tbuckley/cabot-search huggingface dataset:
A phase 1b/2, open label, dose-escalation study of margetuximab (M) in combination with pembrolizumab (P) in patients with relapsed/refractory advanced HER2+ gastroesophageal (GEJ) junction or gastric (G) cancer.
Authors: Daniel V.T. Catenacci, Sunnie S. Kim, Philip Jordan Gold, Philip Agop Philip, Peter C. Enzinger, Joe Coffie, Emmett V. Schmidt, Malcolm Baldwin, Jeffrey L. Nordstrom, Ezio Bonvini, Jon M. Wigginton, Howard S. Hochster, Crystal Shereen Denlinger, Hope Elizabeth Uronis, Johanna C. Bendell, Ronan Joseph Kelly, Jan Kenneth Davidson-Moncada, Albert C. Lockhart
Journal: Journal of Clinical Oncology (2017)

TPS219 Background: Prognosis for advanced HER2+ GEJ and G cancers remains poor, with median survival just beyond one year. Trastuzumab (T) in combination with chemotherapy is the initial treatment of choice, but therapeutic options targeting HER2 beyond T are poorly defined. M is an Fc-enhanced monoclonal antibody (Mab) to HER2 that recognizes with similar affinity the same epitope as T and whose Fc domain, compared to T, binds with increased affinity to the activating CD16A Fc-receptor (FcR) and decreased affinity to the inhibitory CD32B FcR. Preliminary data shows that M monotherapy has clinical activity against HER2+ tumors in GEJ and G cancer patients previously treated with T or other anti-HER2 agents. P is a Mab that blocks the interaction of the immune checkpoint molecule, PD-1, with its ligands, facilitating tumor cell elimination by releasing tumor-associated T cells from exhaustion. Monotherapy P has demonstrated remarkable and durable clinical activity in a Phase I study. Safety profiles of M and P are acceptable and non-overlapping. Methods: This study advances a chemotherapy free combination of M + P treatment for advanced HER2+ GEJ and G cancer patients. Enrolled patients will have relapsed/refractory HER2+ GEJ or G adenocarcinoma with measurable disease that has progressed on T plus first line chemotherapy. HER2+ (IHC 3+ or ISH+) will be confirmed by central review. Two dose levels of M (10mg/kg and 15mg/kg) and a fixed dose of P (200mg) will be evaluated for safety and tolerability. Patients will receive combination treatment once every 21 days for up to 24 months, until confirmed disease progression or intolerable toxicity. Dose expansion will enroll up to 60 patients, with 20 undergoing pre- and on-treatment biopsy. Response will be assessed every 6 weeks for the first 6 months and every 12 weeks thereafter per RECIST v1.1 and immune RECIST to account for response patterns observed with immunotherapies. Primary endpoint is ORR and duration of response, and secondary endpoints include PFS and OS. The study was initiated on January 2016 and is ongoing in North America and Asia. Clinical trial information: NCT02689284.
A prognostic model for predicting breast cancer (BC)-related survival in operable triple-negative (TN) patients (pts).
Authors: Elisabetta Munzone, Edoardo Botteri, Vincenzo Bagnardi, Angela Sciandivasci, Gaetano Aurilio, Laura Adamoli, Angela Esposito, Nicole Rotmensz, Aron Goldhirsch, Franco Nole
Journal: Journal of Clinical Oncology (2012)

1049 Background: TNBC represent a heterogeneous disease in terms of biology, prognosis, and treatment response. We propose a prognostic model to identify homogeneous subgroups of patients and tailor risk-adapted adjuvant therapies indications. Methods: We analyzed 1,049 pts operated in our institute from 1997 to 2007 for early TNBC. Pts who received neoadjuvant chemotherapy (CT), with T4 tumors or previous history of cancer were excluded. Death from BC was the primary endpoint of the study. We calculated an individual predicted risk using a multivariable Cox regression model, with age, tumor size, number of positive lymph nodes and Ki-67 analyzed as continuous covariates, and tumor grade and perivascular invasion as categorical covariates. Results: Median age was 52 years, 562 (53.4%) and 670 (65.1%) pts had a pT1 and pN0 TNBC, respectively. Median Ki-67 was 48%. Adjuvant CT regimens were distributed as follows: classical CMF 388 (37.0%), anthracycline containing regimens 455 (43.4%), taxanes 12 (1.1%), other regimens 66 (6.3%) and no CT 128 (12.2%). After a median follow-up of 6 years, 131 deaths from BC were observed (5-year cumulative incidence 11.9%). At multivariable analysis, age, tumor size, number of positive lymph nodes, Ki-67, tumor grade and perivascular invasion were associated with the risk of death and were included in the prognostic model. Its predictive accuracy was good (C-index 0.73). We subsequently identified three homogeneous prognostic subgroups - low, medium and high-risk - according to the tertiles values of the predicted risk. The outcomes are shown in the table. Conclusions: We could identify homogeneous prognostic subgroups of TNBC pts according to clinical-pathological features. This prognostic model suggests that the use of CT in TN low-risk pts might be questionable. We are currently externally validating this model on a different series of pts. [Table: see text]
Development and external validation of a melanoma risk prediction model using self-assessed risk factors.
Authors: Kylie Vuong, Anne Elizabeth Cust, Bruce Konrad Armstrong, Kevin McGeechan
Journal: Journal of Clinical Oncology (2015)

