The Therapeutic Effectiveness of Neoadjuvant Trastuzumab Plus Chemotherapy for HER2-Positive Breast Cancer Can Be Predicted by Tumor-Infiltrating Lymphocytes and PD-L1 Expression

IntroductionNeoadjuvant trastuzumab plus chemotherapy may affect programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in HER2-positive breast cancer. Discordant results were shown on the correlation between PD-L1 expression or TILs and the effectiveness of neoadjuvant therapy in HER2-positive breast cancer patients. This study aimed to clarify the predictive value of PD-L1 expression and TILs in neoadjuvant therapy in patients with HER2-positive breast cancer.MethodsHER2-positive breast cancer cases receiving neoadjuvant treatment (NAT; n = 155) were retrospectively collected from July 2013 to November 2018. Histopathologic analysis of TILs was performed on hematoxylin and eosin (H&E)-stained sections from pre- and post-NAT specimens. The TIL score as a categorical variable can be divided into high (≥30%) and low (<30%) categories. The expression of PD-L1 was detected by immunohistochemistry, and the percentage of positive membranous staining (at least 1%) in tumor cells (PD-L1+TC) and TILs (PD-L1+TILs) was scored.ResultsIn our study, 87 patients received neoadjuvant chemotherapy alone and 68 received neoadjuvant trastuzumab plus chemotherapy. Multivariate logistic regression analysis confirmed that lymph node metastasis, high TILs, and PD-L1+TILs in pre-neoadjuvant therapy specimens were independent predictors of pathological complete response (pCR) in neoadjuvant therapy (p < 0.05, for all). Among all patients, TILs were increased in breast cancer tissues post-neoadjuvant therapy (p < 0.001). Consistent results were found in the subgroup analysis of the trastuzumab plus chemotherapy group and the chemotherapy alone group (p < 0.05, for both). In 116 non-pCR patients, PD-L1+TC was decreased in breast cancer tissues post-neoadjuvant therapy (p = 0.0219). Consistent results were found in 43 non-pCR patients who received neoadjuvant trastuzumab plus chemotherapy (p = 0.0437). However, in 73 non-pCR patients who received neoadjuvant chemotherapy, there was no significant difference in PD-L1+TC expression in pre- and post-neoadjuvant therapy specimens (p = 0.1465). On the other hand, in the general population, the neoadjuvant trastuzumab plus chemotherapy group, and the neoadjuvant chemotherapy group, PD-L1+TILs decreased after treatment (p < 0.05, for both).ConclusionHigher TIL counts and PD-L1+TILs in pre-neoadjuvant therapy specimens and lymph node metastasis are independent predictors of pCR in patients with HER2-positive breast cancer treated with neoadjuvant therapy. TIL counts, PD-L1+TC, and PD-L1+TILs changed before and after neoadjuvant trastuzumab plus chemotherapy for HER2-positive breast cancer, which may suggest that, in HER2-positive breast cancer, neoadjuvant trastuzumab plus chemotherapy may stimulate the antitumor immune effect of the host, thereby preventing tumor immune escape.

Percutaneous Radiofrequency Ablation Combined With Chemotherapy Versus Chemotherapy Only for Ovarian Cancer Liver Metastasis

PurposeTo compare the feasibility and efficacy of radiofrequency ablation (RFA) combined with chemotherapy and chemotherapy alone in patients with ovarian cancer liver metastasis (OCLM).MethodsIn this retrospective study, a total of 60 patients diagnosed with OCLM between May 2015 to February 2017 were included. All patients with ovarian cancer received chemotherapy and primary cytoreductive surgery before. Thirty patients underwent RFA and chemotherapy, and thirty patients only took chemotherapy. The overall survival (OS), CA-125 levels, and serum AST and ALT levels were compared between the two groups.ResultsIn the RFA group, the 1-,2-, and 3-year OS rates after RFA were 93.3%, 80.0%, and 53.3%, respectively. Serum AST and ALT levels were both elevated after RFA (p=0.0004, p<0.0001). In the chemotherapy group, the 1-,2-, and 3-year OS rates were 79.5%, 60.1%, and 42.1%, respectively. Levels of serum AST and ALT were stable. CA-125 levels for both groups were also available.ConclusionBased on our analysis of a single institution’s series of patients with OCLM, RFA could be a feasibly effective option in the management of OCLM.

