bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced pulmonary carcinoid (APC): 20-year experience at Johns Hopkins (JH).
Authors: Forde Patrick M. , Hooker Craig M. , Illei Peter , Ettinger David S. , Rudin Charles M. , Hann Christine L. , Brahmer Julie R. , Kelly Ronan Joseph 
Published: March 2020

7598 Background: APC is a rare thoracic malignancy with limited prognostic data and a perceived lack of treatment options other than surgical resection. This is the largest series of APC patients (pts) ever reported and contains data on locally advanced and metastatic disease. Here we compare clinical outcomes and treatment responses for typical carcinoid (TC) and atypical carcinoid (AC). Methods: This retrospective cohort includes pts referred to JH from 1992 to 2012. Pts were identified using pathology and medical record databases. Information extracted included, pathology, demographics, stage, prior curative resection, time to relapse, chemotherapy/targeted agents and response rate (RR), date of death/last follow-up. Primary outcome was overall survival (OS), defined as time from diagnosis of advanced disease to death from any cause. Secondary endpoint was recurrence-free survival (RFS), defined as time from curative resection to tumor recurrence. OS and RFS were estimated by using the Kaplan-Meier method and log-rank test comparing TC and AC. Results: 49 APC pts (30 female/19 male; 32 AC/17 TC) were identified. 25 pts had relapsed after previous curative resection. Median RFS (n=25), was significantly longer for TC vs. AC (119 months (m) vs. 66 m, p=0.008). Median OS was 85m and significantly longer for TC vs. AC (122m vs. 48m, p=0.009). 39 (80%) pts received systemic therapy for APC. RR to first-line chemotherapy was 22% (5/23) with all 5 (3 AC, 2 TC) responses occurring in pts receiving cisplatin/etoposide. First-line somatostatin therapy was given to 11 pts with 1 partial response (PR) (9%) and 10 pts with stable disease (5 AC, 5 TC) for a median 15m. 5 pts received first-line targeted agents including sunitinib and gefitinib however no responses were seen. 50% (2/4 pts) RR occurred to second-line temozolomide/capecitabine An ongoing PR > 6m to everolimus occurred in a heavily pretreated AC pt. Conclusions: Both AC and TC may recur many years after resection. This study demonstrates significantly poorer survival for AC in advanced disease. Thoracic oncologists perceive APC as resistant to systemic therapy however here we report that both AC and TC may respond to cisplatin/etoposide, temozolomide/capecitabine and mTOR targeted therapy.
First-in-human dose-finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies: Updated results.
Authors: Camidge D. Ross , Bazhenova Lyudmila , Salgia Ravi , Weiss Glen J. , Langer Corey J. , Shaw Alice Tsang , Narasimhan Narayana I. , Dorer David J. , Rivera Victor M. , Zhang Joshua , Clackson Tim , Haluska Frank G. , Gettinger Scott N. 
Published: March 2020

8031 Background: AP26113 is a novel tyrosine kinase inhibitor (TKI) that potently inhibits mutant activated forms of anaplastic lymphoma kinase (ALK+) and epidermal growth factor receptor (EGFRm), and TKI-resistant forms including L1196M (ALK) and T790M (EGFR). AP26113 does not inhibit native EGFR. Methods: The dose finding phase (3+3 design) of this phase I/II open-label, multicenter study is ongoing in pts with advanced malignancies (except leukemia) refractory to available therapies or for whom no standard treatment exists. Initial dosing is orally once daily. Results: As of 14 Jan 2013, 44 pts were enrolled: 30 mg n=3, 60 mg n=3, 90 mg n=8, 120 mg n=8, 180 mg n=11, 240 mg n=9, 300 mg n=2; 64% female, median age 60 yrs; diagnoses: non-small cell lung cancer (NSCLC, n=37), other (n=7). 26 pts discontinued: 18 disease progression, 6 adverse event (AE), 2 deaths (sudden death, hypoxia; both possibly related). Most common AEs: nausea (45%), fatigue (39%), diarrhea (27%); most common grade 3/4 treatment-related AE: diarrhea (5%). 2 dose limiting toxicities observed: grade 3 ALT increase, 240 mg; grade 4 dyspnea, 300 mg. Doses <300 mg are being explored further. 21 pts had ALK+ history (18 NSCLC, 3 other). Among 18 evaluable ALK+ pts, 10 responded. 15 ALK+ pts had 0 (n=3) or 1 (n=12) prior ALK TKI (crizotinib); of these, 2/3 and 8/12 pts (67%) responded, including 2 complete responses. The longest response is 40 wks (ongoing). 4 of 5 ALK+ pts with untreated or progressing CNS lesions at baseline and with follow-up scans had evidence of radiographic improvement in CNS, including 1 pt resistant to crizotinib and LDK378 (overall response = stable disease). 16 pts had EGFRm history (15 NSCLC, 1 SCLC); 14 pts had ≥1 prior EGFR TKI. Of 12 EGFRm pts with a follow-up scan, 1 pt (prior erlotinib) responded at 120 mg (duration 21 wks, ongoing), 6 pts had stable disease (2 ongoing, duration 7-31 wks). Conclusions: AP26113 has promising anti-tumor activity in ALK+ pts, with initial evidence of activity in EGFRm pts, and is generally well tolerated. Phase II will begin after the recommended phase II dose is determined, with 4 cohorts: crizotinib-naïve NSCLC; crizotinib-resistant NSCLC; EGFR TKI-resistant NSCLC; other tumors. NCT01449461. Clinical trial information: NCT01449461.
Effect of primary tumor size in patients with metastatic non-small cell lung cancer (NSCLC).
Authors: Xia Bing , Gao Feng , Govindan Ramaswamy , Morgensztern Daniel 
Published: March 2020

