Cooperative Trials Research Articles

Impact of Genetic Ancestry on Treatment Toxicity and Racial Disparities in Breast Cancer

Racial disparities in breast cancer are multifactorial and include inferior outcomes and increased rates of serious toxicity in African Americans. The purpose of this review is to evaluate the contribution of race, genetic ancestry, and genomic biomarkers to treatment toxicity and to demonstrate the impact of toxicity on racial disparities. Taxane-induced peripheral neuropathy (TIPN) and congestive heart failure (CHF) are potentially irreversible and life-altering toxicities of curative chemotherapy for breast cancer. Analysis of genetic ancestry, rather than self-reported race, in a large cooperative group adjuvant clinical trial discovered significantly higher rates of both TIPN and CHF in women of African descent compared with European Americans. Importantly, TIPN resulted in more dose reductions of chemotherapy in African Americans, which resulted in worse disease-free survival. Beyond race, significant individual variations in toxicity exist, which may be explained by validated genotypic predictors of TIPN and CHF, reviewed here. Race, in particular genetic ancestry, impacts both tumor and host biology, contributing to toxicity that drives disparities in quality of life and survival. Translating these data into clinical decision-making will benefit from engagement of the African American community to perform clinical trials and develop datasets focused specifically in this population to validate biomarkers and best understand patient preferences.

Recent trends in the results of studies conducted by the Children’s Oncology Group acute lymphoblastic leukemia committee and implications for emerging cooperative trial groups in low- and middle-income countries

Improvements in survival for children with cancer residing in high-income countries have been driven by the results of successive clinical trials conducted by large multi-center cooperative groups. These survival improvements have not translated to low- and middle-income countries (LMICs), where the majority of children with cancer live. The emergence of LMIC cooperative trial groups will help define the optimal treatment for their populations and improve survival. In this manuscript, we outline recent trends in the results of studies conducted by the Children’s Oncology Group (COG) Acute Lymphoblastic Leukemia (ALL) Committee as an example of what can be accomplished through collaborative multi-institutional trials. We also discuss what implications the COG ALL experience holds for trial groups in LMIC settings.

Assessment of enrollment characteristics for Children's Oncology Group (COG) upfront therapeutic clinical trials 2004-2015.

BackgroundImprovements in pediatric cancer survival are attributed to cooperative clinical trials. Under-representation of specific demographic groups has been described in adult and pediatric cancer trials and poses a threat to the generalizability of results. An evaluation of data provided by the Children’s Oncology Group (COG) of upfront trial enrollment for US patients 0 to 29 years old between 2004 and 2015 was performed.MethodsUS cancer cases were estimated using incidence data and US population estimates from the Surveillance, Epidemiology, and End Results Program and compared to observed COG cases. Percent enrollment and standardized ratios of enrollment were calculated across demographic, disease, and socioeconomic groups. The COG website was utilized to quantify available trials and assess age eligibility.Results19.9% of estimated US cancer patients age 0 to 19 years enrolled on COG trials. Younger patients were more represented across diseases and races/ethnicities. Patients with hematologic malignancies were more represented compared to solid and central nervous system (CNS) tumors.ConclusionCOG trial enrollment rates are declining when compared to previously published data, potentially from challenges in pediatric drug development, difficulty designing feasible trials for highly curable diagnoses, and issues ensuring trial availability for the heterogeneous group of solid and CNS tumors. Though racial/ethnic groups and county-level socioeconomic factors were proportionally represented, under representation of the adolescent/young adult (AYA) population and younger patients with solid and CNS tumors remains a concern. Targeted efforts should focus on these subgroups and further research should evaluate AYA enrollment rates across all available trials.

The Beginnings of the Canadian Cooperative Clinical Cancer Trials Program and the AmericanInfluences, 1962-76.

