5-year Event-free Survival Rates Research Articles

The Impact of Induction Treatment Response on the Prognosis of Pediatric Core Binding Factor-Acute Myeloid Leukemia Patients

To explore the impact of induction treatment response on the prognosis of pediatric core binding factor-acute myeloid leukemia (CBF-AML). The result of induce reaction and survival data of 157 pediatric CBF-AML patients in our hospital from September 2008 to December 2018 were retrospectively analyzed．The survival rate of the patients with different degrees of morphological remission after induction chemotherapy was comparative analyzed. Among the 157 children with CBF-AML, 113 (72.4%) patients achieved morphologic leukemia-free state (MLFS) after the first course of induction chemotherapy, 153 (98.1%) patients achieved MLFS after the second course of induction chemotherapy. The 5-year event-free survival (EFS) rate and 5-year overall survival (OS) rate of patients with non-remission (NR) status after the first course of induction of chemotherapy was significantly lower than the patients achieved MLFS and the patients achieved partial remission (PR). The 5-year EFS rate and 5-year OS rate of the patients with PR status after the second course of induction chemotherapy were lower than the patients achieved MLFS, but the difference was not statistically significant. Multivariable analyze showed that NR after the first course of induction chemotherapy and myeloid sarcoma were the independent risk factors affecting EFS of the patients. There were six patients with NR status after the first course of induction chemotherapy, in which all of them harbored t(8;21), three of them with sex chromosome deletion, two of them with myeloid sarcoma. NR status after the first course of induction chemotherapy was the independent risk factor affecting EFS and OS of CBF-AML patients, it can be taken as an indicator for higher risk stratification. PR status after the first course of induction chemotherapy may not be used as a diagnostic criterion for primary drug resistance.

Comparison of the efficiency, safety, and survival outcomes in two stem cell mobilization regimens with cyclophosphamide plus G-CSF or G-CSF alone in multiple myeloma: a meta-analysis

Autologous stem cell transplantation as a frontline treatment for patients with multiple myeloma (MM) requires an adequate peripheral blood stem cell (PBSC) collection before processing. Granulocyte-colony stimulating factor (G-CSF) with or without cyclophosphamide (CTX) is a common regimen for PBSC mobilization; their benefits and risks are controversial. To compare the efficiency, safety, and survival outcomes between the two regimens, we conducted a meta-analysis including 18 studies with 4 prospective and 14 retrospective studies; a total of 2770 patients with MM were analyzed. The CTX plus G-CSF regimen had higher yields of total CD34+ cells (SMD = 0.39, 95% CI (0.30, 0.49)), and higher mobilization rates of the target ⩾ 2 × 106/kg (OR = 3.34, 95% CI (1.82, 6.11)) and 4 × 106/kg (OR = 2.16, 95% CI (1.69, 2.76)) cells. A favorable event-free survival (EFS) (HR = 0.73, 95% CI (0.58, 0.93), p = 0.01) and better 3-year EFS rate (OR = 1.65, 95% CI (1.1, 2.47), p = 0.02) were also reached in the patients with CTX plus G-CSF mobilization, although the risks of admission (OR = 26.49, 95% CI (7.31, 95.97)) and fever (OR = 13.66, 95% CI (6.21, 30.03)) during mobilization were increased, the treatment-related mortality was consistent (p = 0.26). The CTX plus G-CSF regimen was superior to the G-CSF-alone regimen for PBSC mobilization in patients with MM.

Diagnosis-to-Treatment Interval Is an Important Prognostic Factor with a Time-Dependent Effect Predicting Event-Free Survival after 12 Months from First-Line Treatment in Newly Diagnosed Diffuse Large B-Cell Primary CNS Lymphoma

Diagnosis-to-Treatment Interval Is an Important Prognostic Factor with a Time-Dependent Effect Predicting Event-Free Survival after 12 Months from First-Line Treatment in Newly Diagnosed Diffuse Large B-Cell Primary CNS Lymphoma

Retrospective Evaluation of Rituximab, Methotrexate, Procabazine, Vincristine and Etoposide Followed By Consolidation with Rituximab, Aracytine and Ifosfamide for Elderly Patients with Newly Diagnosed Primary CNS Lymphoma

Retrospective Evaluation of Rituximab, Methotrexate, Procabazine, Vincristine and Etoposide Followed By Consolidation with Rituximab, Aracytine and Ifosfamide for Elderly Patients with Newly Diagnosed Primary CNS Lymphoma

A Pilot Review of Outcomes in Pediatric MDS: Validating Methods for a North American Multicenter Study

