tbuckley/cabot-search huggingface dataset:
Increasing use of neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC): Prognostic impact of non-standard of care (SOC) regimens.
Authors: Yaw A. Nyame, Sarah K Holt, Brian Winters, Sarah P. Psutka, Atreya Dash, George R Schade, Daniel W. Lin, Leonidas Nikolaos Diamantopoulos, Petros Grivas, Evan Y. Yu, John L. Gore, Jonathan L. Wright
Journal: Journal of Clinical Oncology (2019)

4532 Background: Cisplatin-based NAC can prolong overall survival (OS) in patients (pts) with MIBC. Utilization of NAC has increased to about 20% of pts with MIBC over the last decade. We evaluated NAC utilization with and without SOC cisplatin-based combination regimens and oncologic outcomes using registry data. Methods: This is a population-based analysis of linked SEER-Medicare data (2004-2011). We identified 4534 pts with MIBC (cT2-4N0-1) undergoing radical cystectomy (RC). Based on pharmacy records data, pts were stratified into 3 groups: SOC, non-SOC, and immediate cystectomy (IC). We used descriptive statistics to compare groups, and multivariate logistic regression to define factors associated with receiving SOC NAC. Competing risk bladder cancer-specific mortality (BCSM) incidence curves were generated and KM analysis was used to assess OS from time of RC. The impact of NAC on OS was evaluated with Cox regression analysis. Results: 694 (15.3%) pts received NAC, increasing from 11% in 2004 to 24.8% in 2011, with 345 (50%) receiving non-SOC, e.g. gemcitabine/carboplatin (49.3%), gemcitabine alone (21.2%), carboplatin alone (14.8%), cisplatin alone (8.4%), and methotrexate/vinblastine/ adriamycin/carboplatin (0.8%). On logistic regression, increasing age (OR 0.91, 95%CI 0.88 – 0.94, p &lt; 0.0001), Hispanic/Latin ethnicity (OR 0.49, 95%CI 0.22 – 1.10, p = 0.08), and ≥moderate renal dysfunction (OR 0.20, 95%CI 0.08 – 0.51, p &lt; 0.001) were associated with lower odds of SOC NAC. Non-SOC NAC was associated with higher BCSM (competing risk) and lower OS (KM) vs. IC and SOC NAC. On multivariable analysis, non-SOC NAC was associated with higher risk of BCSM (HR 1.35, 95%CI 1.06 – 1.72, p = 0.01) and lower OS (HR 1.38, 95%CI 1.11 – 1.70, p = 0.003) vs. SOC NAC. Conclusions: About 50% of pts receiving NAC were not treated with SOC regimens. Non-SOC NAC was associated with higher bladder cancer death risk. This stresses the role of SOC NAC ideally in a multidisciplinary expert setting, as well as the need for timely RC and neoadjuvant clinical trials, including cisplatin-ineligible pts.
Prognostic value of the volume time index (VTI) ratio for patients with appendiceal cancer with peritoneal carcinomatosis treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).