Chemotherapy Combined With Recombinant Human Endostatin (Endostar) Significantly Improves the Progression-Free Survival of Stage IV Soft Tissue Sarcomas

PurposeOur previously study showed that recombinant human endostatin (Endostar) combined with chemotherapy had significant activity to increase the mPFS in patients with advanced sarcomas with tolerable side effects. However, the small cohort size and short follow-up time made it difficult to screen sensitive sarcoma subtypes and determine whether there is an overall survival benefit. With the largest sarcoma cohort to our knowledge, we try to confirm the efficacy and safety of chemotherapy combined with Endostar in stage IV sarcomas, with the specific purpose of finding out the sensitive sarcoma types for this combined treatment.MethodsAfter the exclusion of ineligible patients, 156 patients with stage IV bone and soft tissue sarcomas were included in this study according to the inclusion criteria.ResultsBy the end of follow-up, the ORR was 10.7% (9/84) vs 1.4% (1/72) (p=0.041), the DCR was 26.2% (22/84) vs 5.6% (4/72) (p=0.001) in the combined group and chemotherapy group, respectively. The mPFS of combined group was significantly longer than the chemotherapy group (10.42 vs 6.87 months, p=0.003). The mOS were 26.84 months and 23.56 months, without significant difference (p= 0.481). In osteogenic sarcoma, there was no statistically significant difference in the mPFS between the two groups (p=0.59), while in the soft tissue sarcoma, the mPFS in the combined group was significantly higher than that of the chemotherapy group (11.27 vs 8.05 months, p=0.004). Specifically, undifferentiated polymorphic sarcoma (UPS) was the possible sarcoma subtypes that benefited from the combined therapy. For the 38 UPS patients (28 patients in the combined group and 10 patients in the chemotherapy group), the mPFS in the combined group was up to 14.88 months, while it was only 7.1 months in the chemotherapy group, with a significant difference (p=0.006). The most common adverse events in the combined group were myelosuppression, gastrointestinal reactions and abnormal liver function, without significant difference in two groups.ConclusionChemotherapy plus Endostar could prolong mPFS and improve ORR and DCR in patients with stage IV soft tissue sarcoma, suggesting that the combined therapy could improve the patient prognosis in soft tissue sarcomas, especially the UPS patients.

Immune Checkpoint Inhibitors Combined With Chemotherapy Compared With Chemotherapy Alone for Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis

BackgroundIt is still controversial whether immune checkpoint inhibitors (ICIs) can improve the curative effect when added to original standard chemotherapy treatment for triple-negative breast cancer (TNBC). We compared their antitumor efficacy and adverse effects (AEs) to make a better clinical decision.MethodsSeven databases were searched for eligible articles. Progression-free survival (PFS), overall survival (OS), and AEs were measured as the primary outcomes.ResultsNine randomized controlled trials (RCTs) involving 4,501 patients were included. ICI+chemotherapy treatment achieved better PFS (hazard ratio [HR]: 0.78, [0.70–0.86], p < 0.00001), OS (HR: 0.86, [0.74–0.99], p = 0.04), and complete response (584/1,106 vs. 341/825, risk ratio [RR]: 1.38, [1.01–1.89], p = 0.04). With the prolongation of survival, the survival advantage of ICI+chemotherapy increased compared with chemotherapy. Subgroup analysis suggested that the addition of ICIs might not have a better effect in Asian patients, patients with locally advanced disease, or patients with brain metastases. In the toxicity analysis, more Grade 3–5 AEs and serious AEs were found in the ICI+chemotherapy group. For Grade 3–5 AEs, more cases of diarrhea, severe skin reactions, pneumonitis, hepatitis, and adrenal insufficiency were related to the ICI+chemotherapy group.ConclusionsICI+chemotherapy appears to be better than chemotherapy alone for TNBC treatment, with better OS and PFS. However, its high rates of serious AEs need to be taken seriously.Systematic Review RegistrationPROSPERO Registration: CRD42021276394.

