Adjuvant Treatment Strategies Research Articles

O18: AN EXPLORATION OF THE GENOME OF MUCINOUS ADENOCARCINOMA OF THE RECTUM

Abstract Introduction Mucinous adenocarcinoma (MA) of the rectum accounts for 5-15% of rectal cancers. This histological subtype has been shown to have a worse response to chemoradiotherapy and worse long term outcomes when compared to non-mucinous adenocarcinoma (NMA). The aim of this study was to compare the genomic landscape of rectal MA to rectal NMA. Method Using the BGISEQ PE100 platform, paired end whole genome sequencing was carried out on tumour and matched normal tissue from cases of MA. The Cancer Genome Atlas was interrogated to identify further cases of rectal MA and cases of rectal NMA with sequencing data that could be used as a control group. In-depth bioinformatic analysis was undertaken and the genomic landscapes of the two subtypes were compared. Result A total of 14 cases of MA were compared to 74 cases of NMA. The microsatellite instability-high rate in the MA group was 14.29% vs 4.05% in the NMA group. POLE mutations were found in 5.41% of the NMA group compared to 0.00% of the MA group. KRAS, BRAF and PIK3CA mutations were more frequent in the MA group whereas TP53 and APC mutations were more common in the NMA group. Significant differences between the groups were identified in the most frequently mutated genes. Copy number alteration, mutational signatures, structural variation and microbiome findings will also be described. Conclusion MA of the rectum is not just phenotypically distinct, it is a distinct genotype. This could have implications when considering neoadjuvant and adjuvant treatment strategies in the future. Take-home message Mucinous adenocarcinoma differs from a genomic perspective from non-mucinous adenocarcinoma and this may have implications for treatment strategies in the future

Cymbopogon citratus (DC.) Stapf, citral and geraniol exhibit anticonvulsant and neuroprotective effects in pentylenetetrazole-induced seizures in zebrafish

Ethnopharmacological relevanceCymbopogon citratus (DC.) Stapf (C. citratus) is consumed as an infusion in folk medicine due to its pharmacological properties and action in the central nervous system. Epilepsy is a neurological disorder that affects millions of people. Since the currently available antiepileptic drugs often cause undesirable side effects, new alternative therapeutic strategies based on medicinal plants have been proposed. Aim of the studyThis study aimed to investigate the anticonvulsant and neuroprotective effects of C. citratus essential oil (EO) and hydroalcoholic extract (E1) from its leaves, as well as of its related compounds citral (CIT) and geraniol (GER) against the effects of pentylenetetrazole (PTZ) induced seizures in zebrafish (Danio rerio). Materials and methodsTo evaluate the anticonvulsant properties of the samples, adult animals were pre-treated (by immersion) and subsequently exposed to PTZ solution. The involvement of GABAA receptors in the antiepileptic effects was investigated by the coadministration of flumazenil (FMZ), a known GABAA receptor antagonist. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and nitric oxide (NO) were assessed in zebrafish brain homogenates after PTZ exposure. ResultsAll samples increased the latency time for the first seizure, which was reduced when animals were pretreated with FMZ, suggesting the involvement of GABAA receptors in the observed properties. The association between CIT and GER at the lowest concentration studied showed a synergistic effect on the anticonvulsant activity. Decreases in MDA and NO levels and increases in GSH and CAT levels in the brain of treated animals suggested the neuroprotective effect of the compounds investigated. ConclusionsOur results proved that C. citratus EO, E1, CIT and GER have anticonvulsant effects in zebrafish and could be used as a promising adjuvant therapeutic strategy for epilepsy treatment. Furthermore, zebrafish demonstrated to be an alternative animal model of epilepsy to evaluate the anticonvulsant and neuroprotective effects of C. citratus.

