tbuckley/cabot-search huggingface dataset:
Do all patients with HER2-positive breast cancer require one year of adjuvant trastuzumab?: A systematic review and meta-analysis.
Authors: Paul Stewart, Phillip S. Blanchette, Prakesh S Shah, Xiang Y Ye, R Gabriel Boldt, Ricardo Fernandes, Theodore A. Vandenberg, Jacques Raphael
Journal: Journal of Clinical Oncology (2019)

522 Background: One year of adjuvant trastuzumab (T) remains the standard treatment for patients with HER2 positive breast cancer. Results from randomized trials with diverse non-inferiority margins comparing one year to a shorter duration of adjuvant T were not consistent, particularly with the PERSEPHONE and the final PHARE and Short-HER trials’ results. Our objective was to conduct a systematic review and meta-analysis of randomized trials in patients with HER2 positive breast cancer to assess whether a shorter duration of adjuvant T was non-inferior to one year of treatment. Methods: PubMed, EMBASE and The Cochrane Library were searched for eligible randomized trials. Hazard ratios (HR) for disease free and overall survival (DFS, OS) were weighted using generic inverse variance and pooled in a meta-analysis using random-effects models. The median of non-inferiority margins derived from each trial was calculated to set a non-inferiority margin of 1.29 for the pooled analysis. Subgroup analyses compared survival outcomes by estrogen receptor (ER) status, nodal status, length and timing of trastuzumab treatment. Results: Data of 11,376 patients from 5 trials were analyzed. A shorter duration of T was non-inferior to one year of therapy for DFS (HR 1.13, 95%CI 1.03-1.24) but worse for OS (HR 1.16, 95%CI 1.01-1.32). In addition, the non-inferiority for DFS was met for patients with ER positive disease (HR 1.1, 95%CI 0.95-1.28) and patients treated with 6 months (HR 1.09, 95%CI 0.98-1.22) or sequential T (HR 0.97, 95%CI 0.75-1.27). Conversely, the non-inferiority for DFS was not met for patients with ER negative disease (HR 1.22, 95%CI 1.06-1.41), patients treated with 9 weeks (HR 1.26, 95%CI 1.02-1.55) or concomitant T (HR 1.25, 95%CI 1.07-1.45) and patients with node negative (HR 1.12, 95% 0.93-1.35) or positive (HR 1.16, 95%CI 0.99-1.36) disease. Conclusions: Within the limitations of the available data and the different non-inferiority margins used in randomized trials, a shorter duration of adjuvant T is non-inferior to one year of therapy for DFS in patients with HER2 positive breast cancer, particularly in patients with ER positive disease. Further trials with appropriately chosen non-inferiority margins are needed to confirm the optimal duration of T in patients with low-risk disease.
Randomized phase III trial of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric cancer (JCOG0912).
