completed the survey. Questions about leaving their houses, driving, shopping, friends, and family indicated that patients with cancer are more cautious ( P < 0.001). Cancer patients were up to 20% more likely to distance themselves. No difference was seen in wearing a mask-both groups wore approximately 90% of the time. Most respondents were female (63% versus 71%). Cancer patients were older (>60 y, 69% versus 45%) and less likely to work (52% versus 31%) or less likely to be White collar workers (21% versus 38%). In both groups, 54% marked "not at all anxious." CONCLUSIONS: Cancer patients' responses revealed a distancing behavior that would likely lower the risk exposure to SARS-CoV-2. It is unclear which of the demographic differences would account for this behavior, although remarkably anxiety was not a clear motivating factor. The high acceptance of masks is encouraging. Early publications during the pandemic and patient education suggesting a higher COVID risk for cancer patients may have reduced risk prone behavior. Considering COVID's impact on the vulnerable cancer population and uncertainty in immunosuppressed patients about clearing the virus or adequately responding to a vaccine, further studies about health behavior and health promotion during the pandemic are needed.

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.

The Utility of Differential Scanning Calorimetry Curves of Blood Plasma for Diagnosis, Subtype Differentiation and Predicted Survival in Lung Cancer.

Early detection of lung cancer (LC) significantly increases the likelihood of successful treatment and improves LC survival rates. Currently, screening (mainly low-dose CT scans) is recommended for individuals at high risk. However, the recent increase in the number of LC cases unrelated to the well-known risk factors, and the high false-positive rate of low-dose CT, indicate a need to develop new, non-invasive methods for LC detection. Therefore, we evaluated the use of differential scanning calorimetry (DSC) for LC patients' diagnosis and predicted survival. Additionally, by applying mass spectrometry, we investigated whether changes in O- and N-glycosylation of plasma proteins could be an underlying mechanism responsible for observed differences in DSC curves of LC and control subjects. Our results indicate selected DSC curve features could be useful for differentiation of LC patients from controls with some capable of distinction between subtypes and stages of LC. DSC curve features also correlate with LC patients' overall/progression free survival. Moreover, the development of classification models combining patients' DSC curves with selected plasma protein glycosylation levels that changed in the presence of LC could improve the sensitivity and specificity of the detection of LC. With further optimization and development of the classification method, DSC could provide an accurate, non-invasive, radiation-free strategy for LC screening and diagnosis.

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.

A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN 14-179.

BACKGROUND: Five-year overall survival (OS) for patients with unresectable stage III non-small cell lung cancer (NSCLC) is poor. Until recently, a standard of care was concurrent chemoradiation alone. Patients with metastatic NSCLC treated with anti-programmed death 1 antibodies have demonstrated improved OS. This trial evaluated pembrolizumab as consolidation therapy after concurrent chemoradiation in patients with unresectable stage III disease. METHODS: Patients with unresectable stage III NSCLC received concurrent chemoradiation with cisplatin and etoposide, cisplatin and pemetrexed, or carboplatin and paclitaxel and 59.4 to 66.6 Gy of radiation. Patients with nonprogression of disease were enrolled and received pembrolizumab (200 mg intravenously every 3 weeks for up to 12 months). The primary endpoint was the time to metastatic disease or death (TMDD). Secondary endpoints included progression-free survival (PFS) and OS. RESULTS: The median follow-up for 93 patients (92 for efficacy) was 32.2 months (range, 1.2-46.6 months). The median TMDD was 30.7 months (95% confidence interval [CI], 18.7 months to not reached), which was significantly longer than the historical control of 12 months (P < .0001). The median PFS was 18.7 months (95% CI, 12.4-33.8 months), and the median OS was 35.8 months (95% CI, 24.2 months to not reached). The 1-, 2-, and 3-year OS estimates were 81.2%, 62.0%, and 48.5%, respectively. Forty patients (43.5%) completed 12 months of treatment (median number of cycles, 13.5). Symptomatic pneumonitis (grade 2 or higher) was noted in 16 patients (17.2%); these cases included 4 grade 3 events (4.3%), 1 grade 4 event (1.1%), and 1 grade 5 event (1.1%). CONCLUSIONS: Consolidation pembrolizumab after concurrent chemoradiation improves TMDD, PFS, and OS in comparison with historical controls of chemoradiation alone. Rates of grade 3 to 5 pneumonitis were similar to those reported with chemoradiation alone.

The association between history of traumatic events and health-related quality of life among lung cancer patients.

