tbuckley/cabot-search huggingface dataset:
Case 48-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Joel D. Cooper, Eugene J. Mark
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 27-year-old man was admitted to the hospital because of hemoptysis.The patient was well until 3 1/2 years earlier, when a routine x-ray film of the chest (Fig. 1) showed a mass, 2.5 cm, with well-defined margins in the right lower lobe posteriorly. He was seen at another facility, where he reported no symptoms. He had resided in New Jersey and New York State before moving to Massachusetts. Physical examination was negative. A urinalysis, blood count, erythrocyte sedimentation rate, and an automated scan of 15 blood-chemistry determinations gave normal results, and a tuberculin skin test (PPD, . . .
Genomic-based predictive biomarkers to anti-HER2 therapies: A combined analysis of CALGB 40601 (Alliance) and PAMELA clinical trials.
Authors: Aranzazu Fernandez-Martinez, Maki Tanioka, Cheng Fan, Joel S. Parker, Katherine A. Hoadley, Ian E. Krop, Javier Cortes, Antonio Llombart Cussac, Paolo Nuciforo, Patricia Galván, Tomas Pascual, Ann H. Partridge, Aleix Prat, Lisa A. Carey, Charles M. Perou
Journal: Journal of Clinical Oncology (2019)

571 Background: In HER2-positive breast cancer, new biomarkers of response are needed in order to direct multi-agent anti-HER2 combinations towards patients in whom they are truly needed. CALGB 40601 and PAMELA trials tested neoadjuvant dual HER2 blockade and included gene expression analysis aimed to evaluate different genomic biomarkers of trastuzumab and/or lapatinib benefit. Methods: Gene expression by mRNA sequencing (RNAseq) was performed on 265 and 142 pre-treatment tumors of the CALGB 40601 and the PAMELA clinical trials respectively. Intrinsic subtypes were determined by nCounter PAM50-predictor on the PAMELA samples. A new HER2-positive specific gene-centering method was trained on the PAMELA RNAseq data, and showed a higher concordance with PAM50 predictions obtained from nCounter platform. This method was then applied to CALGB 40601 samples. Results: In the combined cohort, the subtype distribution was 10% Luminal A, 8% Luminal B, 62% HER2-enriched (HER2-E), 10% Basal and 10% Normal-like. The pCR rate was significantly higher in HER2-E vs. not HER2-E subtypes (48.6% vs. 20.7%; P &lt; 0.001). HER2-E subtype correlation, ERBB2 amplicon and B-cell genomic signatures were associated with pCR, while luminal signatures were associated with non-responders. In multivariate analysis HER2-E subtype, ERBB2 mRNA and IgG signature expression were independent predictors of response to paclitaxel + trastuzumab +/-lapatinib (OR = 1.98, OR = 1.51, OR = 1.48, respectively, P &lt;0.05). The event free survival analysis at 5 years in the CALGB 40601 cohort showed a benefit of dual vs single anti-HER2-blockade (HR 0.35, P &lt;0.05). Within the HER2-E, ERBB2-high and IgG–high subpopulations, there were also a benefit of dual vs. single anti-HER2 treatment (HR = 0.32, HR = 0.15, HR =0.15, respectively, P &lt;0.05). Conclusions: Intrinsic subtype, ERBB2 mRNA levels, and IgG genomic signature are independent predictive biomarkers of response in the combined cohort. The clinical implementation of these biomarkers could help to design future escalation/de-escalation clinical trials in the HER2-positive neoadjuvant setting. Support: U10CA180821, U10CA180882, U24CA196171, P50-CA58223, GSK, SPORE, BCRF and SEOM. https://acknowledgments.alliancefound.org .
Association of efficacy of anti-PD-1 immunotherapy in patients with advanced cancer with immune-related adverse events (irAEs).
