1-year Overall Survival Of Patients Research Articles

Survival and Prognosis of Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes Transformed from Myelodysplastic Syndrome

To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) transformed from myelodysplastic syndrome (MDS). The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed. The demographic data and laboratory parameters, cytogenetic karyotypes, target genes of AML detected by next generation sequence, risk stratification, treatment regimen, therapeutic efficacy and survival outcome were documented. Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy. The effects of clinical parameters, risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis. The median overall survival (OS) of the AML-MRC patients was 4.5 months, the 1-year OS rate was 28.3%, and the complete remission (CR) rate after treatment was 33.3%. The univariate analysis showed that age≥60 years, leukocytosis, severe thrombocytopenia, poor-risk group and only accepted hypomethylating agents(HMAs) or supportive therapy were the risk factors affecting OS. COX multivariate analysis showed that thrombocytopenia ( HR=4.46), HMAs therapy (compared to transplantation, HR=10.47), supportive therapy (compared to transplantation, HR=25.80) and poor-risk group (compared to medium-risk group, HR=13.86) were independent hazard factors for median OS of patients with AML-MRC. The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age≥60 years, thrombocytopenia, time of transformation from MDS to AML (TTA)≥3 months, fibrinogen-albumin ratio index (FARI)≥0.07, CONUT score≥5, poor-risk group and supportive therapy. Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age≥60 years ( HR=11.23), thrombocytopenia ( HR=8.71), FARI≥0.07 ( HR=5.19) and poor-risk group ( HR=14.00). The risk factors affecting CR of AML-MRC patients in univariate analysis were age≥60 years, thrombocytopenia, FARI≥0.1, CONUT score≥5, poor-risk group and supportive therapy, while binary logistic regression analysis showed that age≥60 years( HR=7.35), CONUT score≥5 ( HR=9.60), thrombocytopenia ( HR=12.05) and poor-risk group ( HR=32.5) were independent risk factors affecting CR of the patients. The OS of AML-MRC patients is poor, old age(≥60 years old), supportive therapy, HMA therapy, poor-risk, thrombocytopenia, FARI≥0.07 and CONUT score≥5 may be associated with poor prognosis.

Results of pelvic exenteration in patients with cervical cancer: clinical experience

Background. Despite the progress in pelvic exenteration (PE) technique in international oncological practice, it is still debatable for cancer surgeons. The main reasons for its unpopularity are technical complexity, high rate of intra- and postoperative complications (60%), high postoperative mortality (30%), and challenging postoperative rehabilitation of patients.
 Aim. To evaluate long-term outcomes after pelvic exenteration in patients with locally advanced recurrent cervical cancer.
 Materials and methods. From September 2021 to December 2022, 23 PEs were performed, including 12 total and 11 anterior. The mean age was 52.2±10.0 years (range 39–83 years). All patients were diagnosed with locally advanced recurrent cervical cancer: 7 (30%) with stage II, 8 (35%) with stage III, and 8 (35%) with stage IV according to the TNM classification. Histologically, cervical cancer was represented by moderately differentiated squamous cell carcinoma. PE was preceded by the following treatments: neoadjuvant chemotherapy in 17 (74%) patients, surgical treatment in 4 (17%) patients, and chemoradiotherapy in 2 (9%) patients. More than half (56%) of patients achieved grade 2 therapeutic pathomorphism. The advanced disease involved the following adjacent organs: bladder (16; 70%), intestines (13; 56%), uterine endometrium (7; 30%), myometrium and parametrium (4; 17%), fallopian tubes, vagina, and ovary (2; 9%).
 Results. The average follow-up time for patients was 9.4±8.8 months. Median time to progression – 8.7 months [5.9; 10.8]. During the observation period, 78.3% (18/23) of patients died. Progression was recorded in 39.1% (9/23) of patients. The 1-year overall survival of patients was 38.7% (median 8.9 months). The 1-year tumor-specific survival rate was 60.6% (median 14.1 months). The 1- and 3-year progression-free survival (PFS) rates were 63.0 and 49.0% (median, 13.4 months), respectively.
 Conclusion. During the observation period, death occurred in 54.6% (12/23) of cases in the anterior PE group, and in 25% (6/23) in the total group. The median overall survival with anterior PE is 2 times higher compared to total PE (9.6 months versus 4.1 months). Median PFS was 13.4 months. For patients after anterior and total pelvic exenteration, 1-year PFS was 51.9±17.6 and 72.9±13.5; 3-year – 25.9±15.7 and 72.9±13.5 (p=0.178), respectively. Thus, PE is justified and significantly expands the possibilities of surgical treatment.