PURPOSE: Promoting health-related quality of life (HRQOL) is a primary goal of lung cancer treatment. Trauma history and distress can negatively impact HRQOL. DESIGN: A cross-sectional design examined the associations of trauma history, cancer-specific distress, and HRQOL. SAMPLE/METHOD: Sixty lung cancer patients completed questionnaires on trauma history including the number and severity of traumatic events experienced. Cancer-specific distress, HRQOL, and depression were also reported. FINDINGS: As hypothesized, trauma history and cancer-specific distress were negatively associated with HRQOL (all r's > -.27). Depression emerged as a confound in the association between cancer-specific distress and HRQOL. CONCLUSIONS: Retrospectively-reported trauma was linked with poorer HRQOL in lung cancer patients. IMPLICATIONS: Interventions aimed at improving lung cancer patients' HRQOL should consider the possible role of trauma history (both frequency and distress).

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.

Transcription factor c-Maf is a checkpoint that programs macrophages in lung cancer.

Macrophages have been linked to tumor initiation, progression, metastasis, and treatment resistance. However, the transcriptional regulation of macrophages driving the protumor function remains elusive. Here, we demonstrate that the transcription factor c-Maf is a critical controller for immunosuppressive macrophage polarization and function in cancer. c-Maf controls many M2-related genes and has direct binding sites within a conserved noncoding sequence of the Csf-1r gene and promotes M2-like macrophage-mediated T cell suppression and tumor progression. c-Maf also serves as a metabolic checkpoint regulating the TCA cycle and UDP-GlcNAc biosynthesis, thus promoting M2-like macrophage polarization and activation. Additionally, c-Maf is highly expressed in tumor-associated macrophages (TAMs) and regulates TAM immunosuppressive function. Deletion of c-Maf specifically in myeloid cells results in reduced tumor burden with enhanced antitumor T cell immunity. Inhibition of c-Maf partly overcomes resistance to anti-PD-1 therapy in a subcutaneous LLC tumor model. Similarly, c-Maf is expressed in human M2 and tumor-infiltrating macrophages/monocytes as well as circulating monocytes of human non-small cell lung carcinoma (NSCLC) patients and critically regulates their immunosuppressive activity. The natural compound ß-glucan downregulates c-Maf expression on macrophages, leading to enhanced antitumor immunity in mice. These findings establish a paradigm for immunosuppressive macrophage polarization and transcriptional regulation by c-Maf and suggest that c-Maf is a potential target for effective tumor immunotherapy.

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.

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.

Rescue therapy for acute idiopathic thrombocytopenic purpura unresponsive to conventional treatment.

A 61-year-old woman with chronic lymphocytic leukaemia, with Richter's transformation to a diffuse, large, B-cell lymphoma, treated with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone and in complete remission, presented to the hospital after her platelets were found to be 2×10³/µL in outpatient laboratory studies. She initially underwent a platelet transfusion without improvement. This was followed by 4 days of high-dose dexamethasone and intravenous immunoglobulin, which again yielded no meaningful effect. Even a single-dose rituximab failed to achieve a platelet increase after 5 days of monitoring. The patient was then given 2 mg of intravenous vincristine along with a high-dose of dexamethasone and IVIG and demonstrated substantial recovery in platelets to >50×10³/µL within 48 hours. This case study provides an overview of the current management strategies for idiopathic thrombocytopenic purpura that is unresponsive to conventional medical therapy and particularly sheds light on their therapeutic benefits and potential adverse effects.

Treatment and outcomes of non-small-cell lung cancer patients with high comorbidity.

BACKGROUND: The life expectancy of untreated non-small-cell lung cancer (NSCLC) is dismal, while treatment for NSCLC improves survival. The presence of comorbidities is thought to play a significant role in the decision to treat or not treat a given patient. We aim to evaluate the association of comorbidities with the survival of patients treated for NSCLC. METHODS: We performed a retrospective study of patients aged ≥66 years with invasive NSCLC between the years 2007 and 2011 in the Surveillance, Epidemiology, and End Results Kentucky Cancer Registry. Comorbidity was measured using the Klabunde Comorbidity Index (KCI), and univariate and multivariate logistic regression models were used to measure association between receiving treatment and comorbidity. Kaplan-Meier plots were constructed to estimate time-to-event outcomes. RESULTS: A total of 4014 patients were identified; of this, 94.9% were white and 55.7% were male. The proportion of patients who did not receive any treatment was 8.7%, 3.9%, 19.1%, and 23.5% for stages I, II, III, and IV, respectively (p<0.0001). In multivariate analysis, older age, higher stage, and higher comorbidity (KCI ≥3) were associated with a lower likelihood of receiving any treatment. The median overall survival (OS) for untreated and KCI=0 was 17.7 months for stages I and II, 2.3 months for stage III, and 1.3 months for stage IV. The median OS for treated and KCI=0 was 58.9 months for stages I and II, 16.8 months for stage III, and 5.8 months for stage IV (p<0.01). Treatment was an independent predictor of OS in multivariate analysis that included KCI scores. CONCLUSION: Our data suggest that lung cancer patients may derive a survival benefit from therapies, regardless of the presence of comorbidities, although the degree of benefit seems to decrease with higher KCI scores.