Endoscopic resection with adjuvant treatment versus esophagectomy for early-stage esophageal cancer

ObjectiveTo evaluate the outcome following the strategy of endoscopic R0 resection (ER) plus adjuvant treatment (AT) versus esophagectomy for esophageal squamous cell cancer in T1a invading muscularis mucosa (M3)-T1b stage.MethodsWe evaluated the outcomes of 46 esophageal squamous cell cancer (ESCC) patients with T1aM3-T1b stage who underwent ER + AT from the Esophageal Cancer Endoscopic Therapy Consortium (ECETC) and compared these outcomes to 92 patients who underwent esophagectomy. Propensity score matching (1:2) was used, with overall survival (OS) and relapse-free survival (RFS) being compared between the two groups.ResultsDuring a median follow-up of 32 months, there were no statistical differences (P = 0.226) in OS between the two groups. The 1-, 2-, and 3-year overall survival in the esophagectomy group was 95%, 91%, and 84%, respectively. There were no mortalities within three years in the ER + AT group. The RFS between the two groups was also not significantly different (P = 0.938). The 1-, 2-, and 3-year RFS of patients in the esophagectomy group was 90%, 90%, and 83%, respectively, while it was 97%, 94%, and 74% in the ER + AT group, respectively. The local recurrence rates between the two groups were not significantly different (P = 0.277).ConclusionsThis first multicenter analysis showed similar outcomes were found regarding OS and RFS between the two groups in T1aM3-T1b stage patients. ER + AT may be considered in high-risk patients or for those who refuse esophagectomy.

Adjuvant Systemic Therapy after Chemoradiation and Brachytherapy for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis.

Simple SummaryThe standard of care for locally advanced cervical cancer is chemoradiation and brachytherapy. The addition of adjuvant systemic treatment may improve overall survival. A systematic review and meta-analysis were conducted to summarize evidence on survival outcomes, treatment completion and toxicity. Thirty-five articles reporting on 29 different studies were selected from a total of 612 articles published on this topic since 2000. Twelve studies on two different chemotherapy combinations (platinum–pyrimidine antagonist and platinum–taxane) were included for meta-analysis. Both these adjuvant chemotherapy combinations did not yield a survival benefit but did lead to more severe side-effects than chemoradiation only. Therefore, these adjuvant treatment strategies cannot be recommended for unselected patients with locally advanced cervical cancer. Most of the studies on other chemotherapeutic agents did not seem to provide a good balance between efficacy and toxicity either. The evidence on adjuvant immunotherapy for locally advanced cervical cancer is still immature.Background: Standard of care for locally advanced cervical cancer is chemoradiation and brachytherapy. The addition of adjuvant systemic treatment may improve overall survival. A systematic review and meta-analysis was conducted to summarize evidence on survival outcomes, treatment completion and toxicity. Methods: PubMed, EMBASE and Web of Science were systematically searched for relevant prospective and retrospective studies. Two authors independently selected studies, extracted data and assessed study quality. Pooled hazard ratios for survival endpoints were estimated using random effect models. Weighted averages of treatment completion and toxicity rates were calculated and compared by the Fisher exact test. Results: The search returned 612 articles; 35 articles reporting on 29 different studies on adjuvant chemotherapy or immunotherapy were selected for systematic review. Twelve studies on an adjuvant platinum–pyrimidine antagonist or platinum–taxane were included for meta-analysis. The pooled hazard ratios for overall survival were 0.76 (99%CI: 0.43–1.34, p = 0.22) and 0.47 (99%CI: 0.12–1.86, p = 0.16) for the addition of, respectively, a platinum–pyrimidine antagonist or platinum–taxane to chemoradiation and brachytherapy. Completion rates were 82% (95%CI: 76–87%) for platinum–pyrimidine antagonist and 74% (95%CI: 63–85%) for platinum–taxane. Severe acute hematological and gastro-intestinal toxicities were significantly increased by adding adjuvant chemotherapy to chemoradiation and brachytherapy. Conclusions: The addition of adjuvant platinum–pyrimidine antagonist or platinum–taxane after chemoradiation and brachytherapy does not significantly improve overall survival, while acute toxicity is significantly increased. These adjuvant treatment strategies can therefore not be recommended for unselected patients with locally advanced cervical cancer.

Postoperative Adjuvant Treatment Strategy for Locally Advanced Rectal Cancer after Neoadjuvant Treatment.

