Conventional Chemotherapy Group Research Articles

Analysis of sequential chemotherapy efficacy in ovarian epithelial carcinoma, fallopian tube carcinoma and primary peritoneal carcinoma

Objective: To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. Methods: A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel's Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups. Results: (1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups (Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions: Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.

Chronomodulated chemotherapy for locoregionally advanced nasopharyngeal carcinoma: A phase II randomized controlled trial

ObjectiveTo validate the safety and efficacy of chronochemotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC). MethodsParticipants for this phase II randomized controlled trial were recruited from the Department of Head and Neck Oncology at the Affiliated Cancer Hospital of Guizhou Medical University. Patients enrolled (128 in total, 112 in the final analysis) between April 1, 2017, and February 28, 2018, were randomly divided into the chronochemotherapy and conventional chemotherapy groups. In the chronochemotherapy group, docetaxel was intravenously administered between 3:30 a.m. and 4:30 a.m. on day 1, followed by intravenous administration of cisplatin between 10:00 a.m. and 10:00 p.m. from day 1to day 5. In addition, 5-fluorouracil was administered through a continuous intravenous pump between 10:00 p.m. and 10:00 a.m. (2nd day) from day 1 to day 5. In the conventional chemotherapy group, docetaxel (on day 1), cisplatin (on day 2), and 5-fluorouracil (from day 1 to day 5, 120 ​h in total) were administered without time-specific constraints. Both groups underwent intensity-modulated radiation therapy with 6-MV X-rays. The gross target volume (GTV) comprised the nasopharyngeal GTV and cervical lymph node GTV. The primary endpoint was immune function, quantified by measuring dendritic cell and lymphocyte subsets, whereas the secondary endpoints were therapeutic efficacy and incidence of adverse events. Pearson Chi-square test was applied to compare total events between the groups, Mann-Whitney U test was used to compare the DC subsets and toxicities, and Wilcoxon signed-rank test ​was used to compare the continuous variables between the two groups. ResultsChronochemotherapy preserved immune function, as evidenced by elevated levels of myeloid dendritic cells (P ​= ​0.394) and higher CD4/CD8 ratio (P ​= ​0.781). No significant difference in overall response rate, measured as the sum of complete and partial response rates, was observed between the groups (P ​= ​0.711). A reduction in the incidence of vomiting (P ​= ​0.002), stomatitis (P ​= ​0.028), and mucositis (P ​= ​0.028) was observed in the chronochemotherapy group. Leukopenia incidence rate was 83.3 ​% and 92.3 ​% in the chronochemotherapy and conventional chemotherapy groups, respectively (P ​= ​0.232). ConclusionsIn patients with locoregionally advanced NPC, the overall response rate of chronochemotherapy is comparable to that of conventional chemotherapy; however, chronochemotherapy shows fewer adverse events.

Lack of Association Between Immunotherapy and Improvement of Survival for Non-small Cell Lung Cancer Patients With Hemodialysis: A Nationwide Retrospective Cohort Study

BackgroundThe number of patients undergoing hemodialysis continues to increase globally, and the incidence of cancer is high among these patients. Immune checkpoint inhibitors are widely used in patients with advanced cancer, especially non-small cell lung cancer (NSCLC); however, their effectiveness in hemodialysis patients is poorly documented. MethodsThis retrospective cohort study used data from a nationwide database. Patients diagnosed with NSCLC, undergoing hemodialysis, and who started chemotherapy between September 2008 and January 2023 were included. In the intention to treat (ITT) analysis, patients were divided into immune checkpoint inhibitor (ICI) and conventional chemotherapy group, and in the chronological analysis, patients were divided into 2 groups before and after ICI approval. Overall survival (OS) was analyzed using the Kaplan–Meier method with log-rank tests and Cox proportional hazards analyses. A propensity score approach was applied to address confounding factors, and analyses were performed by weighting each patient with the inverse of the estimated propensity score. ResultsWe identified 322 and 389 patients in the ITT and chronological analyses respectively. In both analyses, there were no notable difference of OS between 2 groups (P values by log-rank test 0.933 and 0.248, respectively). The hazard ratios for OS were 0.980 (95% confidence interval [CI]: 0.678–1.415) in the ITT analysis and 0.805 (95% CI: 0.531–1.219) in the chronological analysis. ConclusionThe ICI treatment and approval were not significantly associated with improvement of survival in patients with NSCLC undergoing hemodialysis.