Authors: Hitoshi Katai, Junki Mizusawa, Hiroshi Katayama, Shinji Morita, Takanobu Yamada, Etsuro Bando, Kazunari Misawa, Masakazu Takagi, Akinori Takagane, Shin Teshima, Keisuke Koeda, Souya Nunobe, Takaki Yoshikawa, Masanori Terashima, Mitsuru Sasako
Journal: Journal of Clinical Oncology (2019)

4020 Background: The number of patients undergoing laparoscopy-assisted distal gastrectomy (LADG) has been increasing worldwide. Several retrospective studies have demonstrated equivalent survival after LADG compared to open distal gastrectomy (ODG). However, no confirmatory randomized controlled trials has been published in a peer review journal to evaluate the efficacy of LADG compared with ODG, ensuring strict surgical skill and quality control of surgery. We conducted phase III study to confirm that LADG is not inferior to ODG in efficacy. Methods: Eligibility criteria included histologically proven adenocarcinoma in the middle or lower third of the stomach; clinical stage I tumor (T1N0, T1N1, T2(MP)N0). Patients were preoperatively randomized to ODG or LADG. LADG was performed by accredited surgeon. The extent of nodal dissection was decided according to Japanese gastric cancer treatment guidelines. The primary endpoint is relapse-free survival (RFS) and the secondary endpoints are overall survival (OS), short-term clinical outcomes, and postoperative quality of life. Planned sample size was 920 patients in total, which was determined with at least 80% power, a one-sided alpha of 5%, and a non-inferiority margin for a hazard ratio of 1.54. Before the 1st interim analysis, the primary endpoint was amended from OS to RFS in 2015 because the surrogacy of RFS for OS was demonstrated and the predicted number of events for OS was smaller than expected. Results: A total of 921 patients were randomized (ODG 459, LADG 462) between Mar. 2010 and Nov. 2013. Among 921 patients, 912 patients (99%) underwent assigned surgery. Conversion to ODG was needed for 16 patients (3.5%) in LADG arm mainly due to advanced disease. 5-year RFS was 94.0% (95% CI: 91.4-95.9%) in ODG and 95.1% (92.7-96.8%) in LADG. LADG was non-inferior to ODG for RFS. (HR: 0.84 [90% CI: 0.56-1.27 ( &lt; 1.54)], p for non-inferiority = 0.008). 5-year OS was 95.2% (92.7-96.8) in ODG and 97.0% (94.9-98.2) in LADG (HR: 0.83 [95% CI: 0.49-1.40]). Conclusions: The non-inferiority of LADG to ODG in RFS was confirmed. LADG has been established as one of the standard treatments for clinical stage I gastric cancer. Clinical trial information: UMIN000003319.
Asthma as an outcome: Exploring multiple definitions of asthma across birth cohorts in the Environmental influences on Child Health Outcomes Children's Respiratory and Environmental Workgroup
Authors: Cynthia M. Visness, Tebeb Gebretsadik, Daniel J. Jackson, Jocelyn Biagini Myers, Suzanne Havstad, Robert F. Lemanske, Tina V. Hartert, Gurjit K. Khurana Hershey, Edward M. Zoratti, Lisa J. Martin, Rachel Miller, Diane R. Gold, Anne Wright, Debra A. Stern, James E. Gern, Christine C. Johnson
Journal: Journal of Allergy and Clinical Immunology (2019)
Association of liver-directed local therapy with overall survival in metastatic intrahepatic cholangiocarcinoma.
Authors: Nikhil Sebastian, Eric David Miller, Terence M Williams, Anne M. Noonan, John L. Hays, Dayssy Alexandra Diaz Pardo
Journal: Journal of Clinical Oncology (2019)

e15659 Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive hepatobiliary malignancy characterized by local infiltration and lymph node, lung, and bone metastases. The majority of patients die from tumor-related liver failure. The standard of care for metastatic ICC is chemotherapy (CHT) and the role of local therapy to the liver is unclear. We used the National Cancer Database (NCDB) to compare overall survival (OS) of patients treated with CHT, with and without local radiotherapy (RT) or surgery of the liver. Methods: We evaluated patients with metastatic ICC who received CHT with or without hepatic surgery or external beam RT to a dose ≥ 45 Gy. We used multiple imputation followed by cox proportional hazards and nearest neighbor propensity score matching (1:1, caliper = 0.1) on the basis of age, sex, race, comorbidity score, T-stage, tumor size, N-stage, primary tumor focality, primary tumor vascular invasion, year of diagnosis, insurance status, and treatment facility, as well as presence of bone, lung, and lymph node metastases. Results: We identified 2201 patients who received either CHT alone (n = 2097), or with hepatic surgery (n = 76) or RT (n = 28). Liver-directed local therapy was associated with improved OS on univariate (hazard ratio [HR] = 0.57; 95% CI 0.15 - 0.71; p &lt; 0.001) and multivariate analysis (HR = 0.61; 95% CI 0.49 - 0.75; p &lt; 0.001). There was no difference in OS between RT versus surgery (HR = 1.37; 95% CI 0.76 - 2.46; p = 0.30). After propensity score matching, there were 104 patients in each cohort. Liver therapy continued to be associated with improved OS (HR = 0.60; 95% CI 0.45 - 0.81; p = 0.001). Conclusions: We found that addition of local therapy to the liver with surgery or RT is associated with higher OS when compared to CHT alone in metastatic ICC. These findings should be validated in an independent cohort.