Background Neoadjuvant (chemo) radiotherapy is used as a standard treatment for locally advanced rectal cancer (LARC), but there is no general consensus on either the efficacy of postoperative adjuvant chemotherapy in patients with LARC after neoadjuvant treatment and surgery, or whether the addition of oxaliplatin to adjuvant chemotherapy provides survival benefits. Methods We performed a meta-analysis of data from the PubMed and Embase databases. We included patients with LARC who received neoadjuvant (chemo) radiotherapy and curative surgery. Overall survival (OS), disease-free survival (DFS), toxicity, and compliance were analyzed in the oxaliplatin/fluorouracil- (OX/FU-) based group compared with the FU-based group, and in the chemotherapy group compared with the observation group. Results Twenty studies were included in the analysis. Our results indicated that adjuvant chemotherapy prolonged OS (hazard ratio [HR] = 0.78, 95%CI = 0.67–0.91) in patients with LARC treated with neoadjuvant (chemo) radiotherapy and surgery compared with those in the observation group. Subgroup analysis showed the same results in both the ypStage II and ypStage III groups. Compared with those in the observation group, patients in the chemotherapy group also showed an increase in DFS (HR = 0.75, 95%CI = 0.60–0.93). No significant increase was observed in OS (HR = 1.04, 95%CI = 0.87–1.24) or DFS (HR = 0.98, 95%CI = 0.76–1.27) when oxaliplatin was added to FU-based adjuvant chemotherapy, as compared with the FU-based treatment, and subgroup analysis also indicated no survival benefits in the clinical stage II, clinical stage III, ypStage II, and ypStage III groups. Conclusions For patients with LARC who have already received neoadjuvant (chemo) radiotherapy and curative surgery, adjuvant chemotherapy improves OS over that in the observation group. Adding oxaliplatin to FU-based adjuvant chemotherapy does not confer survival benefits beyond those from FU-based adjuvant chemotherapy.

Adjuvant treatment strategy after curative resection for hepatocellular carcinoma.

Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.

CGAS promotes sepsis in radiotherapy of cancer by up-regulating caspase-11 signaling

Radiotherapy is the most common strategy in the treatment of cancer. However, radiation-induced acute complications, in particular sepsis, render patients in a life-threatening status or lead to delay of therapy that largely influences patients’ overall responses. The understanding of sepsis in radiotherapy is currently scant and effective medicine is not available by far. Here, with WT mice as control, we challenged mice deficient to cGas, Caspase-11, Gsdmd or Asc with cecal ligation and puncture (CLP, a sepsis model) after a treatment of thorax irradiation. We found that radiation robustly upgraded caspase-11 pathway in irradiated region and consequently deteriorated lung injury and mortality in the sepsis model. cGas knockout markedly attenuated radiation-upgraded caspase-11 and restored sepsis. Deficiency of non-canonical inflammasome, caspase-11 and the downstream GSDMD, rather than an AIM2 inflammasome component, ASC, dramatically protected against radiation-promoted injury and mortality in septic mice. The protection may attribute to the inhibition of caspase-11-mediated pyroptosis in endothelial cells of the lung. Thus, blocking cGAS/caspase-11 signaling would be an adjuvant treatment strategy for preventing sepsis in radiotherapy of cancer.

Mechanisms by Which Probiotic Bacteria Attenuate the Risk of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second leading cause of cancer-related deaths worldwide. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) are the major extrinsic risk factors of HCC development. Genetic background is pivotal in HCC pathogenesis, and both germline mutations and single nucleotide polymorphism (SNP) are intrinsic risk factors of HCC. These HCC risk factors predispose to hepatic injury and subsequent activation of fibrogenesis that progresses into cirrhosis and HCC. Probiotic bacteria can mitigate HCC risk by modulating host gut microbiota (GM) to promote growth of beneficial microbes and inhibit HCC-associated dysbiosis, thus preventing pathogen-associated molecular patterns (PAMPs)-mediated hepatic inflammation. Probiotics have antiviral activities against HBV and HCV infections, ameliorate obesity and risk of NAFLD/NASH, and their antioxidant, anti-proliferative, anti-angiogenic, and anti-metastatic effects can prevent the HCC pathogenesis. Probiotics also upregulate the expression of tumor suppressor genes and downregulate oncogene expression. Moreover, metabolites generated by probiotics through degradation of dietary phytochemicals may mitigate the risk of HCC development. These multiple anticancer mechanisms illustrate the potential of probiotics as an adjuvant strategy for HCC risk management and treatment.

