Efficacy Of Postoperative Chemotherapy Research Articles

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives.

Gliomas are the most common primary tumors of the central nervous system, with glioblastoma multiforme (GBM) having the highest incidence, and their therapeutic efficacy depends primarily on the extent of surgical resection and the efficacy of postoperative chemotherapy. The role of the intracranial blood-brain barrier and the occurrence of the drug-resistant gene O6-methylguanine-DNA methyltransferase have greatly limited the efficacy of chemotherapeutic agents in patients with GBM and made it difficult to achieve the expected clinical response. In recent years, the rapid development of nanotechnology has brought new hope for the treatment of tumors. Nanoparticles (NPs) have shown great potential in tumor therapy due to their unique properties such as light, heat, electromagnetic effects, and passive targeting. Furthermore, NPs can effectively load chemotherapeutic drugs, significantly reduce the side effects of chemotherapeutic drugs, and improve chemotherapeutic efficacy, showing great potential in the chemotherapy of glioma. In this article, we reviewed the mechanisms of glioma drug resistance, the physicochemical properties of NPs, and recent advances in NPs in glioma chemotherapy resistance. We aimed to provide new perspectives on the clinical treatment of glioma.

Adding Concomitant Chemotherapy to Postoperative Radiotherapy in Oral Cavity Carcinoma with Minor Risk Factors: Systematic Review of the Literature and Meta-Analysis.

Simple SummaryOral cavity carcinoma (OCC) is the 11th most frequently diagnosed cancer; despite a multimodal treatment, locally advanced OCC, managed by surgery and adjuvant therapies, remains at high risk of recurrence, with a 5-year overall survival (OS) of 51%. The efficacy of postoperative chemotherapy in addition to radiotherapy (POCRT) in low–intermediate risk OCC is a controversial matter in the absence of high-risk features (ENE, R1). To establish the role of POCRT in a population with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI ≥ 5 mm; close margin; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE), we performed a systematic review and meta-analyses focused on OS, disease-free survival (DFS), and local-recurrence-free survival (LRFS). Thirteen studies met the inclusion criteria and were included in the quantitative meta-analyses. Our preliminary results are in favor of POCRT in terms of OS but not conclusive for DFS and LRFS. Further analyses are suggested.When presenting with major pathological risk factors, adjuvant radio-chemotherapy for oral cavity cancers (OCC) is recommended, but the addition of chemotherapy to radiotherapy (POCRT) when only minor pathological risk factors are present is controversial. A systematic review following the PICO-PRISMA methodology (PROSPERO registration ID: CRD42021267498) was conducted using the PubMed, Embase, and Cochrane libraries. Studies assessing outcomes of POCRT in patients with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI ≥ 5 mm; close margin < 2–5 mm; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE) were evaluated. A meta-analysis technique with a single-arm study was performed. Radiotherapy was combined with chemotherapy in all studies. One study only included patients treated with POCRT. In the other 12 studies, patients were treated with only PORT (12,883 patients) and with POCRT (10,663 patients). Among the patients treated with POCRT, the pooled 3 year OS rate was 72.9% (95%CI: 65.5–79.2%); the pooled 3 year DFS was 70.9% (95%CI: 48.8–86.2%); and the pooled LRFS was 69.8% (95%CI: 46.1–86.1%). Results are in favor of POCRT in terms of OS but not significant for DFS and LRFS, probably due to the heterogeneity of the included studies and a combination of different prognostic factors.

Microsatellite instability and Epstein-Barr virus combined with PD-L1 could serve as a potential strategy for predicting the prognosis and efficacy of postoperative chemotherapy in gastric cancer.