1563 Background: Melanoma incidence rates have been increasing in fair-skinned populations, with Australia having the world’s highest melanoma incidence rates. By providing individuals with their overall risk instead of relying on individual risk factors, melanoma risk prediction models may lead to improved risk perception and sun protection behaviours. In addition to their clinical uses, these models may assist in planning intervention trials and population prevention strategies that target particular risk groups. We aimed to develop and validate a melanoma risk model predicting lifetime absolute risk of primary melanoma using self-assessed risk factors. Methods: We used unconditional logistic regression with backward selection to develop the melanoma risk model using the Australian Melanoma Family Study, a population-based case-control-family study with 629 population-based cases with first primary melanoma diagnosed before age 40 years and 535 controls from 2001 to 2005. Relative risk estimates from the model were combined with Australian melanoma incidence and mortality data using the Gail method to obtain lifetime absolute risk estimates. Subsequently we validated the model externally using the Western Australia Melanoma Study, a population-based study with 511 case-control pairs from 1980 to 1981. Multiple imputation was used to handle missing data. Results: Our model, which includes age, sex, state of residence, hair colour, naevus density, first degree family history of melanoma, previous non-melanoma skin cancer and lifetime sunbed use, demonstrated good discriminative performance on both internal [area under the receiver operating curve (AUC) = 0.71 (95% CI 0.68 - 0.73)] and external validation [AUC = 0.63 (0.60 – 0.65)]. Conclusions: The model, which is based on self-assessed risk factors, discriminates well between those with and without melanoma and may be useful in the design of melanoma prevention interventions.
Use of a best-practice advisory to increase survivorship clinic referrals.
Authors: Sheetal Mehta Kircher, Megan Slocum, Sofia F. Garcia, Aubri Veneruso, Alpa Patel, Karen Kinahan, William John Gradishar, Sarika Jain, Lisa E. Flaum, Cesar Santa-Maria, Frank J. Penedo
Journal: Journal of Clinical Oncology (2017)

53 Background: The American College of Surgeons Commission on Cancer require accredited institutions to give patients a survivorship care plan (SCPs) within six months of completing curative intent therapy. However, only a minority are receiving SCP’s. Some institutions have survivorship clinics to deliver comprehensive care, including SCP’s. Insufficient referrals to such clinics are a common barrier due to survivorship not being integrated into oncology workflows. To address this, we developed and implemented a best practice advisory (BPA) alert within our EMR to identify eligible patients and facilitate referrals to the survivorship clinic. Methods: Our pilot included breast cancer patients within medical oncology. The BPA electronic alert criteria included: stage 0-III, new patient encounter within 12 months, no SCP completed or previous referral. Upon triggering, the BPA asks “Does your patient require a SCP?” followed by 3 options: 1) SCP needed- an automatic order is generated, if signed, the BPA will not fire again, if unsigned, it will fire at the next encounter (no sooner than 30 days) and will continue until an order is placed or the response “ SCP not needed” is selected. 2) SCP not needed- the BPA will never trigger again for that patient. 3) Don’t know/still on treatment-the BPA will re-fire in 30 days. Data on frequency of BPA firing and number of referrals was compared 90 days prior and post implementation. Chi-square analysis was used. Results: Between 4/1/2015-3/31/2016, 902 patients were seen with stage 0-III breast cancer at Northwestern. Ninety days prior to implementation of the BPA, 30 patients (3.3%) were referred by 8 oncology providers. In the 90 days following implementation, the BPA fired 845 times (48.5% option 1, 24.8% option 2, 26.6% option 3) and 198 patients (22%) were referred. The difference was statistically significant ( χ 2 = 141.7, p &lt; 0.0001). Conclusions: The implementation of BPAs within an EMR is an effective way to increase referrals to a survivorship clinic, thus increasing the number of patients given SCPs. Challenges identified were having enough staff availible to deal with a rapid increase in referrals, need for refinement of BPA criteria to more precisely identify eligible patients, and provider burden.
Survival of patients considered for participation to contemporary dose-seeking phase trial: Matter of tumour burden, nature of treatment or of dose-levels?
Authors: Juliette Bouchet, Nicolas Isambert, Philippe Alexandre Cassier, Carlos Alberto Gomez-Roca, Stephanie Clisant, Jean-Pierre Delord, Veronique Favre, Peggy Philippe, Isabelle Desmoulins, Alice Levart, Fatima-Zhora Meniai, Nicolas Penel
Journal: Journal of Clinical Oncology (2013)