Case 39-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Mortimer S. Greenberg, Katharine S. Kosinski, Newton E. Hyslop
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 37-year-old man was admitted to the hospital because of jaundice and anemia.He was well until three months earlier, when weakness developed, accompanied by daily headaches that radiated from the nuchal region over the vertex to the frontal area. He experienced postprandial substernal burning pain that lasted for an hour or two, accompanied by nausea. The symptoms continued until two weeks before admission, when he began to have chills and fever with a cough productive of brown sputum occasionally flecked with blood. A physician diagnosed a viral infection and prescribed a cough syrup. Two days later . . .
First-in-human phase 1 study of the antibody-drug conjugate (ADC) SAR408701 in advanced solid tumors: Dose-expansion cohort of patients (pts) with non-squamous non-small cell lung cancer (NSQ NSCLC).
Authors: Anas Gazzah, Sophie Cousin, Valentina Boni, Charles Ricordel, Tae Min Kim, Jin-Soo Kim, Carole Helissey, Itziar Gardeazabal, Mustapha Chadjaa, Aurore Allard, Semra Yoruk, Fabrice Barlesi
Journal: Journal of Clinical Oncology (2019)

9072 Background: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a cell-surface glycoprotein highly expressed in several tumor types. This Phase 1, open-label, dose-escalation, dose-expansion study (NCT02187848) investigated SAR408701, a DM4 conjugated ADC targeting CEACAM5, in pts with advanced solid tumors. During dose escalation, maximum tolerated dose (MTD) of SAR408701 was 100 mg/m 2 IV once every 2 weeks in 14-day cycles. Interim analysis of an ongoing expansion cohort in pts with NSQ NSCLC with CEACAM5 expression in ≥ 50% of the tumor cell population is reported. Methods: SAR408701 was administered at MTD. Primary endpoint: overall response rate (ORR; expansion phase). Secondary endpoints include safety and pharmacokinetics (PK). Tumor assessments were performed every 4 cycles (8 weeks). Results: As of Aug 2, 2018, 22 pts with NSQ NSCLC (21 adenocarcinoma; 1 not yet reported) received SAR408701 at MTD. Median age: 60 years; male: 72.7%; ECOG PS (n = 21): 0 = 38.1%, 1 = 61.9%. Median number of prior anticancer therapies for advanced disease was 3; 66.7% (14/21) received ≥ 3 lines; 59.1% had prior anti-tubulin-based treatments. Pts received a median of 6.5 cycles. 15 pts discontinued due to progressive disease and 1 due to an adverse event (AE; peripheral neuropathy); 6 pts remain on study. ORR was estimated at 22.7% (5/22 pts; 90% CI 11.5–39.9); 40.9% had stable disease. Most frequently occurring all-grade treatment-emergent AEs (TEAEs) were corneal events (40.9%; including keratitis 22.7% [1 Grade 3] and keratopathy 18.2%), dyspnea (31.8%; 5 Grade ≥ 3), asthenic conditions (31.8%) and diarrhea (27.3%). 6 pts had ≥ 1 dose modification due to a TEAE. PK analysis was performed in 14 pts at Cycle 1; mean C max , AUC, clearance and t 1/2z were 53.1 µg/mL, 297 µg.day/mL, 0.685 L/day and 6.19 days, respectively. Conclusions: In pts with advanced NSQ NSCLC and CEACAM5 expression in ≥ 50% of tumor cells, SAR408701 had a favorable safety profile. Interim analysis of 22 pts achieved the predefined boundary for efficacy (≥ 4 of 30 pts). These data support further development in NSQ NSCLC. Funding: Sanofi Clinical trial information: NCT02187848.