Clinical cancer research in Canada entered a new phase in 1971. In that year, the National Cancer Institute of Canada agreed to initiate and support a multidisciplinary cooperative clinical trials program. The first collaborative randomized controlled trial (RCT) for the treatment of advanced Hodgkin's disease was launched in medical centres across the country in December 1971. Simultaneously, in the United States, the National Cancer Act came into effect. To what extent were these Canadian and American developments coincidental? I argue that the cooperative clinical trials program in Canada was timed to coincide with the US declaration of war on cancer, but it was not its corollary. Against the background of this American anti-cancer campaign, the cooperative clinical trials program emerged as a link between the strong radiotherapy tradition in Canada and the new trial infrastructure of chemotherapeutic regimes in the United States. The evolution of the Hodgkin's disease trial serves as a good example to demonstrate how growing collaboration among Canadian and American physician-investigators brought about a large-scale national study. The latter became a prototype of further cooperative oncological RCTs in Canada during the 1970s.

The Pediatric Oncology East and Mediterranean (POEM) group – A regional collaborative platform for childhood cancer healthcare professionals

The Pediatric Oncology East and Mediterranean (POEM) group was established in 2013 as a cooperative platform for physicians, scientists and healthcare professionals from institutions in the East and Mediterranean area with the goal of sharing experiences, initiating cooperative trials and establishing common strategies to achieve optimization of the care of pediatric oncology patients in the region. The mission of POEM group is to continuously improve pediatric oncology care, research, training and advocacy in the East and Mediterranean region by means of integrated teamwork. Our Vision is to be the leading pediatric oncology collaborative group in the East and Mediterranean Region. POEM group is currently at more than 550 registrants from 119 centers in 28 countries regionally. This review summarizes the structure and activities of POEM group since its inception, and highlights identified challenges and future plans.

Bortezomib-Based Transplantation and Consolidation Therapy Followed by Lenalidomide Maintenance for Newly Diagnosed Multiple Myeloma

Bortezomib-Based Transplantation and Consolidation Therapy Followed by Lenalidomide Maintenance for Newly Diagnosed Multiple Myeloma

High-risk Meningioma: Initial Outcomes From NRG Oncology/RTOG 0539

Phase 2 cooperative group meningioma trial assessing the safety and efficacy of risk-adaptive management strategies. This is the initial analysis of the high-risk cohort. High-risk patients were those with a new or recurrent World Health Organization (WHO) grade III meningioma of any resection extent, recurrent WHO grade II of any resection extent, or new WHO grade II after subtotal resection. Patients received intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost technique (60 Gy high dose and 54 Gy low dose in 30 fractions). Three-year progression-free survival (PFS) was the primary endpoint. Adverse events (AEs) were scored per NCI Common Terminology Criteria for Adverse Events version3. Of 57 enrolled patients, 53 received protocol treatment. Median follow-up was 4.0 years (4.8 years for living patients). Two patients withdrew without progression before year 3; for the remaining 51 patients, 3-year PFS was 58.8%. Among all 53 protocol-treated patients, 3-year PFS was 59.2%. Three-year local control was 68.9%, and overall survival was 78.6%. Of 51 patients, 1 patient (1.9%) experienced a late grade-5 necrosis-related AE. All other acute (23 of 53 patients) and late (21 of 51 patients) AEs were grades 1 to3. Patients with high-risk meningioma treated with IMRT (60 Gy/30) experienced 3-year PFS of 58.8%. Combined acute and late AEs were limited to grades 1 to 3, except for a single necrosis-related grade 5 event. These results support postoperative IMRT for high-risk meningioma and invite ongoing investigations to improve outcomes further.