Maintenance Therapy for Recurrent or Metastatic Cervical Cancer: A Multicenter, Cohort Study

Maintenance therapy with alternative agents after chemotherapy was shown to improve the overall survival in some advanced cancers such as breast cancer, lung cancer, ovarian cancer and so on. However, maintenance therapy is not accepted as the standard treatment for recurrent/metastatic cervical cancer. Aim of this study is to elucidate the efficacy of maintenance therapy in cervical cancer and to explore the factors associated with the prognosis of recurrent or metastatic cervical cancer. In this multicenter cohort study, we retrospectively collected patients with a diagnosis of either recurrent or stage IVB cervical cancer to receive first-line chemotherapy with or without maintenance therapy. Patients did not have disease progression with first-line chemotherapy and were divided into maintenance therapy group (Arm A) and conventional chemotherapy group (Arm B). Information on clinical characteristics, metastasis information, treatment outcome and survival of patients was collected using an electronic medical record system. The endpoints of the study were OS and PFS. Data were analyzed for general characteristics and survival using statistical software, and the results were considered statistically significant at P < 0.05. Between January 2019 and July 2021, a total of 270 patients were enrolled from 6 institutions in China. 26 patients were excluded because of short treatment cycles (less than 3 cycles). Finally, a total of 66 patients in Arm A and 178 patients in Arm B were analyzed for survival. The addition of maintenance significantly prolonged overall survival. Overall survival at 3 year was 50.1% in Arm A and 27.8% in Arm B (median overall survival, ≥36 months vs. 22 months; P<0. 001). The median progression-free survival was 21 months in Arm A and 14 months in Arm B (P = 0.025). Univariate survival analysis showed that age, maintenance therapy, combined radiotherapy, and number of extra-pelvic metastases were associated with PFS. Further multifactorial analysis showed that maintenance therapy, combined radiotherapy, and number of extra-pelvic metastases were independent prognostic factors for patients with recurrent or metastatic cervical cancer. The addition of maintenance therapy significantly prolonged overall survival as well as progression-free survival in patients with recurrent or metastatic cervical cancer and did not increase the incidence of serious adverse events. It is time to consider maintenance therapy as the standard treatment after conventional chemotherapy for recurrent or metastatic cervical cancer, rather than waiting for disease progression.

Second curettage versus conventional chemotherapy in avoiding unnecessary chemotherapy and reducing the number of chemotherapy courses for patients with gestational trophoblastic neoplasia: A systematic review and meta-analysis.

Chemotherapy is the recommended treatment for gestational trophoblastic neoplasia (GTN). Second curettage had been advocated to avoid unnecessary chemotherapy and to reduce the courses of chemotherapy; however, consensus has not been reached as there are arguments claiming its inability of inducing complete regression. The present study was performed to clarify the effectiveness of second curettage for avoiding unnecessary chemotherapy and lowering the number of chemotherapy courses in patients with post-molar GTN. Seven predominant electronic databases were searched, including four English databases and three Chinese databases, from the inception of each database until January 31, 2023. Studies were included if they were: (1) human, (2) explicitly indicated exposure to second curettage, (3) explicitly indicated control to conventional chemotherapy, (4) explicitly indicated the participants were patients with gestational trophoblastic neoplasia (GTN), and (5) compared the outcome of interest as the number of the course of chemotherapy. Two authors extracted and analyzed the data independently. Disagreements were reconciled by reviewing the full text by a third author. The data of study location, data collection, study design, number of participants, intervention strategy, control strategy, the follow-up period, outcome, adverse events were analyzed. With regard to avoiding unnecessary chemotherapy, the overall pooled effect size of the second curettage group had a significant advantage over the conventional chemotherapy group with an OR of 0.02 (95% CI: 0.00-0.06). Meanwhile, for reducing the number of chemotherapy courses, the overall pooled effect size of the second curettage group had significant advantage over the conventional chemotherapy group with a mean difference of -2.11 (95% CI: -3.72 to -0.51). The second curettage group had a significant advantage over the conventional chemotherapy group in avoiding unnecessary chemotherapy and reducing the number of chemotherapy courses. Further larger multi-center randomized controlled trials should be conducted to confirm our results and to clarify the optimal patients' group for second curettage in patients with post-molar GTN.