Treatment and Prognosis of Fibrolamellar Hepatocellular Carcinoma: a Systematic Review of the Recent Literature and Meta-analysis

BackgroundFibrolamellar hepatocellular carcinoma (FL-HCC) is a rare disease and current efforts are focused on the prognosis and on the development of efficient and specific treatments. This study aimed to review the latest evidence regarding FL-HCC treatment and prognosis. MethodsA systematic review of the literature over the past 10 years regarding FL-HCC, and meta-analysis of 1-, 3-, and 5-year overall survival (OS) comparing FL-HCC and conventional HCC were performed. ResultsOverall, 1567 articles were screened, of them 21 were selected for the systematic review, and 6 for meta-analysis. Twenty-one studies included a total of 2168 patients with FL-HCC, with a median age ranging from 11 to 56 years. The majority of patients underwent surgical resection or liver transplantation. After a median follow-up ranging from 24 to 58 months, 1-year OS was 67–100% and 5-year OS was 28–65%. A total of 743 patients with FL-HCC and 163,472 with conventional HCC were included in the meta-analysis. There was a significantly improved 1-, 3-, and 5-years OS in the FL-HCC group compared to the conventional HCC group, although high heterogeneity was found. When excluding population-based studies, and including 96 FL-HCC and 221 conventional HCC patients, the heterogeneity was low, and the meta-analysis showed a significantly longer 1-year OS in patients with FL-HCC than conventional HCC; however, there were no differences at 3- and 5-years OS. ConclusionsSurgical resection for FL-HCC is currently the only curative treatment available. FL-HCC is plagued by high-recurrence rates and poor long-term outcomes which may be related to the absence of specific treatment for advanced and recurrent disease.

Efficacy of Local Treatment in Lymph Node Metastasis from Hepatocellular Carcinoma

Introduction: We aimed to investigate the significance of lymph node metastasis from hepatocellular carcinoma and the efficacy of local treatment. Methods: We included patients diagnosed hepatocellular carcinoma with lymph node metastasis. The pattern of lymph node metastasis was evaluated based on imaging examinations and stratified by three locations: regional (group A), beyond regional intra-abdomen (group B), and extra-abdomen (group C) lymph node metastasis. Results: Among 14,474 patients, 852 (5.8%) were identified as having lymph node metastasis. Regarding the location of presentation, group A showed the highest incidence, followed by groups B and C. The 1-year overall survival of patients was 31.7%. The survival significantly differed according to the location of lymph node metastasis. The 1-year overall survival rates were 39.8%, 25.5%, and 22.2% in groups A, B, and C, respectively. All patients underwent systemic treatment, with others receiving additional local treatment. Local treatment yielded superior overall survival compared with no local treatment. After propensity score matching, local treatment was associated with improved survival. Additionally, patients were stratified based on disease status at the time of diagnosis of lymph node metastasis: lymph node alone and combined extra-nodal metastasis. The survival benefits of local treatment were observed in both groups. Conclusions: Our findings demonstrated the clinical significance of lymph node metastasis from hepatocellular carcinoma, which was well discriminated according to location, favoring regional metastasis. In patients with hepatocellular carcinoma presenting lymph node metastasis, active application of local treatment for lymph node metastasis can improve oncologic outcomes.

Treatment Outcome of Gamma Knife Radiosurgery for Brain Metastasis from Thyroid Cancer: Favorable Local Control but Poor Survival

Brain metastasis from thyroid cancer (TCBM) is extremely rare; thus, despite a good treatment outcome for thyroid cancer, TCBM has shown poor clinical outcomes. Considering the short survival and poor general condition of patients with TCBM, stereotactic radiosurgery may be preferred to achieve local control. A total of 25 patients with TCBM who underwent Gamma Knife radiosurgery (GKS) were initially included in this study; however, 3 patients were excluded because of a lack of data. There were 7 men (31.8%) and 15 women (68.2%) and the mean age was 63.7 years. The most common type of thyroid cancer histology was papillary carcinoma. Fourteen patients (63.6%) harbored single brain metastatic tumor and 8 (36.3%) had multiple brain metastatic tumors. The mean duration from thyroid cancer diagnosis to detection of brain metastasis was 7.7 years (range, 0-23 years). The median dose of radiation of GKS was 22 Gy (range, 18-25 Gy). There was no radiation-induced complication after GKS. The median overall survival (OS) was 15 months and the 1-year OS of patients with TCBM was 63%, the 2-year OS was 38%, and the 5-year OS was 28%. The 6-month progression-free survival (PFS) for local recurrence of TCBM was 90.4%, the 1-year PFS was 84%, and the 3-year PFS was 84%. GKS showed favorable local control for TCBM. However, the rate of distant brain metastasis was high and median survival of patients with TCBM was only 15 months.

Haploidentical bone marrow transplantation in patients with relapsed or refractory severe aplastic anaemia in the USA (BMT CTN 1502): a multicentre, single-arm, phase 2 trial