BackgroundMicrosatellite instability (MSI) and Epstein-Barr virus (EBV)-positive molecular subtypes exhibit complex immune responses in gastric cancer (GC), and PD-L1 has emerged as a prognostic biomarker associated with the cancer immune microenvironment. This study aimed to determine the prognostic value of molecular subtypes and whether the addition of PD-L1 would accurately predict the prognosis and guide postoperative chemotherapy for GC patients.MethodsWe performed molecular subtyping of tissue microarray slides from 226 GC patients who were treated with radical gastrectomy. The MSI status and PD-L1 expression were evaluated through immunohistochemistry (IHC) and EBV status through situ hybridization. Multiplex polymerase chain reaction (PCR) was also performed on 50 cases to validate the accuracy of IHC in defining MSI status. Differences in overall survival (OS) were assessed using the Kaplan-Meier method, log-rank test and Cox proportional hazards regression model.ResultsAmong the 226 GC patients, 52 (23.2%) patients were classified as the MSI subtype, 11 (4.9%) were EBV+ subtype, and 161 (71.9%) were MSS (Microsatellite stable) /EBV subtype according to TCGA analysis. Two patients were both positive for MSI and EBV infection. EBV+ cases showed higher PD-L1 positivity than MSI cases and MSS/EBV cases (81.8% vs. 50.0% vs. 35.4%, P = 0.003). Compared with the non-MSS/EBV (MSI or EBV+ cases) subgroup, GC patients with MSS/EBV were associated with the worst outcomes (HR = 1.610, 95% CI [1.0462.479], P = 0.031). MSS/EBV GCs alone could benefit from postoperative chemotherapy (HR = 0.452, 95% CI [0.2990.682], P<0.001), and PD-L1-positive expression could also predict a better prognosis (HR = 0.612, 95% CI [0.3890.962], P = 0.033) in this subgroup. Considering both chemotherapy efficacy and PD-L1 expression in the MSS/EBV subgroup, chemotherapy could improve the prognosis for PD-L1-negative MSS/EBV GCs (HR = 0.357, 95% CI [0.2170.587], P <0.001) but not PD-L1-positive MSS/EBV GCs.ConclusionsMolecular subtyping combined with PD-L1 expression could serve as a potential strategy to better predict prognosis and guide postoperative chemotherapy of GC patients.

Tumor Microenvironment Status Predicts the Efficacy of Postoperative Chemotherapy or Radiochemotherapy in Resected Gastric Cancer

PurposeChemotherapy (CT) and radiochemotherapy (RCT) are currently the standard postoperative treatments for resected gastric cancer (GC). However, owing to a lack of predictive biomarkers, their efficacy is currently suboptimal. As tumor microenvironment (TME) has the potential to determine treatment response, we investigated the association of TME status with the efficacy of fluoropyrimidine (FU)-based postoperative CT/RCT in resected GC.MethodsPatients with transcriptome data were screened and selected in three independent cohorts. Favorable (fTME) and poor TME (pTME) were defined by a transcriptome-based TME qualification method. Immune infiltration and hypoxia were assessed.ResultsA total of 535 patients were eligible. fTME, indicating the presence of immune activation, was characterized by NK cell rather than CD8+ T cell infiltration. However, postoperative CT/RCT improved overall survival and disease-free survival time more evidently in patients with pTME GC than those with fTME GC. Stratified by stage in fTME GC, stage III patients benefited from postoperative CT/RCT while stage Ib/II patients did not. In comparison, patients with pTME GC benefited from postoperative CT/RCT, regardless of stage. Furthermore, fTME was more hypoxic than pTME, accompanied by a stronger expression of thymidylate synthase (TS)—the target of FU. Stage Ib/II fTME GC was the most hypoxic and had the strongest TS expression across all the subgroups stratified by TME status and stage.ConclusionsWe found that fTME, with the enrichment of NK cells, may predict the lack of postoperative CT/RCT efficacy in stage Ib/II GC, which may be associated with hypoxia and TS expression. Further validations and mechanism researches are needed.

Adjuvant chemotherapy improves the prognosis of early stage resectable pulmonary large cell carcinoma: analysis of SEER data.

Pulmonary large cell carcinoma (LCC) is a poorly differentiated and rare tumor with dismal outcome, and there are no recommended treatments for LCC. Little is known about the efficacy of postoperative chemotherapy in patients with early stage LCC. The patients with early stage I/II LCC in the Surveillance, Epidemiology and End Results (SEER) database between 2004 and 2015 were retrospectively reviewed. The overall survival (OS) of patients with LCC at different stages and treatments were evaluated by Kaplan-Meier analysis with log-rank test. Univariate and multivariate Cox proportional risk regression analysis were employed to determine the independent risk factors of OS. Finally, a nomogram was constructed to predict the 1 -, 3- and 5-year OS of early stage LCC patients. A total of 1,099 pulmonary LCC cases were included in this study. 71.8% of patients were over 60 years old, and 66.7% of the tumor lesions located in the upper lobe, followed by the lower lobe (25.7%). Meanwhile, the majority of tumors showed poor differentiation (96.1%). The median OS of surgical patients with or without post-operative adjuvant chemotherapy was 61 and 47 months, respectively. Post-operative chemotherapy was associated with better OS (HR: 0.805; 95% CI: 0.676-0.959, P=0.020). For patients with tumor size >3 cm or IB stage tumor, the prognosis of postoperative chemotherapy was better than that of patients without chemotherapy. Multivariate Cox analysis revealed the age, stage and treatments were independent risk factors of OS for early stage LCC. The nomogram had a calibration index of 0.581. The incidence of LCC was high in the elderly, and it generally had poor differentiation. Post-operative chemotherapy is strongly recommended for patients with LCC at stage IB or higher.