Efficacy of Tyrosine Kinase Inhibitor Combined with Decitabine, Homoharringtonine, Interferon in the Maintenance Therapy of Blast Phase Chronic Myeloid Leukemia

To explore the efficacy of tyrosine kinase inhibitor (TKI) combined with decitabine, homoharringtonine, and interferon regimen as maintenance therapy for blast phase chronic myeloid leukemia (CML-BP). The clinical data of CML-BP patients who received the first major hematological response after induction therapy at The Affiliated Cancer Hospital of Zhengzhou University from June 2015 to December 2021 were analyzed retrospectively. The event-free survival, duration of remission, and overall survival of patients in TKI combined with decitabine, homoharringtonine, interferon group(n=18) and TKI combined with conventional chemotherapy group(n=10) were compared by log-rank test. A total of 28 patients were included, with a median age of 46 (24-58) years old. Kaplan-Meier survival analysis showed that patients in TKI combined with decitabine, homoharringtonine, interferon group had longer event-free survival (7.4 vs 4.3 months, P=0.043, HR＝0.44, 95% CI: 0.17-1.14), duration of overall remission (16.1 vs 6.6 months, P=0.005, HR＝0.32, 95% CI: 0.11-0.89), overall survival (34.3 vs 13.5 months, P=0.006, HR＝0.29, 95% CI: 0.10-0.82) compared with patients in TKI combined with conventional chemotherapy group. The TKI combined with decitabine, homoharringtonine and interferon regimen can significantly prolong the survival of CML-BP patients who obtained the major hematological response compared with TKI combined with conventional chemotherapy regimen.

Combination immunochemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: a systematic review and meta-analysis

ObjectiveTo evaluate the efficacy and safety of combination immunochemotherapy regimens for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).DesignMeta-analysis and systematic review.Data sourcesPubMed, Embase,...

Maintenance therapy for patients with recurrent or metastatic cervical cancer: A multicentre, cohort study.

e17518 Background: Maintenance therapy with alternative agents after chemotherapy was shown to improve the overall survival in some advanced cancers such as breast cancer, lung cancer, ovarian cancer and so on. However, maintenance therapy is not accepted as the standard treatment for recurrent/metastatic cervical cancer. Aim of this study is to elucidate the efficacy of maintenance therapy in cervical cancer and to explore the factors associated with the prognosis of recurrent or metastatic cervical cancer. Methods: In this multicenter cohort study, we retrospectively collected patients with a diagnosis of either recurrent or stage IVB cervical cancer to receive first-line chemotherapy with or without maintenance therapy. Patients did not have disease progression with chemotherapy and were divided into maintenance therapy group (Arm A) and conventional chemotherapy group (Arm B). Information on clinical characteristics, metastasis information, treatment outcome and survival of patients was collected using an electronic medical record system. The endpoints of the study were OS and PFS. Data were analyzed for general characteristics and survival using SPSS25.0 software, and the results were considered statistically significant at P &lt; 0.05. Results: Between January 2019 and July 2021, a total of 270 patients were enrolled from 6 institutions in China. 26 patients were excluded because of short treatment cycles (less than 3 cycles). Finally, a total of 66 patients in Arm A and 178 patients in Arm B were analyzed for survival. The addition of maintenance significantly prolonged overall survival. Overall survival at 3 year was 50.1% in Arm A and 27.8% in Arm B (median overall survival, ≥36 months vs. 22 months; P &lt; 0. 001). The median progression-free survival was 21 months in Arm A and 14 months in Arm B (P = 0.025). Univariate survival analysis showed that age, maintenance therapy, combined radiotherapy, and number of extra-pelvic metastases were associated with PFS. Further multifactorial analysis showed that maintenance therapy, combined radiotherapy, and number of extra-pelvic metastases were independent prognostic factors for patients with recurrent or metastatic cervical cancer. Conclusions: The addition of maintenance therapy significantly prolonged overall survival as well as progression-free survival in patients with recurrent or metastatic cervical cancer and did not increase the incidence of serious adverse events. It is time to consider maintenance therapy as the standard treatment after conventional chemotherapy for recurrent or metastatic cervical cancer, rather than waiting for disease progression.

Study on the effect of Jianpi Yiqi decoction on clinical symptoms, inflammation, oxidative stress, efficacy and adverse reactions in sufferers with colorectal cancer

ABSTRACT Colorectal cancer is a type of cancer that affects the colon or rectum, which are part of the digestive system. It usually develops from small growths called polyps that can turn cancerous over time. This study aimed to investigate the effects of Jianpi Yiqi prescription on clinical symptoms, inflammation, oxidative stress, efficacy, and adverse reactions in colorectal cancer (CRC) patients. A total of 84 CRC patients treated at a hospital from January 2020 to December 2021 were randomly divided into two groups: the conventional chemotherapy group and the Jianpi Yiqi prescription group. Patients in the Jianpi Yiqi group received traditional Chinese medicine on top of conventional chemotherapy. Clinical symptoms and plasma biomarkers were analyzed and compared between the two groups. Results showed that there were significant differences between the two groups before therapy. After therapy, the Jianpi Yiqi group had lower TCM symptom scores, inflammatory factor indices, MDA and SOD levels, and incidence of adverse reactions than the conventional group. Moreover, the total effective rate and tumor stability rate of the Jianpi Yiqi group were higher than those of the conventional group. The study concluded that Jianpi Yiqi prescription had better clinical efficacy in treating CRC patients compared to conventional chemotherapy, with fewer adverse reactions and better inhibition of inflammatory factors and oxidative stress. Overall, this study suggests that Jianpi Yiqi prescription could be a promising complementary therapy for CRC patients, but more research is needed to confirm these findings.