A Randomized Controlled Trial on the Effectiveness of Epidermal Growth Factor-Containing Ointment on the Treatment of Solar Lentigines as Adjuvant Therapy.

Background and Objective: Little is known about the anti-pigmentation effects of whitening agents on solar lentigines. Epidermal growth factor (EGF) has been used as a booster for wound healing in the skin, and it has been suggested to have anti-pigmentation effects. This study aimed to evaluate the effect and safety of EGF-containing ointment for treating solar lentigines with a Q-switched (QS) 532 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (Bluecore company, Seoul, Republic of Korea). Materials and Methods: Subjects who underwent QS 532 nm Nd:YAG laser treatment of solar lentigines were randomly assigned to treatment with an EGF ointment or petrolatum. After the laser procedure, the subjects were administered the test ointment twice a day for 4 weeks. The physician’s assessment of the degree of pigment clearance and patient’s satisfaction were assessed after 4 and 8 weeks. Additionally, the melanin index (MI), erythema index (EI), transepidermal water loss (TEWL), and post-inflammatory hyperpigmentation (PIH) were evaluated. This trial was registered with ClinicalTrials.gov (NCT04704245). Results: The blinded physician’s assessment using 5-grade percentage improvement scale and patient’s satisfaction were significantly higher in the study group than in the control group at the 4th and 8th weeks. The MI was significantly higher in the control group than in the study group at the 4th and 8th weeks. The EI and TEWL did not differ significantly between the two groups at either time point. The incidence of PIH was higher in the control group (37.5%) than in the EGF group (7.14%) at the 8th week. Conclusions: The application of EGF-containing ointment on facial solar lentigines with a QS 532 nm Nd:YAG laser showed efficient and safe therapeutic effects, with less PIH. Thus, EGF-containing ointment could be suggested as the promising adjuvant treatment strategy with a QS laser for solar lentigines.

Chinese herbal medicine injections (CHMIs) for chronic pulmonary heart disease: A protocol for a Bayesian network meta-analysis.

Background:Chinese herbal medicine injections (CHMIs) are frequently used for various refractory diseases including chronic pulmonary heart disease (CPHD). However, due to the diversity of CHMIs treatments, its relative effectiveness and safety remain unclear. In our study, Bayesian network meta-analysis will be used to identify differences in efficacy and safety between diverse CHMI for CPHD.Methods:Relevant randomized controlled trials (RCTs) and prospective controlled clinical trials published in PubMed, Google Scholar, Excerpt Medica Database, Medline, Cochrane Library, Web of Science, China Scientific Journal Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang Database will be systematic searched to identify eligible studies from their establishment to December 2020. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool. Stata14.2 and WinBUGS 1.4.3 software were used for data synthesis. The evidentiary grade of the results will be also evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Results:The results of this study will be published in a peer-reviewed journal, and provide reliable evidence for different CHMIs on CPHD.Conclusions:The findings will provide reference for evaluating the efficacy and safety of different CHMIs for CPHD, and provide a helpful evidence for clinicians to formulate the best adjuvant treatment strategy for CPHD patients.Trial registration number:INPLASY2020120004.

Updates on adjuvant and neoadjuvant treatment strategies for surgically resectable and borderline resectable pancreatic ductal adenocarcinoma.

Pancreatic cancer is the third leading cause of cancer-related mortality in the US. Outcomes for patients with pancreatic cancer are poor as curative approaches are only available to the minority of patients who have localized tumors for which surgery may be an option. The past decade has established fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) as the new standard of care following resection for fit patients with resectable pancreatic tumors. However, most patients will relapse and a large number of patients treated with upfront resection are unable to receive or complete adjuvant chemotherapy. There is therefore considerable interest in neoadjuvant treatment strategies for patients with resectable and borderline resectable pancreatic cancer as a way to provide early systemic treatment of micrometastatic disease, facilitate lymph node downstaging, and increase the likelihood of negative resection margins (R0). This review will focus on key aspects of completed trials evaluating adjuvant therapy in resectable pancreatic cancer and will provide an overview of emerging evidence supporting the use of neoadjuvant treatment strategies for both resectable and borderline resectable pancreatic cancer.

