Research progress in minimal residual disease in locally advanced non-small cell lung cancer / 中华放射肿瘤学杂志

For locally advanced unresectable non-small cell lung cancer (NSCLC), the standard regimen is concurrent chemoradiotherapy (CCRT) followed by consolidation immunotherapy. Nevertheless, the majority of patients will experience recurrence. Traditional imaging examination has its limitations of passively identifying recurrence, unable to forecast the risk in advance. Minimal residual disease (MRD) based on circulating tumor DNA (ctDNA) has become a novel tumor biomarker. Existing studies have demonstrated that the levels of ctDNA initially increase and then decrease during CCRT for NSCLC. Monitoring ctDNA-MRD can not only robustly predict recurrence, but also guide the consolidation immunotherapy, evaluate the efficacy and predict clinical prognosis. Furthermore, ctDNA-MRD can be a reliable biomarker to explore other effective treatments. However, few ctDNA-MRD clinical studies related to guiding consolidation therapy have been performed, with small sample size and low-level evidence. The value of ctDNA-MRD still needs to be confirmed by prospective randomized studies.

Cost-utility analysis of durvalumab for consolidation therapy after chemoradiotherapy for stage Ⅲ non-small cell lung cancer / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer from the perspective of the Chinese health care system. METHODS A Markov model was developed by using updated four-year survival data from the PACIFIC trial in May 2021 and relevant literature. The cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer was evaluated by using quality-adjusted life years （QALYs）as health output index with 20-year simulation time frame and a 2-week cycling period. The costs and health output were discounted using discount rate of 5％；one-way sensitivity analysis and probabilistic sensitivity analysis were used to examine the robustness of the model simulation results. RESULTS The results of the base analysis showed that compared with placebo group ，durvalumab resulted in 0.73 QALYs at an incremental cost of 1 076 062.86 yuan and an incremental cost-utility ratio （ICER）of 1 467 546.54 yuan/QALY，which was much higher than 3-fold per capita gross domestic products （GDP）in 2020（217 713 yuan）as willingness-to-pay （WTP）threshold. The results of one-way sensitivity analysis showed that the price of durvalumab and discount rate had a great impact on ICER. Probabilistic sensitivity analysis showed no cost-effective advantage for durvalumab when the WTP threshold was three times of GDP per capita in 2020 （217 713 yuan）. CONCLUSIONS From the perspective of Chinese health care system ，there is no cost-effective advantage to the use of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer when the WTP threshold was three times of GDP per capita in 2020.

The Treatment and Progress in Consolidation Therapy of APL / 现代生物医学进展

Acute promyelocytic leukemia (APL) was considered to be the most rapidly fatal leukemia,because of serve clinical manifestation,high rate of early death and the low cure rate.APL has achieved great success due to the application of ATRA and ATO.Although the complete remission rate is about 90％,the relapse rate has been reported to be as high as 15％-30％.So reducing the recurrence and improving long-time survival have become the focus of the study.Choosing the reasonable treatment after remission is very important.The post remission therapy usually include consolidation therapy and maintenance therapy,but the optimal strategy has been controversy.Therefore,this artical will review the literature of APL in consolidation therapy.

Clinical observation of intermedium-dose cytarabine for consolidation therapy of elderly patients with acute myelogenous leukemia / 白血病·淋巴瘤

Objective To investigate the effect of postremission consolidation therapy with intermedium-dose cytarabine (MDAC) in elderly patients with acute myelogenous leukemia (AML). Methods Clinical data of 61 elderly AML patients (except M3) in postremission who achieved complete remission (CR) in two period of remission induction program were retrospectively analyzed. Results There were 26 cases in MDAC group and 35 cases in standard-dose cytarabine (SDAC) group. In MDAC group and SDAC group, the relapse free survival (RFS) time were 42.7 months and 16.0 months respectively (P= 0.002), the overall survival (OS) time were 44.6 months and 18.2 months respectively (P= 0.004), and the cumulative relapse frequencies rates were 26.9 % (7/26) and 54.3 % (19/35) respectively (x 2= 4.567, P= 0.033). However, 3 years OS rate of the two groups were 23.1%(6/26) and 8.6%(3/35) (x 2=2.496, P=0.114) , and there was no significant difference in the incidence of adverse reactions between the two groups (all P > 0.05). Conclusion MDAC could improve RFS and OS for the elderly AML patients in postremission who received CR in the early stage, and the incidence of adverse reactions is similar to that of SDAC.

Consolidation, maintenance and continuous therapy for multiple myeloma in the era of novel agents / 肿瘤研究与临床

With the application of novel agents and high-dose chemotherapy with autologous stem cell transplantation(ASCT),the survival time of multiple myeloma(MM) has been significantly prolonged.However,due to the biological characteristics of myeloma and minimal residual disease after initial treatment,the disease courses of most MM patients show a series of remissions and relapses.Hence,it is necessary to apply consolidation and maintenance therapy after ASCT and continuous therapy for transplant-ineligible patients.This paper reviews the advances in consolidation,maintenance and continuous therapy for MM in the era of novel agents.