Combination of Nilotinib and Pegylated Interferon Alfa-2B Results in High Rates of MR4.5 at 24 Months - Primary Analysis of the ALLG CML 11 Pinnacle Study

Combination of Nilotinib and Pegylated Interferon Alfa-2B Results in High Rates of MR4.5 at 24 Months - Primary Analysis of the ALLG CML 11 Pinnacle Study

Roxadustat (FG4592; ASP1517; AZD9941) in the Treatment of Anemia in Patients with Lower Risk Myelodysplastic Syndrome (LR-MDS) and Low Red Blood Cell (RBC) Transfusion Burden (LTB)

Background: Roxadustat (FG-4592) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription. Transient, intermittent HIF activation by roxadustat mimics a physiological response that increases endogenous erythropoietin (EPO) production to near physiologic range and stimulates EPO receptor synthesis. In addition, roxadustat promotes iron metabolism by reducing serum hepcidin to allow absorption of iron from the gut and mobilize iron from cellular storage making more iron available for erythropoiesis. Roxadustat corrected and maintained hemoglobin (Hb) in chronic kidney disease patients in multiple Phase 3 trials irrespective of underlying inflammation. In these studies, roxadustat-treated patients required less IV iron to correct and maintain Hb compared to erythropoiesis-stimulating agent (ESA)-treated patients. MDS is characterized by symptomatic anemia and many patients require RBC transfusion and/or ESA treatment. As response to ESAs varies across sub-populations with limited durability, there is an unmet need for treatment of anemia in LR-MDS. This is the first study to evaluate the effect of roxadustat in treating anemia in primary MDS patients. Methods: This is a two-part study; an open-label (OL), dose-finding segment (N=24) followed by a randomized double-blind (DB) placebo-controlled segment (N=156, 3:2 ratio of roxadustat to placebo). The primary goal of the OL segment is to identify the starting roxadustat dose-level for the DB segment. A total 24 patients in the OL segment have been enrolled in three sequential cohorts with 8 patients in each starting dose cohort (1.5, 2.0, or 2.5 mg/kg). RBC transfusion has been allowed per institutional criteria. Eligible patients were very low, low or intermediate risk primary MDS patients based on the International Prognostic Scoring System Revised classification with <5% bone marrow blasts; had baseline Hb < 10.0 g/dL; were >18 years old; and had LTB defined as receiving 1-4 RBC units per 8 week period. Patients were ineligible if they used an ESA within 8 weeks of the study start; had endogenous EPO levels >400 mIU/mL, or had a del(5q) cytogenetic abnormality. Roxadustat was administered TIW with doses titrated every 8 weeks per a dosing algorithm based on Hb response and transfusion need. Data from the OL segment were evaluated to identify the starting dose for the DB segment (currently enrolling). The primary endpoint is transfusion independence (TI) for ≥56 consecutive days during the first 28 weeks of treatment. The proportion of patients who achieve ≥50% reduction in RBC transfusion over any 8 weeks compared to baseline (8 weeks prior to Day 1) and proportion of patients who achieve TI for ≥20 consecutive weeks are evaluated. Safety and tolerability are assessed by adverse event reporting, percentage of patients progressing to acute myeloid leukemia (AML), and clinical laboratory values. Results: Twenty-four transfusion dependent, LR-MDS patients were enrolled in the OL segment of this global Phase 3 trial. Nine patients (38%) achieved TI for at least 56 consecutive days within the first 28 weeks.Three of 9 patients started at 1.5 mg/kg dose, 1 patient started at 2.0 mg/kg dose and 5 patients started at 2.5 mg/kg dose. At the time of achieving TI, 7 of 9 patients (78%) were on 2.5 mg/kg dose, 1 patient (11%) was on 2.0 mg/kg dose (started with 1.5 mg/kg dose) and one patient (11%) was on 1.5 mg/kg dose. Four patients remained TI for >20 weeks (one at 1.5 mg/kg dose level and three at 2.5 mg/Kg dose-level). One additional patient achieved TI after the initial 28-week dosing period at a dose-level of 3.5 mg/kg (starting dose 2.0 mg/kg). A total of 14 patients (58%) achieved a ≥50% reduction in RBC units in any 8-week period compared to baseline (range of 2-4 RBC units in 8 weeks before dosing); 12 of these patients were at ≥ 2.5 mg/kg dose level when achieving a 50% reduction in transfusion without need for IV iron. The overall safety profile observed is consistent with the patient population under study. Six patients reported 8 treatment-emergent SAEs with none being fatal. No patient has progressed to AML. Full results from the OL segment of the study will be presented. Conclusion: Based on the observed response (TI and transfusion reduction) and safety profile in LR-MDS patients, 2.5 mg/kg was selected as the starting dose for the ongoing 156-patient DB portion of the trial. Disclosures Harrup: Cooperative Trial Group for NeuroOncolog: Other: Collaborative Clinical Trials Group; Cancer Council of Tasmania: Membership on an entity's Board of Directors or advisory committees. Mittelman:Novartis: Honoraria, Research Funding, Speakers Bureau. Bradley:FibroGen Inc.: Employment, Equity Ownership. Saha:FibroGen Inc.: Employment, Equity Ownership. Bartels:FibroGen Inc.: Employment, Equity Ownership. Robert:FibroGen Inc.: Employment, Equity Ownership. Yu:FibroGen Inc.: Employment, Equity Ownership.