Association between chemotherapy and prognostic factors of survival in hepatocellular carcinoma: a SEER population-based cohort study

Hepatectomy and transplantation are the main surgical therapies for HCC patients, and radiotherapy or chemotherapy is often used as adjuvant treatment. Researches have evaluated the independent predictors of HCC, but evidence for factors predicting the efficacy of chemotherapy is rare. Patients diagnosed with HCC between 2010 and 2015 from the SEER database were included and randomly divided into non-chemotherapy and chemotherapy groups. The predictors of CSS and OS were analyzed with the Cox proportional-hazards regression model and Fine and Gray’s competing risk model. Although there was no significant difference in survival analysis between the chemotherapy and non-chemotherapy groups, the cumulative cancer-specific mortality of most HCC patients was decreased in the chemotherapy group. AJCC stage, tumor size, grade, surgery and radiotherapy were predictors of OS and CSS in the non-chemotherapy group, while AJCC stage, tumor size, AFP, grade and surgery in the chemotherapy group. Surgery combined with chemotherapy was applicable to all AJCC stage patients. Surgery was the major treatment option for patients in AJCC I and AJCC II stage, and chemotherapy in AJCC III and AJCC IV stage. In conclusion, the study provided population-based estimates of the prognostic factors in HCC patients with or without chemotherapy.

Effect of Bevacizumab Combined with Neoadjuvant Chemotherapy in Advanced Ovarian Cancer and the Occurrence of Adverse Reactions

Objective: To explore the effect of bevacizumab combined with neoadjuvant chemotherapy in advanced ovarian cancer and the occurrence of adverse reactions. Methods: A total of 80 patients with advanced ovarian cancer, treated in Affiliated People’s Hospital of Inner Mongolia Medical University from June 2019 to December 2020, were randomly divided into two groups. In the chemotherapy group, 40 patients were treated with neoadjuvant chemotherapy, while in the combined group, another 40 patients were treated with bevacizumab combined with neoadjuvant chemotherapy. The therapeutic effects were compared at the end of the treatment cycle. Results: There was no significant difference in the levels of CA125, CEA, and VEGF between the two groups before treatment. However, after the treatment cycle, the levels of CA125, CEA, and VEGF in the combined group were significantly better than those in the chemotherapy group (P < 0.05). At the same time, the incidence of adverse reactions of the chemotherapy group was 67.50%, which was significantly higher than that of the combined group (35.00%; P < 0.05). Conclusion: Bevacizumab combined with neoadjuvant chemotherapy for patients with advanced ovarian cancer has significant curative effect. The combined therapy reduces the levels of tumor markers and inflammatory factors, improves patients’ quality of life, as well as reduces adverse reactions. It has high clinical promotion value.

A Systematic Review and Meta-Analysis on the Number of Adjuvant Temozolomide Cycles in Newly Diagnosed Glioblastoma

BackgroundIn newly diagnosed glioblastoma, radiation with concurrent and adjuvant (six cycles) temozolomide (TMZ) is the established standard of postsurgical care. However, the benefit of extending adjuvant TMZ therapy beyond six cycles has remained unknown.MethodsWe searched PubMed, Web of Science, Scopus, and Embase up to October 1, 2021. The search keywords were “glioblastoma,” “adjuvant chemotherapy,” and their synonyms. The data of randomized clinical trials were extracted and included in this meta-analysis if they had reported patients’ median overall survival (OS) or median progression-free survival (PFS). The standard and extended chemotherapy regimens were considered as adjuvant TMZ up to six cycles and beyond six cycles (up to a total of 12 cycles), respectively. The median OS and median PFS were pooled and compared.ResultsFour studies consisting of 882 patients (461 patients for the standard chemotherapy group and 421 patients for the extended chemotherapy group) were included in this meta-analysis. The extended TMZ regimen was associated with a nonsignificant improvement in PFS [12.0 months (95% CI 9.0 to 15.0) vs. 10.0 months (95% CI 7.0 to 12.0), P = 0.27] without corresponding improvement in OS [23.0 months (95% CI 19.0 to 27.0) and 24.0 months (95% CI 20.0 to 28.0), P = 0.73].ConclusionsIn newly diagnosed glioblastoma, continuing adjuvant TMZ beyond six cycles did not shown an increase neither in PFS nor OS.