2549 Background: We have analyzed the survival of pts considered for participation to contemporary phase 1 trial. Methods: All consecutive pts having signed the PIS/IC have been analyzed. OS have been measured using Kalan-Meier method. RMS had been calculated, RMS (0 to 3) is sum of the following prognostic factors: LDH&gt;ULN, met. sites&gt;2 and albumin &lt;35 g/L. Comparisons have been done with Log-rank tests and Cox model. Results: OS of the entire cohort was 448 days. 73.4% of pts having been enrolled. Among not enrolled pts, 74.1% of pts received another treatment. The OS was 497, 247 and 110 days, in pts enrolled in phase I trial, in pts not enrolled but receiving another treatment and in non-treated pts (p=0.001). After adjustment to RMS and with pts not enrolled but receiving other treatment as reference, the HR was 0.47 (95-CI:0.34-0.66; p=0.0001) in pts enrolled in phase 1 compared and 3.54 (1.92-6.52; p=0.0001) in non-treated pts. We have then more specifically analyzed the pts enrolled in single-agent dose-escalating phase I. The OS was 894, 272 and 395 days in pts receiving the 2 first dose-levels, in those receiving intermediate dose-levels and those receiving the phase 2-recommended dose, respectively (p=0.001). The OS was 328 in pts receiving molecular targeted agent and 539 in those receiving cytotoxic agents (p=0.004). In a multivariate analysis, the nature of investigational agent and the dose-level were not associated with better outcome. The sole prognostic factor for OS in multivariate analysis was the RMS (0+1 vs 2+3: HR=3.80 [1.76-8.20], p=0.01). Conclusions: Inclusion in phase 1 trial was associated with better outcome in both crude analysis and after adjustment to RMS. Among enrolled pts, in multivariate analysis RMS reflecting the tumor burden was the sole prognostic factor, the nature of the drug and the dose-level were not associated with the outcome.
Two phase III studies comparing 6 months of either mFOLFOX6 or XELOX with 3 months of the same regimen as adjuvant chemotherapy in patients with completely resected stage III colon cancer (ACHIEVE) or high-risk stage II colon cancer (ACHIEVE-2).
Authors: Takayuki Yoshino, Toshiaki Watanabe, Masaki Mori, Atsushi Ohtsu, Tsunekazu Mizushima, Kentaro Yamazaki, Eiji Sunami, Kuniaki Shirao, Atsushi Sato, Satoshi Morita, Takeharu Yamanaka, Axel Grothey, Daniel J. Sargent, Junichi Sakamoto, Shigetoyo Saji
Journal: Journal of Clinical Oncology (2014)