Pro-Active Dasatinib Dose Reduction Based on Trough Levels May Minimise Toxicity and Preserve Efficacy - Interim Analysis of the ALLG CML 12 Direct Study

Pro-Active Dasatinib Dose Reduction Based on Trough Levels May Minimise Toxicity and Preserve Efficacy - Interim Analysis of the ALLG CML 12 Direct Study

Abnl Marro: An International Cooperative Trial for Patients with MDS/MPN Overlap Syndromes

Abnl Marro: An International Cooperative Trial for Patients with MDS/MPN Overlap Syndromes

The National Cooperative Trial on Multifactorial Prevention of First Heart Attacks and Coronary Mortality in Free-Living, High-Risk, Middle-Aged American Men, Also Known as JUMBO: A Short Story.

The concept of a multiple risk-factor intervention trial (MRFIT) originated in mid-20th century efforts to determine whether modifying the "risk factors" established by cardiovascular disease epidemiology would prevent heart attacks. The term "MRFIT" probably first appeared in the 1968 report to the National Heart Institute from investigators of the National Diet-Heart Feasibility Study. Based on their pilot experience, they recommended a trial of diet alone. Aware, however, that authorities might agree with the rationale but not the implementation of such a massive and risky undertaking, they also proposed an alternative: whether coronary heart disease was preventable at all by simultaneous intervention on several risk factors; that is, a multiple risk-factor intervention trial. After some years agonizing by serial expert committees, the National Heart Institute opted against an explanatory diet trial and for a pragmatic multiple risk-factor intervention, one designed by Institute staff and operated under contract. Meanwhile, an impatient community of investigators met together in the Makarska Conference, outlined a broad cardiovascular disease prevention policy, and submitted their idealized version of a multiple risk-factor trial, called JUMBO. But the National Heart Institute, because of the plan for its own trial, had no funds left for an investigator-initiated proposal. Hence, this background and story of the MRFIT that wasn't.

373P - Molecular profiling of non-small cell lung cancer (NSCLC) in Asia with targeted next-generation sequencing (NGS): Interim analysis of a co-operative group study (ATORG-001)