Effect of combination of Yiqi Jianpi Yangxue Decoction and chemotherapy on quality of life and adverse reactions of patients with recurrent ovarian cancer

Purpose: To investigate the effect of combined treatment with Yiqi Jianpi Yangxue Decoction and chemotherapy (carboplatin + paclitaxel) on quality of life (QOL) and adverse reactions of patients with recurrent ovarian cancer (ROC).Methods: One hundred and fourteen (114) ROC patients in The Second Children & Women’s Healthcare of Jinan City were split into chemotherapy group (n = 60) and combination group (n = 54), based on whether or not they were treated with Yiqi Jianpi Yangxue Decoction. Differences in clinical efficacy, adverse reactions, levels of tumor marker, levels of immune indexes, and scores on Karnofsky Performance Status (KPS) between the two groups were evaluated.Results: Treatment effectiveness was higher in the combination group than in the chemotherapy group (p < 0.05). Compared with the chemotherapy group, post-treatment levels of HE4 and CA125 in the combination group were lower, while the levels of CD3+, CD4+ and CD8+, and population of NK cells were higher (p < 0.05). After treatment, the KPS score in the combination group was higher than the corresponding score in the chemotherapy group (p < 0.05).Conclusion: Combination of Yiqi Jianpi Yangxue Decoction and chemotherapy (carboplatin + paclitaxel) produces significant enhancement of clinical efficacy in the treatment of ROC. The combination treatment is highly safe, and improves the health status and QOL of patients. Therefore, the combination treatment appears to be suitable for the management of ovarian cancer.

Stem Cells Micro-transplantation in Elderly Patients Aged Over 70 With Acute Myeloid Leukemia: a Multicenter, Prospective, Non-interventional Study

BackgroundThe treatment outcomes of elderly patients aged over 70 with acute myeloid leukemia (AML) have been very disappointing. In comparison, our designed HLA-mismatched hematopoietic stem cell micro-transplantation (MST) has achieved such encouraging treatment results in AML patients as might warrant further investigations of the outcomes of MST for the above mentioned patients. MethodsOne hundred and eleven patients aged 70-88 years were enrolled. Eighty patients were assigned to the high-risk MST or standard MST group according to high-risk prognostic factors. The other thirty-one patients were assigned to either the chemotherapy group or support group. After receiving induction chemotherapy with cytarabine and anthracycline, patients who achieved complete remission (CR) were given another 2 cycles of post-remission therapy with cytarabine. Each chemotherapy regimen was followed by donor stem cell infusion in the MST groups. ResultMST achieved an encouragingly high CR rate in patients (63.8%), even in high-risk patients (54%). It was significantly higher than that in the chemotherapy alone group. The 1-year overall survival (OS) of MST patients was 57.7% and was 68.6% in the high-risk and standard group, respectively, whereas the OS was only 37.3% in the chemotherapy group. The severe infection rate was 36% and 54% in MST and chemotherapy group. No GVHD was observed in MST patients. A larger updated T cell clones was observed in MST patients by T cell receptor repertoire analysis with a Next Generation Sequencing methodology. ConclusionsThese results suggested that MST is a safe and practical treatment regimen conducive to a longer-term survival for AML patients at a highly advanced age.

Oropharynx microbiota transitions in hypopharyngeal carcinoma treatment of induced chemotherapy followed by surgery

Aims To analyze changes in oropharynx microbiota composition after receiving induced chemotherapy followed by surgery for hypopharyngeal squamous cell carcinoma (HPSCC) patients. Methods Clinical data and swab samples of 38 HPSCC patients (HPSCC group) and 30 patients with benign disease (control group, CG) were enrolled in the study. HPSCC group was stratified into two groups: induced chemotherapy group (IC) of 10 patients and non-induced chemotherapy group (nIC) of 28 patients. The microbiota from oropharyngeal membrane was analyzed through 16S rRNA sequencing. Results Alpha-diversity (Shannon and Ace indexes) and weighted UniFrac based beta-diversity severely decreased in the HPSCC group when compared with CG. In pre-operative comparisons, PCoA and NMDS analyses showed microbial structures in the IC group were more similar to CG than nIC. Both IC group and nIC group yielded significantly diverse post-operative communities in contrast to their pre-operative counterparts, evident by the decrease in genera Veillonella and Fusobacterium and increase in genera Streptococcus and Gemella. Given that post-operative oropharynx microbiota showed no difference between IC and nIC groups, the IC group showed less accumulation in anaerobic communities. The abundance of genera Fusobacterium, Parvimonas, Actinomyces were enhanced in the advanced stages (III/IV). Conclusions Oropharynx microbiota in the HPSCC group presents dysbiosis with low diversity and abundance. Induced chemotherapy is beneficial in adjusting the oropharynx microbial environment leading to fewer amounts of anaerobe accumulation after operation. Higher amounts of Fusobacterium in advanced stages (III/IV) may influence the progression of HPSCC.