Effective Adjuvant Chemotherapy Research Articles

Impact of D2 Total Gastrectomy Including Splenectomy for Scirrhous Gastric Cancer in the Era of Effective Adjuvant Chemotherapy.

Total gastrectomy with D2 dissection including splenectomy (TGS) is usually selected for locally resectable scirrhous gastric cancer (SGC), which was established in the era of surgery alone. However, it remains unclear whether TGS for SGC is justified in the era of effective adjuvant chemotherapy. This study included 112 SGC patients, consisting of 60 cases treated between January 2000 and December 2006 (Former group), and 52 cases treated between January 2007 and December 2016 (Latter group). We collected clinicopathological data and then examined the survival and the therapeutic value indexes. The background characteristics were well-balanced, except for sex and physical status. The Latter group might be characterized by frequent female (P = 0.037) and poorer physical status (P = 0.048). Adjuvant chemotherapy was administered to 86.5% of the Latter group and was 11.7% of the Former group (P < 0.001). The 5-year-overall survival rate of the Latter group was 58.7% (95% confidence interval: 43.5-71.1), seems better than that of the Former group (44.5%; 95% confidence interval 31.7-56.6) (hazard ratio = 0.758, P = 0.291). Improvement of the index from the Former group was observed in the Latter group at almost all stations. The ratio of the index between two groups was 1.42 at the D1 station and 1.67 at the D2 station. Index of splenic hilar node ranked similarly high in both groups. The therapeutic value index was improved in almost all nodal stations by S-1 adjuvant chemotherapy, especially in D2 nodes. TGS would be more important for locally resectable SGC in the era of effective adjuvant chemotherapy.

Drug sensitivity tumor cell clusters in malignant peritoneal mesothelioma.

To explore the most effective adjuvant chemotherapy regimen for malignant peritoneal mesothelioma (MPM) through patient derived tumor-like cell clusters (PTC) drug sensitivity test. PTC were cultured in vitro with intraoperative specimens, and drug sensitivity test was performed to calculate the most effective chemotherapy regimen for MPM. The patients were divided into conventional and individualized chemotherapy group according to whether they received PTC drug testing. Univariate and multivariate analyses were conducted to identify independent prognostic factors. Among 186 MPM patients included, 63 underwent PTC culture and drug sensitivity test. The results showed that the most effective chemotherapy regimen was oxaliplatin + gemcitabine. After propensity score matching, a total of 64 patients were enrolled in the following study, including 32 patients receiving individualized chemotherapy guided by PTC drug results as group 1 and 32 patients receiving conventional chemotherapy as group 2. Survival analysis showed that the median OS of group 1 was not reached, significantly longer than that of group 2 (23.5 months) (p < 0.05). Compared with conventional chemotherapy, individualized chemotherapy guided by PTC drug sensitivity tests can prolong patient survival, and oxaliplatin + gemcitabine + apatinib could be the optimal adjuvant treatment regimen for MPM.

Prognostic and predictive value of human equilibrative nucleoside transporter 1 (hENT1) in extrahepatic cholangiocarcinoma: a translational study.

Introduction: Effective (neo) adjuvant chemotherapy for cholangiocarcinoma is lacking due to chemoresistance and the absence of predictive biomarkers. Human equilibrative nucleoside transporter 1 (hENT1) has been described as a potential prognostic and predictive biomarker. In this study, the potential of rabbit-derived (SP120) and murine-derived (10D7G2) antibodies to detect hENT1 expression was compared in tissue samples of patients with extrahepatic cholangiocarcinoma (ECC), and the predictive value of hENT1 was investigated in three ECC cell lines. Methods: Tissues of 71 chemonaïve patients with histological confirmation of ECC were selected and stained with SP120 or 10D7G2 to assess the inter-observer variability for both antibodies and the correlation with overall survival. Concomitantly, gemcitabine sensitivity after hENT1 knockdown was assessed in the ECC cell lines EGI-1, TFK-1, and SK-ChA-1 using sulforhodamine B assays. Results: Scoring immunohistochemistry for hENT1 expression with the use of SP120 antibody resulted in the highest interobserver agreement but did not show a prognostic role of hENT1. However, 10D7G2 showed a prognostic role for hENT1, and a potential predictive role for gemcitabine sensitivity in hENT1 in SK-ChA-1 and TFK-1 cells was found. Discussion: These findings prompt further studies for both preclinical validation of the role of hENT1 and histochemical standardization in cholangiocarcinoma patients treated with gemcitabine-based chemotherapy.