Authors: Josh Karpes, Daniel Dotta, Oliver Fisher, Raphael Shamavonian, Nayef Alzahrani, David L. Morris
Journal: Journal of Clinical Oncology (2019)

e15704 Background: Completeness of cytoreduction score (CC-score) and tumour volume (as expressed by the peritoneal cancer index (PCI)) have been demonstrated as important post-operative prognostic factors in those patients with appendix cancer with peritoneal metastases undergoing CRS/HIPEC. A previous analysis included a pre-operative factor and demonstrated the tumour marker to volume index (CA19-9/PCI) in patients who had low grade appendiceal cancer with peritoneal metastases was an independent prognostic factor for overall survival (OS). This analysis aims to evaluate VTI as a prognostic factor in low- and high-grade appendix neoplasms with peritoneal dissemination managed with CRS/HIPEC. Methods: A retrospective cohort study of all patients diagnosed with appendiceal cancer with peritoneal dissemination managed with CRS/IPC from 1996 to 2017 was performed by analysing the survival effect of the ratio of tumour volume to the time between initial tumour resection and CRS/HIPEC. VTI was stratified into low versus high groups, and tumour grade was divided into low grade: diffuse peritoneal adenomucinosis (DPAM); and high grade: peritoneal mucinous carcinomatosis (PMCA). Results: Two hundred and sixty-four patients were included. For both DPAM and PMCA, there was no statistically significant difference in overall survival between patients with a low versus high VTI. For both low and high VTI in DPAM, the median survival was not reached, p= 0.586. For PMCA, those with a low VTI had an overall survival of 63 months (95%CI 48-NR), versus those with a high VTI 69 months (95%CI 45-NR), p= 0.97. There was no statistically significant difference in the median recurrence free survival (RFS) between low and high VTI for both DPAM and PMCA. Conclusions: The volume to time ratio for appendix cancer with peritoneal dissemination was not an independent prognostic indicator for overall survival in patients undergoing CRS/HIPEC, suggesting that this index is not a valuable pre-operative planning tool.
Extracorporeal membrane oxygenation for acute respiratory distress syndrome due to <i>Pneumocystis</i> pneumonia
Authors: Klaus Stahl, Heiko Schenk, Benjamin Seeliger, Olaf Wiesner, Julius J. Schmidt, Johann Bauersachs, Tobias Welte, Christian Kühn, Axel Haverich, Marius M. Hoeper, Sascha David
Journal: European Respiratory Journal (2019)

<b>Extracorporeal membrane oxygenation (ECMO) may be justified in immunocompromised patients with <i>Pneumocystis</i>-associated acute respiratory distress syndrome, and an awake ECMO strategy might be feasible in selected patients</b>http://bit.ly/2YFyrOK
Expression and heterodimerization of Type A and B Cholecystokinin Receptors in Gallbladder cancer.
Authors: Abhijit Chandra, Jaya Nigam, Madhumati Goel, Devendra Parmar, Leena Khare Satyam
Journal: Journal of Clinical Oncology (2019)

e15655 Background: Gallbladder cancer is the most common malignancy of the biliary tract and endemic in Northern India. The prognosis of gallbladder cancer remains dismal despite any treatment because of late presentation and aggressive tumor biology. Cholecystokinin (CCK) is present in abundance in gallbladder tissue and mediates function through two structurally related receptors, the type A (CCKAR) and B (CCKBR) receptors. Previously, heterodimerization of CCKAR and CCKBR receptor has been demonstrated in vitro, and was shown to bind natural agonists normally but exhibited agonist stimulated cellular signaling, promoting cell growth. In this study we examined the expression level of CCKAR and CCKBR in resected gallbladder tissue samples and also attempted to determine the dimerization status of CCKAR and CCKBR receptors in gallbladder cancer comparing them to cholelithiasis and normal gallbladder tissue. Methods: Tissue samples from resected normal gallbladder (n = 10), cholelithiasis (n = 25) and gallbladder cancer (n = 25)) were evaluated for the expression of CCKAR and CCKBR by immunohistochemistry. Determination of CCKAR and CCKBR expression was also done by western blot in representative samples from each of these tissue types while their dimerization status was evaluated by immunoprecipitation. Results: By Immunohistochemistry technique, positive CCKAR expression was observed in 80% gallbladder cancer, 84% cholelithiasis, 90% normal gallbladder, P = 0.76. However significantly higher expression of CCKBR was noted in gallbladder cancer (60%) as compared to cholelithiasis (25%) and normal gallbladder (20%), P = 0.013. We also observed progressively increasing level of expression of CCKAR and CCKBR in gallbladder cancer as compared to cholelithiasis and normal gallbladder by western blot. In addition, we also observed a higher level of heterodimer formation in gallbladder cancer compared to cholelithiasis and normal gallbladder using immunoprecipitation technique. Conclusions: Our results provide the first evidence of increasing trend of heterodimerization of CCKAR and CCKBR in gallbladder cancer which has potential clinical and therapeutic significance.