TPS3655 Background: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration was established to prospectively combine/analyze data from several randomized trials conducted around the world to test whether three months of oxaliplatin-based adjuvant therapy (FOLFOX4/ mFOLFOX6 or XELOX) is non-inferior for disease-free survival (DFS) to six months of the same therapy in patients with stage III or high-risk stage II colon cancer. ACHIEVE (JFMC47-1202-C3) and ACHIEVE-2 (JFMC48-1301-C4) are in progress as part of the IDEA project. Methods: The ACHIEVE and ACHIEVE-2 trials, conducted by the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC), are open-label, randomized, phase III, multicenter studies in Japanese patients with completely resected stage III or high-risk stage II colon cancer, respectively. Main eligibility criteria are adenocarcinoma of the colon; ECOG performance status of 0-1; age 20 years or older; registration within eight weeks of curative resection; starting oxaliplatin-based chemotherapy within two weeks after registration; and adequate organ function. Allocation is done centrally with a 1:1 ratio using randomization stratified by the primary site, number of lymph nodes involved, regimen, age, and participating center for stage III, or by depth of invasion, number of lymph nodes examined, regimen, age, and participating center for high-risk stage II. The primary endpoint is to evaluate whether treatment for three months is not inferior to six months in terms of relapse-free survival (RFS), which is defined as time to colon cancer recurrence or death from any cause. Main secondary endpoints include DFS, overall survival (OS) and adverse events. The target sample size is 1,200 patients for stage III and 500 patients for high-risk stage II. As of February 2014, 992 patients have been randomized for stage III. Enrollment for high-risk stage II starts in February 2014. Study ID: UMIN 000008543 for ACHIEVE and UMIN 000013036 for ACHIEVE-2. Clinical trial information: UMIN 000008543 and UMIN 000013036.
Venetoclax and obinutuzumab in chronic lymphocytic leukemia
Authors: Kirsten Fischer, Othman Al-Sawaf, Anna-Maria Fink, Mark Dixon, Jasmin Bahlo, Simon Warburton, Thomas J. Kipps, Robert Weinkove, Sue Robinson, Till Seiler, Stephen Opat, Carolyn Owen, Javier López, Kathryn Humphrey, Rod Humerickhouse, Eugen Tausch, Lukas Frenzel, Barbara Eichhorst, Clemens-M. Wendtner, Stephan Stilgenbauer, Anton W. Langerak, Jacque J. M. van Dongen, Sebastian Böttcher, Matthias Ritgen, Valentin Goede, Mehrdad Mobasher, Michael Hallek
Journal: Blood (2017)
Family history of cancer and clinical outcome in pediatric oncology.
Authors: Joshua David Schiffman, Ken R Smith, Zachary Burningham, Wendy Kohlmann, Karen Curtin
Journal: Journal of Clinical Oncology (2012)

9525 Background: We previously reported in a small study (n=363) that children diagnosed with cancer who have a family history of cancer (FHC) may have worse prognosis than those without FHC, specifically children diagnosed with Hodgkin Disease (HD) and acute lymphoblastic leukemia (ALL) (Eichstadt et al., ASCO 2009). The Utah Population Database (UPDB), a unique resource, includes a Surveillance Epidemiology and End Results (SEER) registry (the Utah Cancer Registry) record-linked to extensive genealogies for 6.5 million people in which most Utah families are represented. A majority of pedigrees include ≥3 generations and several span 7+ generations. The UPDB provides an accurate, objective assessment of FHC. We expanded our original study by examining cancer mortality of 4,482 pediatric cases (age ≤18) diagnosed from 1966-2009 with adequate follow-up (median 9.5 years) and family information. Methods: We compared survival from cancer-caused mortality for pediatric cases diagnosed from 1966-2009 with FHC of any cancer diagnosed &lt;80 yo in 1st-degree, 2nd-degree, or 3rd-degree relatives to pediatric cases without FHC. Nonparametric estimates of survivor function were determined by the life-table method and a log-rank test of homogeneity was used to test for differences between pediatric probands with FHC compared to no FHC. Results: Overall survival was significantly lower in children with positive FHC (n=1,128) than in children with no FHC (n=3,354) independent of stage (p&lt;0.0001; 10yr survival, 69% with FHC vs.78% with no FHC). We observed lower survival in children with any leukemia and FHC (n=279) compared to children with leukemia and no FHC (n=871; p&lt;0.0001). In particular, cases with ALL and FHC had lower survival (p&lt;0.0001; 10yr survival, 61% vs. 75%). Pediatric lymphoma cases had lower survival when positive for FHC (n=150) vs. no FHC (n=428; p&lt;0.0001), specifically for an HD diagnosis (p=0.0004; 10yr survival, 83% vs. 94%). Conclusions: Pediatric cancer cases with FHC of any cancer (children or adults) have decreased survival compared to cases with no FHC, specifically in children diagnosed with ALL or HD, thus validating our earlier findings. Familial factors likely contribute to increased pediatric cancer mortality.
From law to reality: Factors influencing the pattern of additional screening examinations for women with dense breasts after implementation of a breast density notification law in Texas.
Authors: Bharti Jasra, Sally Goudreau, Stephen Seiler, Charles Edward Wall, Jingsheng Yan, James F. Huth, Roshni Rao, Aeisha Rivers, Rachel D. Wooldridge, Xian-Jin Xie, A. Marilyn Leitch
Journal: Journal of Clinical Oncology (2015)