Effect of Epirubicin Plus Paclitaxel vs Epirubicin and Cyclophosphamide Followed by Paclitaxel on Disease-Free Survival Among Patients With Operable ERBB2-Negative and Lymph Node–Positive Breast Cancer

Adjuvant therapy is an important and effective treatment for breast cancer. However, there is a lack of head-to-head clinical trials comparing the regimens epirubicin plus paclitaxel (EP) vs epirubicin and cyclophosphamide followed by paclitaxel (EC-P) in breast cancer. To evaluate the noninferiority of a cyclophosphamide-free (EP) regimen compared with the standard EC-P regimen for patients with operable hormone receptor-positive, ERBB2 (formerly HER2)-negative, lymph node-positive breast cancer. This prospective, open-label, phase 3, noninferiority randomized clinical trial was conducted from June 1, 2010, to June 30, 2016, in the Cancer Hospital, Chinese Academy of Medical Sciences, Beijing. Patients with hormone receptor-positive, ERBB2-negative, lymph node-positive operable breast cancer were included and randomized into 2 treatment groups. Data were analyzed from June 30, 2016, to November 1, 2022. Patients received adjuvant epirubicin (75 mg/m2) and paclitaxel (175 mg/m2) every 3 weeks for 6 cycles (EP regimen) or epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for 4 cycles followed by paclitaxel (175 mg/m2) every 3 weeks for 4 cycles (EC-P regimen) as the intention-to-treat (ITT) population. The primary outcome was disease-free survival (DFS), and the secondary outcomes included overall survival (OS), distant DFS, and safety. A total of 900 patients were registered, and 813 eligible patients (median age, 48 [IQR, 41-56] years) were randomly assigned to the EP group (n = 407) or the EC-P group (n = 406) after the surgical procedure. Through a median follow-up of 93.6 (IQR, 60.9-114.1) months, the hazard ratio (HR) of DFS for EP vs EC-P was 0.82 (95% CI, 0.62-1.10; 5-year DFS, 86.0% vs 80.6%; noninferior P = .001). The 5-year OS for the ITT population treated with the EP or the EC-P regimen was 94.7% vs 95.0%, respectively (HR, 0.95 [95% CI, 0.61-1.49]). Patients in the EP group had more frequent toxic effect events than those in the EC-P group. In this prospective, open-label, phase 3, randomized clinical trial, the EP regimen was noninferior to the EC-P regimen. These findings supported that the EP regimen could be an effective adjuvant chemotherapy regimen for women with ERBB2-negative breast cancer. ClinicalTrials.gov Identifier: NCT01134523.

Impact of D2 Gastrectomy for Locally Advanced Gastric Cancer in the Era of Effective Adjuvant Chemotherapy.

Gastrectomy with D2 dissection has been established as the standard procedure for locally advanced gastric cancer in the era of surgery alone. However, no consideration has been given to the efficacy of dissection in the era of effective adjuvant chemotherapy. This study included 1298 advanced gastric cancer patients, consisting of 725 cases treated between January 2000 and December 2006 (Former group), and 573 cases treated between January 2007 and July 2015 (Latter group). Clinicopathological data were collected, survival and the therapeutic value index were determined. The background characteristics were well balanced, except for age, tumor location, and intraoperative blood loss. The Latter group showed the following characteristics: an older population (p < 0.001), a frequent upper location (p = 0.008), and less blood loss (p < 0.001). Adjuvant chemotherapy was administered to 75.2% of the Latter group and was 9.4% in the Former group. The 5-year overall survival rate of the Latter group was 75.7% (95% confidence interval: 71.7-79.1), significantly better than that of the Former group (70.0%, 95% confidence interval: 66.5-73.2) (p = 0.025). Improvement in the index from the Former group was observed in the Latter group at almost all stations. The ratio of the index between these two groups was 1.09 at the D1 station and 1.19 at the D2 station. The therapeutic value index was improved in all nodal stations by S-1 adjuvant chemotherapy, regardless of whether the D1 or D2 nodes were involved. D2 gastrectomy would be still important for locally advanced gastric cancer in the era of effective adjuvant chemotherapy.