BACKGROUND: Pediatric myelodysplastic syndromes (MDS) constitute a heterogeneous group of rare blood disorders characterized by dysplastic, ineffective hematopoiesis that portends a poor prognosis. We completed a North American survey of clinical approaches to pediatric MDS, which demonstrated a lack of national consensus on diagnosis and treatment. Little progress has been made to improve outcomes and there is no modern data on the demographics, clinical characteristics, and outcome of children and adolescents with MDS in Northern America. There is a critical need for a North American retrospective study which will serve as a reference for future prospective clinical trials. To validate the accuracy of our proposed clinical response criteria and to ensure the functionality of our retrospective database, we completed a pilot 12-year retrospective chart review documenting the diagnosis and outcomes of children and adolescents with confirmed or suspected diagnosis of MDS. METHODS: We conducted a retrospective chart review of subjects between 0 and 24 years of age at diagnosis, diagnosed between January 2008 and December 2020 with primary or secondary MDS at the Children's Hospital Colorado. Demographics, disease characteristics, treatment, and outcomes were recorded on 18 subjects. Diagnosis was made based on the 2016 World Health Organization (WHO) Classification of MDS. Overall survival (OS) was measured from time of diagnosis to death. Event-free survival (EFS) was measured from time of diagnosis to first event (death, relapse, or refractory event necessitating additional therapy). Overall Response was determined by using three criteria - Cytopenia Response, Blast Response, and Cytogenetic Response (Table 1). Categorical variables were summarized using frequency and percentage (n, %) and continuous variables with median and interquartile range (median, IQR). Kaplan Meier (KM) curves were reported for OS and EFS, with patients censored at the last follow-up date if an event did not occur. RESULTS: Of eighteen subjects, sex was represented equally (50% female) with a median (IQR) age of 14.3 years (9.8,17). Four (23%) presented with refractory cytopenia of childhood, 8 (45%) with overt bone marrow blasts, and 6 (33%) with MDS-Unclassified with diagnosis based on various MDS-defining cytogenetic abnormalities accompanied by peripheral cytopenias. Five (28%) had a genetic predisposition, 6 (33%) were deemed treatment-related, and 7 (39%) were idiopathic with no identifiable cause. A cytogenetic defect of chromosome 7 was identified in 9/17 (53%) of subjects. Ten (56%) received a form of cytoreductive therapy prior to hematopoietic stem cell transplant (HSCT); 8 (80%) were treated with a demethylating agent (2 decitabine monotherapy, 4 azacitidine monotherapy, and 2 dual therapy azacitidine and venetoclax). Seventeen (94%) underwent HSCT from a variety of donor sources including 2 matched-related bone marrow, 2 matched-related peripheral blood, 4 matched-unrelated bone marrow, 1 matched-unrelated peripheral blood, 6 matched-unrelated cord-blood, and 2 haplo-identical bone marrow. Eleven (61%) were alive at last follow up, however, only 8 (44%) remained in Complete Remission. The 1-year survival rate was 83% (95% CI: 67%-100%), 3 year was 58% (37%-92%), and 5 year was 44% (21%-90%) (Figure 1). Fourteen (78%) experienced an event. The 1-year EFS rate was 28% (95% CI: 13%-59%) and 5-year EFS rate was 19% (6%-55%) (Figure 1). CONCLUSION: Despite advances in cytoreduction and HSCT, we found pediatric MDS to remain a highly morbid disease with a 5-year OS of 44%, 1-year EFS of only 28%, and inadequate first-line therapies. Attempts to improve outcomes require the development of standardized diagnostic and clinical response criteria. This study piloted clinical response criteria on a single-institution cohort. Statistical power is limited by small sample size, therefore, we have secured funding to complete a large multi-center North American retrospective in collaboration with the North American Pediatric Aplastic Anemia Consortium (NAPAAC). The multi-center study will help validate proposed clinical response criteria and guide the development of the first prospective interventional trials for pediatric MDS in North America. Disclosures No relevant conflicts of interest to declare.

The Comparison of Frontline Lower-Dose Dasatinib 50 Mg/Day to Standard-Dose Dasatinib 100 Mg/Day in Newly Diagnosed Chronic Myeloid Leukemia: A Propensity Score Analysis

The Comparison of Frontline Lower-Dose Dasatinib 50 Mg/Day to Standard-Dose Dasatinib 100 Mg/Day in Newly Diagnosed Chronic Myeloid Leukemia: A Propensity Score Analysis

A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial

AbstractThe prognosis for infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of hematopoietic stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcome was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial, infants with ALL were stratified into 3 risk groups (low risk [LR], intermediate risk [IR], and high risk [HR]) according to KMT2A status, age, and presence of central nervous system leukemia. Children's Oncology Group AALL0631 modified chemotherapy with the addition of high-dose cytarabine in early intensification was introduced to KMT2A-r patients, and the option of HSCT was restricted to HR patients only. The role of minimal residual disease (MRD) was also evaluated. Ninety eligible infants were stratified into LR (n = 15), IR (n = 19), or HR (n = 56) risk groups. The 3-year event-free survival (EFS) rate for patients with KMT2A-r ALL (IR + HR) was 66.2% (standard error [SE], 5.6%), and for those with germline KMT2A (KMT2A-g) ALL (LR), the 3-year EFS rate was 93.3% (SE, 6.4%). The 3-year EFS rate was 94.4% (SE, 5.4%) for IR patients and 56.6% (SE, 6.8%) for HR patients. In multivariable analysis, female sex and MRD ≥0.01% at the end of early consolidation were significant factors for poor prognosis. Risk stratification and introduction of intensive chemotherapy in this study were effective and were able to eliminate HSCT for a subset of infants with KMT2A-r ALL. Early clearance of MRD seems to have translated into favorable outcomes and should be incorporated into risk stratifications in future trials. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.