The Choice of Either Conventional Chemotherapy or Inotuzumab Ozogamicin as Bridging Regimen Does Not Appear To Impact Clinical Response to CD19-Directed CAR-T Therapy in Pediatric B-ALL

Bridging therapy (BT) given during the period between T-cell collection and initiation of lymphodepleting chemotherapy is indicated for most children with B-cell acute lymphoblastic leukemia (B-ALL) undergoing treatment with tisagenlecleucel (tisa-cel), a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy. Both conventional chemotherapy agents and B-cell directed antibody-based therapies such as antibody-drug conjugates and bispecific T-cell engagers have been used as systemic forms of BT. The purpose of this retrospective study was to evaluate if there are detectable differences in clinical outcomes based on the type of BT given (conventional chemotherapy or inotuzumab). A retrospective analysis was performed on all patients treated with tisa-cel at Cincinnati Children's Hospital Medical Center for B-ALL with bone marrow disease (with or without extramedullary disease). Patients who did not receive systemic BT were excluded. Only 1 patient received blinatumomab as BT and was therefore not included in this analysis to focus the analysis on the use of inotuzumab. Pre-infusion characteristics and post-infusion outcomes were collected. Fisher's exact test was used for categorical variables, and t-test or Mann-Whitney test was used for continuous parametric and non-parametric variables respectively. Mantel-Cox was used for survival analyses. Thirty-two patients received BT before CD19 CAR-T for medullary leukemia; 24 received conventional chemotherapy, and 8 received inotuzumab ozogamicin (InO). Cohorts were evenly matched regarding CAR-T indication, recipient age, and median CAR-T cell dose. There were no significant differences between the groups for attaining a minimal residual disease (MRD)–negative complete response after CAR-T, the percentage of patients who maintained prolonged B-cell aplasia, or the median duration of B-cell aplasia. Thirty-seven percent of patients in the conventional chemotherapy group and 43% in the antibody-based therapy group relapsed, with a median time to relapse in both groups of 5 months. No differences in event-free survival, the cumulative incidence of relapse, or overall survival were seen between the two groups. Initial response to tisa-cel, relapse rate, and survival were similar between patients who received BT with conventional chemotherapy or InO therapy. Because low disease burden at the time of infusion is a positive prognostic factor, choice of bridging regimen should focus on therapy that is anticipated to effectively lower disease burden and minimize treatment-related toxicity. Given the limitations associated with the single center retrospective analysis, a larger, multicenter study is needed to further explore these findings.

Superior survival outcome of blinatumomab compared with conventional chemotherapy for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia: a propensity score-matched cohort analysis.

Blinatumomab showed a higher complete remission (CR) rate and a safe bridging to allogeneic hematopoietic cell transplantation (allo-HCT) in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). We tried to analyze the outcome of blinatumomab compared with the real-world historical data. We expected superior outcome of blinatumomab compared with historical conventional chemotherapy. We conducted a retrospective study using real-world data in the Catholic Hematology Hospital. Total 197 consecutive cases of R/R BCP-ALL were treated with conventional chemotherapy (n = 113) or blinatumomab, which was available since late 2016 (n = 84). Patients who achieved CR underwent allo-HCT if donor was available. We conducted a propensity score-matched cohort analysis using 5 criteria of age, CR duration, cytogenetics, previous allo-HCT, and salvage lines between historical group and blinatumomab. Each cohort consisted of 52 patients. In blinatumomab group, CR rate was higher (80.8% versus 53.8%, p = 0.006) and more patients proceeded to allo-HCT (80.8% versus 46.2%, p < 0.001). Among the CR patients with available minimal residual disease (MRD) results, 68.6% in blinatumomab group and 40.0% in conventional chemotherapy group were MRD-negative. Regimen-related mortality during the chemotherapy cycles was significantly higher in the conventional chemotherapy group (40.4% versus 1.9%, p < 0.001). Estimated 3-year overall survival (OS) was 33.2% (median, 26.3 months) after blinatumomab, and 15.4% (median, 8.2 months) after conventional chemotherapy (p < 0.001). Estimated 3-year non-relapse mortality were 30.3% and 51.9% (p = 0.004), respectively. In multivariate analysis, CR duration < 12 months showed more relapses and poor OS, and conventional chemotherapy showed higher non-relapse mortality and poor OS. Matched cohort analysis showed superior outcomes of blinatumomab compared with conventional chemotherapy. However, large numbers of relapses and non-relapse mortalities continue to occur even after blinatumomab followed by allo-HCT. Novel therapeutic strategies are still needed for R/R BCP-ALL.