Authors: Jacobo Rogado Revuelta, Nuria Romero-Laorden, Jose Miguel Sanchez Torres, Vilma Pacheco-Barcia, Anabel Ballesteros, Ana Maria Ramos-Levi, Reyes Arranz, Alicia Lorenzo, Pedro Gullón, Ana Garrido García, Jose Maria Serra, Olga Donnay, Magdalena Adrados, Pablo Costas, Javier Aspa, Arantza Alfranca, Maria Dolores Fenor De La Maza, Rebeca Mondejar, Ramon Colomer
Journal: Journal of Clinical Oncology (2019)

e14064 Background: Cancer immune therapy has shown benefit in many cancer types, although it may initiate autoimmune-related disorders in some patients. We have attempted to establish whether the incidence of irAEs after the use of nivolumab or pembrolizumab in advanced malignancies is associated with anti-PD-1 treatment efficacy. Methods: We retrospectively reviewed all clinical records of patients treated with single-agent nivolumab or pembrolizumab for advanced cancer from january 2016 until september 2018. IrAEs were identified clinically and graded as per the CTCAE v.4.0. Efficacy was evaluated with objective response rate (ORR, iRECIST criteria), progression-free survival (PFS) and overall survival (OS). Uni and multivariate tests were performed to determine the association between irAEs and ORR, PFS or OS. Results: We identified 110 patients. Primary diagnoses were lung cancer (n = 78), melanoma (n = 10), head and neck carcinoma (n = 7), renal carcinoma (n = 5), Hodgkin's lymphoma (n = 3), urothelial carcinoma (n = 3) and gallbladder adenocarcinoma, hepatocellular carcinoma, gastric adenocarcinoma and Merkel cell carcinoma (n = 1 each). IrAEs were observed in 40 patients (36.4%). The most frequent irAEs were hypothyroidism (n = 15), nephritis (n = 5) and hyperthyroidism (n = 4). Objective response was observed in 45 patients (40.9%), median PFS was 5 months (0.5-32 months) and median overall survival was 24.5 months (3-110 months). Thirty-three of the 40 patients with irAEs had objective response (82.5%) in contrast with 12 of the 70 cases without irAEs (17%) (OR 22.78, 95% CI 5.9-87.0, P &lt; 0.000001). PFS in patients with irAEs was 10 months and 3 months in those without irAEs (HR 2.4, P = 0.004). OS in patients with irAEs was 32 months and 22 in those without irAEs, without statistically significant differences. Conclusions: In advanced cancer treated with nivolumab or pembrolizumab, patients who developed irAEs showed a significantly improved efficacy (ORR of 82.5% and PFS of 10 months) over patients without irAEs (ORR of 17% and PFS of 3 months).
Emergency department (ED) visits and hospitalizations in survivors of childhood cancer in the Childhood Cancer Survivor Study.
Authors: Valerie Arsenault, Weiyu Qiu, Qi Liu, Jennifer Yeh, Wendy Leisenring, Kirsten K. Ness, Gregory T. Armstrong, Tara O. Henderson, Alexandra Maria Walsh, K Robin Yabroff, Kevin C. Oeffinger, Melissa M. Hudson, Yutaka Yasui, Paul C. Nathan
Journal: Journal of Clinical Oncology (2019)

10056 Background: Chronic health conditions are frequent among childhood cancer survivors and lead to increased health care resource utilization. We compared rates of ED visits and hospitalizations between survivors and siblings. Methods: Analyses included 10,762 ≥5-year survivors and 2,069 siblings who completed a questionnaire from 2014-2016. We calculated ED visits and non-obstetric hospitalizations in the last 12 months per 1,000 person-years (PY) and evaluated cause-specific hospitalization rates using ICD-10 categories. Multivariable Poisson regression models evaluated predictors of survivor visits. Results: Median age in survivors and siblings was 35.3 years (interquartile range [IQR] 29.0-43.1) and 42.9 years (IQR 35.6-50.2), respectively; time from cancer diagnosis was 27.8 years (IQR 21.7-34.1). 