Relapsed severe aplastic anaemia is a marrow failure disorder with high morbidity and mortality. It is often treated with bone marrow transplantation at relapse post-immunosuppressive therapy, but under-represented minorities often cannot find a suitably matched donor. This study aimed to understand the 1-year overall survival in patients with relapsed or refractory severe aplastic anaemia after haploidentical bone marrow transplantation. We report the outcomes of BMT CTN 1502, a single-arm, phase 2 clinical trial done at academic bone marrow transplantation centres in the USA. Included patients were children and adults (75 years or younger) with severe aplastic anaemia that was refractory (fulfilment of severe aplastic anaemia disease criteria at least 3 months after initial immunosuppressive therapy) or relapsed (initial improvement of cytopenias after first-line immunosuppressive therapy but then a later return to fulfilment of severe aplastic anaemia disease criteria), adequate performance status (Eastern Cooperative Oncology Group score 0 or 1, Karnofsky or Lansky score ≥60%), and the presence of an eligible related haploidentical donor. The regimen used reduced-intensity conditioning (rabbit anti-thymocyte globulin 4·5 mg/kg in total, cyclophosphamide 14·5 mg/kg daily for 2 days, fludarabine 30 mg/m2 daily for 5 days, total body irradiation 200 cGy in a single fraction), related HLA-haploidentical donors, and post-transplantation cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. Additionally, for GVHD prophylaxis, mycophenolate mofetil was given orally at a dose of 15 mg/kg three times a day up to 1 g three times a day (maximum dose 3000 mg per day) from day 5 to day 35, and tacrolimus was given orally or intravenously from day 5 to day 180 as per institutional standards to maintain a serum concentration of 10-15 ng/mL. The primary endpoint was overall survival 1 year after bone marrow transplantation. All patients treated per protocol were analysed. This study is complete and is registered with ClinicalTrials.gov, NCT02918292. Between May 1, 2017, and Aug 30, 2020, 32 patients with relapsed or refractory severe aplastic anaemia were enrolled from 14 centres, and 31 underwent bone marrow transplantation. The median age was 24·9 years (IQR 10·4-51·3), and median follow-up was 24·3 months (IQR 12·1-29·2). Of the 31 patients who received a transplant, 19 (61%) were male and 12 (39%) female. 13 (42%) patients were site-reported as non-White, and 19 (61%) were from under-represented racial and ethnic groups; there were four (13%) patients who were Asian, seven (23%) Black, one (3%) Hawaiian/Pacific Islander, and one (3%) more than one race, with seven (23%) patients reporting Hispanic ethnicity. 24 (77%) of 31 patients were alive with engraftment at 1 year, and one (3%) patient alive with autologous recovery. The 1-year overall survival was 81% (95% CI 62-91). The most common grade 3-5 adverse events (seen in seven or more patients) included seven (23%) patients with abnormal liver tests, 15 (48%) patients with cardiovascular changes (including sinus tachycardia, heart failure, pericarditis), ten (32%) patients with gastrointestinal issues, seven (23%) patients with nutritional disorders, and eight (26%) patients with respiratory disorders. Six (19%) deaths, due to disease and unsuccessful bone marrow transplantation, were reported after transplantation. Haploidentical bone marrow transplantation using this approach results in excellent overall survival with minimal GVHD in patients who have not responded to immunosuppressive therapy, and can expand access to bone marrow transplantation across all populations. In clinical practice, this could now be considered a standard approach for salvage treatment of severe aplastic anaemia. Attention to obtaining high cell doses (>2·5 × 108 nucleated marrow cells per kg of recipient ideal bodyweight) from bone marrow harvests is crucial to the success of this approach. US National Heart, Lung, and Blood Institute and US National Cancer Institute.

Clinical Outcomes of Patients With Unresectable Primary Liver Cancer Treated With Yttrium-90 Radioembolization With an Escalated Dose

PurposeYttrium-90 (90Y) radioembolization with an escalated dose has been shown to improve clinical outcomes compared with standard dose radioembolization, but there are few data on the local control of primary liver tumors. We reported the clinical outcomes of patients with unresectable primary liver tumors treated with 90Y radioembolization with an escalated dose. Methods and MaterialsClinical data of patients with unresectable hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and biphenotypic tumors (cHCC-CC) treated with radioembolization with an escalated dose (≥150 Gy) between 2013 and 2020 with >3 months follow-up were retrospectively reviewed. The primary endpoint was freedom from local progression. Clinical response was defined by Modified Response Evaluation Criteria in Solid Tumours and toxic effects were assessed using Common Terminology Criteria for Adverse Events version 5.0. ResultsFifty-three patients with HCC and 15 patients with CC/cHCC-CC were analyzed. The median dose delivered was 205 Gy (interquartile range, 183-253 Gy) and 198 Gy (interquartile range, 154-234 Gy) for patients with HCC and CC/cHCC-CC, respectively. The 1-year freedom from local progression rate was 54% (95% confidence interval [CI], 38%-78%) for patients with HCC and 66% (95% CI, 42%-100%) for patients with CC/cHCC-CC. For patients with HCC, United Network for Organ Sharing nodal stage 1 (P = .01), nonsolitary tumors (P = .02), pretreatment α-fetoprotein of >7.7 ng/mL (P = .006), and ≤268 Gy dose delivered (P = .003) were predictors for local progression on multivariate Cox analysis. No patients with HCC who received a dose >268 Gy had a local tumor progression. The 1-year overall survival for patients with HCC was 74% (95% CI, 61%-89%). After radioembolization, 5 (7%) patients had grade 3 ascites, and 4 (6%) patients had grade 3/4 hyperbilirubinemia. ConclusionsTreatment of unresectable primary liver tumors with 90Y radioembolization with an escalated dose was safe and well tolerated. Delivery of >268 Gy may improve local tumor control of HCC. Determination of the maximum tolerated dose needs to be performed in the context of future prospective dose-escalation trials to further evaluate the safety and efficacy of such an approach.