Clinical characteristics and prognostic analysis of 458 children with high-risk neuroblastoma in a single center

Objective: To summarize the clinical characteristics of high-risk neuroblastoma (HR-NB) in a single center, analyze the prognostic factors of HR-NB. Methods: The clinical data of children with HR-NB who were treated and followed up at the hematology-oncology center of Beijing Children's Hospital from February 1, 2007 to June 30, 2018 were analyzed retrospectively. The clinical features were summarized. Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. The last follow-up time was June 30, 2019. Results: A total of 458 children with HR-NB were enrolled in this study, including 265 males (57.9%) and 193 females (42.1%), the age at diagnosis was 40.0 months (4.5-148.0 months), the follow-up time was 22.0 months (0.2-138.0 months) and the time of tumor progression or recurrence was 15 months (1-72 months). The 5-year event-free survival (EFS) rate was (31.2±2.6)% and the 5-year overall survival (OS) rate was (43.9±3.2)%. The 5-year EFS rate and 5-year OS rate in 142 hematopoietic stem cell transplantation (HSCT) patients with bone marrow metastases were better than that in 196 non-transplantation cases with bone marrow metastases ((26.5±4.5)% vs. (25.1±3.6)%, χ²=13.773, P=0.001; (38.1±5.5)% vs. (35.7±4.7)%, χ²=9.235, P=0.002); 128 transplantation patients with bone metastases had higher 5-year EFS rate and 5-year OS rate than 188 non-transplantation cases with bone metastases ((28.5±5.0)% vs. (26.7±3.8)%, χ²=10.222, P=0.001; (37.1±6.0)% vs. (36.2±4.8)%, χ²=7.843, P=0.005). The 5-year EFS rate was higher in 37 HSCT patients with MYCN amplification than in 49 non-transplantation cases with MYCN amplification ((26.8±8.0) % vs. (20.5±6.4) %, χ²=5.732, P=0.017). No significant difference was found in 5-years OS rate between transplantation group with MYCN amplification and non-transplantation group with MYCN amplification ((31.4±8.6) % vs. (26.2±7.4) %, χ²=3.230, P=0.072). Univariate survival analysis showed that lactate dehydrogenase (LDH)≥1 500 U/L was associated with poor prognosis of patients with MYCN amplification (χ²=6.960, P=0.008). Multivariate Cox analysis showed bone marrow metastasis and LDH≥1 500 U/L were independent risk factors for poor prognosis of patients with non-MYCN amplification (HR=2.427, 1.618;95%CI：1.427-4.126, 1.275-2.054, P<0.05) for both comparisons. Conclusions: LDH≥1 500 U/L was the poor prognostic factor for patients with MYCN amplification. The bone marrow metastasis and LDH≥1 500 U/L were the poor prognostic factors for HR-NB patients with non-MYCN amplification. HSCT can improve the prognosis of patients with bone or bone marrow metastasis. It can also retard the time of progression or recurrence for patients with MYCN amplification.

Abstract 1998: Predictive and prognostic role of T- and B-cell receptor repertoire in HER2-positive breast cancer: An analysis of the NeoALTTO clinical trial

Abstract Background: Disease relapse is observed in a significant proportion of HER2-positive breast cancer (BC) patients with residual disease (RD) after neoadjuvant treatment, as well as in a subgroup of those achieving pathological complete response (pCR). As the host immune response plays a key role in modulating the activity of anti-HER2 agents, we investigated the association of T- and B-cell receptor (TCR and BCR) repertoires with pCR and event-free survival (EFS) in the NeoALTTO phase 3 trial. Methods: RNA sequencing (RNAseq) data from baseline tumor biopsies were available for 254 patients out of the 455 enrolled in the study. Among those, 166 did not achieve a pCR defined as ypT0/is. Matched RNAseq data from RD samples were available for 43 cases. TCR/BCR repertoires were extracted from RNAseq data using the MiXCR software. TCR and BCR read counts, number of clones, evenness, Shannon entropy, Gini index, length of the complementarity determining region 3, top and second top clone proportion were evaluated. Survival analysis was performed using univariate and multivariate (adjusted for tumor size, nodal status, grade, estrogen receptor [ER] status, age and treatment arm) Cox proportional hazard models, while logistic regressions were used for pCR. False discovery rate (FDR) was obtained using Benjamini &amp; Hochberg method. Results: Baseline TCR top (odds ratio [OR]=0.63 [95% CI 0.46-0.87], FDR=0.021) and second top (OR=0.57 [0.41-0.79], FDR=0.004) clone proportion were significantly associated with a lower probability of achieving pCR in the multivariate analysis. BCR evenness (hazard ratio [HR]=1.5 [1.2-2], FDR=0.015) and Gini index (HR=0.66 [0.52-0.85], FDR=0.015) were significantly associated with EFS in the multivariate analysis. In residual disease, BCR evenness and Gini index showed a similar trend in the EFS univariate analysis, while TCR read counts, number of clones, and entropy were associated with lower HR (P&amp;lt;0.05), although FDR were borderline significant (0.05&amp;lt;FDR&amp;lt;0.1). A model to predict EFS including baseline BCR evenness, ER status, stromal tumor-infiltrating lymphocyte level, and pCR was able to identify 3 groups with good, intermediate and poor prognosis (Kaplan-Meier 5-year EFS rates of 95%, 80% and 58%, respectively). Of note, about 63%, 45% and 12% of the patients achieved a pCR in the three prognostic groups, respectively. Conclusions: In the NeoALTTO trial, the presence of an evenly distributed BCR repertoire was associated with worse EFS. A model integrating baseline immune-related and clinical features was able to identify patients with excellent prognosis despite RD or, conversely, with poor prognosis after pCR. We envision that our model has the potential to allow the personalization of post-operative treatment strategies after both pCR and RD in HER2-positive BC. Further validation of our findings is warranted. Citation Format: Mattia Rediti, David Venet, Françoise Rothé, Tao Qing, Marion Maetens, Ian Bradbury, Miguel A. Izquierdo, Serena Di Cosimo, Florentine Hilbers, Mohammed Bajji, Nadia Harbeck, Michael Untch, David L. Rimm, Stephen Chia, Minetta C. Liu, Cristina Saura, Jens Huober, Paolo Nuciforo, Roberto Salgado, Sherene Loi, Lajos Pusztai, Christos Sotiriou. Predictive and prognostic role of T- and B-cell receptor repertoire in HER2-positive breast cancer: An analysis of the NeoALTTO clinical trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1998.