24.2% of survivors and 16.2% of siblings had ≥1 ED visit (p &lt; 0.001); rates were 521/1,000 PY for survivors and 246/1,000 PY for siblings (age/sex-adjusted relative rate [RR] 2.0; 95% confidence interval [CI] 1.7 - 2.3). Factors associated with increased survivor ED visits were black race (RR 1.6, CI 1.2-2.0), being obese (RR 1.4, CI 1.2-1.7) or underweight (RR 1.9, CI 1.2-3.0), female sex (RR 1.3, CI 1.1-1.5), younger age (p = 0.02) or abdomen/pelvis (RR 1.2, CI 1.1-1.4) or brain irradiation (RR 1.2, CI 1.0-1.4). 13.3% of survivors and 8.3% of siblings had ≥1 hospitalization (p &lt; 0.001); rates were 219/1,000 PY for survivors and 130/1,000 PY for siblings (RR 1.9; CI 1.3 - 2.9). Factors associated with increased survivor hospitalizations were female sex (RR 1.3, 1.1-1.5), younger age (p &lt; 0.0001), being obese (RR 1.3, CI 1.0-1.6) or underweight (RR 1.5, 95% CI 1.1-2.2) or platinum chemotherapy exposure (RR 1.6, CI 1.3-2.0). The most common indications for hospitalization were diseases of the digestive (21.9/1,000 PY; CI 18.7 - 25.7) and circulatory (20.9/1,000 PY; CI 17.8 – 24.4) systems. Leukemia survivors had the highest ED visit and hospitalization rates. Conclusions: Childhood cancer survivors had a 2-fold increased likelihood of an ED visit or hospitalization compared with their siblings. This increases the economic burden on survivors and the health care system.
The impact of steroid use on efficacy of immunotherapy among patients with lung cancer who have developed immune-related adverse events.
Authors: Kazushige Wakuda, Taichi Miyawaki, Eriko Miyawaki, Nobuaki Mamesaya, Takahisa Kawamura, Haruki Kobayashi, Shota Omori, Kazuhisa Nakashima, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami, Keita Mori, Masahiro Endo, Toshiaki Takahashi
Journal: Journal of Clinical Oncology (2019)

e20583 Background: Systemic steroids use before starting immune checkpoint inhibitors (ICI) has negative impacts on survival. The aim of this study was to evaluate whether steroid against immune-related adverse events (irAE) reduces efficacy in patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed patients who had advanced NSCLC and undergone ICI therapy between December 2015 and June 2018. Patients whose irAE was treated with ≥ 10mg/day of predonisone were classified into steroid group (S), otherwise into non-steroid group (N). Results: A total of 257 patients (pts) were treated with ICI and irAEs was observed in 103 pts (40%). Twenty-eight pts were S-group and 75 patients were N-group. There was no significant difference in age, sex, stage, performance status, histology, smoking status, gene alteration, expression of PD-L1, or treatment line between the groups. Main irAEs included pneumonitis (43% in S-group / 12% in N-group), diarrhea or colitis (25% / 9%), rash (21% / 20%), and hypothyroidism (14% / 37%). Grade 2 or higher irAEs were pneumonitis in 39% / 0%, diarrhea or colitis in 21% / 5%, hypothyroidism in 7% / 19%. Among S-group, steroids were used for pneumonitis in 11 pts, diarrhea or colitis in 7 pts, stomatitis in 2 pts, and rash in 2 pts. There was no significant difference in overall survival (median; 14.5 vs 30.0 months, P = 0.30, Hazard ratio, 0.69), progression-free survival (median; 7.8 vs 9.6 months, p = 0.11, Hazard ration, 0.65), and objective response rate (46% vs 41%, p = 0.64), respectively. Conclusions: Systemic steroid was mainly used in pts with ≥Gr2 pneumonitis or colitis. This study indicated that steroids use did not reduce efficacy of ICI. Thus, steroid should not be avoided in patients with moderate to severe irAEs with concern over reducing efficacy.