BackgroundThere is an expanding list of therapeutically relevant biomarkers for NSCLC and effective molecular profiling is paramount. We sought to comprehensively and prospectively evaluate the molecular epidemiology of NSCLC in Asia and ascertain the extent of access to relevant therapies. The study is being conducted by the Asian Thoracic Oncology Research Group (ATORG) – an academic co-operative lung cancer trials group in Asia. MethodsATORG-001 is a prospective, multi-centre study of NSCLC patients (pts) throughout Asia. Eligible pts must have good performance status (ECOG ≤2), adequate organ function and ≤3 prior lines of cytotoxic chemotherapy. Archival tissue specimens are sent to a central laboratory in Singapore (Singapore General Hospital) for profiling, consisting of NGS with the Oncomine Focus Assay (52 gene panel including fusions) and PD-L1 immunohistochemistry. Results are returned to investigators in a clinically relevant timeframe. Baseline demographics, pre-existing molecular profile and prior treatment details are collected. Treatment and pt outcomes are followed for 2 years. Recruitment commenced in Jan 2019 in 3 sites (National Cancer Centre Singapore, Chinese University of Hong Kong, University Malaya Medical Centre). We report an interim analysis for the first 27 of a planned 500 pts. ResultsAs of 01 Jul 2019, 27 pts have enrolled with median age 67 yrs (range 46-79), 59% male, 81% adenocarcinoma, 52% stage IV, 37% non-smokers, median lines of prior therapy 1 (range 0-6) and 85% with no known oncogenic driver. Pre-existing mutation status was known in 89% for EGFR and 63% for ALK. Median turnaround time from tissue acquisition to profiling results was 22 days (range 15-74). New alterations were most common in KRAS (19%), MYC (15%), CDK4 (7%) and ERBB2 (7%). Potentially actionable new alterations were found in 7 (26%) pts, including KRAS G12C mutation (7%), BRAF G469A mutation (4%), ERBB2 exon 20 insertion (4%), ERBB2 amplification (4%), FGFR2 amplification (4%) and MET exon 14 skipping mutation (4%). ConclusionsEnrolment is ongoing with additional sites and countries planned to comprehensively evaluate the molecular epidemiology of NSCLC in Asia. Legal entity responsible for the studyAsian Thoracic Oncology Research Group. FundingAsian Thoracic Oncology Research Group, Novartis. DisclosureA.C. Tan: Travel / Accommodation / Expenses: ASLAN Pharmaceuticals. All other authors have declared no conflicts of interest.

TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol

IntroductionStereotactic body radiotherapy (SBRT) is a non-invasive alternative to surgery for the treatment of non-metastatic prostate cancer (PC). The objectives of the Novel Integration of New prostate radiation schedules with...

Performance and Profitability of Fungicides for Managing Soybean White Mold: A 10-Year Summary of Cooperative Trials.

White mold, caused by Sclerotinia sclerotiorum, is a yield-limiting disease of soybean in Brazil. Uniform fungicide trials have been conducted annually since 2009. Data from 74 cooperative field trials conducted over a 10-year period were assembled. We selected five fungicides applied two times around flowering: dimoxystrobin plus boscalid (DIMO+BOSC), carbendazim plus procymidone (CARB+PROC), fluazinam (FLUZ), fluopyram (FLUO), and procymidone (PROC). For comparison, thiophanate-methyl (TMET) applied four times was also included as a low-cost treatment. Network models were fitted to the log of white mold incidence (percentages) and log of sclerotia mass data (grams/hectare) and to the nontransformed yield data (kilograms/hectare) for each treatment, including the untreated check. Back-transformation of the meta-analytic estimates indicated that the lowest and highest mean (95% confidence interval [CI]) percent reductions in incidence and sclerotia mass were 54.2 (49.3 to 58.7) and 51.6% (43.7 to 58.3) for TMET and 83.8 (79.1 to 87.5) and 87% (81.9 to 91.6) for CARB+PROC, respectively. The overall mean (95% CI) yield responses ranged from 323 kg/ha (247.4 to 400.3) for TMET to 626 kg/ha (521.7 to 731.7) for DIMO+BOSC, but the variance was significantly reduced by a binary variable (30% threshold) describing disease incidence in the untreated check. On average, an increment of 352 kg/ha was estimated for trials where the incidence was >30% compared with the low-disease scenario. Hence, the probability of breaking even on fungicide costs for the high-disease scenario was >65% for the more effective, but more expensive fungicide (FLUZ) than TMET. For the low-disease scenario, profitability was less likely and depended more on variations in fungicide cost and soybean price.

Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study

Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma. In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21-2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10-5 sensitivity threshold, assessed by multiparametric flow cytometry; both p<0·0001). Median progression-free survival from first randomisation was not reached in either group (hazard ratio 0·47, 95% CI 0·33-0·67, p<0·0001). 46 deaths on study were observed (14 vs 32, 0·43, 95% CI 0·23-0·80). The most common grade 3 or 4 adverse events were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), and stomatitis (13% vs 16%). D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma. The Intergroupe Francophone du Myélome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.

Assessment of enrollment characteristics for Children’s Oncology Group (COG) upfront therapeutic clinical trials 2004-2015.

6564 Background: Improvements in pediatric cancer survival are attributed to cooperative clinical trials. Under representation of specific demographic groups has been described in adult and pediatric cancer and poses a threat to the generalizability of trial results. A comprehensive evaluation of data provided by the Children’s Oncology Group (COG) of upfront trial enrollment for US patients 0 to 29 years old between 2004 and 2015 was performed to assess for disparities in participation. Methods: Estimates of cancer cases were calculated using the Surveillance, Epidemiology, and End Results registry and the US Census and compared to observed COG cases. Percent enrollment and Standardized Ratios of enrollment were calculated across various demographic, disease, and socioeconomic groups. The COG website was utilized to quantify available upfront trials during the study period and assess age eligibility criteria. Results: 21.3% of estimated US cancer patients age 0 to 19 years enrolled on COG trials. Younger patients were consistently more represented across disease types and race/ethnicities. Patients with hematologic malignancies were more represented compared to solid and central nervous system (CNS) tumors. Conclusions: COG clinical trial enrollment rates are declining, which may be due to challenges in pediatric drug development, difficulty designing feasible trials for highly curable diseases, and issues in ensuring trial availability for the heterogeneous group of solid and CNS tumors. Though racial/ethnic groups and county-level socioeconomic factors were proportionally represented, under representation of the adolescent/young adult (AYA) population and younger patients with solid and CNS tumors remain significant concerns. Targeted enrollment efforts should focus on the identified subgroups and further research should evaluate AYA enrollment across all available trials to provide continued treatment advances for all patients.

AAML 1421, a phase I/II study of CPX-351 followed by fludarabine, cytarabine, and G-CSF (FLAG) for children with relapsed acute myeloid leukemia (AML): A Report from the Children’s Oncology Group.

10003 Background: Effective regimens with favorable toxicity profiles are needed for heavily pre-treated children with relapsed AML. AAML1421 is a Phase I/II study of CPX-351, a liposomal preparation of cytarabine and daunorubicin demonstrating efficacy in adults. AAML1421 sought to determine the recommended Phase 2 Dose (RPD2) of CPX-351 and the response rate (complete response (CR) + complete response without platelet recovery (CRp)) after up to 2 cycles of therapy. Methods: Children &gt; 1 and ≤ 21 years of age with relapsed/refractory AML were eligible for dose finding, and those in first relapse were eligible for efficacy. A modified rolling six design was used for dose-limiting toxicity (DLT) assessment which occurred in Cycle 1. Dose level 1 (DL1) was 135 units/m2 on days 1, 3, and 5 with a single dose de-escalation to 100 units/m2 if DL1 was intolerable. The Efficacy Phase used a Simon-two stage design. The response rate was determined after up to 2 cycles of therapy (Cycle 1: CPX-351; Cycle 2: FLAG). The Overall Response Rate (ORR) was defined as CR+CRp+CRi (CRi = CR with incomplete hematologic recovery). Results: Thirty-eight patients (pts) enrolled: 6 in dose-finding and 32 in the efficacy phase. DLT occurred in 1/6 patients and was a grade 3 decrease in ejection fraction(EF). This was the only Grade 3 cardiac toxicity. Therefore, 135 units/m2 on days 1, 3, 5 was the RP2D. All dose finding pts were eligible for efficacy determination. One pt in the efficacy phase was unevaluable. The most common ≥ Grade 3 toxicities in Cycle 1 included fever/neutropenia (45%), infection (47%), and rash (40%). There was no toxic mortality. Best responses included 20 CR (54%), 5 CRp (14%), and 5 CRi (14%). Seventy percent achieved best response after cycle 1. Twenty-one of 25 patients with CR/CRp had no detectable residual disease (RD) (84%) by flow cytometry. HSCT was used as consolidation in 23/29 responders (79%); 18 of 23 (78%) had no detectable RD prior to HSCT. Conclusions: The RP2D of CPX-351 is 135 units/m2/dose on days 1, 3, 5. CPX-351 was well tolerated and protocol therapy was effective with CR+CRp rates of 68.3% (90% CI 52.9% to 78.0%) and ORR (CR+CRp+CRi) of 81.1% (90% CI 67.4% to 88.8%). AAML1421 response rates are superior to any published North American cooperative group clinical trial for children with AML in first relapse. Clinical trial information: NCT02642965.