Dose-intensive regimen treatment for small-cell carcinoma of the ovary of hypercalcemic type (SCCOHT)

PurposeSmall cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is a rare and rapidly lethal disease affecting young women. Cytoreductive surgery associated with chemotherapy followed by a high dose chemotherapy regimen (HDC) demonstrated improved outcomes in a unique prospective and several retrospective studies, and this report aimed to confirm these results in an independent and larger cohort. MethodsBetween 2006 and 2018, we conducted a multicentric prospective study on 44 women diagnosed with SCCOHT. Patients were treated homogeneously with optimal cytoreductive surgery and chemotherapy protocol for four to six cycles (PAVEP). In case of complete response, patients received HDC with stem-cell support, followed by pelvic radiotherapy. The primary endpoint was the event-free survival (EFS) in the per-protocol cohort. Secondary analysis explored the effect of HDC with outcomes. ResultsMean age at diagnosis was 33 years old (range 13.8–75.8). 14 patients presented with stage FIGO I, 21 with stage III and 9 with stage IV. Median follow-up was 53.4 months. 38 patients underwent optimal surgery with up to 6 cycles of PAVEP. 30 received HDC, and 21 pelvic radiotherapy. 21 relapses were reported leading to death for 18 patients. Median EFS in the per-protocol cohort was 18.2 months, and 2-year EFS rate was 40%. HDC was significantly associated with better overall survival (p < .001). Grades 3/4 adverse events were frequent but, in most cases, manageable, although one grade-5 adverse-event occurred during HDC. ConclusionIntensive regimen containing multidrug chemotherapy, HDC and pelvic radiotherapy, for the management of SCCOHT, demonstrated encouraging survival and should be proposed for all patients. However, the significant toxicity cost associated is of concern and it should be restricted to expert centers.

Abstract A65: Alveolar soft part sarcoma in children and adolescents: A single-institute retrospective analysis

Abstract Background: Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor that typically affects young patients. Because of the rarity of the disease, the standard treatment is not established. The aim of this study is to evaluate the clinical characteristics and treatment outcomes of pediatric ASPS. Method: A retrospective study was conducted on children and adolescents treated for ASPS at a single center between 2000 and 2018. Results: A total number of 11 patients were evaluated. Median age at diagnosis was 12.6 (range 3.8-16.3) years. Nine (82%) were female. The most common primary sites were limbs (64%). IRS postsurgical clinical group (IRS CG) was I in 2 (18%), III in 3 (27%), and IV in 6 (55%) patients. Of 9 patients with IRS CG III and IV who received chemotherapy, one had a complete response, two had a partial response, and six had progressive disease. One patient showed SD to sunitinib. The 5-year event-free survival (EFS) and overall survival (OS) rates were 31% and 88%, respectively. The 5-year EFS rate by primary site was 50% for the 7 patients with extremity and 0% for the 4 patients with head and neck (P-value = 0.001). The 5-year OS rate by the primary site was 100% for the 7 patients with extremity and 50% for the 4 patients with head and neck (P-value = 0.027). Conclusion: Localized ASPS has a good prognosis after total resection. If the primary site is head and neck, the prognosis is poor due to difficulty in surgical resection. Chemotherapy and radiation therapy have limitations in the cure for patients with metastatic disease. Further studies of ASPS need to achieve development in treatment. Citation Format: Se Na Kang, Jung Yoon Choi, Bo Kyung Kim, Hong Yul Ahn, Kyung Taek Hong, Hyoung Jin Kang, Han Soo Kim, Jung Eun Cheon, Sung Hye Park, Hee Young Shin. Alveolar soft part sarcoma in children and adolescents: A single-institute retrospective analysis [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A65.

Clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor and prognostic analysis

To study the clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor (cPNET), as well as the risks factors for poor prognosis. A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with cPNET from June 2012 to September 2018. The 42 children had a median overall survival (OS) time of 2.0 years and a median event-free survival (EFS) time of 1.3 years; the 1-, 3-, and 5-year OS rates were 76.2%±6.6%, 41.4%±8.7%, 37.3%±8.8% respectively, and the 1-, 3-, and 5-year EFS rates were 64.3%±7.4%, 32.7%±8.0%, 28.0%±8.1% respectively. The univariate analysis showed that there were significant differences in the OS and EFS rates among the children with different patterns of surgical resection, chemotherapy cycles, and risk grades (P<0.05), and there was also a significant difference in the OS rate between the children receiving radiotherapy and those not receiving radiotherapy (P<0.05). The multivariate Cox regression analysis showed that chemotherapy cycles and risk grade were independent influencing factors for EFS and OS rates (P<0.05). The EFS and OS rates increased with the increase in chemotherapy cycles and the reduction in risk grade. Multimodality therapy with surgery, chemotherapy, and radiotherapy is an effective method for the treatment of cPNET in children. Early diagnosis and treatment and adherence to chemotherapy for as long as possible may improve EFS and OS rates.

Outcome analysis of stage I epithelial-predominant favorable-histology Wilms tumors: A report from Children's Oncology Group study AREN03B2.

Stage I epithelial-predominant favorable-histology Wilms tumors (EFHWTs) have long been suspected to have an excellent outcome. This study investigates the clinical and pathologic features of patients with stage I EFHWTs to better evaluate the potential for a reduction of chemotherapy and its associated toxicity. All patients registered in the Children's Oncology Group (COG) AREN03B2 study between 2006 and 2017 with stage I EFHWTs were identified. EFHWTs were defined as tumors with at least 66% epithelial differentiation, regardless of the degree of differentiation. Clinical information was abstracted from COG records. Event-free survival (EFS) and overall survival (OS) were calculated and compared between groups based on age and therapy. The 4-year EFS rate was 96.2% (95% confidence interval, 92%-100%), and the OS rate was 100%; EFS and OS did not statistically significantly differ with the age at diagnosis (<48 vs ≥48 months; P=.37) or treatment (EE4A vs observation only; P=.55). Six events were reported. Three patients developed contralateral tumors and did not otherwise relapse; none of these had nephrogenic rests or a recognized predisposition syndrome. Three patients developed metastatic recurrence; all 3 had received EE4A as their primary therapy after nephrectomy. These findings demonstrate an excellent outcome for stage I EFHWTs with >95% EFS and OS. These data support the utility of investigating the treatment of stage I EFHWTs with observation alone after nephrectomy.

Efficacy of Local Control Strategies for Ewing Sarcoma After Neoadjuvant Chemotherapy: A Network Meta-analysis

This network meta-analysis aimed at comparing the efficacy of local control strategies after neoadjuvant chemotherapy in patients with Ewing sarcoma. Network meta-analysis was used to synthesize direct and indirect evidence in a network of trials that compare multiple interventions and has the potential to rank the competing treatments according to the studied outcome. There are three treatment options for local Ewing's sarcoma after neoadjuvant chemotherapy, namely surgery, radiotherapy and surgery plus radiotherapy (SR). Records of 2540 patients from 11 studies were analyzed. Potentially relevant studies were retrieved from PubMed and Embase, and screened according to inclusion and exclusion criteria. Hazard ratios and the associated 95% confidence intervals were used to describe the efficacy of different interventions on 5-year local recurrence rate and 5-year event-free survival rate. Surface under the cumulative ranking curve (SUCRA) was calculated for ranking probabilities of different treatment. Compared with radiotherapy, surgery had better efficacy [local recurrence, OR (95% CI) 0.48 (0.33 - 0.87)] and SR had a similar effect as surgery [local recurrence, OR (95% CI) 0.50 (0.29 - 0.82)]. There were no statistically significant differences between three different local control strategies in 5-year local recurrence rate. SUCRA values suggested that surgery was better than SR for 5-year local recurrence rate (0.79 vs 0.70) and 5-year event free survival rate (0.67 vs 0.50), respectively. Both surgery and SR were superior to radiotherapy in reducing 5-yer local recurrence of patients with Ewing sarcoma after neoadjuvant chemotherapy. Surgery had higher efficacy than SR on improving the prognosis of patients.

High CD38 expression in childhood T-cell acute lymphoblastic leukemia is not associated with prognosis.

Prognostic factors are not well exploited in childhood T-cell acute lymphoblastic leukemia (T-ALL). The aim of this study was to analyze the prognostic role of CD38 as well as minimal residual disease (MRD) and other biological factors in T-ALL. Immunophenotyping of bone marrow (BM) at diagnosis and MRD levels were determined using a standard panel of antibodies by 4-colour flow cytometry. A total of 96 children with T-ALL were enrolled. The results showed that 97.9% of T-ALL patients were positive for CD38 with a median level of 85.3%. CD38-high group had a worse early treatment response than the CD38-low group. However, CD38 levels were not associated with prognosis, albeit CD38-high group had a worse 5-year event free survival rate (55.1% vs. 66.6%, P> 0.05) and a higher 5-year cumulative incidence of relapse (35.6% vs. 19.8%, P> 0.05). Very high MRD levels (> 10%) were related to the worse survival. Neither flow cytometry based minimal residual disease (MRD) levels nor CD38 expression levels showed significant relation to the hazard of relapse (P> 0.05). We conclude that T-ALL has a high level of CD38 expression which is not associated with prognosis. Very high MRD level (> 10%) is related to the worse survival, however, FCM based MRD detection does not convey a significant prognostic value.