Benefits from Adjuvant Chemotherapy in Patients with Resected Non-Small Cell Lung Cancer: Possibility of Stratification by Gene Amplification of ACTN4 According to Evaluation of Metastatic Ability.

Simple SummaryThe establishment of biomarkers that can identify individuals at high risk of early recurrence after surgery will be an important issue in decision-making for perioperative therapy. In this review, we describe potential biomarkers for predicting the likelihood of recurrence in patients who undergo surgery for stage I NSCLC. ACTN4 is a possible biomarker for identifying patients at high risk of postoperative recurrence, and patients with gene amplification of ACTN4 might thus benefit the most from adjuvant chemotherapy.Surgical treatment is the best curative treatment option for patients with non-small cell lung cancer (NSCLC), but some patients have recurrence beyond the surgical margin even after receiving curative surgery. Therefore, therapies with anti-cancer agents also play an important role perioperatively. In this paper, we review the current status of adjuvant chemotherapy in NSCLC and describe promising perioperative therapies, including molecularly targeted therapies and immune checkpoint inhibitors. Previously reported biomarkers of adjuvant chemotherapy for NSCLC are discussed along with their limitations. Adjuvant chemotherapy after resective surgery was most effective in patients with metastatic lesions located just outside the surgical margin; in addition, these metastatic lesions were the most sensitive to adjuvant chemotherapy. Thus, the first step in predicting patients who have sensitivity to adjuvant therapies is to perform a qualified evaluation of metastatic ability using markers such as actinin-4 (ACTN4). In this review, we discuss the potential use of biomarkers in patient stratification for effective adjuvant chemotherapy and, in particular, the use of ACTN4 as a possible biomarker for NSCLC.

HER-2-mediated nano-delivery of molecular targeted drug potently suppresses orthotopic epithelial ovarian cancer and metastasis

The treatment of epithelial ovarian cancer (EOC) has made slow progress due to absence of effective adjuvant chemotherapy that is capable of preventing tumor relapse and metastasis. Molecular targeted drugs such as PARP and PLK1 inhibitors appear to be promising new treatments for EOC. The low EOC cell uptake, poor selectivity and pronounced toxicity, however, greatly compromise their clinical efficacy. Herein, we report that HER-2-mediated nano-delivery of clinical PLK1-targeted drug, volasertib (Vol), while causing little toxicity potently suppresses orthotopic EOC and metastasis. Anti-HER-2 antibody, trastuzumab (Tra), was conjugated onto Vol-loaded polymersomes via click chemistry yielding Tra-PVol with a size of 33 nm and optimally about 5 Tra per polymersome. Tra-PVol exhibited clearly stronger uptake and anti-tumor activity (IC50 = 59 nM) in HER-2 overexpressing SKOV-3 cells than free Vol and non-targeted PVol controls. Both biodistribution and therapeutic studies in orthotopic SKOV-3-Luc tumor-bearing mice displayed that Tra-PVol induced significantly better tumor deposition and retardation than PVol and that intraperitoneal administration outperformed intravenous administration. More interestingly, Tra-PVol was shown to effectively suppress the intraperitoneal metastasis and to markedly prolong the survival time of SKOV-3-Luc tumor-bearing mice. This HER-2 directed molecular therapy emerges as a potential treatment strategy toward EOC.