Registration of ‘Goldenhart’, a Two‐Rowed Spring Food Barley

‘Goldenhart’ (Reg. No. CV‐368, PI 688445) is a two‐rowed spring hull‐less food barley (Hordeum vulgare L.) developed by the USDA‐ARS, Aberdeen, ID, in cooperation with the University of Idaho Agricultural Experiment Station, and released in 2017. Goldenhart is derived from the cross of 02HR 4590/‘CDC Fibar’ and was advanced through modified bulk pedigree F1– F5. Goldenhart was tested at the USDA‐ARS, and all other cooperative trials, as line 2Ab09‐X06F058HL‐31. Goldenhart was tested over 40 location years and has shown better yield under irrigated conditions than ‘CDC Alamo’ and ‘Transit’ and better yield in dryland areas than all the current two‐rowed spring hull‐less food barley cultivars, ‘Julie’, Transit, and CDC Alamo. Moreover, Goldenhart has shown significantly higher yields than Transit, the barley check with similar β‐glucan concentration, in both irrigated and dryland conditions. Goldenhart will be a good hull‐less cultivar and a better alternative than Transit in the food barley production market.

Multidisciplinary team approach for pediatric thoracic tumors: new horizons and oldies but goldies

Pediatric thoracic tumors are a heterogeneous group of neoplasms, accounting for 15–20% of all malignant tumors in childhood. The origin of these tumors can be either primitive or secondary to several solid tumors that metastasize at the thoracic level. These diseases require a complex approach, in which a combination of chemotherapy, radiotherapy and surgery play a fundamental role. The complexity of a multidisciplinary approach requires specialized centers where all the professional figures needed are trained and experienced to guarantee the best possible treatment for these little patients. In fact, the care of children requires the collaborations of many disciplines and individuals: pediatric oncologists, radiation therapists, surgeons, radiologists, and pathologists work collaboratively with nurses, physician’s assistants, social workers, psychologists, nutritionists, physiotherapists, pharmacists, educators, teachers, and of course, parents and families. This means that children and families often need to travel great distances to receive state-of-art care, frequently with considerable costs and enormous strains on family and other social anchors that are so essential for normal children development. Nowadays, pediatric oncology pays more and more attention to new aspects, even not strictly medical ones, by resorting to interventions aimed at improving the quality of life. As a discipline, pediatric oncology also stands as a paradigm for cancer research. The majority of children diagnosed with cancer are enrolled in cooperative clinical trials that provide state-of-the-art therapy at the centres across the world. This strong collaboration and cooperation, that is the milestone of the pediatric cancer community, allowed the creation of networks fundamental for translational research discoveries and new investigators.