Abstract OT2-01-04: Phase IB-II combination neoadjuvant chemotherapy with docetaxel plus atezolizumab plus herceptin SC and pertuzumab (TAHP) for patients with HER2-positive early breast cancer and subsequent atezolizumab plus herceptin SC and pertuzumab (AHP) adjuvant therapy after surgery (Neo-PATH)

Abstract Background Dual HER2-targeting with trastuzumab and pertuzumab combined with cytotoxic chemotherapy as neoadjuvant treatment increased rate of pathologic complete response to 50-65%. Subset of HER2-positive breast cancer has shown adaptive immune infiltrates which was correlated with better prognosis, including whom treated with dual anti-HER2 treatment. Immune checkpoint inhibitor including anti-PD-L1 modulate tumor microenvironment to restore tumor-induced or antibody-treatment induced immunosuppression. Here we investigate an efficacy of combining immunotherapy with anti-HER2 treatment as a neoadjuvant treatment in clinical stage II-III, HER2-positive breast cancer. Trial design This is a Phase Ib-II single arm study of six cycles of neoadjuvant docetaxel, atezolizumab, trastuzumab SC, and pertuzumab combination in patients with HER2-positive breast cancer. After 6 cycles of TAHP, surgery followed by 12 cycles of adjuvant atezolizumab, trastuzumab SC, and pertuzumab(AHP) will be performed. Patients without pCR will receive additional four cycles of doxorubicin and cyclophosphamide between surgery and adjuvant AHP. Eligibility criteria - Locally advanced, inflammatory, or early stage histologically confirmed invasive carcinoma of breast - HER2-positive breast cancer (immunohistochemistry score 3+, or HER2 SISH (or FISH, CISH) positive) - Primary tumor size&amp;gt;2cm or histologically or cytologically confirmed ipsilateral axillary lymph node metastases by fine needle aspiration (clinical stage IIA-IIIC by TNM 7th staging system) - ECOG Performance status 0-1 Specific aims Primary endpoint is a rate of pathologic complete response (pCR) after neoadjuvant docetaxel, atezolizumab, trastuzumab SC, and pertuzumab. Secondary endpoints are comparison of 3-year event free survival rate, disease free survival, and overall survival according to pCR achievement, toxicities, quality of life parameters, biomarker analyses (PD-L1 expression, immune signature, PIK3CA pathway, tumor mutation burden) for pCR and survival, multiomic profiling of tumor tissue using F1CDx. Statistical methods For sample size calculation, we used a Simon’s two-stage optimal design, with a 80 % power and 10% significance. The expected sample size is 60 to test the null hypothesis of pCR rate of ≤ 50% versus the alternative hypothesis of pCR rate of ≥ 65%. Stage 1: If pCR were observed in ≤ 12 patients among the first 23 patients, the alternative hypothesis will be rejected and the study will be discontinued Stage 2: If pCR were observed in ≥ 13 patients among the first 23 patients, additional 37 patients will be accrued (a total of 60 patients). If pCR were observed in &amp;gt; 34 patients, the null hypothesis will be rejected. Considering drop-out rate of 10%, we will accrue 67 patients. Our planned study duration is 42 months (patients accrual 6 months, follow up duration 36 months). Citation Format: Hee Kyung Ahn, Ji- Yeon Kim, Koung Jin Suh, Gun Min Kim, Sung Hoon Sim, Ki Hyeong Lee, Kyung Hae Jung, Seok- Ah Im, Yeon Hee Park. Phase IB-II combination neoadjuvant chemotherapy with docetaxel plus atezolizumab plus herceptin SC and pertuzumab (TAHP) for patients with HER2-positive early breast cancer and subsequent atezolizumab plus herceptin SC and pertuzumab (AHP) adjuvant therapy after surgery (Neo-PATH) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-01-04.

Abstract P1-18-01: Risk of recurrence and death in patients with early HER2-positive breast cancer who achieve a pathological complete response (pCR) after different types of HER2-targeted therapy: A retrospective exploratory analysis