Impact of adjuvant chemotherapy with S-1 on survival in patients with type 4 and large type 3 gastric cancer.

98 Background: The prognosis of patients with linitis plastica (type 4) and large ulcero-invasive-type (type 3) gastric cancer is reported to be extremely poor. In stage II/III gastric cancer, adjuvant chemotherapy with S-1 is a standard treatment in Japan. However, the efficacy of postoperative chemotherapy with S-1 in these types of patients with dismal prognosis is unknown. The aim of this study is to evaluate the impact of adjuvant chemotherapy with S-1 on survival in type 4 and large type 3 gastric cancer patients. Methods: A total of 152 patients with clinically resectable type 4 and large type 3 gastric cancer who underwent R0 or R1 surgery from 2002 to 2014 were included. The survival outcome between patents with surgery alone and patients who received adjuvant S-1 was compared using a 1:1 propensity score matching method. Results: Patients with adjuvant S-1 were significantly younger (67 vs 74 y, p = 0.009), had higher incidence of T4 (90 vs 62%, p &lt; 0.001), N2-3 (84 vs 63%, p = 0.008), and cytology positive (52 vs 29%, p = 0.006) than in surgery alone patients. Before matching, median survival time (MST) was not different in surgery alone (n = 52) and adjuvant S-1 (n = 100) (31.3 vs 35.8 months, p = 0.41). Propensity score matching yielded 48 patients (24 patients in each group). After matching, baseline characteristics were well balanced between the two groups. Survival in patients with adjuvant S-1 was significantly better than in surgery alone patients (MST: 50.3 vs 15.4 months, p = 0.002). Cox proportional hazard analysis revealed adjuvant S-1 treatment was selected as independent prognostic factor (HR: 0.38, 95%CI: 0.18-0.76, p = 0.006), as well as lavage cytology (HR: 3.9, 95%CI: 1.8-8.9, p &lt; 0.001). Conclusions: Adjuvant chemotherapy with S-1 may have a strong impact on survival in type 4 and large type 3 gastric cancer patients. The efficacy of this treatment will be further demonstrated in the future clinical trials.

The differences on efficacy of oxaliplatin in locally advanced colon cancer between mucinous and nonmucinous adenocarcinoma.

Until now, it remains unclear how to best use the histological subtype in clinical practice. This study aimed to compare differences in the efficacy of postoperative chemotherapy among different histological subtypes of colon adenocarcinomas. Using the Surveillance, Epidemiology, and End Results‐Medicare database, 51,200 patients with stage II or III primary colon carcinomas who underwent resection for curative intent between 1992 and 2008 were included. The survival benefit was evaluated using a Cox proportional hazards model, interaction analyses, and propensity score‐matched techniques. There was no significant difference in survival for low‐risk stage II mucinous adenocarcinoma (MA) or nonmucinous adenocarcinoma (NMA) between 5‐FU and oxaliplatin‐treated groups (P = 0.387 for MA, P = 0.629 for NMA). Patients with high‐risk stage II NMA who received the oxaliplatin chemotherapy regimen had significantly improved cancer‐specific survival (CSS) compared with the 5‐FU group (P = 0.004), while those with MA saw no improvement (P = 0.690). For stage III tumors, patients with NMA who received the oxaliplatin chemotherapy regimen had significantly improved CSS compared with the 5‐FU group (P < 0.001), while those with MA saw no improvement (P = 0.300). There were significant interactions between chemotherapy regimen and histological subtype. For patients with resected colon cancer who received 5‐FU‐based postoperative chemotherapy, oxaliplatin chemotherapy prolongs CSS for stage III and high‐risk stage II NMA. Conversely, there was no similar improvement with addition of oxaliplatin for patients with stage III or stage II MA.