A Randomised Evaluation of Low-Dose Cytarabine Arabinoside Plus Lenalidomide Versus Single-Agent Low-Dose Cytarabine Arabinoside in Older Patients with Acute Myeloid Leukaemia: Results from the LI-1 Trial

Background: Many patients with Acute Myeloid Leukemia (AML) diagnosed after 60 years of age are not considered suitable for intensive remission induction chemotherapy, either due to co-morbidities or frailty associated with advanced age. Despite treatment with either a hypomethylating agent or low-dose cytarabine arabinoside (LDAC), survival is usually poor, with 1-year survival after LDAC of 24-37% in NCRI AML16 and historical arms of LI-1. Combination therapy with additional agents represents an attractive option, and has the potential to improve patient outcomes without substantially increasing toxicity. Lenalidomide (Revlimid TM) is an immunomodulatory drug, used to treat myeloma, and some cases of myelodysplastic syndrome, and has potent antineoplastic, anti-angiogenic, anti-inflammatory and pro-erythropoietic properties. Early-phase trials of lenalidomide in AML have demonstrated clinical activity with acceptable toxicity.Aim: To assess the efficacy and tolerability of LDAC+lenalidomide versus LDAC alone in patients aged 60+ unsuitable for intensive therapy. The aim was to double 2-year survival from 11% to 22% (HR 0.69).Methods: LI-1 was an international multicentre, multi-arm, randomised phase II trial developed to study the efficacy and tolerability of novel non-intensive therapies in AML using a “pick a winner” design. LDAC was given at 20mg BD SC on days 1-10 of each course. Lenalidomide was administered orally once daily in a flat 10mg dose for 21 days, where day 1 is day 1 of LDAC with courses occurring at 5-week intervals for courses 1-4. Patients considered to be benefitting after 4 courses, i.e. in remission or stable disease, could continue to receive treatment until disease progression, either with LDAC+lenalidomide at 6-week intervals, or lenalidomide only at 4-week intervals if patient had experienced significant toxicity. Toxicities were recorded using CTCAEv3. Primary objectives included overall survival (OS), complete remission (CR + CRi) achievement, reasons for failure, duration of response (CR/CRi), relapse rates and deaths in first CR. Secondary objectives included toxicity, supportive care requirements, and Quality of Life assessments (measured using EORTC QLQ-30, EQ5D and HADS tools).Results: Between Jan-17 and Jun-19, 202 patients from Denmark (8%), New Zealand (16%) and the UK (76%) were randomised. Median age was 78 years (range 62-89). Overall, 58% were male; 76% de novo AML, 20% secondary AML, and 4% high risk MDS; 1% favourable, 66% intermediate, 19% adverse and 14% unknown cytogenetics; WHO performance status 0 for 15%, 1 for 58%, 2 for 22% and 3 for 5%. Median of 2 courses (range 0-24; mean 3.28) was delivered in LDAC arm and 1 course in LDAC+lenalidomide arm (range 0-25; mean 3.48).Overall response (CR/CRi) was achieved in 40/202 patients (20%), (LDAC+lenalidomide 25%, LDAC 14%, OR 0.45 (0.22, 0.93), P=0.031). 30-day mortality was not significantly increased (19% in both arms); and 2-year OS showed no significant difference (14% vs 11.5%, HR 0.94 (0.69, 1.29, P=0.719). Median OS was 3.5 vs 4.6 months; HR 0.96 (0.71, 1.30), P=0.80. 1-year OS for patients that didn't enter CR/CRi was 6.8% for LDAC+lenalidomide vs 16.9% for LDAC (P=0.028). Cause of death for the majority of patients was resistant/recurrent disease: 45(53%) vs 47(58%). Most adverse events (AEs) were grade 1/2 in both arms. During cycle 1, there were 78 vs 51 grade 3/4 AEs in the LDAC+lenalidomide and LDAC arms, respectively (P=0.02). This included 5 thrombotic events in the LDAC+lenalidomide arm (4 grade 3 and 1 grade 4) and none in the LDAC arm. In course 1, supportive care requirements were higher in terms of both days of antibiotics (7 vs 3; p=0.001) and hospitalisation days (11 vs 6.5; p=0.005) for the LDAC+lenalidomide arm. There was no difference in transfusion requirements.Conclusions: Despite improving the CR/CRi rate, the combination of lenalidomide+LDAC did not improve OS, relapse-free survival or time in remission in elderly patients with AML. The addition of lenalidomide to LDAC resulted in increased toxicity, including episodes of thrombosis, as well as increased supportive care requirements. Alternative strategies to improve survival for elderly patients with AML remain a significant clinical need.Acknowledgements: We are grateful to Blood Cancer UK for funding the trial and Celgene for providing drug and additional support for this IIS.Fig 1: OS All patients [Display omitted] DisclosuresCopland: Astellas: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Incyte: Honoraria, Research Funding, Speakers Bureau; Jazz: Honoraria, Speakers Bureau; Cyclacel Ltd: Research Funding. Russell: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Speakers Bureau; Astellas: Membership on an entity's Board of Directors or advisory committees; Jazz: Research Funding, Speakers Bureau. OffLabel Disclosure:Off label use of lenalidomide in combination with low dose cytarabine will be discussed in the setting of elderly unfit AML.

Primary Squamous Cell Carcinomas Arising in Intracranial Epidermoid Cysts: A Series of Nine Cases and Systematic Review.