Abstract Background: The current standard of care for patients achieving a pCR after HER2-targeted therapy plus chemotherapy in the neoadjuvant setting is to continue HER2-targeted therapy in the adjuvant setting. The aim of this exploratory data analysis is to report the risk of recurrence and death after neoadjuvant systemic therapy in Roche-sponsored neoadjuvant trials in patients with HER2-positive early breast cancer who achieved a pCR. Methods: Data from the HannaH (NCT00950300), NeoSphere (NCT00545688), TRYPHAENA (NCT00976989), BERENICE (NCT02132949), and KRISTINE (NCT02131064) studies were pooled. Neoadjuvant → adjuvant therapeutic regimens analyzed were trastuzumab → trastuzumab (H→H), pertuzumab plus trastuzumab → trastuzumab (PH→H), and pertuzumab plus trastuzumab → pertuzumab plus trastuzumab (PH→PH). pCR was defined as the absence of residual invasive cancer in the resected breast specimen and in the axillary lymph nodes (ypT0/Tis ypN0) after neoadjuvant systemic therapy. Event-free survival (EFS) was defined as the time from the date of randomization to the date of disease recurrence or progression (local, regional, distant, or contralateral) or death due to any cause. EFS rates were estimated using the Kaplan-Meier method. A Cox regression model was used to explore factors associated with EFS. Results: 1764 patients were included in the analysis. The median duration of follow up was shorter in the PH→PH group compared to the PH→H and H→H groups (Table). Overall, patients with a pCR had an increased EFS probability compared to those with residual disease (unadjusted hazard ratio=0.33; 95% confidence interval [CI]: 0.25– 0.43]), and this was maintained in patients stratified by hormone receptor status and disease stage. The 3-year EFS rates in patients who achieved a pCR were 87% (95% CI: 82%–90%) in the H→H group, 92% (95% CI: 87%–95%) in the PH→H group, and 95% (95% CI: 90%–97%) in the PH→PH group. Conclusions: Overall, patients who attained a pCR have a better long-term outcome compared to those with residual disease, regardless of ER status or clinical stage. Some patients who achieved a pCR still had a risk of relapse. A limitation of this exploratory data analysis was the smaller number of patients with stage III disease at baseline and shorter follow-up in the PH→PH group compared to the other groups. Overall(N=1764)H→H (HannaH; NeoSPHERE)(n=703)PH→H (NeoSPHERE; TRYPHAENA)(n=439)PH→PH (BERENICE; KRISTINE)(n=622)Median Duration of Follow-up (months)42.067.961.122.3Disease StageStage II934 (52.9)285 (40.5)204 (46.5)445 (71.5)Stage III806 (45.7)397 (56.5)235 (53.5)174 (28.0)Hormone Receptor StatusPositive783 (44.4)328 (46.7)223 (50.8)232 (37.3)Negative963 (54.6)372 (52.9)215 (49.0)376 (60.5)Unknown18 (1.0)3 (0.4)1 (0.2)14 (2.3)pCR status773 (43.8)236 (33.6)185 (42.1)352 (56.6)Type of recurrence in patients who achieved a pCRDistant recurrence41 (5.3)26 (11.0)10 (5.4)5 (1.4)Local recurrence17 (2.2)12 (5.1)5 (2.7)0Regional recurrence6 (0.8)3 (1.3)2 (1.1)1 (0.3)New contralateral breast cancer2 (0.3)2 (0.8)00 Citation Format: Sandra M Swain, Harrison Macharia, Javier Cortes, Chau Dang, Luca Gianni, Sara Hurvitz, Christian Jackisch, Andreas Schneeweiss, Dennis Slamon, Pinuccia Valagussa, Yolande du Toit, Dominik Heinzmann, Adam Knott, Chunyan Song, Patricia Cortazar. Risk of recurrence and death in patients with early HER2-positive breast cancer who achieve a pathological complete response (pCR) after different types of HER2-targeted therapy: A retrospective exploratory analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-01.

Clinical characteristics and prognosis analysis of childhood B-cell acute lymphoblastic leukemia with TEL-AML1 fusion gene positive

Objective To investigate the clinical characteristics and prognosis of children B-cell acute lymphoblastic leukemia (B-ALL) with TEL-AML1 fusion gene positive. Methods Clinical characteristics, therapeutic effects and prognostic factors of 55 children B-ALL patients with TEL-AML1 fusion gene positive in Children's Hospital of Shanxi from January 2013 to June 2018 were retrospectively analyzed. Kaplan-Meier method was used to evaluate 3-year event-free survival (EFS) rate and overall survival (OS) rate. Influencing factors of EFS and OS were evaluated by using Cox regression analysis. Results TEL-AML1 fusion gene was positive in all 55 children, and no other fusion gene positive was merged. There were 4 patients (7.3%) ≥10 years old. At initial diagnosis, 33 patients (60.0%) had hepatomegaly, 28 patients (50.9%) had splenomegaly, and 27 patients (49.1%) had superficial lymphadenectasis. There were 5 patients (9.1%) with white blood cell count ≥50×109/L, and 19 patients (34.6%) had abnormalities of chromosome. All the 55 children were divided into the low risk group [36 cases (65.5%)], the intermediate risk group [18 cases(32.7%)], high risk group [1 case (1.8%)] according to Morphology, Immunology, Cytogenetics and Molecular Biology (MICM) and adjusted risk. After regular treatments, 50 patients achieved complete remission (CR) on the 15th day. The CR rate after one-course of induction therapy was 100.0%. On the 33rd day, 43 patients (78.2%) had minimal residual disease (MRD) <10-4, 12 patients (21.8%) had MRD≥10-4 and MRD<10-2, 1 patient (1.8%) had MRD≥10-3 at the 12th week. During three to six months, the negative rate of fusion gene was 61.8% (34/55). There were 3 deaths (5.5%), and one (1.8%) of them died of recurrence, and the recurrence time was 27 months from the initial diagnosis; the other 2 cases (3.6%) died of infection during chemotherapy. In 55 patients, the 3-year EFS rate and OS rate was 90.3% and 93.2%, respectively. The 3-year EFS rate and OS rate in the low risk group was 100.0% both; the 3-year EFS rate and OS rate in the intermediate risk group was 78.7% and 86.6%, respectively; the 3-year EFS rate and OS rate in the high risk group was 0 both and one died. EFS rate and OS rate in low risk group were higher than those in the intermediate risk group, and the differences were statistically significant (P < 0.05). The EFS rate was 92.0% and 0 at the 12th week MRD<10-3 group and MRD≥10-3 group, and OS rate was 95.0% and 0 at the 12th week MRD<10-3 group and MRD≥10-3 group (P < 0.05). Cox multivariate analysis showed that MRD at the 12th week was an independent risk factor influencing EFS and OS (OR= 2.971, 95% CI 1.330-6.633, P= 0.008; OR= 2.884, 95% CI 1.295-6.419, P= 0.009). Conclusions Children B-ALL patients with TEL-AML1 fusion gene positive have a low recurrence rate, high survival rate and good prognosis. Risk stratification and the 12th week MRD are the influencing factors of the prognosis. Key words: Leukemia, B-cell; Gene fusion; Child; Survival; Prognosis