Effect of Body Mass Index on the Prognosis of Mantle Cell Lymphoma

To explore the correlation between different body mass index (BMI) and prognosis of mantle cell lymphoma (MCL). The clinical characteristics and biological indices of 108 patients with MCL treated in Fujian Medical University Union Hospital were retrospectively analyzed, and the effects of different BMI on overall survival (OS) and progression-free survival (PFS) were analyzed. The correlation between BMI and B symptoms, LDH and Ki-67 was further observed. Furthermore，the differences of BMI between Autologous peripheral blood stem cell transplantation(Auto-PBSCT) and conventional chemotherapy groups were explored. Among 108 patients, the median age at diagnosis was 59（25-79） years old, and the male to female ratio was 4.4∶1. 88.89% of patients with Ann Arbor staging III-IV, 63.89% with bone marrow involvement, and 49.07% with splenic infiltration. Patients with BMI ≥ 24 kg/m2 were divided into two groups: the high BMI group and the low BMI group. The 5-year PFS and OS of patients in the low BMI group were 31.9% and 47.0%, respectively, while those in the high BMI group were 64.6% and 68.7%, respectively. The incidence of death in the high BMI group was lower than that of the low BMI group (P＜0.01). In multivariate analysis, BMI was an independent predictor of PFS (HR=0.282; 95% CI: 0.122-0.651; P=0.003) and an independent predictor of OS (HR=0.299; 95% CI: 0.129-0.693; P=0.005). Also, patients with B symptoms had a lower BMI than those without B symptoms (P=0.01), but BMI had no effect on patients' LDH and Ki-67. The prognosis of 16 patients treated with Auto-PBSCT was significantly better than that of the conventional chemotherapy group. There was no significant difference in BMI between Auto-PBSCT group and conventional chemotherapy group. BMI is an independent prognostic factor for PFS and OS in MCL, and may be influenced by the effect of B symptoms on BMI.

Antigen Directed Therapy Pre-Transplant Confers Superior Post-Transplant Survival Outcome Compared to Conventional Chemotherapy in Pediatric Patients with Relapsed and Refractory B-ALL

Background: Hematopoietic stem cell transplant (HCT) represents the most effective mean to achieve cure for children, adolescents and young adults with relapsed or refractory (R/R) B-ALL. Among the several disease-specific and transplant-specific characteristics evaluated so far, achievement of minimal residual disease (MRD) negative complete remission (CR) prior to HCT is the strongest independent prognostic factor of post-HCT outcome. Antigen directed therapies (ADT) such as blinatumomab, inotuzumab ozogamicin and chimeric antigen receptor (CAR) T-cell are very effective at inducing MRD-negative remission and offer an alternative approach for disease control in patients with chemo-resistant disease. We hypothesized that ADT may provide a more durable disease control and lesser morbidity than conventional chemotherapy (CT) and therefore we sought to explore whether the type of treatment (ADT or CT) adopted to achieve MRD negative CR prior to HCT, impacts post-HCT outcomes. Patients and methods: This is a retrospective, multi-institutional cohort study of patients (pts) with R/R B-ALL who received an allogeneic HCT in MRD negative CR between 2010-2021. Patients were eligible if they were ≤30 years at time of diagnosis of R/R B-ALL, had received either CT or ADT (blinatumomab, CAR T-cell, inotuzumab ozogamicin with or without preceding chemotherapy) for the treatment of R/R B-ALL and had achieved MRD negative CR (<0.01% blasts by flow cytometry) prior to HCT. Patients with isolated extramedullary relapse or acute leukemia of ambiguous lineage or history of prior HCT were excluded. Patients were categorized as being in the "CT" or "ADT" group based on whether they received conventional CT or ADT as last cycle that led to MRD negativity prior to HCT. The primary objective of the study was to compare the EFS, OS and treatment related mortality (TRM) from time of transplant according to the therapy (ADT vs. CT) received pre-HCT. Kaplan-Meier or Aalen-Johansen estimates were used to estimate survival rates and curves were compared using logrank or Gray's tests. Results: Seventy-six pts from 7 centers met eligibility criteria; 38 pts (50.0%) received ADT and 38 pts (50.0%) received chemotherapy as last cycle prior to HCT. Demographic, disease and treatment characteristics are summarized in Table 1; notably, more pts in the ADT group had refractory leukemia and more pts had received ≥4 cycles of therapy before achieving MRD negative remission in the ADT group than in the CT group. The 5-yr. EFS and OS for the entire cohort were 53% and 67%, respectively. EFS was superior in the ADT group compared to the CT group (5-yr. EFS 64% vs. 42%, p=0.04; Figure 1). OS was also superior in the ADT group (85% vs. 47%, p=0.0008; Figure 1). In a univariable and multivariable prognostic model for OS that included age, race, having relapsed or refractory disease and CT or ADT as pre-HCT therapy, pre-HCT therapy was the only significant prognostic factor (p<0.001); in a similar model for EFS, pre-HCT therapy was the only significant prognostic factor in the univariable analysis (p=0.04) but not in the multivariable analysis. There was no difference in the incidence of acute GVHD, rate of immune reconstitution at day 100, time to engraftment and cumulative incidence of relapse between the two groups. However, the CT group appeared to have a higher rate of both TRM (33.0% vs. 8%, p=0.01) and relapse related mortality, although not significant for the latter (19% vs. 7% p=0.12). Conclusion: This multicenter study shows that having received ADT prior to HCT may be beneficial when compared to conventional chemotherapy for patients with R/R B-ALL who receive a HCT in MRD negative CR. Patients who received ADT experienced a superior EFS and OS primarily due to a significantly lower TRM, despite having received more cycles of therapy prior to proceeding to HCT. There was no difference in the relapse rate among the two groups further supporting the notion that MRD negative CR is the single most important predictor of post-HCT relapse. Further analysis is ongoing to identify specific factors that could explain the difference in post-HCT mortality among the 2 groups. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Meta-analysis of the efficacy and safety of sintilimab for treating advanced non-small cell lung cancer.