Systemic immune-inflammation index to predict prognosis of elderly patients with newly diagnosed solid tumors.
Authors: Chan Li, Wei Tian, Feng Zhao, Meng Li, Qin Ye, Yuquan Wei, Tao Li, Ke Xie
Journal: Journal of Clinical Oncology (2019)

e14517 Background: Cancer in the elderly has become a common problem due in part to the increase in life expectancy. Compared to younger counterparts, the biological characteristics of tumors and their responsiveness to therapy may differ in elderly patients, and the elderly also can have a decreased tolerance to anticancer therapy. In addition, there is less evidence from clinical trials to guide physicians in treating aged patients with solid tumors. It would be highly useful to have a simple and powerful indicator of their prognosis. In this paper we evaluated the predictive value of the Systemic Immune-inflammation Index, SII, in determining the one-year survival in elderly patients with newly diagnosed solid tumors. Methods: Data from 118 patients, 70 to 89 years of age with newly diagnosed solid tumors in 2014 were retrospectively analyzed. The patients were divided into two groups according to age: (1) 70-75 years of age and (2) over 75 years of age. We calculated SII from the equation, SII = P x N/L, where P, N and L are the preoperative peripheral blood platelet, neutrophil and lymphocyte counts per liter respectively. The optimum cutoff point for SII for a favorable prognosis was determined to be 390×10 9 cells/L. For evaluation of SII as a prognostic indicator, the patients were divided into high SII ( &gt; 390×10 9 cells /L) and low SII (≤ 390×10 9 cells/L) groups. Individual values were used to determine the relationship between SII and one-year survival in the two age groups. Results: A high SII &gt; 390×10 9 cells/L was correlated with poor one-year survival (χ² = 7.658, P = 0.006). Patients with low SII had improved survival. Conclusions: SII was a robust indicator of one-year survival in elderly patients with newly diagnosed solid tumors. Patients in the high SII group showed poor prognosis compared to patients with a low SII score. [Table: see text]
Trans-aTTom: Breast Cancer Index for prediction of endocrine benefit and late distant recurrence (DR) in patients with HR+ breast cancer treated in the adjuvant tamoxifen—To offer more? (aTTom) trial.
Authors: John Bartlett, Dennis Sgroi, Kai Treuner, Yi Zhang, Tammy Piper, Ranelle C. Salunga, Ikhlaaq Ahmed, Kristen M Basnet, Elena Brachtel, Sarah Pirrie, Catherine A. Schnabel, Daniel William Rea
Journal: Journal of Clinical Oncology (2019)

505 Background: The aTTom study is a prospective phase III trial that randomized 6953 HR+ women to stop or continue tamoxifen (TAM) for 5 more years after completing at least 4 years of prior TAM. Results at 9 years of median follow-up demonstrated fewer breast cancer recurrences (21% vs 25%; RR= 0.86 [95% CI 0.77-0.96]; P = 0.006) and reduced breast cancer mortality (13% vs 15%; HR= 0.91 [95% CI 0.80-1.04]; P = 0.18) but increased incidence of endometrial cancer with longer TAM use (P &lt; 0.0001). The Breast Cancer Index (BCI) is a gene expression–based signature that stratifies patients based on the risk of overall (0-10y) and late (post-5y) DR and predicted the likelihood of benefit from extended endocrine therapy in MA.17. This Translational aTTom (Trans-aTTom) study is a large-scale validation of the predictive ability of BCI for extended endocrine therapy (EET) benefit. Methods: Patients treated in the aTTom trial with available primary tumor tissue were eligible for this multi-institutional prospective-retrospective study. Primary and secondary endpoints were recurrence-free interval (RFI) and disease-free interval (DFI), respectively. Statistical significance level for RFI was set at 0.0336 as per statistical plan. Kaplan-Meier and Cox proportional hazards regression analysis with time-varying coefficients were used to test the predictive activity of BCI by HoxB13/IL17BR (H/I) status (High vs Low). Likelihood ratio test based on Cox regression was used to evaluate treatment by biomarker interaction. Results: 2637 tumors were centrally assessed for ER, PR and HER2 status leading to 1822 HR+ patients analyzed (1018 N0, 583 N+). Initial results from patients with N+ disease at 12 years of median follow-up showed 287 (49%) were classified as H/I-High and 296 (51%) were classified as H/I-Low. H/I High patients showed a statistically significant benefit of 9.8% in RFI with 10y vs 5y of TAM (HR=0.35 [95% CI 0.15-0.85]; P=0.027), whereas H/I Low patients showed no benefit (-0.2% RFI; HR=1.07 [95% CI 0.69-1.65]; P=0.77). A statistically significant interaction between continuous BCI and treatment was demonstrated (P = 0.02). Conclusions: These data provide further validation and establish level 1B evidence for BCI as a predictive biomarker for preferential benefit from EET in HR+ breast cancer.