8041 Background: Primary tumor size is a known prognostic factor for patients with early stage NSCLC treated with either surgery or radiation therapy. Although tumor volume has been associated with outcomes in patients with metastatic disease, it is labor intensive and rarely reported outside of a clinical trial. Since the primary tumor size is more commonly described, we evaluated its prognostic impact in patients with metastatic disease. Methods: The SEER was searched for patients with stage M1b NSCLC, with known tumor (T), lymph node (N) status, and diagnosed between 2004 and 2008. Patients with T0 and malignant pleural effusion were excluded. Tumor size is reported as the largest diameter and was subdivided into S1 (0.1-3 cm), S2 (3.1-5 cm), S3 (5.1-7 cm) and S4 (7.1-20 cm), roughly corresponding to T1, T2a, T2b and T3. Overall survival (OS) was estimated by the Kaplan-Meier method, while the hazard ratios (HR) were estimated and compared by Cox proportional hazard models. Results: Tumor size was available in 21879 (84.4%) out of 25919 patients with complete TNM staging. The frequencies of S1, S2, S3 and S4 were 33.4%, 33.8%, 17.1% and 13.7% respectively. 1-year OS rates for S1 to S4 were 34%, 27.9%, 24.0% and 19.0% respectively. Primary tumor size was an independent predictor for OS after adjustment for age, gender, race, histology, T and N status (p < 0.0001). The decreased OS from each subsequent category of tumor size was statistically significant in both univariate and multivariable analyses (Table). Conclusions: Primary tumor size is readily available and represents a significant prognostic factor for survival in patients with stage M1b NSCLC, independently of T and N status. [Table: see text]
Success and failure rates of tumor genotyping techniques in routine pathologic samples with non-small cell lung cancer.
Authors: VanderLaan Paul A , Yamaguchi Norihiro , Folch Erik , Kent Michael S , Gangadharan Sidharta P , Majid Adnan , Goldstein Michael , Huberman Mark , Costa Daniel Botelho 
Published: March 2020

8050 Background: Identification of somatic molecular alterrations in NSCLC has become evidence-based practice. The success and failure rate of using commercially-available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation and ALK FISH. Methods: Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples sent for routine tumor genotype in clinical practice. Results: Mean age was 65, 61.2% women, 75.9% white, 27.8% never-smokers, 73.8% had advanced NSCLC and 86.1% adenocarcinoma histology. Tumor tissue was obtained from surgical biopsies in 48.8%, core biopsies in 17.9% and as cell blocks from aspirates/fluid in 33.3%. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. In the 207 tumors in which the three tests were ordered concurrently, the success rate for EGFR was 92.3%, for KRAS 91.8% and for ALK FISH 89.9%. The highest failure rates were observed when the tissue was obtained from core biopsies (30.8%, 20.5% and 30.8% for EGFR, KRAS and ALK tests, respectively) and bone specimens (23.1%, 15.4% and 23.1% for EGFR, KRAS and ALK tests, respectively). In specimens obtained from bone, the failure rate was significantly higher in non-surgical than surgical specimens (40% vs 0%, p=0.024 for EGFR) and decalcified than non-decalcified samples (60% vs 5.5%, p=0.021 for EGFR). Conclusions: The success rate of multiple tumor genomic analyses techniques for EGFR, KRAS and ALK gene abnormalities using routine lung cancer tissue samples was ~90%. The highest failure rates occurred in tumors obtained from core biopsies and in bone samples from core biopsies with decalcification; specimens that may need to be scrutinized before submission to molecular studies. Tumor genotype techniques are feasible in most other samples obtained with current tumor acquisition methods, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special tissue acquisition or manipulation.
Final overall survival (OS) results of a noncomparative phase II study of bevacizumab (B) plus first-line chemotherapy or second-line erlotinib (E) in nonsquamous NSCLC (ns-NSCLC) patients with asymptomatic untreated brain metastases (BM) (BRAIN).
Authors: Besse Benjamin , Le Moulec Sylvestre , Senellart Hélène , Mazieres Julien , Barlesi Fabrice , Dansin Eric , Robinet Gilles , Perol Maurice , Moro-Sibilot Denis , Soria Jean-Charles 
Published: March 2020