Lung cancer is the leading cause of death from malignant tumors in China, and non-small cell lung cancer (NSCLC) accounts for >80% of all types of lung cancer. Novel immunotherapeutic agents targeting programmed death protein-1 (PD-1) and its ligands [programmed death ligands (PD-L)1 and 2] have emerged as important therapeutic measures and trends in the treatment of advanced NSCLC. Sintilimab (trade name, Daboshu) is a humanized IgG4 monoclonal antibody targeting PD-1 that was developed by Innovent Biologics and Eli Lilly and Company. Studies have shown that sintilimab has the characteristics of high affinity, long-lasting stability and an increased target occupancy rate, and that it is a broad-spectrum drug. The present study uses a meta-analysis to evaluate the safety and efficacy of sintilimab in treating advanced NSCLC. The PubMed, Cochrane Library, Embase, Chinese Biomedical Literature, China National Knowledge Infrastructure, VIP Chinese Science and Technology Journal and Wanfang Medical databases were searched from their establishment until October 2021. Randomized controlled trials of patients with NSCLC who were treated with conventional chemotherapy (chemotherapy) plus sintilimab treatment or sintilimab alone, compared with a chemotherapy group, were included, and a meta-analysis was performed using RevMan 5.3 software. The findings revealed that there was no significant difference between the conventional chemotherapy group and the sintilimab group in terms of the overall incidence of adverse drug reactions (ADR) or grade 3–5 ADRs (risk ratio, 1.04; 95% confidence interval, 0.96-1.14; P=0.33), respectively. Sintilimab coupled with chemotherapy outperformed standard chemotherapy in treating advanced NSCLC. The ADRs did not differ considerably from those of conventional chemotherapy, which will help in the assessment of the clinical efficacy of sintilimab combined with chemotherapy and conventional chemotherapy in treating advanced NSCLC.

Increased risk of incident diabetes after therapy with immune checkpoint inhibitor compared with conventional chemotherapy: A longitudinal trajectory analysis using a tertiary care hospital database

Aims/hypothesisImmune checkpoint inhibitor (ICI) has been emerged as a promising cancer treatment. However, ICI use induces immune-related adverse events, including diabetes mellitus. We compared the risk of new-onset diabetes between patients receiving an ICI and those receiving conventional chemotherapy (CC). MethodsUsing a tertiary care hospital database, we included cancer patients without a previous history of diabetes who were treated with either CC or an ICI. One-to-five nearest neighbor propensity matching was applied, and the risk of diabetes was estimated using a Cox proportional hazards model. Latent class growth modeling was performed with a trajectory approach to determine distinct clusters that followed similar glucose trajectory patterns over time. ResultsAmong 1326 subjects, 1105 received CC, and 221 received an ICI. The risk of new-onset diabetes was significantly higher in the ICI group than the CC group (adjusted hazard ratio 2.454, 95 % confidence interval 1.528–3.940; p < 0.001). The ICI group had a higher proportion of subjects in the trajectory cluster with an increasing glucose pattern than the CC group (10.4 % and 7.4 %, respectively). Within the ICI group, the subjects with an increasing glucose pattern were predominantly male and associated with enhanced lymphocytosis after ICI administration. ConclusionsICI therapy is associated with an increased risk of incident diabetes compared with CC. The glucose levels of patients treated with an ICI, especially males and those with prominent lymphocytosis after ICI treatment, need to be monitored regularly to detect ICI-associated diabetes as early as possible.

