bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-sectional imaging utilization for EGFR, EML/ALK, and KRAS mutant non-small cell lung cancer.
Authors: Bomberger Thomas , Kikano Elias , Laukamp Kai , Smith Daniel Arnold , Gupta Amit , Ansari-Gilani Kianoush , Dowlati Afshin , Ramaiya Nikhil H.
Published: May 2019

e20663

Background: Targeted therapies for specific genotypic subsets of non-small cell lung cancer (NSCLC) patients have had drastic effects on overall survival at all stages. However, the NCCN guidelines have remained relatively static with respect to initial evaluation, staging, response, and imaging surveillance. In this study we evaluated 3 cohorts of patients, two with a specific targetable mutation (EGFR and EML/ALK) and one without a targetable mutation available (KRAS), for cross-sectional imaging utilization in the initial presentation and surveillance of disease. Methods: Retrospective analysis of imaging studies for patients with NSCLC who received treatment and follow-up between 2007 and 2018 was completed. CT, MRI, and PET imaging data were collected from the picture archiving system. Additional clinical data collected included age, race, smoking history, and dates of diagnosis and death. Results: 153 NSCLC patients were identified with positive EGFR (n = 65), EML/ALK (n = 15), or KRAS (n = 73) mutations. Patients averaged an age of 64 at diagnosis, with a distribution of 38% male, 62% female, 29% current smokers, 48% former smokers, and 23% never smokers. Mean duration between date of diagnosis and death for each group was 1099 ± 770 days (EGFR), 1139 ± 924 days (EML/ALK), and 542 ± 602 days (KRAS). Compared to the KRAS group, the EML/ALK group had higher utilization of chest CTs (p = 0.044), pulmonary embolus CTs (p = < 0.001), abdominopelvic CTs (p = 0.004), and PET CTs (p = 0.006). The EGFR group had significantly fewer pulmonary embolus CTs (p = < 0.001) and higher numbers of non-brain MRIs (p = 0.004) compared to the KRAS group, as well as fewer abdominopelvic CTs (p = 0.034) compared to the EML/ALK group. Conclusions: Different genotypes of NSCLC with available targetable mutations show statistically significant differences in cross-sectional imaging utilization compared to those without targetable mutations. [Table: see text]
Diverse RB1 mutations and co-occurring molecular alterations in advanced NSCLC.
Authors: Huang Jie , Peng Lun-Xi , Yang Jin-Ji , Wu Yi-Long
Published: May 2019

e20672

Background: Retinoblastoma transcriptional corepressor 1 (RB1) mutation is strikingly more frequent in non-small cell lung cancer (NSCLC) with SCLC transformation (SCLC-T) than that remain NSCLC. However, NSCLC patients harboring RB1 mutations do not necessarily transform to SCLC. Thus, exploring RB1 mutation frequency and co-occurring genomic alterations is potentially important to understand the SCLC-T mechanism. Methods: We investigated 47 NSCLC pts with RB1 aberrations at our institution. Submitted samples (tissue, plasma, cerebrospinal fluid and pleural effusion) were analyzed using next-generation sequencing across at least 139 genes (139-520). Demographics, molecular features and outcomes were analyzed. Results: Among 47 pts (27F/20M), median age was 58. Twenty (47%) had brain metastases and 7 (15%) underwent SCLC-T. A total of 39 types of RB1 mutations were identified, in which copy number deletion is the most common (40%). RB1 mutations were present from early NSCLC and were detected in 88%(29/33), 82%(9/11), 70%(9/13) and 42% (20/48) of tissue, pleural effusion, CSF and plasma samples, respectively. The most frequent co-occurring alterations were TP53 (100%, 95%) and EGFR (100%, 93%) in both SCLC-T group and non-transformed group. Besides, mutations involving in the PI3K pathway were often detected: PIK3CA (57%, 20%), AKT (43%, 10%), PTEN (14%, 15%), MET (14%, 15%), NTRK1 (14%, 13%). Notably, RB1 also co-occurred with ALK fusion (1/47). Moreover, SCLC-T group harbored significant higher frequency of RB1 mutation compared with non-transformed group. Conclusions: RB1 mutations in NSCLC are associated with a trend toward SCLC-T, and the mechanisms may be increased frequency of RB1 mutations and co-occurring similar molecular alterations to those in SCLC.
Association of allele frequency of EGFR mutation with efficacy of EGFR TKIs in advanced non-small cell lung cancer.
Authors: Li Xiang-Meng , Yang Jin-Ji , Wu Yi-Long
Published: May 2019

e20678

Background: Next-generation sequencing (NGS) is beneficial to precision medicine. However, it remains elusive whether the epidermal growth factor receptor ( EGFR) mutant allele frequency (MAF) tested by NGS is predictive for tyrosine kinase inhibitors (TKIs) therapy in advanced non-small-cell lung cancer (NSCLC). Methods: We enrolled 194 advanced NSCLC EGFR mutant patients receiving erlotinib or gefitinib orally. A total of 196 baseline tissue samples from a phase III clinical trial (CTONG 0901; clinicaltrials.gov No.NCT01024413) between July 2009 and 2014 were analyzed by a panel of 168 lung cancer-related genes NGS. The median EGFR MAF was 25.8% (range, 1.4%-86.2%). Patients were divided into MAF low group (1.4%-25.8%) and high group (25.8%-86.2%). We defined PFS as the time of randomization to confirmed disease progression or death from any cause. OS was calculated from randomization to the last visit or death from any cause. Tumor response was assessed by investigators according to RECIST version 1.1. Survival was estimated using the Kaplan-Meier method. The relationship between the response of TKIs and EGFR MAF were evaluated by Pearson Chi-square test or Fisher’s exact test. Results: The median age was 58.7 years (range,31.2- 85.1), 92 (47.4%) were male, 41(21.1%) were smokers,189 (97.4%) had adenocarcinoma, 105 (54.1%) patients were identified as carrying EGFR exon 19 deletion, while one patient with the co-existence of T790M mutation. 85 (43.8%) patients harbored EGFR exon 21 L858R mutation. After 5 weeks of treatment, the initial response was assessed. No significant difference was observed in initial response between the high and low groups ( P = 0.502). The difference in best response to EGFR-TKIs between the groups was not significant ( P = 0.557). Objective response rate (ORR) was 56.2% and 57.5% respectively. There was no significant difference in median PFS [11.2 (95% CI,10.0 -12.3) vs 12.4 (95% CI,10.3-14.5) months, P = 0.509] between the groups. The high group was not significantly superior to the low group in median OS[20.5 (95% CI,18.0-23.0) vs 23.1 (95% CI,19.3-27.0) months, P = 0.500]. Conclusions: EGFR mutant allele frequency tested by NGS is not associated with the efficacy of EGFR TKIs in advanced NSCLC.
TP53 mutations in EGFR mt+ NSCLC IV as a predictive factor for ORR, PFS, and OS irrespective of T790M.
Authors: Roeper Julia , Lueers Anne Christina , Falk Markus , Tiemann Markus , Otto-Sobotka Fabian , Griesinger Frank
Published: May 2019