8059 Background: The non-comparative BRAIN study (NCT00800202) is the first trial to evaluate efficacy/acceptable safety of B in pts with ns-NSCLC and untreated BM. We report final efficacy/safety results. Methods: Eligible pts (stage IV ns-NSCLC; PS 0–1; untreated, asymptomatic BM ineligible for surgery/radiosurgery) received until unacceptable toxicity/disease progression: 1st-line B ≤6 cycles (15mg/kg q3w) plus carboplatin (AUC 6 q3w) and paclitaxel (200mg/m2 q3w; B+CP; n=67); or 2nd-line B plus E (150mg/day; B+E; n=24). Primary endpoint is 6-month progression-free survival (PFS). Six-weekly assessments included mandatory brain MRI. The trial could be halted if there were >3 (B+CP) or >2 (B+E) brain hemorrhages (ICH). Results: Baseline (BL) characteristics are reported. With a median follow-up of 16.3 (B+CP) and 11.8 months (B+E), efficacy data are summarized. Adverse events (AE) were comparable with those in previous trials of B. Only 1 grade ≥3 bleeding AE (grade 3, extracranial site; B+E) and only one ICH event (grade 1, resolved; B+CP) occurred. Most frequent cause for B withdrawal was progression: intracranial only in 20.9% (B+CP) and 16% (B+E); extracranial only in 50.7% (B+CP) and 54.2 % (B+E). Conclusions: The finalBRAIN results demonstrate promising efficacy and acceptable safety of B with 1st-line chemotherapy or 2nd-line E in ns-NSCLC pts with asymptomatic untreated BM. Clinical trial information: NCT00800202. [Table: see text]
Incidence, characteristics, and survival of patients with EGFR-mutant lung cancers with EGFR T790M at diagnosis identified in the lung cancer mutation consortium (LCMC).
Authors: Kris Mark G. , Oxnard Geoffrey R. , Johnson Bruce E. , Berry Lynne D , Chen Heidi , Kwiatkowski David J. , Iafrate Anthony John , Wistuba Ignacio Ivan , Franklin Wilbur A. , Aisner Dara , Sequist Lecia V. , Khuri Fadlo Raja , Garon Edward B. , Pao William , Rudin Charles M. , Schiller Joan H. , Haura Eric B. , Minna John D. , Bunn Paul A. 
Published: March 2020

8085 Background: Somatic T790M mutations are detected in 62% of EGFR-mutant lung cancers with acquired resistance to EGFR TKIs, and have rarely been identified in the tumor at diagnosis and/or within the germline DNA. Multiplexed genotyping by the LCMC permitted us to evaluate the incidence of T790M at diagnosis, co-mutations, and survival of patients with this driver. Methods: The 14 member LCMC prospectively tested tumors of patients with lung adenocarcinomas in CLIA laboratories for mutations in EGFR and 9 other genes. We assayed T790Mby Sequenom, Snapshot, or Sanger sequencing. Germline DNA was not collected. Results: In the 987 tumors tested, 209 had mutations in EGFR alone: 25 T790M (2.5%) , 157 sensitizing EGFR mutations (exon 19 del, L858R, L861Q, G719X) without T790M, 23 exon 20 ins, 4 other mutations. 13 additional cases harbored mutations in EGFR and another driver; 2 with both T790M and PIK3CA. In each of the 27 EGFR-mutant cases with T790M, a coincident EGFR mutation was detected (18 exon 19 del, 9 L858R, 1 exon 20 ins). EGFR T790M was found more often than EGFR exon 20 ins or mutations in HER2 (1.9%), BRAF (1.6%), or PIK3CA (0.7%). Patients with T790M: 77% women, 81% never smokers, median age 55 (range 38-79), stage IV at diagnosis 81%, PS 0/1 100%. Characteristics did not differ from persons with sensitizing mutations and no T790M. Median survival from the diagnosis of metastatic disease for patients with EGFR-mutant lung cancers was 3.5 yrs with T790Mand 4.0 yrs without (p=0.926). Conclusions: T790M mutations were detected at diagnosis in 3% of adenocarcinomas and always coincident with another EGFR mutation. Cases with T790M represent 13% of all cases of EGFR- mutant lung cancer. Characteristics and survival for patients with EGFR- mutant lung cancers with T790M at diagnosis were similar to individuals with sensitizing mutations and no T790M. The observed incidence of T790M exceeded that of the other actionable targets HER2, BRAF, and PIK3CA. Trials should study this unique population identified by routine multiplexed genotyping. Supported by 1RC2CA148394-01 and the National Lung Cancer Partnership. Clinical trial information: NCT01014286.
Randomized phase II study of pemetrexed plus carboplatin followed by pemetrexed versus paclitaxel plus carboplatin followed by pemetrexed in advanced nonsquamous, non-small cell lung cancer (LOGIK 0904).
Authors: Takayama Koichi , Inoue Koji , Takeshita Masafumi , Tashiro Naoki , Harada Taishi , Seto Takashi , Imanaga Tomotoshi , Fujimoto Noriko , Nakagaki Noriaki , Kawasaki Masayuki , Kishimoto Junji , Ichinose Yukito 
Published: March 2020