ObjectivePrimary squamous cell carcinomas (PSCCs) arising in intracranial epidermoid cysts (IECs) are very rare, and their management and prognostic factors remain unclear. This study aimed to enunciate the clinical features and suggest a treatment protocol based on cases from the literature and the cases from our institution.MethodsThe clinicoradiological data were obtained from nine patients with PSCCs arising in IECs, who underwent surgical treatment at Beijing Tiantan Hospital between July 2012 and June 2018. We also searched the PubMed database using the keywords “epidermoid cyst(s)” or “epidermoid tumor(s)” combined with “malignant” or “malignancy” or “intracranial” or “brain” or “squamous cell carcinoma” between 1960 and 2020. Risk factors for overall survival (OS) were evaluated in the pooled cohort.ResultsThe mean age of our cohort was 51.2 ± 8.3 years (range: 39–61 years), which included eight males and one female. Gross total resection (GTR) was achieved in three patients, while non-GTR was achieved in six patients. Radiotherapy was administered to five patients. After a median follow-up of 16.7 ± 21.6 months (range: 3–72 months), eight patients died with a mean OS time of 9.75 ± 6.6 months (range: 3–23 months). In the literature between 1965 and 2020, 45 cases of PSCCs arising in IECs were identified in 23 males and 22 females with a mean age of 55.2 ± 12.4 years. GTR, non-GTR, and biopsy were achieved in six (13.3%), 36 (80%), and three (6.7%) cases, respectively. After a mean follow-up of 12.7 ± 13.4 months (range: 0.33–60 months), 54.1% (20/37) patients died, and recurrence occurred in 53.6% (15/28) patients. A multivariate analysis demonstrated that postoperative radiotherapy (p = 0.002) was the only factor that favored OS. The Kaplan–Meier analysis showed that, compared with no radiotherapy (median survival time: 4 months), radiotherapy (median survival time: 24 months) had significantly prolonged OS (p = 0.0011), and GTR could not improve OS (p = 0.5826), compared with non-GTR. The 1-year OS of patients with or without radiotherapy was 72.5% or 18.2%, respectively.ConclusionMalignant transformation of IEC into PSCC was prevalent in elderly patients, with slight male predominance. GTR of previous benign IECs is recommended. For remnant benign IECs, close follow-up should be performed. Postoperative radiotherapy for PSCCs could bring survival benefit. GTR of these malignant intracranial tumors is difficult when they involve important brain structures. Future studies with larger cohorts are necessary to verify our findings.

CART therapy followed by allo-HSCT for patients with B-cell acute lymphoblastic leukemia relapsing after the first hematopoietic stem cell transplantation

目的观察嵌合抗原受体T细胞（CART）序贯二次异基因造血干细胞移植（allo-HSCT）治疗移植后复发急性B淋巴细胞白血病（B-ALL）的疗效。方法回顾性分析2015年10月至2020年6月在河北燕达陆道培医院接受二次allo-HSCT的41例B-ALL患者的临床资料，入选患者均为移植后骨髓形态学或髓外复发且二次移植前接受CART治疗。结果全部41例患者中男21例、女20例，二次移植时中位年龄为16（3～46）岁。移植后骨髓复发31例（75.6％）、髓外复发5例（12.2％）、骨髓和髓外复发5例（12.2％）。复发后接受CD19-CART治疗35例（85.4％）、CD22-CART治疗2例（4.9％）、CD19-CART联合CD22-CART治疗4例（9.8％）。二次移植后预期3年总生存（OS）率为48.9％（95％ CI 23.0％～70.6％）、无白血病生存（LFS）率为41.8％（95％ CI 17.3％～64.9％），累积复发率（RI）为8.8％（95％ CI 2.9％～26.4％），非复发相关死亡率（NRM）为51.1％（95％ CI 31.2％～83.6％）。首次移植后复发时间≤6个月组（10例）二次移植后1年OS率低于复发时间>6个月组（31例）［45.0％（95％ CI 12.7％～73.5％）对75.0％（95％ CI 51.4％～88.8％），P＝0.017］。结论CART序贯二次allo-HSCT可使部分造血干细胞移植后复发B-ALL患者获得长生存，但NRM较高，移植方案有待进一步改进。

Validation of the REVEAL Prognostic Models in Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension.

No previous studies have investigated the predictive performance of the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) prognostic equation and simplified risk score calculator in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). We aimed to validate these prediction tools in an external cohort of patients with SLE-PAH. In this study, the validation cohort consisted of patients with SLE-PAH registered in a prospective, multicenter, nationwide database between November 2006 and May2016. The follow-up of patients was censored at 1 year. Discrimination, calibration, model fit, and risk stratification of the REVEAL prognostic equation and simplified risk score calculator were validated. As a result, a total of 306 patients with SLE-PAH were included. The 1-year overall survival rate was 91.5%. The C-index of the prognostic equation was 0.736, demonstrating reasonably good discrimination, and it was greater than that for the simplified risk score calculator (0.710). The overall calibration slope was 0.83, and the Brier score was 0.079. The risk of renal insufficiency and World Health Organization Functional Class III (WHO FC III) were underestimated, and the risk assigned to a heart rate >92 bpm in the REVEAL prognostic models was not observed in our validation cohort. Both model discrimination and calibration were poor in the very high-risk group. In conclusion, the REVEAL models exhibit good discriminatory ability when predicting 1-year overall survival in patients with SLE-PAH. Findings from both models should be interpreted with caution in cases of renal insufficiency, WHO FC III, and heart rate >92 bpm.

Association between Platelet Count with 1-year Survival in Patients with Cancer Cachexia.