THU0550 MYCOPHENOLATE MOFETIL (MMF) IN DEFINED AND UNDEFINED INTERFERONOPATHIES
Authors: Carmela Gerarda Luana Raffaele, Gian Marco Moneta, Silvia Federici, Manuela Pardeo, Claudia Bracaglia, Fabrizio De Benedetti, Antonella Insalaco
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Type I interferonopathies are genetic disorders characterized by an up-regulation of type I interferon (IFN) activity. An increased expression of type I IFN regulated genes, IFN signature (IS), is described in these conditions. They are characterized by autoinflammation and varying degrees of autoimmunity or immunodeficiency. Some patients with a phenotype strongly suggestive for type I interferonopathy with a high IS, do not show any mutations in known type I interpheronopaties related genes, being classified as undefined <h3>Objectives:</h3> To evaluate the effect of mycophenolate mofetil (MMF) in patients with defined and undefined type I interferonopathy <h3>Methods:</h3> 7 patients with type I interferonopathy followed at a Pediatric Rheumatology center, were included. Leucocyte (WBC) and platelet count, hemoglobin (Hb), CRP, ESR, serum amyloid A (SAA), autoantibodies, complement levels and IS, were assessed before and after 5-7 months of MMF treatment (600 mg/m2 BID). IS was determined by qPCR (high scores &gt;1.42) <h3>Results:</h3> Patient 1 and 2 presented respectively with SAVI and Aicardi-Goutieres syndrome. The others were classified as undefined. In patient 1(table), treated with JAK1/2 inhibitor, MMF was followed by decrease of inflammatory markers and resolution of lung involvement; in patient 2 to an increase in Hb and normalization of inflammatory markers. Among patients with an undefined phenotype the addition of MMF to low dose prednisone led to complete resolution of inflammation. A reduction of the antinuclear antibodies titre was observed in patients 2, 3 and 7 and a normalization of complement level in patients 3, 4 and 7. Patient 5 had normal inflammatory markers already before the beginning of MMF possibly due to previously administered immunosuppressive treatment. Despite all patients presented a significant improvement of clinical picture after 5 months of MMF treatment, the IS decreased only in 4/7 patients while it remain stable or increased in the others <h3>Conclusion:</h3> Our data suggest that mycophenolate mofetil might be an effective therapy in patients with type I interferonopathy leading to improvement of clinical and laboratory features thus allowing a glucocorticoid sparing <h3>Disclosure of Interests:</h3> Carmela Gerarda Luana Raffaele: None declared, Gian Marco Moneta: None declared, Silvia Federici: None declared, Manuela Pardeo: None declared, Claudia Bracaglia: None declared, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Antonella Insalaco: None declared
Use of a granulocyte colony-stimulating factor for the prevention of febrile neutropenia in the era of value-based care.
Authors: Bruce A. Feinberg, Kevin Lord, Jonathan Kish, Jalyna R. Laney, Dhruv Chopra, Djibril Liassou
Journal: Journal of Clinical Oncology (2019)

e12601 Background: Value based care design is intended to encourage responsible use of medical resources to optimize cost effective delivery of quality patient care. Febrile neutropenia (FN) is a potentially life-threatening condition associated with myelosuppressive chemotherapy (chemo). Clinical guidelines and product label recommend granulocyte colony stimulating factors (G-csf) use for the primary prevention of FN in patients with clinically significant FN risk. This study evaluated the real-world use of primary prevention pegfilgrastim (PPP), a sustained release G-csf, in metastatic breast cancer (mBC) patients. Methods: Patients who had initiated systemic chemo from Jan-2013 to Dec-2017 were identified from a third-party, administrative claims database using medical and pharmacy claims (ICD-9/10 codes for both BC and metastases) were selected. Patients who received any HER2 and/or any oral or infused hormonal therapies, or had another malignant diagnosis, were excluded. FN risk: low &lt; 10%, moderate 10-20% and high &gt; 20%, was assigned to chemo drugs/regimens using multiple source data (e.g. Lexicomp). If patients received combination chemo, the assigned risk level was the highest risk of any individual agent. Patients administered a moderate or high FN risk (MHR) regimen were considered at “significant clinical risk”. The frequency of use of PPP in MHR and in low FN risk (LR) was calculated per line (L) of therapy. Results: 10,342 patients met the selection criteria. Mean age at initiation of treatment was 61.7 years (SD = 12.12). Total number of patients with exposure to MHR regimens were 4,601 (44%). By line of therapy, the proportion of patients prescribed PPP was: 1L MHR = 32%, 1L LR = 1%; 2L MHR = 12%, 2L LR = 1%; 3L MHR = 6%, 3L LR = 1%; 4L MHR = 6%, 4L LR = &lt; 1%; 5L MHR = 5%, 5L LR = &lt; 1%; and 6L MHR = 6, 6L LR = 1%. Conclusions: The observed rate of PPP use with LR chemo was exceptionally low and consistent with cost effective, high quality, evidence-based medicine. PPP use with MHR chemo was in the minority and declined with consecutive lines of treatment suggesting the need to study clinical outcome variances in mBC patients receiving MHR chemo with and without PPP.