8111 Background: PARAMOUNT study confirmed the improvement of overall survival with continuation maintenance chemotherapy with pemetrexed (PEM) compared with placebo after 4 cycles of cisplatin plus PEM induction chemotherapy recently. JMEN study also showed the usefulness of switch maintenance with PEM after 4 cycles of platinum doublet without PEM. In this study, we conducted the randomized phase II study comparing switch or continuation maintenance chemotherapy with PEM after standard doublet regimen. Methods: Histologically/cytologically confirmed stage IIIb or IV non-squamous NSCLC patients with mesurable disease, ECOG PS 0-1, age over 20 years and adequate organ function were eligible for the study. Randomization was stratified by gender and stage of disease. Patients received 3 cycles of PEM 500 mg/m2 plus CB AUC6 (Arm 1) or PAC 200 mg/m2 plus CB AUC6 (Arm 2). All patients with non-PD after induction chemotherapy continued PEM 500 mg/m2 until PD. Primary endopoint is progression-free survival (PFS). Results: 140 pts were enrolled and assigned to Arm 1 or Arm 2 randomly. The clinical data of 132 pts were used as full analysis set (median age 64.5 yrs (42-83), 85 male, 120 stage IV, 58 PS0, 127 adenocarcinoma, 46 never smoker). 42 pts had prior treatment including 9 sugery, 1 adjuvant chemotherapy, 24 radiotherapy and 8 others. In both arms, 50% of pts entered into the maintenance treatment with PEM after completion of 3 cycles induction chemotherapy. The median PFS was 92 days in Arm 1 and 143 days in Arm 2, respectively. Cox-proportinal Hazard ratio was 0.827, and 95% HR confidential interval was 0.563-1.248. Stratified Log-Rank test showed no significant difference in both arms. Conclusions: There was no significant difference for PFS in PEM plus CB follwed by PEM and PAC plus CB followed by PEM. Clinical trial information: 000005008.
Outcomes of prognostic disclosure: Effects on advanced cancer patients’ prognostic understanding, mental health, and relationship with their oncologist.
Authors: Enzinger Andrea Catherine , Zhang Baohui , Balboni Tracy A. , Schrag Deborah , Prigerson Holly Gwen 
Published: March 2020