Alfa-feto protein (AFP) as a predictor of outcome for children with germ cell tumors: A report from the malignant germ cell international consortium.
Authors: Allison Frances O'Neill, Caihong Xia, Mark D. Krailo, Furqan Shaikh, Farzana D. Pashankar, Deborah F Billmire, Thomas Arthur Olson, James F. Amatruda, Doojduen Villaluna, Marcio H. Malogolowkin, Carlos Rodriguez-Galindo, A. Lindsay Frazier
Journal: Journal of Clinical Oncology (2019)

10036 Background: There are several studies describing the correlation between unsatisfactory tumor marker decline and poor prognosis in adult patients treated for germ cell tumors. In pediatric patients the data is limited. We therefore retrospectively analyzed data collected from pediatric patients treated on the Children’s Oncology Group (COG) Protocol AGCT0132 to determine whether a relationship exists between AFP decline and outcome. Methods: One hundred and thirty-one patients with germ cell tumors enrolled on Children’s Oncology Group Protocol AGCT0132 were eligible for analysis of AFP decline. Serum AFP half-life was calculated from levels collected post-operatively and after the start of chemotherapy, excluding values in the first 7 days of chemotherapy to accommodate unpredictable increases in the initial days of treatment. AFP decline was defined as automatically satisfactory (AFP normalized within the first two AFP measures following the start of chemotherapy), calculated satisfactory (AFP half-life ≤7 days following the start of chemotherapy), and unsatisfactory. Results: The 3-year event-free survival (EFS) was 87 % (95% confidence interval-CI: 79-92 %) for patients with a satisfactory decline and 62 % (95% CI: 31-82 %) for patients with an unsatisfactory decline (p = 0.006). In stratified analyses, this effect was limited to patients ≥11 years of age and with standard risk (SR2) disease ((p = 0.002 and p = 0.004, respectively). Three-year overall survival for patients with satisfactory versus unsatisfactory decline was not statistically significant. Conclusions: This study is the first to show an association between AFP decline and EFS in pediatric patients. Although there is no statistically significant association between tumor marker decline and overall survival, recognition of patients at high-risk of relapse may allow for early intensification of therapy and impact the rationale for future clinical trial design.
Randomized phase 2 study of maintenance pemetrexed (Pem) versus observation (Obs) for patients (pts) with malignant pleural mesothelioma (MPM) without progression after first-line chemotherapy: Cancer and Leukemia Group B (CALGB) 30901 (Alliance).