Effectiveness of the Sanyin Formula Plus Chemotherapy on Survival in Women With Triple-Negative Breast Cancer: A Randomized Controlled Trial.

PurposeTo evaluate the efficacy of the Sanyin formula (SYF) plus conventional standard chemotherapy in operable triple-negative breast cancer (TNBC) patients, a randomized controlled trial was implemented at 5 hospitals and cancer centers in China between May 23, 2016, and October 31, 2019.Materials and MethodsFemale patients aged 18 to 80 years with operable TNBC after definitive surgery were screened and enrolled. The exclusion criteria included metastatic disease, other tumors, or locally advanced disease. Patients were randomly divided into groups SYF plus conventional standard chemotherapy and placebo plus conventional standard chemotherapy at a ratio of 1:1. The primary endpoint of the investigation was disease-free survival (DFS), and secondary endpoints included overall survival (OS) and toxicity.ResultsA total of 252 operable female TNBC patients were randomized to receive SYF plus conventional standard chemotherapy (N = 127) or a placebo plus conventional standard chemotherapy (N = 125). At a median follow-up of 51 months, 5-year DFS time was longer in those assigned to SYF plus conventional standard chemotherapy compared with placebo plus conventional standard chemotherapy (94.2%vs 85.5%, hazard ratio [HR] = 0.40; 95%CI, 0.17-0.97; P = 0.034). The absolute benefit for 5-year DFS was 8.7% in the SYF plus conventional standard chemotherapy group. No statistically significant difference was observed in OS between the two groups (P = 0.23). Patients with negative node status benefited more from SYF plus conventional standard chemotherapy treatment (HR = 0.21, P-interaction = 0.013) in accordance with the exploratory subgroup analyses of DFS.ConclusionsThe results of the present study suggest that the traditional Chinese medicine SYF plus conventional chemotherapy regimens is an effective alternative adjuvant chemotherapy strategy for female operable TNBC patients.Clinical Trial Registrationhttps://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR-IPR-16008590.

Perihilar cholangiocarcinoma: a surgeon's perspective

Perihilar cholangiocarcinoma (PHC) is defined anatomically as tumors located in the extrahepatic biliary tree proximal to the origin of the cystic duct. However, as the boundary between the extrahepatic and intrahepatic bile ducts is not well defined, PHC potentially includes two types of tumors: one is the extrahepatic type, which arises from the large hilar bile duct, and the other is the intrahepatic type, which has an intrahepatic component with invasion of the hepatic hilus. The new American Joint Commission on Cancer tumor-node-metastasis staging system for PHC was well revised; an important revision is that the Bismuth type IV was removed from T4 stage determinants. Most patients with PHC present with obstructive jaundice, and preoperative biliary drainage is mandatory. Previously, percutaneous transhepatic biliary drainage was used in many centers; however, it has been accepted that endoscopic nasobiliary drainage is the most suitable method for PHC. Recently, inside-stents have also been adopted for biliary drainage, with favorable results. Portal vein embolization is widely performed as presurgical treatment for patients undergoing extended hepatectomy to minimize postoperative liver dysfunction. Surgical resection of PHC is technically demanding and continues to be the most difficult challenge for hepatobiliary surgeons. Because of advances in diagnostic and surgical techniques, surgical outcomes and survival rates after resection have steadily improved. However, survival rates, especially for patients with lymph node metastasis, are unsatisfactory, and establishing a protocol for effective adjuvant chemotherapy is an urgent task. Further synergy of endoscopists, radiologists, oncologists, and surgeons is required to conquer this intractable disease.

The prospects of DNA damage repair variants guiding platinum compounds in the treatment of triple negative breast cancer

Triple negative breast cancer (TNBC) is prone to recurrence and metastasis, which is the subtype of poorest prognosis. Chemotherapy is the main treatment, although there is lack of effective adjuvant chemotherapy regimens. The unsatisfactory efficacy of chemotherapy has been a bottleneck in improving the outcome of TNBC. Platinum compounds act directly on DNA to kill tumor cells, and they have a stronger killing effect on tumor cells carrying DNA damage repair (DDR) defects, which is an important entry point to improve the efficacy of TNBC. Biomarkers for predicting the efficacy of platinum drugs in TNBC treatment have always been a hot topic. The DDR pathway contains a large number of related genes, and recent studies have shown that deficiencies in the DDR pathway may be associated with the efficacy of platinum drugs, which is expected to be a biomarker for predicting the efficacy of platinum drugs in breast cancer treatment.