e17507 Background: Given the increased risk of breast cancer associated with dense breasts and the limitations of screening mammography, 19 states including Texas, have passed laws requiring notification of women of their breast density. This study evaluates patient and physician factors which influence women having additional imaging and the breast cancer detection rate. Methods: A retrospective study was done at a University Hospital in Texas. Chart review was done to identify women with normal mammogram but dense breasts one year before and after implementation of breast density law. Results: In the pre-law group, 37 % had dense breasts among 12,099 women with normal mammograms. Additional imaging was done in 6.6%. High risk women were more likely to get additional imaging, 21% vs. 6% in low risk women (p = 0.0001).The biopsy rate following additional imaging was 1% with no breast cancers detected. Within the post-law group, 33% had dense breasts among 17,272 women with normal mammograms. Additional imaging was done in 5%. High risk women were more likely to get additional imaging, 14% vs. 5% in low risk women (p = 0.0001). 7% of women older than 50 had additional imaging vs. 4% of women younger than 50 (p = 0.0001).The biopsy rate was 3.4 %, with one breast cancer diagnosed and surgery performed in 2.5% women. The table below shows specialty of physicians referring for screening mammogram. In patients who received additional imaging in the post-law group, 48% were initially referred by surgeons, 12% by gynecologists, and 24% by internists, vs. 18% by surgeons, 33% by gynecologists and 46% by internists in the pre-law group (p = 0.0001). Conclusions: Breast density law failed to increase the rate of additional imaging in women with dense breasts. Factors resulting in increased likelihood of additional imaging included: high risk score, older than 50, and referral by a surgeon. Education of referring physicians about the significance of breast density and the availability of enhanced imaging may improve the efficacy of the law to increase breast cancer detection in women with dense breasts. Referring Physician (%) Pre Law Post Law Internist 50 45 Surgeon 19 12 Gynecologist 28 21
Relapsed or refractory primary mediastinal B-cell lymphoma: Evaluation of outcome of a minority from 125 patients treated at a single institution.
Authors: Joanna Romejko-Jarosinska, Anna P. Dabrowska-Iwanicka, Ewa Paszkiewicz-Kozik, Elzbieta Wojciechowska-Lampka, Jan Andrzej Walewski
Journal: Journal of Clinical Oncology (2014)

e19549 Background: Primary mediastinal B-cell lymphoma (PMBL) is a distinct entity of large B-cell lymphoma representing 2%–4% of non-Hodgkin’s lymphomas. The treatment based on rituximab (R) plus chemotherapy results in 78%-93% event free survival. Patients who do not respond to first-line treatment or relapse early are usually not cured. The aim of this study was to evaluate outcome of patients with PMBL after second-line therapy due to recurrent/refractory disease (rrPMBL). Methods: We retrospectively identified 18 (14%) rrPMBL from 125 PMBL patients treated at out institution between 2004 and 2013. Patients received salvage treatment including high-dose methotrexate and high-dose cytarabine (n=10), cisplatin-based regimens (n=4) or other chemotherapy (n=4). Eight patients underwent autologous stem cell transplantation (ASCT). Results: Median age (range) was 28 (20–42), clinical stage IVB - 15/18, pericardial effusion – 7, and all patients had IPI score 3-4 at diagnosis. Most patients received R-CHOP as first line therapy (n=13). Median time to progression (range) was 7 (1–13) months from the beginning of treatment. In 13 patients, disease was refractory, and 5 patients had early relapse. CNS relapse occurred in 3 patients. The overall response rate and complete remission rate for second treatment was 44% and 27.5%, respectively. With a median follow up of 16 (1-101) months, 1-yr and 2-yr overall survival (OS) from progression/relapse was 67% (95% C.I.: 56%, 78%) and 38% (95% C.I.: 25%, 50%), respectively. 2-year OS for relapsed and refractory patients was 71% and 29%, respectively (p<0.05). There was no difference in OS between patients who underwent ASCT and who did not. Conclusions: Patients with PMBL who relapse after or are resistant to the primary treatment are characterized by extremely advanced disease at baseline. The outcome of patients with refractory disease is significantly worse compared to patients who relapse after a response to initial therapy despite highly intensive second-line treatment applied. Notably, myeloablative treatment with ASCT does not seem to improve the outcome.