Prediction of metastatic castrate-resistant prostate cancer response to abiraterone or enzalutamide by a baseline blood-based CTC gene expression signature.
Authors: Michael Joseph Lariviere, Naomi B. Haas, Yauheniya Cherkas, Karl Nielsen, Brad Foulk, Jaymala Patel, Denis Smirnov, David J. Vaughn, Ravi K. Amaravadi, Samantha L. Savitch, Krishna Majmundar, Thomas H. Buckingham, Stephanie S. Yee, Jeremy Jones, Sumanta K. Pal, Erica L. Carpenter
Journal: Journal of Clinical Oncology (2019)

e16529 Background: Prostate cancer is the most common cancer in men in the U.S., with 30% 5-year overall survival (OS) for patients (pts) with metastases. To take a precision medicine approach to the management of metastatic castrate-resistant prostate cancer (mCRPC), we developed a blood circulating tumor cell (CTC)-based test to identify mCRPC pts most likely to benefit from abiraterone (abi) or enzalutamide (enza). Methods: In this multi-institution prospective study, men with mCRPC were enrolled prior to starting abi (1,000 mg/d plus prednisone 10 mg/d) or enza (160 mg/d). At baseline (BL), 12 w, and progression, blood samples were collected for CellSearch-based CTC enumeration and qPCR-based gene expression analysis. Results: 69 pts (median age 68 y [50-82]) received abi (n = 25) or enza (n = 44) and had evaluable blood samples. Consistent with prior publications, among 43 pts with BL CTC &gt; 0, clearance of detectable CTCs (BL CTCs &gt; 0 and 12 w CTCs = 0), was achieved in 24 patients (55.8%), and was associated with greater median OS (31 mo vs. 18 mo, log-rank p = 0.03). The 43 pts with BL CTC &gt; 0 were then randomly divided into training (n = 31) and validation (n = 12) sets. Baseline gene expression data for the training set was used to develop a model to predict CTC clearance, starting with a panel of 141 expressed genes/isoforms including those associated with prostate cancer. Of the models tested, random forest yielded the best performance, with respective training and validation set sensitivity of 0.7 and 1, specificity 0.75 and 0.71, AUC 0.88 and 0.91. Top genes identified include those previously associated with disease – HOXB13, ESRP2, KLK3, GRHL2, and KRT19, among others. Conclusions: A gene expression signature from a baseline blood sample with CellSearch-enriched CTCs can predict clearance of detectable CTCs in response to abi/enza with high AUC and may give insight into molecular mechanisms of response. A prospective study with a larger number of patients will be required to further validate our findings. Ultimately, this blood test has the potential to select the patients most likely to benefit from second-generation antiandrogen vs. non-hormonal systemic treatment.
Personalized response-driven adjuvant therapy after combination ipilimumab and nivolumab in high-risk resectable stage III melanoma: PRADO trial.