Effect of idarubicin combined with medium-dose arabinoside in intensive chemotherapy on the prognosis of acute myeloid leukemia / 白血病·淋巴瘤

Objective To explore the efficacy and feasibility of idarubicin combined with medium-dose arabinoside in intensive chemotherapy for acute myeloid leukemia (AML). Methods Fifty remittent patients with induced chemotherapy who underwent the intensive consolidation therapy with medium-dose arabinoside from January 2010 to January 2015 in hematology department of General Hospital of Beijing Military Area were considered as the treatment group. The single arabinoside (2 g/m 2, 1/12 h, d1-3) treatment for 50 cases in the same period were considered as the control group. Two groups were performed with 6 courses sequential. There were 28 males, 22 females in the treatment group, and average age was 27.6 years (18-52 years), with 3 cases of M 1, 27 cases of M2, 8 cases of M4, 12 cases of M5. In the control group, there were 30 males, 20 females, and average age was 26.8 years (16-50 years), with 2 cases of M1, 30 cases of M2, 8 cases of M4, 10 cases of M5. Then the complications and disease-free survival of two groups were observed respectively. Results Follow-up was done until June 2015. In the treatment group, 1 case died of pulmonary infection, 2 cases died of septic shock and 3 cases died of pulmonary infection, 1 case died of septic shock in the control group. The treatment related mortality of both groups were 6 % (3/50), 8 % (4/50), the related relapse rates were 32 % (16/50), 52 % (26/50), the disease-free survival rates were 62 % (31/50), 40 % (20/50) respectively in two groups. Conclusion Compared with the single arabinoside, the intensive consolidation therapy with medium-dose arabinoside and idarubicin for the treatment of AML has gained lower relapse rate and the related mortality, and the DFS rate has been improved significantly, which need further clinical application.

Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia

In adults with non-promyelocytic acute myeloid leukemia (AML), high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years) who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69) received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles). The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27) received an intermediate-high-dose (<27 g/m2), and group 3 (n=35) received a very-high-dose (≥27 g/m2). Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients). The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21) and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96) than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival.

Hexamethylmelamine as Consolidation Treatment for Patients with Advanced Epithelial Ovarian Cancer in Complete Response after First-Line Chemotherapy

The aim of this study was to assess the efficacy of consolidation therapy with hexamethylmelamine (HMM) in patients with advanced epithelial ovarian cancer (EOC). Patients treated at our hospital between January 1997 and November 2006 and in documented clinical complete response from advanced ovarian cancer following front-line platinum-based therapy were retrospectively analyzed. The patients treated with HMM were compared to the patients of matched counterpart without consolidation therapy. Of 102 patients enrolled, 49 were treated with HMM and 53 received no consolidation treatment. For patients with HMM and observed patients, the mean age were 54.6 and 55.6 yr; the distribution of stage was similar (P=0.977); the optimal surgery was performed in 36 (73.5%) and 44 (83%) (P=0.336); the recurrence rate were 27 (55.1%) and 33 (62.3%) (P=0.463); and the median progression-free survival were 38 months and 21 months for patients with HMM and observed patients (P=0.235). No treatment-related adverse events were reported during the follow-up period. Although this study failed to show the significant survival benefit of consolidation therapy with HMM in patients with advanced EOC, we consider that our study can contribute data to investigate the effectiveness of consolidation therapy in epithelial ovarian cancer.

The Treatment of Adult Acute Myelogenous Leukemia with AD Induction Therapy Followed by Consolidation Therapy with Intermediate Dose Ara-C; Long Term Follow-up Results / 대한혈액학회지

BACKGROUND: This study was to evaluate the therapeutic efficacy of consolidation therapy based on intermediate dose Ara-C in patients with newly diagnosed acute myelogenous leukemia (AML) in Seoul National University Hospital. And also, this study was to assess the toxicities of the treatment. METHODS: We have reviewed retrospectively our experience of patients with newly diagnosed non-M3 AML between January 1993 and July 1997. They were treated with induction chemotherapy with Ara-C 200mg/m2/d over 24 h for 7 days and daunorubicin 45mg/m2/d daily for 3 days. The patients achieving complete remission (CR) are to receive the 3 courses of consolidation chemotherapy based on intermediate dose of Ara-C 1,000mg/m2 given over 2h every 12 h for a total of eight to ten doses. Patients having HLA-matched sibling donors with informed consent could receive allogeneic bone marrow transplantation (BMT). RESULTS: One hundred and fifteen patients were reviewed. The median age was 41 years (range, 16-69) and median follow-up was 75 months. The CR rate was 72.2%. The median disease-free survival (DFS) of patients receiving consolidation therapy and allogeneic BMT was 21 months and 26.5 months, respectively. The overall survival (OS) was 13 months for patients not-receiving consolidation therapy, 21 months for consolidation therapy, and 31 months for allogeneic BMT, respectively. The rate of treatment-related mortality of consolidation therapy was 14% and cause of all deaths was infection. But in allogeneic BMT, that mortality rate was 42%; 2 infections, 2 veno-occlusive diseases and 1 cyclophosphamide-induced cardiomyopathy. CONCLUSION: Patients receiving consolidation therapy with intermediate dose Ara-C had longer DFS and OS. But their DFS and OS was not superior to that of patients receiving allogeneic BMT. In addition, that result was inferior to that of patients receiving high dose Ara-C based consolidation therapy, compared with other previous studies. However, this study was retrospective and so further prospective study will be required for comparing different doses of Ara-C consolidation therapy versus BMT.