Risk of pneumonitis in non-small cell lung cancer patients with preexisting interstitial lung diseases treated with immune checkpoint inhibitors: a nationwide retrospective cohort study.

Chemotherapy for non-small cell lung cancer (NSCLC) patients with preexisting interstitial lung diseases (ILDs) increases the risk of developing pneumonitis. However, the association between pneumonitis and immune checkpoint inhibitors (ICIs) and related factors remains unclear. We conducted a retrospective cohort study using a nationwide inpatient database. We included patients (aged ≥ 20years) newly diagnosed with ILD and NSCLC and who started chemotherapy (ICIs or conventional chemotherapy) between January 2016 and December 2019. The primary endpoint was the onset of pneumonitis. We estimated the cumulative incidence function of pneumonitis and compared it with patients taking ICIs and patients receiving conventional chemotherapy using Gray's test. We calculated the subdistribution hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of pneumonitis using Fine and Gray's model to adjust for sex, age, smoking status, histology of NSCLC, surgical history, and medical histories, considering death as the competing risk. We identified 1177 patients (mean age 72years, 13.8% female), of which 328 and 849 were in the ICI and conventional chemotherapy groups, respectively. There was no significant difference in the cumulative incidence function of pneumonitis between the two groups (p = 0.868). The adjusted subdistribution HR for the incidence of pneumonitis was 1.08 (95% CI: 0.74-1.57). Age (≥ 65years) (HR: 1.86, 95% CI: 1.11-3.10) and smoking history (HR: 2.04, 95% CI: 1.02-4.11) were associated with developing pneumonitis. The risk of developing pneumonitis with ICIs for NSCLC patients with preexisting ILD was similar to that with conventional chemotherapy.

Comparison between talazoparib and conventional chemotherapy in the treatment of HER2-positive breast cancer patients: A retrospective study.

BackgroundThe benefits of talazoparib compared with conventional chemotherapy in HER2-negative advanced breast cancer (ABC) remain unclear.MethodsPatients older than 18 years, with a deleterious germline BRCA1/2 (gBRCA1/2) mutated, metastatic, or locally advanced and HER2-positive breast cancer were enrolled. Patient data including age, menostatus, tumor grade, pathologic tumor size, lymph node status, and whether they had received adjuvant radiation or chemotherapy was collected. The primary outcomes of the study were disease-free survival (DFS), which was defined as the time from randomization to death or recurrence due to any reason, and overall survival (OS), which was defined as the time from randomization to death due to any reason. P<0.05 was considered to be statistically significant.ResultsA total of 136 patients were finally enrolled in the present retrospective study, including 62 patients in the talazoparib group (group A) and 74 in the conventional chemotherapy group (group B). After a median follow-up of 70.9 months [95% confidence interval (CI): 68.3–78.5], both DFS and OS did not differ significantly between the two groups (P=0.658 and P=0.690, respectively). The exploratory subgroup analyses further validated the robustness of the primary results across the subgroups.ConclusionsTalazoparib was not better than conventional chemotherapy in terms of DFS and OS for the treatment of gBRCA1/2 mutated HER2-positive breast cancer patients.

Effect of Neoadjuvant Chemotherapy on Angiogenesis and Cell Proliferation of Breast Cancer Evaluated by Dynamic Enhanced Magnetic Resonance Imaging.

Background Breast cancer is the uncontrolled proliferation of breast epithelial cells under the action of various carcinogenic factors. The evaluation of early efficacy of neoadjuvant chemotherapy for breast cancer is helpful to change the treatment plan in time. On this basis, dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) was used to evaluate the effects of neoadjuvant chemotherapy on angiogenesis and cell proliferation in breast cancer. Objective To evaluate the effect of neoadjuvant chemotherapy on angiogenesis and cell proliferation of breast cancer by dynamic enhanced DCE-MRI. Method 80 breast cancer patients were divided into the routine chemotherapy group (3 cycles) and neoadjuvant chemotherapy groups (3 cycles) of 40 cases each from January 2018 to June 2021. Based on conventional imaging, DCE-MRI was performed with Intera Achieva 3.0 TMR superconducting MR scanner before and after treatment. The quantitative indexes, MRI parameters, cell proliferation expression, and DCE-MRI angiogenesis were compared between the two groups. Result The inhibition rate, Vepost, Ktranspre, ADC, Bax, Alexi, and Aurora in the neoadjuvant chemotherapy group were significantly higher than those in the conventional chemotherapy group (P < 0.05), while Kep, Ktrans, and Nek2 were significantly lower than those in the conventional chemotherapy group (P < 0.05). Vepre (cm3), Ktranspre (ml/min/100 cm3), and Ve had no significant difference (P > 0.05). Conclusion The quantitative parameters, MRI parameters, proliferation, and expression of DCE-MRI in breast cancer patients with different chemotherapy regimens are quite different. They can be applied to the diagnosis of neoadjuvant chemotherapy in breast cancer patients with angiogenesis and cell proliferation.