Clinical analysis of a modified LMB89 Group C regimen in the treatment of pediatric high-risk Burkitt lymphoma

目的分析改良LMB 89 C组方案治疗高危儿童伯基特淋巴瘤的疗效。方法对2007年1月至2017年4月接受改良LMB 89 C组方案治疗的172例初治高危伯基特淋巴瘤患儿进行回顾性分析。结果全部172例患儿中位发病年龄6（1~14）岁，男144例（83.7%），女28例（16.3%），St.Jude分期Ⅱ、Ⅲ、Ⅳ期分别为2例（1.2%）、54例（31.4%）、116例（67.4%），46例（26.7%）为白血病期，52例（30.2%）存在中枢神经系统（CNS）侵犯。危险度分组：C1组（CNS1，无睾丸/卵巢侵犯）65例，C2组[CNS2和（或）睾丸/卵巢侵犯]55例，C3组（CNS3）52例。145例联合应用利妥昔单抗。10例未缓解并进展至死亡，5例复发，治疗相关死亡率为2.9%。中位随访时间36.0（0.5~119.0）个月，全组3年总生存（OS）率为（88.9±2.4）%、3年无事件生存（EFS）率为（87.9±2.6）%。C1、C2、C3组3年EFS率分别为（96.9±2.1）%、（90.9±3.9）%、（73.4±6.5）%，C3组低于C1组（χ2=12.939，P=0.001）和C2组（χ2=6.302，P=0.036）。C3组中利妥昔单抗联合化疗、单纯化疗患儿的3年EFS率分别为（79.3±6.8）%、（44.4±16.6）%（χ2=5.972，P=0.015）。多因素分析结果显示，临床分期Ⅳ期（包括白血病期）、中期评估有瘤灶为预后不良的危险因素[HR=4.241（95%CI 1.163~27.332），P=0.026；HR=32.184（95%CI 11.441~99.996），P<0.001]。结论改良LMB 89 C组方案对于高危儿童伯基特淋巴瘤具有较理想的疗效。

Evaluation of survival by ADCC status: Subgroup analysis of SB3 (Trastuzumab Biosimilar) and reference trastuzumab in patients with HER2-positive early breast cancer at three-year follow-up.

580 Background: SB3 is an approved biosimilar of reference trastuzumab (TRZ). At additional 2-year follow-up after completing neoadjuvant and adjuvant treatment, there was a difference in event-free survival (EFS), but no difference in overall survival (OS) between SB3 and TRZ. Upon monitoring quality attributes of TRZ, a marked downward shift in antibody-dependent cell-mediated cytotoxicity activities (ADCC) was observed in TRZ lots with expiry dates from Aug 2018 to Dec 2019. Some of the lots were used in the Phase III study. This is a post-hoc analysis of EFS and OS by ADCC status from a 3-year follow-up to investigate the difference in EFS between SB3 and TRZ. Methods: After completion of neoadjuvant and adjuvant therapy in patients with HER2 positive early breast cancer, patients from selected countries participated in a 5-year follow-up study (NCT02771795). Within the TRZ group, patients exposed to at least one shifted ADCC lot and those never exposed to shifted ADCC lot during neoadjuvant period were considered as “Exposed” and “Unexposed,” respectively. EFS and OS after 3-year follow-up was analyzed by ADCC status in the long-term follow-up set. Results: 367 patients (SB3, N = 186; TRZ, N = 181) were enrolled in the follow-up study. Within TRZ, 55 patients were Unexposed and 126 patients were Exposed. At a median follow-up duration of 40.8 months in SB3 and 40.5 months in TRZ, 3-year EFS rates were 92.5% in SB3, 94.5% in Unexposed, and 82.5% in Exposed and OS rates were 97.0%, 100%, and 90.6%, respectively. Exposed was associated with decreased EFS compared to Unexposed (HR 0.14, 95% CI 0.04-0.51, p= 0.003). There was a trend of decreased OS in Exposed compared to Unexposed, however, there was no significant difference (HR 0.14, 95% CI 0.02-1.15, p= 0.068). Between SB3 and Unexposed, no difference was observed in EFS (HR 1.06, 95% CI 0.33-3.44, p= 0.923), or OS (HR 0.54, 95% CI 0.05-5.44, p= 0.600). Conclusions: Within the TRZ group, Exposed showed significantly lower EFS compared to Unexposed, and a similar trend was observed in OS with no statistical significance. Between SB3 and Unexposed, no significant difference in EFS or OS was observed. Clinical trial information: NCT02771795.