Cost-effectiveness of programmed cell death protein 1/programmed death-ligand 1 inhibitors (aPD1/aPDL1) varies widely.
Authors: Benjamin P Geisler, Leesa L. Pridham, M. Cecilia Monge B., Tali M. Johnson, Jonathan Karnon, Elad Sharon
Journal: Journal of Clinical Oncology (2019)

e18351 Background: Immunotherapy with aPD1/aPDL1 has been shown to be efficacious for a range of indications. However, cost-effectiveness has only been demonstrated for some. Our goal was to compare incremental costs and effects across Food and Drug Administration (FDA) approved aPD1/aPDL1 using a standardized value framework. Methods: aPD1/aPDL1 randomized controlled trials (RCTs) were obtained from the FDA's 2014-18 approval lists. Restricted mean Overall (OS) and Progression-Free Survival (PFS) were extrapolated to 10 years via best-fitting (Akaike/Bayesian information criterion) parametric function (Kaplan-Meier survival curves digitized via Henley&amp;Hoyle approach). Average wholesale price for experimental and comparator regimens from approval year’s Micromedex Red Book (IBM Watson Health, Cambridge, MA) were applied to either median treatment duration or mean extrapolated PFS, assuming the entire cohort was treated with no dose reductions. For multicenter RCTs with physician’s choice of the comparator, we assumed the regimen most likely used in the U.S. Incremental cost-effectiveness ratios (ICER) were discounted at 3% per annum. Results: Undiscounted OS gains with aPD1/aPDL1 after extrapolation to 10 years ranged from 0.72 to 1.89 LYs as compared to between 0.13 and 0.27 LYs at the end of the RCT. Discounted additional costs for aPD1/aPDL1 ranged from about -$1,700 to $348,312. Crude estimates of the incremental cost per LY gained vary widely, with ICERs for PACIFIC and Impower150 beyond $150,000/LY in both analyses, and additionally Keynote 024 and Checkmate 214 in the analysis that assumed treatment to the end of PFS. Conclusions: Value for money appears to vary widely across indications and comparators, from cost-saving to low-value. Common extrapolation-based analyses of aPD1/aPDL1-based regimens can help elucidate differences in value. The presented analyses are preliminary. Further assessment of extrapolation methods, downstream costs and quality of life effects are required. [Table: see text]
Associations between pretreatment body mass index and presence of post-treatment nutrition impact symptoms in head and neck cancer survivors.