Extent of Resection in Glioma-A Review of the Cutting Edge.

Modern glioma surgery has evolved from the principal belief that safe, maximal tumor resection improves symptom management, quality of life, progression-free survival, and overall survival in both low-grade and high-grade glioma. However, in the absence of level I data, the overwhelming support for this idea is derived largely from retrospective series. As a result, the influence of increasing extent of resection and reducing tumor burden on the efficacy of postoperative chemotherapy and radiotherapy, and survival, remains inadequately defined. This situation is particularly true because gliomas represent a widely heterogeneous group of tumors with varying behaviors and prognoses rooted in their complex molecular profile. The neurosurgical community has made a large effort to define the clinical benefits of maximizing tumor resection, with particular attention paid to the ever-evolving understanding of glioma molecular heterogeneity. Important new technologies have been developed concurrently to mitigate neurologic risks related to the pursuit of maximizing extent of resection. These advances reflect the modern goal of glioma surgery to find the optimal balance between tumor removal and neurologic compromise. We review the current literature supporting safe, maximal resection for gliomas.

Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer

We investigated the relationship between the p53-dependent apoptotic pathway and the survival of patients with gastric cancer, retrospectively, to elucidate new biomarkers of uracil/tegafur (UFT) chemotherapy. We examined the expression of p53, p21, Bax, and myeloid cell leukemia 1 (Mcl-1) proteins immunohistochemically in 105 patients who underwent curative gastrectomy for gastric cancer invading the serosa. Postoperative oral UFT was prescribed for 1 year. Kaplan-Meier survival curves were compared with the two-sided log-rank test. Positive staining for p53, p21, Bax, and Mcl-1 proteins was found in 63.8, 52.4, 39.0, and 72.4% of the subjects, respectively. Survival time did not differ significantly between the patients with and those without p53, p21, and Bax expression. However, patients with Mcl-1- tumors survived longer than those with Mcl-1+ tumors. Postoperative UFT treatment did not improve survival; however, adjuvant UFT significantly prolonged the survival of patients with p53-, p21-), Bax+, or Mcl-1+ tumors, but not of patients with p53+, p21+, Bax-, or Mcl-1- tumors. The efficacy of adjuvant chemotherapy for gastric cancer may be affected by the status of apoptosis-related proteins such as p53, p21, Bax, and Mcl-1. However, because susceptibility to apoptosis did not explain the sensitivity of chemotherapeutic agents, further investigation of the mutual interaction between apoptosis-related proteins is required.

Preoperative versus postoperative chemotherapy in patients with resectable non-small cell lung cancer: Systematic review and indirect comparison meta-analysis of randomized trials

7546 Background: A large number of trials evaluated the efficacy of postoperative chemotherapy after resection for lung cancer. A smaller number evaluated preoperative chemotherapy for potentially resectable lung cancer, but no direct comparison has yet been published comparing the two approaches. Methods: We conducted a systematic review of randomized trials, extracted time-to-event data using Parmar methods (when not reported), used random effects meta-analysis to evaluate overall and disease survival treatment effects and performed indirect comparison using surgery (without chemotherapy) as the common comparison. Results: 112 publications were identified and 56 potentially relevant trials retrieved for more detailed evaluation. In total, 17 were excluded for repeat data and data from 8 studies could not be extracted for meta-analysis, leaving 31 randomized trials involving over 10,000 participants, with 21 trials administering postoperative and 10 trials administering preoperative chemotherapy. For ove...

Role of glutathione-dependent peroxidase in regulation of lipoperoxide utilization in malignant tumors.

Glutathione content, the activity of glutathione-dependent enzymes (glutathione reductase, glutathione peroxidase, and glutathione S-transferase), and also SOD (superoxide dismutase) and catalase were studied in human malignant tumors (uterus, breast, and ovaries) and normal tissues. Glutathione level and the activity of glutathione-dependent enzymes were 2-3 times higher in the malignant tumors than in normal tissues. A negative correlation between the level of glutathione and glutathione-dependent enzymes (glutathione peroxidase and glutathione S-transferase) in tumors and the efficacy of postoperative chemotherapy may characterize the degree of tumor resistance to chemotherapy and therefore may have prognostic value. Low SOD and catalase activity and high activity of glutathione-dependent enzymes in tumors suggest that glutathione peroxidase and glutathione S-transferase play a major role in peroxide utilization in malignant tumors.