Authors: Irene Reijers, Elisa A. Rozeman, Alexander M. Menzies, Bart A. Van De Wiel, Hanna Eriksson, Karijn Suijkerbuijk, Astrid Aplonia Maria Van Der Veldt, Ellen Kapiteijn, Geke Hospers, Willem M.C. Klop, Andrew Spillane, Richard A. Scolyer, Inge Marie Svane, Lars Bastholt, Henrik Schmidt, James M.G. Larkin, Alexander Christopher Jonathan Van Akkooi, Georgina V. Long, Christian U. Blank
Journal: Journal of Clinical Oncology (2019)

TPS9605 Background: Adjuvant (adj) immune checkpoint inhibition (ICI) improves relapse free survival (RFS) in stage III melanoma patients (pts). However, preclinical and translational data suggest that neo-adjuvant (neoadj) treatment might be favorable due to broader immune activation. The phase 1b OpACIN study comparing neoadj to adj IPI plus NIVO demonstrated a high pathological response rate (pRR) of 78% complicated by 90% gr 3-4 immune-related adverse events (irAEs). The phase 2 OpACIN-neo trial tested safety and efficacy of three different schemes of neoadj IPI+NIVO and identified two cycles of IPI 1mg/kg + NIVO 3mg/kg as well tolerated (20% gr 3-4 irAEs), with a high pRR of 77%. In both trials, none of the pts with a pathologic response have relapsed after a median follow-up of 30 and 8.3 months. In stage IV melanoma, long-term benefit is observed in patients achieving CR with ICI, even after cessation of therapy. This raises the question of whether a therapeutic lymph node dissection (TLND) can be omitted when a deep pathologic response with neoadj IPI+NIVO is achieved. Methods: The aim of this international multi-center investigator-initiated phase 2 PRADO extension study is to confirm the pRR and toxicity of 2 cycles of neoadjuvant IPI 1mg/kg + NIVO 3mg/kg (the preferred OPACIN-neo regimen) and to test response-driven subsequent therapy i.e. omitting surgery and adjuvant ICI based on the pathological response. 100-110 pts with stage IIIB/C melanoma and a measurable lymph node (≥15mm according to RECIST 1.1) will receive two cycles of IPI 1mg/kg + NIVO 3mg/kg after marker placement into the largest lymph node metastasis. After six weeks, pts will undergo resection of the index lymph node. For pCR/near pCR, pts will not undergo TLND; For pPR, pts will undergo TLND; and for pNR, pts will undergo TLND and start adjuvant NIVO or targeted therapy +/- radiotherapy for 52 weeks. Primary endpoints are pRR of marked lymph node and RFS at 24 months. Baseline biopsies, blood samples (week 0, 6, 12) and faeces (week 0, 6) will be collected for translational research analyses. The first patient in this trial was included in October 2018; 22 patients have been enrolled. Clinical trial information: NCT02977052.
BIONADEGE: Genomic profiling of small bowel adenocarcinoma from the NADEGE prospective cohort.
Authors: Thomas Aparicio, Magali Svrcek, Julie Henriques, Pauline Afchain, Astrid Lièvre, David Tougeron, Johan Gagniere, Eric Terrebonne, Guillaume Piessen, Jean-Louis Legoux, Cedric Lecaille, Marc Pocard, Jean-Marc Gornet, Aziz Zaanan, Sandrine Lavau-Denès, Thierry Lecomte, Mourad Benallaoua, Sabine Helfen, Dewi Vernerey, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2019)

4140 Background: Small bowel adenocarcinoma (SBA) is a rare tumour. Large genomic analyses with prognostic assessments are lacking. Methods: BIONADEGE is an ancillary study of the NADEGE cohort that enrolled 347 patients (pts) with SBA from 2009 to 2012. Next generation sequencing investigates the presence of 740 hot spot somatic mutations in 46 genes involved in carcinogenesis. The MSI (MicroSatellite Instable) status was assessed using 5 microsatellites. The MMR (MisMatch Repair) status was assessed by immunochemistry (4 antibodies). Results: A total of 196 tumour samples were collected and 125 pts had conclusive results for mutation analysis. The clinical and tumours characteristics were comparable in the NADEGE and BIONADEGE cohort except for metastatic stage at diagnostic underrepresented in the BIONADEGE cohort (17.7%) due to missing tumour sample. A predisposing disease was reported in 25 (20.0%) cases (among them 14 Lynch syndromes and 7 Crohn diseases). The number of mutation observed was 0 in 9.6% pts, only 1 in 32.0%, 2 in 26.4% and ≥3 in 32.0%. The most frequent genomic alteration were KRAS (44.0%), TP53 (38.4%), PIK3CA (20.0%), APC (18.4%), SMAD4 (14.4%) and ERBB2 (7.2%). Altogether, a genomic alteration was observed in 90.3% of tumour. KRAS mutation were more frequent in synchronous metastatic tumour than in localized tumour (72.7% vs 38.2%, p = 0.003). There was no significant difference of mutation rate according to primary location for the most frequently altered gene. With caution to small sample, IDH1 mutation is more frequent and APC mutation never seen in Crohn disease. The rate of dMMR tumor was 38.6% in localized tumour and 0% in synchronous metastatic tumour. After a median follow-up of 55 months (95%CI [44-63]), M0 stage, pN0, pT1-2 were associate with better survival in univariate analysis. No significant prognostic value of genomic alteration was associated with OS. dMMR status was associate with a better prognosis for OS in pts with MMR status determined by immunohistochemistry (HR = 0.55 [0.29-1.01], p = 0.055). Conclusions: A high frequency of targetable alteration is observed in SBA. There is several specificities according to predisposing disease. No association between genomic alteration and prognostic was observed except a trend for a better prognosis associate with dMMR.