e20679

Background: The impact of TP53 mutations in EGFR mt+ pts on PFS and OS is controversial, and different classifications of TP53 mt+ with respect to functional and potential predictive impact have been published. Therefore, we retrospectively analyzed the impact of TP53 aberrations on ORR, PFS and OS in a cohort of EGFR mt+ NSCLC IV pts (UICC 7) using different classifications of TP53 mutations. Methods: 75 EGFR mt+ NSCLC IV pts were analyzed for TP53 co-mutations. TP53 mt+ were classified according to Poeta et al. into (1) disruptive vs. non-disruptive, according to structural prediction and biophysical characteristics into (2) pathogenic vs. non-pathogenic and finally into (3) exon 8 vs. non-exon 8 mutations according to Crino et al.. The endpoints ORR according to Recist 1.1, PFS and OS were calculated by Kaplan Meier. Results: 69 of the 75 EGFR mt+ pts (92%) had a common mutation in EGFR E19/21. In 59/75 pts (79%) material was sufficient for successful TP53 analysis. TP53 mt+ were found in 29/59 pts (49%), 16/59 (27%) had a TP53 disruptive mt+, 13/59 (22%) a TP53 non-disruptive mt+ and 30/59 a TP53 WT configuration. Using the structural/biophysical classification, 7/59 (12%) had a TP53 non-pathogenic and 22/59 (37%) a TP53 pathogenic mt+. Of the 29 mutated pts, 6 had a TP53 Exon 8 mt+. Median PFS on 1st line TKI was 12 vs. 18 months for non-disruptive/disruptive mt+ vs. WT (p < 0.004), 11 vs. 17 months for pathogenic vs. non-pathogenic/WT (p < 0.0001), and 7 vs. 12 vs. 18 months for exon 8 vs. non-exon 8 vs. WT (p < 0.006). Median OS was 24 vs. 42 months in non-disruptive/disruptive mt+ vs. WT (p < 0.0009), 23 vs. 42 months in pathogenic vs. non-pathogenic/WT (p < 0.001) and 12 vs. 28 months for TP53 exon 8 vs. non-exon 8 mt+ (p < 0.024). Additionally ORR was significantly impacted by TP53 mt+. In rebiopsy samples on acquired resistance, no new TP53 mutations were observed and there were no correlations of TP53 mutations with clinical factors and the EGFR mt+ type including T790M. Conclusions: TP53 seems to be a frequent co-mutation in EGFR mt+ NSCLC and has a strong impact on all clinical endpoints on TKI therapy. These data might have an impact on the management and follow up of pts with TP53 mt+. Furthermore, there is an urgent need for further therapeutic approaches in this patient group.
The clinical prognostic factors in advanced lung adenocarcinoma patients with different EGFR mutation subtype.
Authors: Wang Yudong , Yan Jianzhu , Zuo Jing , Fan Zhisong , Wang Long , Xu Xiaoli , Liu Fengling , Wei Suju , Jiang Da
Published: May 2019

e20680

Background: The prognostic factors of advanced NSCLC patients with EGFR mutation subtypes remains controversial. This study aimed to investgate the association of clinical prognostic factors with EGFR-TKI efficacy in advanced lung adenocacinoma patients with different EGFR mutation subtypes. Methods: The clinical characteristics, treatment and survival data of advanced lung adenocarcinoma patients with EGFR sensitive mutations who were treated with Icotinib (Betta Pharmaceuticals, China) from January 2011 to December 2017 in our medical center were reviewed. The prognositic factors of patients between with EGFR exon 19 deletion (19-Del) and exon 21 Leu858Arg mutation (L858R) were retrospectively analyzed by using the Kaplan-Meier method, the chi-square test, and multivariate Cox hazards model. Results: A total of 187 patients were enrolled in the study, including 104 patients with EGFR19-Del and 83 patients with EGFR21-L858R. The results showed that no significant difference in mPFS between the two groups (19-Del vs. L858R: 15.0 months, 95% CI 17.2-32.8months vs. 13.0 months 95% CI 11.7-14.3 months, p = 0.347), while the mOS of patients with 19-Del (35months, 95% CI 28.6-41.4 months) was significantly better than that of patients with EGFR21-L858R (25 months, 95%CI 17.2-32.8 months, p = 0.020). For PFS, liver metastasis was an independent prognostic factor in EGFR19-DEL patients (HR 5.009, 95%CI 1.296-19.354, p = 0.019), while gender (HR 5.881, 95%CI 2.105-16.431, p = 0.001), smoking status (HR 6.972, 95%CI 2.851-17.049, p = 0.001), lymph node metastasis (HR 2.676, 95%CI 1.002-7.148, p = 0.050) were independent prognostic factors in patients with L858R. As for OS, age (HR 1.080, 95%CI 1.017-1.147, p = 0.012), brain metastases (HR 23.166, 95%CI 3.946-136.009, p = 0.001), liver metastases (HR 14.088, 95%CI 1.782-111.385, p = 0.012), renal or adrenal metastasis (HR 10.558, 95%CI 1.480-75.326, p = 0.019), TKI initial efficacy (HR 6.638, 95%CI 2.743-16.067, p = 0.001) were independent prognostic factors in patients with 19-del, however, the initial efficacy of TKI (HR 6.089, 95% CI 2.669-13.893, p = 0.001) was an independent prognostic factor in patients with L858R. Conclusions: The mOS of patients with EGFR 19-Del treated with Icotinib was significantly better than that of patients with L858R, while the mPFS of both were similar. Moreover, there are significant differences in prognostic factors of advanced lung adenocarcinoma patients between with 19-Del and L858R subtypes, which may be helpful for the clinical treatment strategy of EGFR-TKI.
Overcoming acquired osimertinib-resistance in EGFR-mutant advanced non-small lung cancer mediated by activating BRAF V600E mutation.
Authors: Abdulla Diana S.Y. , Scheffler Matthias , Kobe Carsten , Persigehl Thorsten , Schmidt Matthias , Fassunke Jana , Merkelbach-Bruse Sabine , Michels Sebastian Yves Friedrich , Nogova Lucia , Koleczko Sophia , Fischer Rieke Nila , Riedel Richard , Drzezga Alexander , Büttner Reinhard , Wolf Juergen
Published: May 2019