Promotion of vascular integrity in sepsis through modulation of bioactive adrenomedullin and dipeptidyl peptidase 3.

Sepsis represents one of the major medical challenges of the 21st century. Despite substantial improvements in the knowledge on pathophysiological mechanisms, this has so far not translated into novel adjuvant treatment strategies for sepsis. In sepsis, both vascular tone and vascular integrity are compromised, and contribute to the development of shock, which is strongly related to the development of organ dysfunction and mortality. In this review, we focus on dipeptidyl peptidase 3 (DPP3) and adrenomedullin (ADM), two molecules that act on the vasculature and are involved in the pathophysiology of sepsis and septic shock. DPP3 is an ubiquitous cytosolic enzyme involved in the degradation of several important signalling molecules essential for regulation of vascular tone, including angiotensin II. ADM is a key hormone involved in the regulation of vascular tone and endothelial barrier function. Previous studies have shown that circulating concentrations of both DPP3 and ADM are independently associated with the development of organ failure and adverse outcome in sepsis. We now discuss new evidence illustrating that these molecules indeed represent two distinct pathways involved in the development of septic shock. Recently, both ADM‐enhancing therapies aimed at improving endothelial barrier function and vascular tone and DPP3‐blocking therapies aimed at restoring systemic angiotensin responses have been shown to improve outcome in various preclinical sepsis models. Given the current lack of effective adjuvant therapies in sepsis, additional research on the therapeutic application of these peptides in humans is highly warranted.

Multimodal Risk-Adapted Treatment in Surgical Patients With Synovial Sarcoma: A Preoperative Nomogram-Guided Adjuvant Treatment Strategy.

Background: Synovial sarcoma is characterized by heterogeneous clinical manifestations, making it difficult to evaluate individual patients' prognoses and design personal treatment schemes. We established an effective preoperative nomogram to predict cancer-specific survival (CSS) and present a risk-adapted adjuvant treatment strategy in surgical patients with synovial sarcoma.Methods: This retrospective study included patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with synovial sarcoma between 1996 and 2015. The patients were randomly divided into training and validation groups. The predictors were selected using univariate and multivariate Cox hazards models. The nomogram performance was verified for its discriminatory ability and calibration. We further stratified the patients into different risk groups according to the nomogram scores and compared the efficacy of chemotherapy, radiotherapy, and combination of radiotherapy and chemotherapy.Results: There were 915 patients enrolled in our study, with 874 patients either alive or dead due to synovial sarcoma. We established a nomogram to predict 5-year CSS based on independent factors, including sex, age, grade, tumor size, location, and extent (all p < 0.05). Our model showed a consistently good discriminatory ability and calibration for predicting 5-year CSS in both the training (c-index = 0.78, 95% CI 0.75–0.81) and validation (c-index = 0.73, 95% CI 0.68–0.78). Based on their nomogram scores, we divided patients into 5 groups. Compared to patients without adjuvant treatment, nomogram I patients with adjuvant treatment had no improvements in 5-year CSS (100.0% vs. 100.0%), nomogram II patients had higher 5-year CSS with radiotherapy or chemotherapy (92.9% vs. 72.2%, p = 0.015), nomogram III patients had higher 5-year CSS with combination of chemotherapy and radiotherapy (70.1% vs. 47.2%, p = 0.004), nomogram IV patients had higher 5-year CSS with radiotherapy (41.3% vs. 15.6%, p = 0.015), and nomogram V patients had no improvements in 5-year CSS rates with adjuvant treatment (28.9% vs. 16.9%, p = 0.18).Conclusion: The nomogram showed a satisfactory discriminatory ability and calibration for predicting 5-year CSS in synovial sarcoma patients. Based on this nomogram, we stratified synovial sarcoma patients according to risk levels, which enabled us to provide a useful grouping scheme that can inform multimodal risk-adapted treatment in synovial sarcoma.

Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)–Positive Breast Cancer

The neoadjuvant treatment options for ERBB2-positive (also known as HER2-positive) breast cancer are associated with different rates of pathologic complete response (pCR). The KATHERINE trial showed that adjuvant trastuzumab emtansine (T-DM1) can reduce recurrence in patients with residual disease compared with patients treated with trastuzumab; however, T-DM1 and other ERBB2-targeted agents are costly, and understanding the costs and health consequences of various combinations of neoadjuvant followed by adjuvant treatments in the United States is needed. To examine the costs and disease outcomes associated with selection of various neoadjuvant followed by adjuvant treatment strategies for patients with ERBB2-positive breast cancer. In this economic evaluation, a decision-analytic model was developed to evaluate various neoadjuvant followed by adjuvant treatment strategies for women with ERBB2-positive breast cancer from a health care payer perspective in the United States. The model was informed by the KATHERINE trial, other clinical trials with different regimens from the KATHERINE trial, the Flatiron Health Database, McKesson Corporation data, and other evidence in the published literature. Starting trial median age for KATHERINE patients was 49 years (range, 24-79 years in T-DM1 arm and 23-80 years in trastuzumab arm). The model simulated patients receiving 5 different neoadjuvant followed by adjuvant treatment strategies. Data analyses were performed from March 2019 to August 2020. There were 4 neoadjuvant regimens: (1) HP: trastuzumab (H) plus pertuzumab (P), (2) THP: paclitaxel (T) plus H plus P, (3) DDAC-THP: dose-dense anthracycline/cyclophosphamide (DDAC) plus THP, (4) TCHP: docetaxel (T) plus carboplatin (C) plus HP. All patients with pCR, regardless of neoadjuvant regimen, received adjuvant H. Patients with residual disease received different adjuvant therapies depending on the neoadjuvant regimen according to the 5 following strategies: (1) neoadjuvant DDAC-THP followed by adjuvant H, (2) neoadjuvant DDAC-THP followed by adjuvant T-DM1, (3) neoadjuvant THP followed by adjuvant DDAC plus T-DM1, (4) neoadjuvant HP followed by adjuvant DDAC/THP plus T-DM1, or (5) neoadjuvant TCHP followed by adjuvant T-DM1. Lifetime costs in 2020 US dollars and quality-adjusted life-years (QALYs) were estimated for each treatment strategy, and incremental cost-effectiveness ratios were estimated. A strategy was classified as dominated if it was associated with fewer QALYs at higher costs than the alternative. In the base-case analysis, costs ranged from $415 833 (strategy 3) to $518 859 (strategy 4), and QALYs ranged from 9.67 (strategy 1) to 10.73 (strategy 3). Strategy 3 was associated with the highest health benefits (10.73 QALYs) and lowest costs ($415 833) and dominated all other strategies. Probabilistic analysis confirmed that this strategy had the highest probability of cost-effectiveness (>70% at willingness-to-pay thresholds of $0-200,000/QALY) and was associated with the highest net benefit. These results suggest that neoadjuvant THP followed by adjuvant H for patients with pCR or followed by adjuvant DDAC plus T-DM1 for patients with residual disease was associated with the highest health benefits and lowest costs for women with ERBB2-positive breast cancer compared with other treatment strategies considered.

Combined Adjuvant Chemotherapy and Radiation Therapy Improves Disease-Free Survival for Uterine Serous Cancer

PurposeUterine serous carcinoma (USC) is a rare but aggressive endometrial cancer histology. We reviewed outcomes for patients with USC to identify the best adjuvant treatment strategy. Methods and MaterialsWe retrospectively identified 162 patients with The International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA USC treated at our institution. Baseline characteristics, treatment details, clinical outcomes, and toxicity data were recorded. ResultsMedian follow-up was 3.4 years (0.3-26 years). A variety of adjuvant therapy strategies were employed: 14% no adjuvant therapy, 28% radiation alone, 15% chemotherapy alone, and 43% combined chemotherapy and radiation. Distant metastasis was the most common type of recurrence (37% at 5 years). For patients with stage I-IVA disease, there were no significant differences in outcomes by treatment type. For patients with stage I-II disease (70% of the cohort), disease-free survival was significantly higher after chemotherapy (alone or with radiation therapy, P = .005) and after combined chemotherapy and radiation compared with all other treatments (P = .025). Toxicity outcomes were favorable, with minimal grade 3 and no grade 4 or 5 events. ConclusionsPatients with USC experience high rates of recurrence and mortality. Distant metastasis is the most common pattern of failure for all stages. For patients with early-stage disease, combined chemotherapy and radiation improves 5-year disease-free survival compared with either single adjuvant treatment alone or no adjuvant treatment. The relatively large group of patients with USC included in this study may account for our ability to detect this improvement whereas clinical trials have failed to do so, possibly owing to the relatively small percentages of patients with USC enrolled.