Adherence to adjuvant endocrine therapy after breast cancer in Sweden 2008-2010: A nationwide survey.
Authors: Anne Andersson, Anna Von Wachenfeldt Väppling, Anna De Jong, Lennarth Nyström
Journal: Journal of Clinical Oncology (2019)

523 Background: In estrogen receptor (ER) positive early breast cancer (EBC) adjuvant endocrine therapy (AET) is crucial to reduce recurrence and mortality. Previous studies have shown that adherence to AET is lower than expected and could negatively affect outcome. Since the year of 2000, BC patients in Sweden are treated in accordance to national guidelines. Treatment is offered at a low cost for the patient. The aim of the study was to estimate the adherence to AET in Sweden by regions and age groups. Methods: Women with a first primary EBC diagnosis 2008-2010 were identified through the Swedish Cancer Registry (SCR). Individual tumour and treatment data were retrieved from the Swedish National Breast Cancer Registry (SNBCR). Patients with ER negative tumours, small tumours (≤ 10 mm) and metastatic disease was excluded from the study since there were no indication to AET. Likewise, were individuals with AET registered to be administered by a third part excluded. Dispensed treatment from pharmacies was obtained through the Swedish Prescription Registry and medication possession rate (MPR) was calculated as number of dispensed doses divided by treatment duration in days. Good adherence to treatment in a patient was set at MPR ≥ 80 %. Adherence was calculated for 3 and 5 years. Results: Twenty-one thousand sixteen (21 016) individuals with a first primary BC between 2008 and 2010 was identified through SCR of which 20 596 were registered in the SNBCR. A total of 10 176 met the inclusion criteria in the study. Adherence after 3 years was 88.0 % and after 5 years 82.5 %. Adherence differed between regions in Sweden and was positively associated with age at diagnosis between 41-74 years. Urban areas had a lower adherence than rural areas (80.7 % vs 83.6 %; p= &lt;0.001). Conclusions: Adherence to AET in Sweden was good, although there were differences by age and urban and rural areas. Further studies are needed to identify factors affecting differences in adherence, with the purpose of initiate actions to increase adherence to AET in ER positive EBC patients.
Frequency and causes of oncologists’ burnout in community practices.