e20682

Background: There is growing insight in the mechanisms underlying resistance to the 3rdgeneration EGFR inhibitor osimertinib. Unlike resistance to 1stgeneration inhibitors, these mechanisms not necessarily lead to sequential targeted therapy approaches. Here we report on the treatment of two patients with acquired resistance to osimertinib with a new detected BRAF V600E mutation as resistance mechanism. Methods: We identified two patients with EGFR-T790M-mutant advanced NSCLC with progression on osimertinib and detection of a new BRAFV600E mutation in a tumor rebiopsy by next-generation sequencing (NGS). No other known resistance mechanism beside T790M loss in one patient was found. Osimertinib was discontinued and BRAF-targeted combination therapy with dabrafenib and trametinib at standard dose was initiated. We monitored the clinical course with sequential 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) / computed tomography (CT) assessing maximum standard uptake value (SUVmax), sequencing based liquid biopsies and tumor marker assessment. Results: Patient (1) with EGFR del19 (E746_A750del), preserved T790M mutation and acquired BRAF V600E mutation showed reduction in FDG uptake of 18% after 2 weeks of dabrafenib/trametinib that demonstrated a slight increase of 12% in a FDG-PET/CT scan 4 weeks thereafter and combination treatment has been continued. Patient (2) with EGFR del19 (E746_A750del), T790M loss and new BRAF V600E mutation showed continuous metabolic (+8% and + 39%, respectively) and morphologic progression after 2 and 4 weeks of dabrafenib and trametinib. A tumor rebiopsy showed no additional molecular changes. We changed the treatment to osimertinib and dabrafenib combination and observed an impressive metabolic response (-33%) after 2 weeks by FDG-PET/CT. Conclusions: BRAF V600E mutation has recently been described as a novel molecular resistance mechanism in osimertinib-resistant EGFR-mutant NSCLC. We describe one patient where combined BRAF/MEK inhibition with no additional EGFR-inhibition resulted in a preliminary feasible tumor control, but confirmatory CT staging is pending. In a second patient, co-inhibition of EGFR and BRAF pathway with osimertinib and dabrafenib was needed to overcome BRAF-mediated osimertinib resistance resulting in an impressive early tumor response that was not observed to either single-target inhibition of EGFR or BRAF. FDG-PET/CT was able to monitor tumor dynamics. Updated data will be presented.
The interplay between PD-L1 and vimentin in NSCLC patients: An exploratory analysis.
Authors: Bronte Giuseppe , Puccetti Maurizio , Cravero Paola , Ravaioli Sara , Tumedei Maria Maddalena , Ulivi Paola , Burgio Marco Angelo , Verlicchi Alberto , Delmonte Angelo , Cappuzzo Federico , Crino Lucio , Bravaccini Sara
Published: May 2019

e20688

Background: The immune modulation is emerging as a key strategy in non-small cell lung cancer (NSCLC) patients management. PD-L1 has been the only biomarker validated for immunotherapy but it holds many limitations. Vimentin is one of the marker for epithelial-to-mesenchymal transition (EMT), a biological process which favors immune escape. We explored two issues: the correlation between PD-L1 and Vimentin expression in NSCLC samples and the prognostic value of PD-L1 and vimentin concordance in NSCLC patients. Methods: We collected all the NSCLC samples evaluable for both PD-L1 and Vimentin and recorded the relative available clinical and survival data, if written informed consent was present. PD-L1 and Vimentin were retrospectively assessed through immunohistochemistry (IHC) by using prediluted antibodies clones SP263 (Ventana Medical Systems, Tucson, AZ, USA) and anti Vimentin V9 (Ventana Medical Systems) on Benchmark XT Platform (Ventana Medical Systems). Biomarker expression was detected and semiquantitatively quantified as the percentage of immunopositive tumor cells on the total of tumor cells. We correlated PD-L1 and Vimentin expression through linear regression. We compared survival of patients with both PD-L1 and Vimentin 0% and all the others via Kaplan-Meier method by using MedCalc software version 18.11.3. Results: Ninety-nine samples underwent PD-L1 and Vimentin IHC analysis. A weak positive statistically significant correlation was found between the 2 biomarkers (r = 0.41; p < 0.001). For 40 patients survival data (from first NSCLC diagnosis) were available. Survival analysis showed that PD-L1 and Vimentin negative patients (n = 12) experienced not statistically significant longer survival (HR = 0.35; 95%CI: 0.08-1.51; p = 0.16). Conclusions: These preliminary findings suggest that an interplay can exist between PD-L1 and vimentin in NSCLC, but analysis in a wider population is necessary. Studies on the significance of this interplay for immunotherapy efficacy should be designed.
End-of-life care and prognosis of elderly patients with advanced cancer in palliative care unit.
Authors: Hiramoto Shuji , Tamaki Tomoko , Tetsuo Hori , Kikuchi Ayako , Yoshioka Akira , Kirishima Toshihiko
Published: May 2019