Clinical Features and Treatment Outcome of Resectable Pulmonary Large Cell Neuroendocrine Carcinoma

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine carcinoma of the lung that accounts for only 1% to 3% of all lung cancers and was re-classified as a distinct neuroendocrine group. There is an emerging need for an agreement on the best strategy for managing pulmonary LCNEC. Here, we reviewed our institutional experiences and tried to suggest the appropriate treatment directions for resectable pulmonary LCNEC. A total of 72 patients were pathologically diagnosed as pulmonary LCNEC between January 2005 and December 2018 in the Yonsei cancer center. We considered curative surgery first for patients with early-stage tumors or some advanced-stage tumors with resectable status, unless they were medically inoperable. Adjuvant treatment option was decided after considering each patient’s clinical and pathologic features. Consequently, 39 patients with stage I to III LCNEC (I: 18, II: 12, III: 9) underwent curative resection of the primary tumor, and these patients were included in this study cohort. In stage I, 6 (33%) patients received surgery alone, and 12 (67%) patients received adjuvant chemotherapy. In stage II, 2 (17%) patients received surgery alone and 10 (83%) patients received adjuvant chemotherapy. In stage III, only 1 (11%) patient received surgery alone, and 8 (89%) received adjuvant treatment, include 6 with adjuvant chemotherapy, 2 with sequential chemotherapy and radiotherapy (RT), and 1 with adjuvant concurrent chemoradiotherapy. With a median follow-up of 30 months, the median overall survival (OS) was 58.8 months and 3-year, 5-year rates were 58% and 47%, respectively. The median recurrence-free survival (RFS) was 24 months and 3-, and 5-year rates were 47% and 39%, respectively. In the univariate analysis for OS, older age (≥67) and SCLC-mixed histology were poor prognostic factors (p = 0.019, p = 0.001 (vs. pure LCNEC), and 0.015 (vs. NSCLC-mixed)), respectively. These 2 factors were independently associated with OS also in multivariate analysis (p = 0.036, 0.003, and 0.015). SCLC-mixed histology was the only significant factor for poor RFS. In the entire cohort, recurrences occur in 17 patients (44%). Most of the recurrence patterns were very extensive even at first recurrence; 14 distant metastases (m/c, 82%), 8 local recurrences, and 8 regional (all mediastinal lymph node) recurrences. Our study demonstrated that surgery ± adjuvant treatment could achieve favorable survival outcomes in pulmonary LCNEC. Some factors such as older age and mixed histology with SCLC made the overall prognosis worse, regardless of the stage, which proposed the need for adjuvant treatment strategies by a multidisciplinary approach. More aggressive treatments than NSCLC as mediastinal RT for node-positive patients, new chemotherapy regimens, or prophylactic cranial irradiation could be considered. Further studies in a larger cohort would be needed to draw more definitive conclusions.

Traditional Chinese medicine for oral squamous cell carcinoma: A Bayesian network meta-analysis protocol.

Background:Traditional Chinese medicine is frequently used for malignant tumors in China, but in clinical practice, most practitioners choose appropriate Chinese medicines based on personal experience. In our study, Bayesian network meta-analysis will be used to identify differences in efficacy and safety between diverse traditional Chinese drugs for oral squamous cell carcinoma (OSCC).Methods:Relevant randomized controlled trials and prospective controlled clinical trials were searched from Medline, PubMed, Cochrane Library, Google Scholar, Excerpt Medica Database, Web of Science, China National Knowledge Infrastructure, China Scientific Journal Database, Chinese Biomedical Literature Database, and Wanfang Database from their establishment to September 2020. Study selection and data extraction will be performed independently by 2 researchers. Aggregate Data Drug Information System and R software were used for data synthesis. The evidentiary grade of the results will be also evaluated.Results:The results of this study will be published in a peer-reviewed journal, and provide reliable evidence for different traditional Chinese drugs on OSCC.Conclusions:The findings will provide reference for evaluating the efficacy and safety of different traditional Chinese medicine for OSCC, and provide a helpful evidence for clinicians to formulate the best adjuvant treatment strategy for OSCC patients.Trial registration number:INPLASY202090082.