Surgical resection alone is effective treatment for ovarian immature teratoma in children and adolescents: A report of the Pediatric Oncology Group and the Children’s Cancer Group

Objective: In both adult women and children the potential for malignant recurrence from ovarian immature teratoma has prompted the standard use of chemotherapy after complete resection of the primary tumor. The efficacy of postoperative chemotherapy in children and adolescents with ovarian immature teratoma, however, has not been established. A pediatric intergroup trial (INT 0106) was designed to determine the need for postoperative chemotherapy in patients with ovarian immature teratoma after management with surgical resection only. Study Design: Between 1990 and 1995, 44 patients with completely resected ovarian immature tumor and without postoperative chemotherapy, who were able to undergo assessment, were accrued. Tumor tissue was evaluated by central pathology review to confirm diagnosis and determine tumor grading of immature neural elements. Patients were followed carefully for recurrence of disease with appropriate diagnostic imaging and serum marker studies. Results: Thirty-one patients had pure ovarian immature teratoma with a tumor grade of 1 (n = 17), 2 (n = 12), or 3 (n = 2). Age at diagnosis ranged between 1.5 and 15 years (median, 10). Of the 29 patients studied, the serum α-fetoprotein level was elevated in 10 (34%); the median level was 25 ng/ml. Thirteen patients had ovarian immature teratoma plus microscopic foci of yolk sac tumor. Tumor grade was 1, 2, or 3 in 1, 6, and 6 patients, respectively. Age ranged between 6 and 20 years (median, 12). In the 12 patients evaluated for serum α-fetoprotein, 10 (83%) had elevated levels; the median level was 262 ng/ml. The 4-year event-free and overall survival for the ovarian immature teratoma group and for the ovarian immature teratoma plus yolk sac tumor group was 97.7% (95% confidence interval, 84.9%-99.7%) and 100%, respectively. The only yolk sac tumor relapse occurred in a child with ovarian immature teratoma and yolk sac tumor who was then treated with chemotherapy and is alive and free of disease 57 months after recurrence. Conclusion: The results of this study suggest that surgery alone is curative for most children and adolescents with resected ovarian immature teratoma of any grade, even when elevated levels of serum α-fetoprotein or microscopic foci of yolk sac tumor are present. This experience strongly supports avoiding the long-term effects of chemotherapy in most children with ovarian immature teratoma by reserving postoperative therapy for cases with relapse. (Am J Obstet Gynecol 1999;181:353-8.)

Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors

Neuraxis radiation therapy (RT) for primary intracranial tumors is associated with major late effects if administered to very young children. To control residual tumor and to delay RT, we treated eight young children (median age 6.5 months) with primary central nervous system (CNS) tumors using combination chemotherapy: cisplatin, 20 mg/M2/day plus VP-16, 75 mg/M2/day i.v. for 5 days, given q. 3-6 weeks for 8 cycles. The tumors were medulloblastoma (one), malignant ependymoma (two), primitive neuroectodermal tumor PNET (two), malignant glioma (two), astrocytoma (one). Six had measurable disease; three had positive cerebrospinal fluid (CSF) cytopathology. All patients with measurable tumor had initial objective responses (three) complete response [CR], one partial response [PR], two minor response [MR], including cytopathology (three CR of three) and metastatic deposits (two CR of two). One patient relapsed during chemotherapy. Median time to disease progression was 17.5 months; median survival was 34 months. Three patients, none of whom received RT, have prolonged progression-free intervals of 47-67 months to date. Neurodevelopmental progress continued during and after chemotherapy. Chemotherapy toxicity was mild. Median neutrophil nadir was 312/mm3, platelets 72,000. Fever during neutropenia occurred in six of 61 courses. Moderate high-frequency auditory losses were detected in three patients, and mild renal injury (GFR less than 70 ml/min) was detected in two of seven evaluable children. This pilot study demonstrates the apparent efficacy and mild toxicity of 5 day courses of cisplatin plus VP-16, with delayed RT, in young children with CNS neoplasms. A POG treatment protocol that incorporates cisplatin plus VP-16 is evaluating primary chemotherapy with delayed radiotherapy in larger numbers of pediatric brain tumor patients.