Authors: Katherine G. Douglas, Sylvia L. Crowder, Laura S. Rozek, Gregory T. Wolf, Anna Arthur
Journal: Journal of Clinical Oncology (2019)

e17547 Background: The objective of this study was to determine if pre-treatment body mass index (BMI) is associated with the presence of self-reported, nutrition impact symptoms (NIS) 1-year post-treatment in head and neck cancer (HNC) survivors. We hypothesize that higher pre-treatment BMI may be associated with fewer reported NIS post treatment. Methods: This was a longitudinal study of 430 HNC survivors recruited from the University of Michigan Head and Neck Specialized Program of Research Excellence (HN-SPORE) study. Participants completed a pre-treatment health questionnaire which included self-reported height and weight. NIS were assessed at 1-year post-treatment using a Likert scale ranging from 1 (not at all) vs 5 (extremely) bothered by symptoms. Eight individual NIS were assessed (trismus, xerostomia, bothered chewing, dysphagia liquids, dysphagia solids, taste changes, mucositis, and shoulder or neck pain). Individual symptoms were summed to create a symptom summary score. Self-reported pre-treatment height and weight were used to calculate BMI in kg/m 2 . BMI was categorized as 1) underweight, 2) normal weight, 3) overweight and 4) obese. Pearson partial correlations between pre-treatment BMI status and individual post-treatment NIS and post-treatment NIS summary score were examined. Covariates included age, sex, tumor site, disease stage, smoking, alcohol consumption, and HPV status. Results: BMI was significantly inversely associated with bothered chewing, dysphagia liquids, dysphagia solids, taste alterations, and shoulder pain (p &lt; 0.05). BMI was also significantly inversely correlated with the overall symptom summary score. Conclusions: Higher pre-treatment BMI may be associated with reduced risk of post-diagnosis symptom burden in HNC survivors. Funding: NIH/NCI P50CA097248; Hatch project 1011487; Carle-Illinois Cancer Scholars for Translational and Applied Research Fellowship.
ALINA: A phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive (<i>ALK</i>+) non-small cell lung cancer (NSCLC).
Authors: Benjamin J. Solomon, Jin Seok Ahn, Fabrice Barlesi, Rafal Dziadziuszko, Makoto Nishio, Alice Tsang Shaw, Walter Bordogna, Christoph Meyenberg, Yi-Long Wu
Journal: Journal of Clinical Oncology (2019)

TPS8569 Background: Patients with early-stage NSCLC (stage IA–IIIA) account for ~40% of cases at diagnosis; despite surgery, 5-year survival rates are low. Platinum-based adjuvant chemotherapy is the standard of care (SoC) for stage II–IIIA disease. Although patients with stage IA NSCLC do not benefit from adjuvant chemotherapy, patients with stage IB disease and large tumors (≥4cm) do. Adjuvant chemotherapy produces a 4–5% increase in 5-year survival rates, leaving significant unmet need for improved treatments. Approximately 5% of patients with NSCLC harbor an oncogenic fusion of the ALK gene. Treatment of advanced ALK+ NSCLC with ALK inhibitors improves efficacy and safety compared with chemotherapy. Alectinib, a potent ALK inhibitor, is the SoC first-line treatment for advanced ALK+ NSCLC. The ongoing ALINA trial will compare alectinib versus chemotherapy as adjuvant treatment for patients with stage IB–IIIA ALK+ NSCLC. Methods: ALINA is a randomized, multicenter, open-label phase III study investigating the efficacy and safety of adjuvant alectinib versus chemotherapy in ALK+ NSCLC (confirmed by an FDA-approved and CE-marked test). Adult patients (≥18 years) with completely resected stage IB (tumors ≥4cm) to IIIA disease and ECOG PS 0–1 are eligible for inclusion. Patients (N=255) from ~170 centers across ~30 countries will be randomized 1:1 to receive twice-daily alectinib 600mg for 24 months or four 21-day cycles of platinum-based chemotherapy (cisplatin 75mg/m 2 [day 1] plus vinorelbine 25mg/m 2 [days 1 and 8] or gemcitabine 1250mg/m 2 [days 1 and 8] or pemetrexed 500mg/m 2 [day 1]) according to local prescribing information. Stratification factors are disease stage (stage IB [≥4cm] vs stage II vs stage IIIA) and race (Asian vs non-Asian). Treatment will continue until planned completion, disease recurrence, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first. The primary endpoint is disease-free survival per investigator; secondary endpoints are overall survival, safety, and pharmacokinetics. Clinical trial information: NCT03456076.