e23011

Background: Prognosis of end-of-life characteristics, which are indicators of palliative care, especially in elderly cancer patients, remains unclear. Methods: We retrospectively analyzed 510 patients who died of advanced cancer at our hospital from August 2011 to August 2016. The patients were divided into two groups: elderly patients (over 80 years old, N = 140) and non-elderly patients (under 80 years old, N = 370). The number of patients (306 male and 204 female) with gastro-esophageal, biliary-pancreatic, colorectal, lung, breast, urological, gynecological, hepatocellular, and other cancers were 114, 98, 82, 84, 25, 36, 20 and 51, respectively. The primary endpoint of the study was to analyze the relationship of end-of-life symptoms, treatment, and chemotherapy with age. The secondary endpoint was to identify the prognostic factors in elderly patients with advanced cancer at the end-of-life. Results: ECOG Performance Status of 0.1 was recorded for 12 patients and 2-4 for 498 patients. The prevalence rate of cancer pain in elderly patients was 19.3%, which was significantly lower than that in non-elderly patients (31.4%). Fatigue in elderly patients was 27.9%, which was significantly lower than that in non-elderly patients (37.6%). Continuous deep sedation usage in elderly patients was 12.9%, which was significantly lower than that in non-elderly patients (28.9%). The mean opioid dose in elderly patients was 23.3mg/day, which was significantly lower than that that in non-elderly patients (43.8mg/day). The rate of more than one line of chemotherapy for elderly patients was 44.4%, which was lower than that for non-elderly patients (65.4%). The rate of use of more than one type of cytotoxic agent in the last regimen for elderly patients was 13.3%, which was lower than that for non-elderly patients (30.8%). Consciousness level was recognized as a significant prognostic factor (HR 1.714, p = 0.048) using multivariate analysis of prognosis in elderly patients at the end-of-life. Conclusions: End-of-life symptoms and the intensity of end-of-life treatment, including chemotherapy, were lesser in elderly patients as compared to non-elderly patients. Consciousness level was a significant prognostic factor in elderly patients at the end-of-life.
Treatment and outcome of elderly patients with PCNSL: A Beaumont experience.
Authors: Pang Yifan , Gbadamosi, MD. Bolanle , Bakhsh Saaquib , Gaikazian Susanna S. , Jaiyesimi Ishmael A.
Published: May 2019

e23012

Background: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy. Prognosis remains poor, and data on clinical characteristics or outcomes are limited, particularly in the elderly. In the literature, age over 50 is a major poor prognostic factor. Herein, we report our experience of PCNSL in elderly patients. Methods: The electronic medical records from 2007 to 2015 of the Beaumont Health System were analyzed. Patients with non-Hodgkin’s Lymphoma (NHL) were reviewed and those with PCNSL were identified. Results: Of the 617 NHL patients, 21 (3.4%) had PCNSL, 12 (57.1%) were male and 17 (81.0%) Caucasian. Median age was 76 (range, 55 to 83), and the majority 18 (85.7%) were above age 65. Deep brain lesions occurred in 11 (52.4%) patients. Eighteen (85.7%) received treatment, including 3/18 (16.7%) with high-dose methotrexate (HD-MTX) only, 5/18 (27.8%) HD-MTX plus rituximab (MR), 2/18 (11.1%) HD-MTX with vincristine and procarbazine, 7/18 (38.9%) MR and other chemotherapy, and 1/18 (5.6%) temozolomide and rituximab. MTX dose ranged from 1.8 to 8 g/m2 (median, 3.5 g/m2). The number of treatment cycles ranged from 1 to 11 (median, 3). Whole brain radiation was given to 4 (22.2%) patients with refractory disease after systemic chemotherapy. None of the patients received definitive radiation. Overall response rate was 44.4%, including 4/18 (22.2%) CR and 4/18 (22.2%) PR. Median survival was 4.0 months (95% CI, 2.3 to 5.7 months). At the time of data collection (November, 2018), only four patients were alive. Causes of death included disease progression (58.8%), neutropenic sepsis (23.5%), and MTX toxicity, predominantly acute kidney injury and severe gastrointestinal mucositis (17.7%). Age, lesion depth, treatment, and other clinical characteristics did not impact survival (all p > 0.05). Conclusions: Although HD-MTX remained the backbone of therapy for most patients, we observed a heterogeneous treatment pattern in our elderly patient population. More than 50% had primary refractory diseases, while about 40% had treatment related mortality. This study further emphasized the need for more trials enrolling elderly patients with PCNSL, utilizing novel agents, and investigating molecular prognostic markers.
Estimating survival time in older adults receiving chemotherapy for advanced cancer.
Authors: Moth Erin , Blinman Prunella , Stefanic Natalie , Naganathan Vasi , Martin Andrew James , Grimison Peter S. , Stockler Martin R. , Beale Philip James , Kiely Belinda Emma
Published: May 2019