Background: Changes in platelet count (PLT) are strongly associated with patient survival and may be clinically indicative of certain underlying diseases. However, there were few studies on the prognosis of patients with cancer cachexia.Objective: The purpose of this study was to investigate the relationship between PLT and 1-year survival in patients with cancer cachexia.Methods: We performed a nested case-control study of data from a multicenter clinical study of cancer. There were 252 patients with cancer cachexia whose survival time was less than or equal to 1 year and 252 patients with cancer cachexia whose survival time was more than 1 year meeting the inclusion criteria. The mortality risk and the adjusted risk were estimated by logistic regression and displayed as odds ratios (ORs) and 95% confidence intervals (95% CIs).Results: PLT was negatively correlated with 1-year overall survival (OS) of patients with cancer cachexia (increased per standard deviation (SD): OR = 1.29; 95% CI: 1.05-1.60; P = 0.018). The higher the PLT, the lower the OS of patients. When classified by dichotomy (D1 < 296×109/L, D2 ≥ 296×109/L), OS of patients in the D2 group was worse (OR = 2.18; 95% CI: 1.38-3.47; P = 0.001). When classified by quartile (Q1- Q3 < 305×109/L, Q4 ≥ 305×109/L), OS of patients in the Q4 group was poorer (OR = 1.82; 95% CI: 1.14-2.94; P = 0.013). In addition, patients with a low PLT (< 296×109/L) and either a high total bilirubin (TBIL) (≥ 17.1 µmol/L) or a smoking history had poor 1-year survival. Based on our primary cohort study, we conducted a survival analysis of 3130 patients with cancer cachexia and found that OS was better in patients with low PLT (< 296×109/L).Conclusion: PLT was negatively correlated with 1-year overall survival of patients with cancer cachexia.

Blinatumomab or Inotuzumab Ozogamicin as Bridge to Allogeneic Stem Cell Transplantation for Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia: A Retrospective Single-Center Analysis

BackgroundBlinatumomab and inotuzumab ozogamicin are now widely used to treat relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Patients and MethodsWe have reported the clinical course of 34 adult patients with r/r B-ALL receiving blinatumomab or inotuzumab ozogamicin at our institution from 2009 to 2019. ResultsBlinatumomab-based salvage therapy was applied for overt r/r B-ALL (n = 13) or minimal residual disease (MRD) positivity (n = 5). Of the 13 patients with r/r B-ALL, 9 (69%; 95% confidence interval [CI], 39%-91%) achieved complete remission (CR), with 78% of CR patients (95% CI, 40%-97%) reaching MRD negativity. MRD negativity was also achieved in all 5 patients treated for MRD positivity. The 1-year overall survival of patients receiving blinatumomab for r/r B-ALL and MRD positivity was 54% (n = 13; 95% CI, 26%-81%) and 80% (n = 5; 95% CI, 44-100), respectively. In the inotuzumab ozogamicin group, all 16 patients were treated for overt r/r B-ALL. The rate of CR was 94% (95% CI, 70%-100%), with 67% (95% CI, 38%-88%) of CR patients reaching MRD negativity. The 1-year OS after the first application of inotuzumab ozogamicin was 46% (95% CI, 18%-74%). Of those patients receiving blinatumomab and inotuzumab ozogamicin as a bridge-to-transplant strategy, 79% and 80%, respectively, proceeded to allogeneic stem cell transplantation. The most frequent drug-specific adverse events were similar to those previously reported, including cytokine release syndrome, capillary leak syndrome, and neurotoxicity for blinatumomab and transplant-associated veno-occlusive disease of the liver for inotuzumab ozogamicin. ConclusionTogether with previous observations from phase III clinical trials, these data suggest that blinatumomab and inotuzumab ozogamicin are highly effective salvage regimens in r/r B-ALL.

HANNA: Real-world outcomes from an observational study with nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck in Germany.

6532 Background: Nivolumab has demonstrated efficacy in clinical trials of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). As only limited real-world data are available, we describe the use of nivolumab and its outcomes in routine clinical practice. Methods: HANNA is a prospective, observational study of patients with R/M SCCHN treated with nivolumab in 56 hospitals and practices in Germany. In total, 385 patients will be followed for ≤ 5 years from treatment initiation until death, withdrawal of consent, loss of follow-up/record, or end of study. The primary objective is overall survival (OS). Secondary objectives include baseline characteristics, safety profiles, and quality of life (QOL) assessment. Results: By November 2019, data from 311 patients were available. Median follow-up was 3.5 months. Baseline characteristics were male, 81.7%; median age, 63 years; history of smoking, 73.3%; Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1, 60.8%; ECOG PS 2/3, 29.6%. Location of primary tumor was oropharynx, 38.3%; hypopharynx, 20.9%; oral cavity, 22.8%; larynx, 11.6%; others, 6.4%. 55.6% of R/M SCCHN patients progressed ≤ 6 months after platinum-based therapy, whereas 43.4% were platinum-sensitive (progressed &gt; 6 months after platinum-based therapy). Nivolumab was received by 25.1% of patients as first therapy after platinum-based chemo- or radiochemotherapy, by 62.1% as second therapy, and by 12.9% as later line therapy. Median treatment duration was 4.6 months. OS at 1 year was 43.3%. 1-year OS for patients with ECOG PS 0 was 75.9%; ECOG PS 1, 41.2%; and ECOG PS 2, 27.3%. Platinum-sensitive patients had higher 1-year OS probability (51.6%). Drug-related adverse events (grade 1/2) and serious adverse events (grade 3/4) were observed in 28.9% and 10.0% of patients, respectively. Interim QOL data (per FACT-H&amp;N and EQ-5D questionnaire) indicated a tendency toward stabilization or slight improvement. We will present an update of the data with longer follow-up (data cut March 2020). Conclusions: HANNA represents one of the largest real-world datasets for nivolumab in R/M SCCHN and comprises a more diverse set of patients than the phase 3 CheckMate 141 trial, including patients with higher ECOG PS, age, and platinum sensitivity. Outcomes from HANNA show that the improved OS, safety, and QOL seen with nivolumab in the real-world setting are consistent with the outcomes from CheckMate 141. Clinical trial information: NCT03114163 .