Authors: Arkadiusz Z. Dudek, Xiaofei F. Wang, Lin Gu, Tom Stinchcombe, Robert Arthur Kratzke, Everett E. Vokes, Hedy L. Kindler
Journal: Journal of Clinical Oncology (2019)

8517 Background: Standard front-line chemotherapy for advanced MPM is (Pem and a platinum; optimal treatment duration is unknown. We performed a randomized phase 2 trial (NCT01085630) to determine if continuation of single-agent Pem after 4-6 cycles of Pem-platinum would improve progression-free survival (PFS). Methods: Eligible pts had histologically confirmed unresectable MPM, and performance status (PS) 0-1. Pts with at least stable disease following 4-6 cycles of Pem-platinum were stratified by first-line regimen (cis- or carboplatin) and histology (epithelioid versus other) and randomized 1:1 to Obs or continuation of Pem until progression. The primary endpoint was PFS. We assumed that Obs produced a median (m) PFS of 3 months (mo) and Pem would yield a 100% improvement in mPFS to 6 mo; 60 eligible pts (30 per arm) were to be randomized. Results: 72 pts from 30 sites registered 12/10-6/16. The study closed early due to slow accrual once 53 pts were randomized; 49 eligible pts (22 Obs, 27 Pem) are included in the efficacy analysis. Pt characteristics (Obs/Pem): age: median (range) 70 (39-85)/70 (52-87); male 68%/78%; PS 0 27%/33%; epithelioid histology 77%/70%; first-line cisplatin 27%/26%. A median of 4 cycles of Pem (range 1-33) was delivered; 22% of pts required dose modification. mPFS was 3 mo on Obs and 3.4 mo on Pem (hazard ratio (HR) 0.99; 95% CI: 0.51-1.90; p=0.9733). Median overall survival (mOS) was 11.8 mo for Obs, and 16.3 mo for Pem (HR 0.86; 95% CI 0.44-1.71; p=0.6737). Toxicities ≥ grade 3 on Pem included anemia 8%, lymphopenia 8%, neutropenia 4%, and fatigue 4%; there were no grade 5 toxicities. A higher baseline level of serum mesothelin related peptide (SMRP) was associated with worse PFS (HR 1.861, p=0.049). Baseline osteopontin did not significantly affect PFS (p=0.3630). Conclusions: Although it was well tolerated, maintenance Pem following initial Pem/platinum doublet chemotherapy does not improve PFS in MPM patients. High baseline SMRP was associated with shorter PFS. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org . Clinical trial information: NCT01085630.
Insurance status and racial disparities in detection of early-stage breast cancer.
Authors: Naomi Ko, Susan Hong, Robert Winn, Gregory Sampang Calip
Journal: Journal of Clinical Oncology (2019)

e18121 Background: Racial/ethnic minority women are diagnosed with later stage breast cancer. This study identifies the extent insurance can affect stage differences among a large, diverse population of breast cancer patients in the U.S. Methods: Retrospective, population-based study of women aged 40-64 years diagnosed with stages I-III breast cancer in the Surveillance, Epidemiology and End Results Program between 2010 and 2014. The primary outcome was risk of diagnosis with locally-advanced (stage III) versus early stage breast cancer (stages I-II). Causal mediation analyses were conducted to determine effects of race/ethnicity and proportion of observed differences mediated by health insurance status on earlier stage. Results: A total of 124,415 women (104,468 insured and 19,947 uninsured /Medicaid) were included. Among women with health insurance, a lower proportion was diagnosed with locally-advanced breast cancer compared to uninsured/Medicaid-covered women (11% versus 21%). In multivariable models, non-Hispanic Black (OR = 1.50, 95% CI 1.43-1.58), American Indian/Alaskan Native (OR = 1.38, 95% CI 1.11-1.72) and Hispanic (OR = 1.35, 95% CI 1.28-1.42) women had higher odds of being diagnosed with locally-advanced disease compared to non-Hispanic White women. When adjusting for health insurance and other socioeconomic factors, associations between race/ethnicity and risk of locally-advanced breast cancer were attenuated (non-Hispanic Black: OR = 1.30, 95% CI 1.23-1.37; American Indian/Alaskan Native: OR = 1.15, 95% CI 0.91-1.45; Hispanic: OR = 1.16, 95% CI 1.09-1.22). Approximately half (48% to 50%) of racial differences in risk of locally advanced disease were mediated by health insurance. Conclusions: We find that half of the observed racial/ethnic disparities in upstaging at diagnosis are mediated by health insurance coverage.