e23017

Background: Best-case, worst-case, and typical scenarios for survival time, based on an oncologist’s estimate of expected survival time (EST), have proven accurate in a range of advanced cancers. We sought the accuracy and prognostic significance of such estimates, and of a simple, pragmatic rating of frailty, in older adults starting chemotherapy. Methods: Participants (pts) were aged 65 or older and starting a new line of chemotherapy for advanced cancer. For each pt at baseline, their treating oncologist recorded an individualised estimate of EST (median survival in a group of similar patients), ECOG performance status (PS), and rating of frailty with the single-item, Clinical Frailty Scale from the Canadian Study of Health and Aging. We hypothesised that estimates of EST would be unbiased (approximately 50% of pts would live longer than their EST); imprecise ( < 33% would live for 0.67 to 1.33 times their EST); and, that simple multiples of the EST would provide accurate individualised scenarios for survival time, i.e. approximately 10% of pts would die within ¼ of their EST, 10% would live longer than 3 times their EST, and 50% would live from half to double their EST. We identified independent predictors of observed survival time (OST) with multivariable Cox regression. Results: Baseline characteristics of the 102 pts were: median age 74 (range 65-86), 1st line chemotherapy in 67%, colorectal cancer in 33%, PS 0 or 1 in 80%, and frailty rating of vulnerable to frail in 35%. The median EST was 15 months (range 4-60), median follow-up time was 19 months (range 0-27), and median OST was 15 months (range 0.5-27+). As hypothesized, 54% of pts lived longer than their EST, 30% lived within 0.67 to 1.33 times their EST, 56% lived half to double their EST, and 9% lived ≤1/4 of their EST. Follow-up was too short to observe those who will live ≥3 times their EST. Independent predictors of OST were frailty (HR 2.8, 95%CI 1.6-4.9, p = 0.0004) and EST (HR 0.96, 95%CI 0.93-0.99, p = 0.03). Conclusions: Oncologists’ estimates of EST were unbiased, imprecise, and accurate for formulating scenarios for survival time. A simple, pragmatic rating of frailty by the treating oncologist was a strong predictor of OST even after accounting for their estimate of EST.
Evaluation of readmission rates for gastrointestinal bleeds in high risk oncologic patients.
Authors: Babar Laila , Bakalov Veli , Monga Dulabh K. , Chahine Zena , Ashraf Obaid
Published: May 2019

e23031

Background: Gastrointestinal bleeding (GIB) results in high rates of hospital admissions, readmissions, significant morbidity and high healthcare cost. To lower readmission rates, Medicare mandates public reporting, however it does not differentiate between patient populations. GIB is a complex disease with treatment selection and patient outcome changing with different patient populations. We must identify vulnerable groups and high risk characteristics. Malignancy is a hypercoaguable disease and when combined with atrial fibrillation or history of clots, it can increase stroke and pulmonary embolism risk. These patients require anticoagulation putting them at a higher risk of bleeding. In our study, we identified cancer patients with atrial fibrillation and evaluated reasons for differences in readmission rates for GIB. Methods: We queried our EMR for a list of patients from April 2016-April 2018. Inclusion criteria was admission for GIB, a history of cancer, atrial fibrillation, DVT or PE. Patients were divided into groups with and without readmission for GIB, and differences in characteristics were analyzed. Odds ratios(OR) with p-value 0.05 and confidence interval (CI) 95% were calculated. Results: Of 111 patients, 57 met our inclusion criteria, 32 male and 25 female with average age 78.8 years. 18 patients required readmission, 12 for GIB. 32% of our population was readmitted within 30 days of discharge, 21% was readmitted for a GIB. BMI > 30(OR:0.28; CI 0.15-0.54; p = 0.0002), ICU admission during hospitalization(OR:0.083; CI 0.019-037; p = 0.0011), and lower GI tract as site of bleeding (OR:0.54; CI 0.30-0.98; p = 0.04) were associated with a lower incidence of readmission for GIB. Administration of blood transfusion (OR:2.80; CI 1.58-4.99; p = 0.0004)and discharge disposition to skilled facility(OR:1.93; CI 1.04-3.57; p = 0.036) was associated with a higher incidence of readmission. There was no difference with type of anticoagulation. Conclusions: The readmission rates for GIB in our population (32%) was higher than the national average (12%). Cancer patients requiring anticoagulation have a drastically different hospital course and outcomes than healthy patients and should have different quality metrics and treatment algorithms. This will also make Medicare penalties more accurate.
Elderly patients have limited access to systemic therapy for metastatic renal cell carcinoma (mRCC) and shorter overall survival in Russia, Belarus and Kazakhstan.
Authors: Tsimafeyeu Ilya , Krasny Sergei , Nurgaliyev Nurzhan , Varlamov Ilya , Petkau Vladislav , Safina Sufia , Zukov Ruslan , Mazhbich Mikhail , Statsenko Galina , Novikova Olga , Zaitsev Igor , Kaidarova Dilara , Shatkovskaya Oxana , Moiseyev Pavel , Rolevich Alexander , Evmenenko Alesya , Popova Irina L. , Vladimirova Liubov Yu
Published: May 2019

e23033

Background: Russia, Belarus and Kazakhstan are countries of the Eurasian Economic Union with upper-middle-income economies. Limited sources of the healthcare system could affect the treatment of individual cancer patients. The data on the treatment outcomes of elderly patients with mRCC are limited in these countries. RENSUR3 registry study assessed real-world data on the use of therapies in mRCC and overall survival (OS) in this population. Methods: Patients from Russia, Belarus and Kazakhstan were included in the retrospective multicenter registry study. To be eligible, patients were required to have mRCC diagnosed from January 2015 to January 2016. Anonymized data were collected through an online registry. The outcomes of interest were OS, patient characteristics and treatment patterns. Results: 1,094 adult mRCC patients were identified. Mean age at diagnosis of mRCC was 62.3 (SD, 11.2) years. 447 (41%) patients were 65 years and older. In total, 595 (54.4%) patients received systemic therapy for metastatic disease. 58% of elderly patients were not treated compared to 37% of younger patients. Cytokines were the most commonly used treatment in elderly patients (115 of 189 patients, 61%) while targeted therapy was more widely used in younger patients (223 of 406, 55%). Median OS was 12.7 months (95% CI 11.3-14.1) and 9.3 months (7.7-9.9) for patients aged < 65 and ≥65 years, respectively (P < 0.0001). Conclusions: More than half of elderly patients received no systemic therapy or had only cytokines for mRCC in Russia, Belarus and Kazakhstan which doubtless negatively affected OS in this population. Novel therapies should be considered as life-saving and a priority in elderly patients.
Spiritual and psychological distress in older and the oldest-old living with advanced cancer patients (O-OOAdCa) in a comprehensive cancer center.
Authors: Delgado-Guay Marvin Omar , De La Cruz Maxine Grace Jaucian , Pang Linda , Williams Janet L. , Bruera Eduardo
Published: May 2019