9519 Background: Many oncologists are reluctant to discuss life expectancy with advanced cancer patients. We examined the frequency of prognostic disclosure and its impact on patients’ prognostic understanding, the patient-doctor relationship, and psychological distress. Methods: Coping with Cancer was an NCI-funded, multi-site prospective cohort of 726 patients with advanced incurable cancer, enrolled 2002-2008. At baseline, patients were asked if their oncologist had ever discussed prognosis, and if so what estimate was communicated. Patients also estimated their prognosis. The therapeutic alliance scale measured patient-doctor relationship, and the McGill QOL instrument assessed symptoms of depression and anxiety. Multivariable analyses (MVA) assessed relationships between prognostic disclosure and psychological symptoms, controlling for confounds. Results: Among this cohort of terminally ill patients (median survival 4mos), most (72%) wanted to be told their life expectancy. Only 19.8% (104/525) of patients had received a prognostic estimate from their oncologist (median estimate 6mos; IQR 6-15mos). When queried about factors informing their prognostic understanding, 85.9% of patients cited personal or religious beliefs; only 11.7% cited a physician’s estimate. Of the 299 patients willing to estimate their life expectancy, patients who had been previously informed of their prognosis were substantially more realistic in their own estimate (median 12mos v 48mos, Wilcoxon test p<0.001). Moreover, patients’ and oncologists’ prognostic estimates were significantly correlated (ρ=0.49, p<0.001). Prognostic disclosure was not associated with poor patient-doctor relationship rating (Fisher’s Exact, p=0.625), nor was it associated with depressive symptoms (β 0.06, p=0.242) or anxiety (β 0.06, p=0.234) in MVA. Conclusions: Few advanced cancer patients are informed of their life expectancy, although most want this information. Prognostic disclosure is associated with substantial improvement in patients’ prognostic understanding, without compromising the patient-doctor relationship or increasing psychological distress.
Comparison of preoperative screening tools predicting postoperative complications in oncogeriatric surgical patients.
Authors: Huisman Monique , Van Leeuwen Barbara , Ugolini Giampaolo , Montroni Isacco , Stabilini Cesare , Spiliotis John , de'Liguori Carino Nicola , Farinella Eriberto , Stanojevic Goran , Nestorovic Milica , Veering Dettie , Salawu Abdulazeez , de Bock G. , Audisio Riccardo A. 
Published: March 2020

9557 Background: In the onco-geriatric surgical population it is important to identify patients at increased risk of adverse post-operative outcome in order to effectively implement preventive measures and to improve outcome in this population. There is need for a time saving and efficient screening tool. Our aim was to determine the predictive ability of the Mini Mental State Examination (MMSE), Brief Fatigue Inventory (BFI) and Timed “Up & Go” (TUG) concerning the occurrence of a major post-operative complication in a series of elderly patients undergoing elective surgery for solid tumors. Methods: In an international cohort, 329 patients ≥70years undergoing elective surgery for solid tumors were prospectively included. Primary endpoint was the incidence of a major complication during the first 30 days after surgery. Pre-operatively the MMSE, BFI and TUG were scored. TUG depicts the time needed to stand up from a chair, walk 3 meters, turn around, walk back and sit down. Data were analyzed using multivariable logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (95%-CI). Results: The majority of patients underwent major surgery (n=219; 66.6%). A total of 71 (22.1%) patients experienced major complications. TUG, MMSE and BFI, adjusted for center, gender and minor or major surgery, were independent predictors of the occurrence of major post-operative complications (see Table). Conclusions: Screening tools are able to predict major post-operative complications in onco-geriatric surgical patients. TUG is most specific in identifying patients at risk and could be considered to allocate preventive measures effectively. [Table: see text]
Provider-patient communication about cost of care: Results from a national patient education program.
Authors: Ahmed Ivy A. , Harvey Allison , Amsellem Marni , Smith Thomas J. 
Published: March 2020

9578 Background: A 2010 NIH study indicates direct cancer care expenditures will reach $158 billion in the U.S. by 2020, impacting millions of Americans. The cost of insurance for a family of 4 has increased from $6000 (2000) to over $16,000 (2011). Medical debt is a significant cause of personal bankruptcy, even if insured. The financial realities posed by costs associated with cancer care greatly complicate a cancer diagnosis. The most recent American College of Physicians Ethics Manual recommends all parties must interact honestly, openly, and fairly. (Snyder L, et al. Ann Int Med 2012, p86) This analysis explores the occurrence and value of patient-provider communication surrounding costs associated with care in a national survey of those affected by cancer. Methods: From 2011-12, 505 individuals attending Frankly Speaking About Cancer: Coping with the Cost of Care workshops completed a survey assessing experiences about the costs of cancer care. This is a Cancer Support Community national evidence-based educational program. All attendees (n=708) were eligible to complete survey. Results: Most attendees (71.3%) responded. The majority (62.4%) were people with cancer/survivors; the remainder included spouses/partners, family members, and 8.7% were health care professionals. Most (80.8%) were Caucasian, and averaged 57.2 years. Of those with cancer, 89.9% were insured at diagnosis. 59.4% reported no one on their health care team initiated a discussion about the financial aspects of their care. Included in this figure, 22.7% actively sought information from health care team, and 36.7% received no information about cost. When topic was initiated, it was by social workers (16.2%), physicians (12.3%), nurses (6.3%) or financial specialists (8.2%). When information was provided, 72.1% found it somewhat or very useful. Also, regardless of provider discussion, respondents independently sought resources for managing costs, such as other patients (44.2%), the Internet (41.5%), and patient support organizations (38.1%). Conclusions: Patients want financial information but do not receive it. These data highlight the need and value of providers initiating a dialogue about the cost of cancer care with patients.