Survival outcomes based on sequence of therapy using FOLFIRINOX and nab-paclitaxel + gemcitabine in metastatic pancreatic ductal adenocarcinoma.

657 Background: Optimal sequence of therapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) is unknown. FOLFIRINOX (FFX) and Gemcitabine + Nab-paclitaxel (AG) are standard first line (1L) therapies. They have never been prospectively compared. Therefore, we retrospectively compared the overall survival (OS) of patients treated with 1L AG and second line (2L) FFX compared to those treated with 1L FFX and 2L AG. Methods: Patients with mPDAC treated with 1L FFX followed by 2L AG, or vice versa were identified using the Flatiron Health EHR-derived nationwide database. To avoid immortal time bias, patients who received no 2L were included. OS from the initiation of 1L was compared with Kaplan Meier curves and log rank analysis. A cox model, stratified by deciles of propensity score (PS), was used to estimate the effect of treatment on OS with adjustment for differences between the groups. Results: 3,042 patients were identified. 2001 patients received 1L AG. Among these patients, 1446 received 2L FFX, and 555 received no 2L. 1041 patients received 1L FFX. Among these patients, 496 received 2L AG, and 545 received no 2L. Median OS and 1-year OS for those treated with 1L AG followed by 2L FFX or no therapy was 6.1 months (95% CI:5.6 – 6.5) and 25% (95% CI: 0.23 – 0.28). Median OS and 1-year OS for patients treated with 1L FFX followed by AG or no therapy was 8.7 months (95% CI: 7.9 – 9.2) and 36% (95% CI: 0.33 – 0.39). The propensity stratified hazard ratio between these two groups was 0.76 (95% CI: 0.69 – 0.83), favoring 1L FFX. Median OS for patients treated with 1L FFX and 2L AG versus 1L AG and 2L FFX was not significantly different (12.0 m vs. 12.5 m; HR 1.04; 95% CI: 0.90 - 1.20). Conclusions: In this analysis of real-world data, 1L FFX was associated with increased OS in propensity analysis. For patients who received both FFX and AG, median OS was similar, regardless of the sequence.

Ex Vivo Interferon Gamma Production by Peripheral Immune Cells Predicts Survival in Lung Adenocarcinoma

BackgroundLung cancer is one of the most lethal malignancies, with a 5-year survival rate < 20% in patients with stage IV lung cancer. Impaired host immunity is associated with lung cancer pathogenesis, and interferon gamma (IFN-γ) plays an important role in antitumor immune surveillance. We evaluated the clinical significance of ex vivo production of IFN-γ in patients with lung adenocarcinoma. Patients and MethodsWe reviewed the medical records of 109 treatment-naive patients with lung adenocarcinoma who had undergone IFN-γ releasing assay. Differences in the IFN-γ level in nil and mitogen tubes were defined as ex vivo IFN-γ production. Correlation analysis was performed to evaluate the correlation between ex vivo IFN-γ production, cancer staging, and Eastern Cooperative Oncology Group performance status. The optimal cutoff values of low and high ex vivo IFN-γ production were estimated using receiver operator characteristic curve analysis. Cox proportional hazard analyses were used to evaluate the prognostic factors of 1-year overall patient survival. ResultsEx vivo IFN-γ production correlated with N stage, M stage, cancer staging, and Eastern Cooperative Oncology Group performance status. Low ex vivo IFN-γ production (ex vivo IFN-γ production ≤ 7.79 IU/mL) was independently associated with 1-year overall survival (odds ratio = 3.289; 95% confidence interval, 1.573-6.872; P = .002). Additionally, low ex vivo IFN-γ production was an independent predictor of 1-year overall survival in patients with stage IV cancer (odds ratio = 3.156; 95% confidence interval, 1.473-6.760; P = .003). ConclusionEx vivo IFN-γ production before treatment might be a useful biomarker for predicting prognosis in patients with lung adenocarcinoma.