e23041

Background: Older adults living with cancer may experience multiple physical, emotional and spiritual symptoms. Limited literature describing the frequency of psychological and spiritual distress in O-OOAdCa. Methods: Retrospective chart review of patients seen by the Palliative Care team from January 2013 to December 2016. We randomly sampled 200 patients aged < 65, 200 patients aged 65 - < 85) and 41 consecutive patients ≥85). Using the ESAS-FS, determined the frequency, and correlates of self-reported Spiritual Pain (SP) and Anxiety (Anx) and Depression (Dep) among these patients. Psycho-spiritual distress was defined as the presence of SP ≥1/10, Anx ≥2/10, and Dep ≥2/10. Results: 52% were female, 61% white, and 48% with ECOG of 2 in the group < 65, 48% were female, 61% white, and 43% an ECOG of 2 from group 65 to 84, and 49% were female, and 83% white, and 49% an ECOG of 3 from the group > 85 years. Spiritual Pain was present in 101/200 (51%) in the group < 65 vs. 61/187 (36%) in group 65-84 vs. 15/54 (29%) in ≥85, p = 0.004. Anxiety was present in 130/200 (65%), vs. 120/187 (65%), vs. 35/54(65%) per group respectively, p = NS. Depression was present in 109/200 (55%), vs. 100/187 (54%), vs. 29/54 (54%), respectively per group, p = NS. Psycho-spiritual distress was present in 65/200 (33%), vs. 44/187 (24%), vs. 11/54 (20%) per group respectively, P = NS. Logistic regression showed gender female correlated with higher psycho-spiritual distress (OR:2.08, p = 0.012), fatigue OR:1.32, p = 0.01, Well-Being OR:1.32, p = 0.02, Financial Distress OR:1.63, p = 0.00, age group < 65, OR:9.24, p = 0.03. Conclusions: High prevalence of Anxiety, Depression and Spiritual Pain in O-OOAdCa. Less frequency of Spiritual Pain in the Oldest-Old when compared with the rest of the population. Highlights the importance of an integrative Psycho-spiritual care to this population. More research is needed.
Empowering lung cancer survivors and family members to “breathe easier”: Adaptation and evaluation of a m-health intervention.
Authors: McDonnell Karen Kane , Owens Otis L , Beer Jenay M , Smith Kasey , Kennedy Taylor , Acena Dane , Gallerani David
Published: May 2019

e23046

Background: Survivors of lung cancer often experience a myriad of symptoms that have devastating effects on their physical and psychological functioning such as dyspnea, fatigue, and stress. To combat these symptoms, the American College of Chest Physicians has recommended the use of complementary therapies. Mindfulness-based Cancer Recovery (MBCR) can empower survivors, and caregivers who often cope with their own health problems and the stress related to caring for a survivor. Our goal is to deliver a tailored, culturally sensitive, MBCR intervention to survivors and family members via a mHealth app. Methods: This research was comprised of four phases. Phase I was the development and testing of an 8-week in-person intervention called Breathe Easier with survivors and family members (dyads). Phase II adapted Breathe Easier into a mHealth app prototype utilizing user-centered design. Phase III was a focus-group evaluation of the usability and acceptance of the mHealth app prototype by survivors and family members. Phase IV was comprised of additional interviews with an African-American subset of survivors and family members to assess the cultural sensitivity of the mHealth app. Results: Findings from the in-person intervention (n = 62) showed that all agreed the intervention materials were acceptable, different levels of yoga, breathing exercises, and meditations helped them, and involving a family member was important. Preliminary analyses showed survivors had less dyspnea and perceived stress over time (T1 vs T2). Both groups had improved fatigue and sleep scores. Findings from the mHealth app design and acceptance evaluation were organized into two primary categories: usefulness and ease of use. User-friendly design recommendations included aesthetic appeal, navigation layout, and display of content. Furthermore, potential health outcomes, privacy concerns, and comparison to in-person interventions also influenced app usefulness and acceptance. Lastly, findings from our cultural sensitivity assessment demonstrated that the mHealth app was culturally sensitive for African-Americans, but some changes were recommended. Conclusions: MBCR interventions hold great promise for improving the lives of racially diverse survivors of lung cancer and family members. An mHealth app will increase accessibility. However, special consideration of app design is needed to ensure future acceptance and longer-term usage.
Preliminary result of phase II study of megestrol combined with 5-hydroxytryptamine 3 inhibitor and dexamethasone for the prevention of nausea and vomiting induced by high emetogenic chemotherapy.
Authors: Wu Qiong , Luo Suxia , Li Ning , Deng Wenying , Ma Yijie , Yang Xinyi
Published: May 2019