Effects of Afatinib on Development of Non-Small-Cell Lung Cancer by Regulating Activity of Wnt/β-Catenin Signaling Pathway.

Lung cancer has been one of the deadliest cancers in the world. Afatinib is an ErbB family irreversible blocker that was authorized by the FDA and EMA in 2013 for the treatment of advanced EGFR mutation-positive NSCLC. Therefore, we aim to discover the impact of Afatinib on the development of non-small-cell lung cancer (NSCLC) via modulating the Wnt/β-catenin signaling pathway. The objective remission rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in 22 patients with clinical NSCLC were analyzed as follow-up targets after Afatinib therapy. The differences between the effects of Afatinib treatment and DDP+PEM treatment for conventional chemotherapy were used to measure NSCLC cell proliferation by CCK-8 assay; then those on NSCLC apoptosis were measured by flow cytometry. Patients who received Afatinib had better ORR, DCR, PFS, and OS than those in the conventional chemotherapy group. Meanwhile, CCK-8 assay shows that the number of colony formation of NSCLC cells after Afatinib treatment was less than that in the DDP+PEM group. And NSCLC apoptosis was higher than that in the DDP+PEM group. Phenomenologically, experimental results show that Afatinib can affect the behaviors of NSCLC cells. After treating NSCLC cells with Afatinib, the protein expressions of three serum tumor markers (CEA, CA125, and CY-FRA21-1) were detected by Western blotting, with the findings indicating that the protein expressions in NSCLC cells treated with Afatinib were lower than those of the DDP+PEM group, which indicates that Afatinib treatment can reduce the expressions of tumor markers, and inhibit the development of tumors. Afatinib can affect the progression of NSCLC by modulating the Wnt/β-catenin signaling pathway's activity as a new potential therapeutic drug for NSCLC.

190-OR: Increased Risk of Incident Diabetes after Therapy with Immune Checkpoint Inhibitor Compared with Conventional Chemotherapy: A Longitudinal Trajectory Analysis Using a Tertiary Care Hospital Database

Immune checkpoint inhibitors (ICI) have been emerged as a promising option for cancer treatments. However, ICI use induces immune-related adverse events including diabetes mellitus. We investigated the risk of new-onset diabetes in patients receiving ICI compared with conventional chemotherapy (CC) . Using a tertiary care hospital database, we included cancer patients without previous history of diabetes and treated with either CC or ICI. One-to-five nearest neighbor propensity matching was applied, and the risk for diabetes was estimated using a Cox proportional hazards model. Latent class growth modeling was performed in a trajectory approach to determine distinct clusters following a similar glucose trajectory pattern over time. Of 1,326 subjects, 1,1received CC, and 221 received ICI. The ICI group had a significantly higher cumulative incidence of diabetes compared with those in the CC group (log-rank p &amp;lt; 0.001) . In addition, the risk of new-onset diabetes was significantly increased in the ICI group compared to the CC group (adjusted hazard ratio 2.454, 95% confidence interval 1.528-3.940; p &amp;lt; 0.001) . The proportion of subjects in the trajectory cluster with an increasing glucose pattern was higher in the ICI group than in the CC group (10.4% for the ICI group and 7.4% for the CC group) . Among the ICI group, subjects with an increasing glucose pattern were predominantly male and associated with enhanced lymphocytosis after ICI administration. In conclusion, ICI therapy is associated with an increased risk of incident diabetes compared with CC. Glucose levels in the subjects treated with ICI need to be regularly monitored for earlier detection of ICI-associated diabetes, especially males and those with prominent lymphocytosis after ICI treatment. Disclosure K.Jeong: None. M.Lee: None. Y.Park: None. Y.Rhee: None. Funding Grant of the Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (KHIDI) , funded by the Ministry of Health &amp; Welfare, Republic of Korea. (grant number: HI19C0189) , and the Bio &amp; Medical Technology Development Program of the National Research Foundation (NRF) , funded by the Korean government (MSIT) (NRF2019M3E5D4064682) .