Authors: Chadi Nabhan, Bela Bapat, Yolaine Smith, Andrew Klink, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2019)

e18375 Background: Physician burnout, which is often characterized as exhaustion of physical or emotional strength because of prolonged stress or frustration, has become a worsening phenomenon in medicine. Some have suggested that the rate of burnout among oncologists may be higher than other specialties. Methods: US oncologists/hematologists were queried via a web-based survey from Sep-Nov 2018. Physicians were asked about frequency of burnout symptoms, drivers of burnout, and management of increasing workload. Results: Among the 163 physicians surveyed, 46.0% felt substantial amount of stress at work. Most physicians felt emotionally (85.3%) and physically (86.5%) exhausted. Majority of physicians felt lethargic (66.9%), ineffective (63.8%), and/or detached (62.6%). Additionally, 57.1% of physicians described their practice atmosphere as busy or very busy. In a typical workweek, 92.6% stated they needed additional time, beyond time allocated to clinical care, to complete work responsibilities (23.3% needed 1-3 hours; 15.3% needed ≥10 hours). Most (81.6%) physicians felt lack of work life balance as one of their main stressors. Electronic health record (EHR) responsibilities caused moderate to excessive stress among 66.9% of physicians, 79.1% physicians worked on EHR at home. Other sources of excessive stress were changing reimbursement models (33.1%), interactions with payers (31.3%), increasing patient and caregiver demands (30.7%). Due to increasing demands, 19.6% physicians have considered retiring early, while 14.7% physicians have considered changing their career path. However, 62.6% of physicians stated they had optimal or good control over their workload. To combat burnout, physicians’ practices have used following strategies: employed APPs (46.0%), invested in information technology (33.1%), and/or hired additional administrative staff (31.3%). Conclusions: Most oncologists in the US experience burnout and require additional time beyond that allocated to clinical care to complete their workload. The discordance between oncologists feeling burdened by stress and exhaustion while claiming good control over those same burdens is noteworthy. Additional follow-up will assess whether remedial strategies are effective.
Fatigue in long-term survivors of acute promyelocytic leukemia (APL) and its association with other symptoms and functional limitations.
Authors: Fabio Efficace, Massimo Breccia, Giuseppe Avvisati, Francesco Cottone, Tamara Intermesoli, Erika Borlenghi, Paola Carluccio, Francesco Rodeghiero, Francesco Fabbiano, Mario Luppi, Claudio Romani, Marco Sborgia, Stefano D'Ardia, Francesco Nobile, Nicola Cantore, Monica Crugnola, Gianpaolo Nadali, Sergio Amadori, Marco Vignetti, Francesco Lo-Coco
Journal: Journal of Clinical Oncology (2019)

e23073 Background: Despite cancer survivorship research for patients with solid tumours is increasing, there is paucity of data for patients with hematologic malignancies. We aimed to: 1) investigate factors associated with development of fatigue in long-term APL survivors; 2) describe prevalence of other key symptoms and functional limitations by fatigue severity. Methods: The current analysis is based on 244 APL survivors with a median follow-up from diagnosis of 14.3 years, who were recruited in a large multicenter study. Fatigue was evaluated with the validated FACIT-Fatigue scale. Multivariate linear regression analysis was used to investigate factors associated with self-reported fatigue and key clinical and treatment-related variables were also considered in the analysis. Patients were also divided into two groups based on the FACIT-Fatigue median score identifying a low fatigue (LF) and a high fatigue (HF) group. Prevalence (i.e., not present, mild and moderate to severe) of key symptoms and functional limitations, measured with the EORTC QLQ-C30, were also analyzed by fatigue severity. Results: Multivariate analysis showed that a lower age at diagnosis (p = .002), absence of comorbidities (p = .001) and a greater social support (p = .004) were independently associated with lower fatigue. Patients in the HF group had a significantly higher prevalence of many symptoms, including: pain (p &lt; .001), dyspnea (p &lt; .001), insomnia (p &lt; .001), appetite loss (p = .010), nausea and vomiting (p = .026) and diarrhea (p = .002) than patients in the LF group. As an example, whilst in the HF group there were 61% of patients also reporting pain (with any level of concern), in the LF group there were only 26% of patients reporting pain. Also, HF patients reported a significantly higher prevalence of functional limitations including: physical, role, social, emotional and cognitive functioning (each with p &lt; .001). Conclusions: Our data provides novel information of factors that are independently associated with fatigue severity in long-term APL survivors. Greater fatigue is also associated with a substantial burden of other symptoms and functional limitations.