e23049

Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing treatment-related side effects and have a strong impact on treatment adherence. A triplet antiemetic regimen, which is composed of neurokinin-1 receptor antagonist (NK1 RA), 5-hydroxytryptamine 3 (5-HT3) inhibitor and dexamethasone, is recommended by current antiemetic guidelines. However, NK1 RA is not available in hospital and more expensive for Chinese patients. Megestrol is currently known as more effective appetite stimulants in patients with cachexia or loss of appetite, but its antiemetic properties are less well known. Therefore, the aim of this study was to further evaluate the efficacy and safety of megestrol for the prevention of CINV. Methods: Patients treated with high emetogenic chemotherapy (HEC) were randomly divided into experimental group and control group. The antiemetic regimen of control group: 5-HT3 inhibitor 5mg/d, dexamethasone 12mg/d1, 8mg/d2-4. The regimen of experimental group: the use of 5-HT3 inhibitor and dexamethasone was the same as that of control group, and each patient took megestrol 160mg orally from the first day of chemotherapy for 10 days. Digestive tract reactions were daily evaluated after beginning of HEC. Primary end point was rate of complete response to vomiting and nausea. Results: From September 7 to December 31, 2018, 60 patients were enrolled and randomized in the study. The delayed nausea and vomiting rates were significantly lower in experimental group than control group (nausea: 63.3% vs 83.3%; vomiting: 13.3% vs 33.3%; p< 0.00). The control group was significantly higher rate of Grade 3-4 vomiting than that of the experimental group (20% vs 0%, p< 0.01). Conclusions: Megestrol, combined with dexamethasone and 5-HT3 inhibitor, has been shown to be able to successfully control CINV and no increase side effects during HEC. Clinical trial information: ChiCTR1800017953. [Table: see text]
Implementing a web-based patient reported outcomes (PRO) assessment: Uptake, usability, and lessons learned.
Authors: Jacobs Linda A. , Blauch Abigail N. , Pucci Donna A. , DeMichele Angela , Palmer Steven C
Published: May 2019

e23062

Background: PRO assessment has the potential to improve patient-provider communication, yet has been difficult to implement in practice. We developed and pilot-tested a web-based PRO assessment (Assessing Concerns at End of Treatment, ACE) within an existing cancer survivorship clinic to ascertain practicality, usability, and uptake by both patients and providers. Methods: ACE is a brief PRO assessment that interfaces with the patient-portal and delivers results into the electronic medical record (EMR). Prior to visit eligible patients were asked to complete a series of measures including a 19-item instrument assessing severity of physical and emotional difficulties and desire for assistance. These results were then made available to providers during the visit through the EMR. Patients were provided up to 3 reminder calls/emails to prompt completion. Eligibility included a breast cancer (BC) diagnosis up to 5 years prior to a scheduled survivorship visit, no current cancer treatment aside from hormonal therapies, and access to the internet. Results: Over 27-months 779 eligible BC survivors were approached and asked to participate, and 566 (73%) agreed. The ACE survey was completed by 332 (59%) of these patients prior to their visit. The most common difficulties reported were Fatigue (86.6%), Worry (75.4%), Difficulty Sleeping (74.8%), and Pain (72.2%). Patients most commonly requested assistance for Aching Joints (31.2%), Fatigue (29%), Difficulty Sleeping (28.6%), and Weight Gain (25.7%). Providers reported being burdened by the information provided and few referrals were made in response to ACE. Technical difficulties were encountered frequently and required more maintenance than initially anticipated. Conclusions: Most eligible patients agreed to complete ACE, however a minority actually did so despite repeated contacts. Lack of buy-in from providers was an obstacle, as were technical difficulties. Difficulties with physical and emotional issues were common, but desire for assistance was less so, and resulted in few referrals. Although practicable, questions remain about the cost vs. benefit of a web-based PRO assessment with survivors.
Implementing strain imaging to identify early childhood cancer survivors at risk for cardiovascular disease.
Authors: Bottinor Wendy , Godown Justin , Coburn Gary , Soslow Jonathan , Borinstein Scott C.
Published: May 2019

e23070

Background: In patients receiving active chemotherapy, myocardial strain has prognostic utility for risk of subsequent cardiomyopathy. We hypothesized a decrement in strain in early off-treatment childhood cancer survivors (CCS) is prognostic for developing cardiomyopathy. Methods: Retrospective analysis was performed in 22 CCS. Global longitudinal strain (GLS) and global circumferential strain (GCS) were assessed at baseline and on the first end-of-treatment study with adequate imaging quality. Parametric methods assessed the association between changes in GLS/GCS and cardiovascular outcomes. Results: All CCS had normal echocardiograms at baseline and on the first end-of-treatment study . On long-term follow up 5/22 developed echocardiographic abnormalities defined as either left ventricular ejection fraction < 55% (n = 4) and/or left ventricular mass Z score < -2.0 (n = 4). Mean age at diagnosis was (mean ± SEM) 13.0 ± 1.3 and 10.7 ± 1.2, p = 0.37 for those without and with long-term abnormalities respectively. Patients who developed long-term echocardiographic abnormalities had a greater decrement in GCS between baseline and fist end-of-treatment echocardiograms (-6.9 ± 0.9% vs -0.7 ± 1.2%, p = 0.011) and a trend towards greater decrement in GLS (-1.5 ± 1.3% vs 1.2 ± 0.7%, p = 0.069). In early off-therapy CCS an absolute change in GCS of 7% was associated with subsequent cardiovascular dysfunction within 10 years. Conclusions: Change in GCS of 7% or greater from baseline to first end-of-treatment echocardiogram may identify CCS at risk for cardiomyopathy on long-term follow up and offer a window for early intervention. Strain imaging may provide an early method of identifying CCS at higher risk for developing cardiomyopathy on long-term follow up. These survivors may benefit from increased surveillance or early intervention with cardioprotective therapies.
Knowledge and attitudes of permanent chemotherapy-induced alopecia among health care providers.
Authors: Stoehr Jenna Rose , Kosche Cory , Choi Jennifer N.
Published: May 2019