The association of right ventricular dysfunction with in-hospital and 1-year outcomes in anterior myocardial infarction

In anterior ST-segment elevation myocardial infarction (STEMI), attention paid mainly to the left ventricle. The predictive significance of right ventricular (RV) dysfunction in patients with anterior STEMI has been frequently neglected. In this study, we evaluated the prognostic effect of RV dysfunction on in-hospital and long-term outcomes in patients with first anterior STEMI. A total of 350 patients without known coronary artery disease with first anterior STEMI and treated with primary percutaneous coronary intervention were prospectively enrolled in this study. In-hospital and long-term outcomes were compared between two groups of with or without RV dysfunction. In-hospital mortality was significantly higher in the RV dysfunction group (26.7% vs. 1.6%, P < 0.001). The RV dysfunction group also had a higher incidence of cardiogenic shock, recurrent myocardial infarction, target lesion revascularization and stent thrombosis. The 1-year overall survival in patients with and without RV dysfunction was 62.2% and 95.0% respectively. After multivariable analysis, RV dysfunction remained as an independent predictor for in-hospital and long-term mortality. RV dysfunction is an independent predictor of cardiogenic shock, recurrent myocardial infarction, and, in-hospital and long-term mortality in anterior STEMI. Therefore, attention should be paid to the function of right ventricle as in the left ventricle after anterior STEMI.

Metronomic Chemotherapy and Radiotherapy as Salvage Treatment in Refractory or Relapsed Pediatric Solid Tumours

Metronomic chemotherapy (mctx) combined with radiation therapy (rt) is an emerging anticancer strategy. The aim of the present study was to assess the efficacy of mctx combined with rt as salvage treatment in children with refractory or relapsed solid malignancies. This prospective study enrolled patients with refractory or relapsed pediatric solid tumours from January 2013 to January 2015. Treatment consisted of 3-12 courses of mctx in all patients, followed by rt in patients who experienced local recurrence, distant metastases, or both. Each course of mctx consisted of oral celecoxib 100-400 mg twice daily (days 1-42), intravenous vinblastine 3 mg/m(2) weekly (weeks 1-6), oral cyclophosphamide 2.5 mg/m(2) daily (days 1-21), and oral methotrexate 15 mg/m(2) twice weekly (days 21-42). Statistical methods used were the log-rank test and binary logistic regression. A favourable disease response (partial response or stable disease) was seen in 49 of 64 patients (76.6%), with mild acute toxicity occurring in 41 (64%). After a median follow-up of 14 months, 1-year overall survival was 62%. Pattern of disease relapse (p < 0.0001), time from initial treatment to relapse (p = 0.0002), and response to treatment (p < 0.0001) significantly affected survival. Age was the only factor that significantly correlated with treatment toxicity (p = 0.002; hazard ratio: 3.37; 95% confidence interval: 1.53 to 7.35). Combining mctx with rt resulted in a favourable response rate, minimal toxicity, and 62% 1-year overall survival in patients with heavily pretreated recurrent disease. Patients with localized late recurrence or disease progression are the most likely to benefit from this regimen.

Arterial blood supply of hepatocellular carcinoma is associated with efficacy of sorafenib therapy.

To explore the efficacy of sorafenib in treating hepatocellular carcinoma (HCC) and its relationship with the computed tomography (CT) and magnetic resonance imaging (MRI) features of HCC, analyze the prognostic factors of HCC patients treated with sorafenib, and investigate the relationship between imaging findings and outcomes. A total of 38 HCC patients who were treated with sorafenib from April 2009 to December 2010 were included in this study. HCCs were classified as good arterial supply and poor arterial supply according to the intensity enhancement on CT scan or MRI. Clinical data were collected and the survival time was calculated by Kaplan-Meier method. Among these 38 patients [35 (92.1%) were males] treated with sorafenib, the median age was (53.3±11.1) years. Tumors in 17 patients had good arterial supply while those in the remained 21 patients had poor arterial supply. The median survival time (MST) was 10.7 months (95% CI, 8.7-12.7) and the 1-year overall survival (OS) was 41.0%. The MST and 1-year OS in patients with tumors with good arterial supply were 12 months (range, 4-20 months) and 52.9%, respectively, compared with those of 7 months (range, 1-16 months) and 23.8% in patients with tumors with poor arterial supply (P=0.002). Patients with BCLC stage B tumors had longer MST and higher OS than those with BCLC stage C tumors, although the differences were not statistically significant. Multivariate analysis showed that arterial supply of tumors remained statistically predictive for OS (HR =0.22; 95% CI, 0.07-0.67; P=0.008). Arterial blood supply is an independent predictor for survival in HCC patients treated with sorafenib, and patients with tumors with good arterial supply benefit more than those with tumors with poor arterial supply.

Meta-Analysis of Circulating Endothelial Cells and Circulating Endothelial Progenitor Cells as Prognostic Factors in Lung Cancer.

The aim of this study was to analyze the prognostic implications of pretreatment circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPCs) for the survival of patients with lung cancer. Relevant literature was identified using Medline and EMBASE. Patient clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with CEC and CEPC positive rates before treatment were extracted. STATA 12.0 was used for our analysis and assessment of publication bias. A total of 13 articles (8 for CEC and 5 for CEPC, n=595 and n=244) were pooled for the global meta-analysis. The odds ratio (OR) for OS predicted by pretreatment CECs was 1.641 [0.967, 2.786], while the OR for PFS was 1.168 [0.649, 2.100]. The OR for OS predicted by pretreatment CEPCs was 12.673 [5.274, 30.450], while the OR for PFS was 4.930 [0.931, 26.096]. Subgroup analyses were conducted according to clinical staging. Odds ratio (OR) showed the high level of pretreatment CECs only correlated with the OS of patients with advanced lung cancer (stage III-IV). High counts of CECs seem to be associated only with worse 1-year OS in patients with lung cancer, while high level of pretreatment CEPCs correlate with both worse PFS and OS.