Predicting therapy response by analysis of metastasis founder cells: emerging perspectives for personalized tumor therapy

ABSTRACT Introduction Circulating tumor and disseminated cancer cells can be detected after surgical removal of the primary tumor in non-metastatic patients. Despite being considered the prime targets of adjuvant therapy, they have not been implemented into clinical decision making yet. Areas covered Here we review the recent progress in understanding the biology of circulating tumor cells and disseminated cancer cells as well as the technical challenges associated with quantification, isolation, and preclinical model development. We highlight the first examples of clinical studies in which metastasis founder cells have been used as surrogate markers in adjuvant cancer patients and address the current hurdles in implementing these in routine clinical application. Finally, we provide a perspective on how the combination of technologies to detect and isolate metastasis founders, single-cell multi-omics, development of preclinical models, and their drug responses in specific niches could improve personalized adjuvant treatment strategies. Expert opinion The specific target cells of adjuvant cancer treatment are metastasis founder cells that remain in the body of the patients after surgical removal of the primary tumor. We, therefore, believe that the success of adjuvant therapies will be improved by implementing circulating and disseminated cancer cells in future clinical decision making.

Transcatheter hepatic arterial chemoembolization combined with Kangai injection for hepatitis B virus-related hepatocellular carcinoma: A protocol for a PRISMA-compliant meta-analysis.

Kangai injection, a well-known insect-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy and safety of Kangai injection for patients with HBV-related HCC through the meta-analysis. All available randomized controlled trials (RCTs) and high-quality prospective cohort studies that investigated the efficacy and safety of Kangai injection for patients with HBV-related HCC were searched from ten electronic databases including Google Scholar, PubMed, Excerpt Medica Database (Embase), Cochrane Library, Medline, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJ) Chinese, Biomedical Literature Database (CBM) and Wanfang Database. Papers in Chinese or English published from January 2000 to September 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 researchers. The clinical outcomes including overall response rate (ORR), disease control rate (DCR), quality of life (QoL), clinical symptoms, virological indicators, immune function and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the literatures was also evaluated. The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HBV-related HCC patients. Our study will draw an objective conclusion of the efficacy of Kangai injection on curative effect (ORR and DCR), clinical symptoms, virological indicators, QoL, and immune function in patients with HBV-related HCC. INPLASY202090014.

Growth Inhibition of Nasopharyngeal Carcinoma Cells Mediated by p53 Gene-Containing Nanolipid Composites.

To study the growth inhibition and cell cycle changes in nasopharyngeal carcinoma (CNE1) cells after transfection with p53 gene. A mixture of nano-liposomes and plasmid containing p53 was used for transfecting CNE1 cells. Cellular apoptosis was examined after transfection using the CCK-8 reagent method with flow cytometry. The results showed that a ratio of nanoliposome/p-ORF-GFP of 3.5:1 showed the highest transfection efficiency in CNE1 cells. The cells transfected with a mixture of composites in this proportion showed significant apoptosis of up to 50-70%. In addition, we observed that cell cycle changes-measured using flow cytometry-as well as cellular apoptosis were accelerated after administration of composites. The CCK-8 kit was used to determine the viability of nano-liposome-encapsulated p53 transfected cells. In vitro experiments showed that the combination significantly inhibited the growth of CNE1 cells with an inhibition rate of approximately 63.8%. Therefore, the nanocomposites have a significant effect on inhibiting the growth of CNE1 cells. Through the investigation of apoptosis and cell cycle changes in CNE1 cells we found that the nanoliposome-encapsulated p53 gene can inhibit growth in these cells, and might therefore serve as a novel treatment strategy for adjuvant treatment of nasopharyngeal carcinoma and ca also reduce incompatibility issues with radiotherapy and chemotherapy. This method can also provide technical and theoretical support for the development of novel drugs.