e23074

Background: Reports of permanent chemotherapy-induced alopecia (PCIA) are increasing in the field of oncodermatology, but there is a dearth of information regarding how it is recognized and managed by health care providers (HCPs) across different medical specialties. Methods: An electronic survey was distributed to HCPs (resident physicians, attending physicians, and nurse practitioners) in the departments of dermatology, oncology, and general internal medicine (GIM) within one Midwestern hospital system. Results: Of the 60 participants (response rate: 12%), there were 19 from dermatology, 18 from oncology, and 23 from GIM. Responses were analyzed with descriptive statistics and chi-square tests. There was a significant difference in the number of subjects that had heard of PCIA prior to starting the survey (Derm: 79%, Onc: 28%, GIM: 26%, p < 0.05). A larger percentage of Dermatology and Oncology HCPs knew the correct definition of the condition (alopecia persisting > 6 months) than GIM (42% and 44% vs. 17%) and had encountered patients with the condition (47% and 44% vs. 22%). More providers in Dermatology and GIM knew how to diagnose PCIA compared to Oncology (84% and 83% vs. 67%). Dermatology HCPs were the only participants who had attempted to treat patients with PCIA. HCPs across the three specialties believed that patients would accept PCIA treatment that was topical, oral, injectable, and required frequent administration or monitoring, but not treatment that was expensive or high risk. A majority of HCPs surveyed (93%) agreed that the diagnosis of PCIA is important. However, there was a significant difference in the confidence of HCPs in diagnosing and managing PCIA. A minority of dermatology HCPs (2/19) specified that they would refer to an alopecia or oncodermatology specialist, while a majority of oncology and GIM HCPs would refer to dermatology. Conclusions: The results of this survey identify significant knowledge gaps about PCIA amongst HCPs. Therefore, education and multidisciplinary engagement should be pursued in order to improve awareness, diagnosis, referral, and management of PCIA in the survivorship care of cancer patients.
A prospective study of anti-mullerian hormone (AMH) as a predictor of chemotherapy-induced menopause.
Authors: Koczwara Bogda , Ullah Shahid , Abbas M Nazim , Scott-Hoy Alex , Young Fiona , Kichenadasse Ganessan , Karapetis Christos Stelios , Roy Amitesh Chandra , Sukumaran Shawgi , Ross David M. , Khattak Muhammad Adnan , Atkinson Elinor , Martin Hilary
Published: May 2019

e23076

Background: Chemotherapy-induced premature menopause is a distressing side effect of cancer treatment. Currently there are no validated tools to predict the loss of ovarian function. Anti-Mullerian hormone (AMH) in healthy women correlates with ovarian reserve and predicts menopause but its utility in chemotherapy-treated patients is underexplored. We examined the utility of AMH levels as a predictor of chemotherapy-induced amenorrhea at 1-year post chemotherapy - a reliable surrogate for chemotherapy-induced menopause. Methods: Premenopausal women, 45 years or younger, about to receive curative chemotherapy for breast cancer or lymphoma, without ovarian suppression, were assessed for menopausal symptoms using Menopausal Symptom Score (MSS), quality of life (QOL) using EORTC – QLQ-C30 questionnaire, and had serum AMH, oestradiol, FSH, LH collected prior to first chemo, and at 3 and 6 weeks, at completion and 12 months after chemotherapy. Results: Twenty-two premenopausal women, median age 40.5 (37-43) were enrolled. Twenty became amenorrhoeic during chemotherapy and four had return of menses at 1 year after treatment completion. Median AMH level at baseline was 12.9 pmol/L (IQR 5.2 – 26.5), fell sharply following first chemotherapy and remained low at < 3pmol/L (IQR < .3 ) at 1 year with only 2 subjects with AMH levels above 3 pmol/L. Women who regained menses at 12 months had higher baseline AMH than those who remained amenorrheic (p < 0.001). Older age was associated with lower AMH at baseline and at 1 year. Median MSSs increased significantly at 1 year: 0.8 (IQR 0.5-1.8) versus 0.3 (IQR 0-0.4) (p = 0.5). While there was no significant change in QOL scores between baseline and 1 year, there was a significant negative correlation between menopausal symptom score and QOL at 1 year (p = 0.03). Conclusions: In this small study, pre-treatment AMH correlated with amenorrhea at 1-year post chemotherapy suggesting potential role of AMH levels in counselling women regarding their reproductive potential post chemotherapy. Further research in a larger sample of women is needed.
Development of the patient-reported outcomes (PRO) based survival prediction model for survivors who underwent lung cancer surgery.
Authors: Sim Jin-Ah , Kim Young Ae , Lee Jong Mog , Kim Moon Soo , Zo Jae Ill , Shim Young Mog , Yun Young Ho
Published: May 2019

e23084

Background: To construct a prognostic model of 5-year survival among disease-free survivors who underwent lung cancer surgery using socio-clinical and patient-reported outcomes (PRO), and to compare its predictive performance with that of a traditional model based on known clinical variables. Methods: Data on 809 survivors who underwent lung cancer surgery between 2001 and 2006 in two Korean tertiary teaching hospitals were used. The training data set was utilized to generate the prediction model and the remaining 20% was employed as a testing set to estimate the model’s accuracy. Three Cox proportional hazard regression models were constructed and compared that of 5-year survival prediction ability through the evaluation of their performance in terms of discriminative and calibration ability. The three models were constructed with: 1) only clinical and socio-demographic variables, 2) only PROs, and 3) variables from model 1 and 2 considered altogether. The performance of each 5-year survival prediction model was evaluated using C-statistics and Hosmer-Lemeshow-type χ2-statistical analyses. Results: From the validation set, the C-statistics for the model 1, 2, and 3 were 0.70 (95% confidence interval [CI], 0.67−0.73), 0.77 (95% CI, 0.74−0.80), and 0.81 (95% CI, 0.78−0.84), respectively. In this study, model 3 (including PRO and other variables together) showed the highest discriminative and calibration ability compared to others. Conclusions: The findings suggested that the PRO included model in addition to clinical and socio-demographic variables, is more accurate in the survival prediction of lung cancer survivors than models constructed with only well-known socio-clinical variables.