Effect of Adjuvant Paclitaxel and Carboplatin on Survival in Women With Triple-Negative Breast Cancer

The value of platinum-based adjuvant chemotherapy in patients with triple-negative breast cancer (TNBC) remains controversial, as does whether BRCA1 and BRCA2 (BRCA1/2) germline variants are associated with platinum treatment sensitivity. To compare 6 cycles of paclitaxel plus carboplatin (PCb) with a standard-dose regimen of 3 cycles of cyclophosphamide, epirubicin, and fluorouracil followed by 3 cycles of docetaxel (CEF-T). This phase 3 randomized clinical trial was conducted at 9 cancer centers and hospitals in China. Between July 1, 2011, and April 30, 2016, women aged 18 to 70 years with operable TNBC after definitive surgery (having pathologically confirmed regional node-positive disease or node-negative disease with tumor diameter >10 mm) were screened and enrolled. Exclusion criteria included having metastatic or locally advanced disease, having non-TNBC, or receiving preoperative anticancer therapy. Data were analyzed from December 1, 2019, to January 31, 2020, from the intent-to-treat population as prespecified in the protocol. Participants were randomized to receive PCb (paclitaxel 80 mg/m2 and carboplatin [area under the curve = 2] on days 1, 8, and 15 every 28 days for 6 cycles) or CEF-T (cyclophosphamide 500 mg/m2, epirubicin 100 mg/m2, and fluorouracil 500 mg/m2 every 3 weeks for 3 cycles followed by docetaxel 100 mg/m2 every 3 weeks for 3 cycles). The primary end point was disease-free survival (DFS). Secondary end points included overall survival, distant DFS, relapse-free survival, DFS in patients with germline variants in BRCA1/2 or homologous recombination repair (HRR)-related genes, and toxicity. A total of 647 patients (mean [SD] age, 51 [44-57] years) with operable TNBC were randomized to receive CEF-T (n = 322) or PCb (n = 325). At a median follow-up of 62 months, DFS time was longer in those assigned to PCb compared with CEF-T (5-year DFS, 86.5% vs 80.3%, hazard ratio [HR] = 0.65; 95% CI, 0.44-0.96; P = .03). Similar outcomes were observed for distant DFS and relapse-free survival. There was no statistically significant difference in overall survival between the groups (HR = 0.71; 95% CI, 0.42-1.22, P = .22). In the exploratory and hypothesis-generating subgroup analyses of PCb vs CEF-T, the HR for DFS was 0.44 (95% CI, 0.15-1.31; P = .14) in patients with the BRCA1/2 variant and 0.39 (95% CI, 0.15-0.99; P = .04) in those with the HRR variant. Safety data were consistent with the known safety profiles of relevant drugs. These findings suggest that a paclitaxel-plus-carboplatin regimen is an effective alternative adjuvant chemotherapy choice for patients with operable TNBC. In the era of molecular classification, subsets of TNBC sensitive to PCb should be further investigated. ClinicalTrials.gov Identifier: NCT01216111.

Haematological Toxicities Following Treatment of Childhood Hepatoblastoma with Intensive Multiagent Chemotherapy

Background: Hepatoblastoma is a rare malignant liver tumour that occurs almost exclusively in childhood. Although surgical resection is the foundation of curative therapy, with the use of effective neoadjuvant and adjuvant chemotherapy the 5 years overall survival of patient with hepatoblastoma had recently reached up to 80% to 90 %. But the frequency and severity of haematological toxicity is one of the major concerns of intensive chemotherapy. Objective: To evaluate the frequency and severity of haematological toxicities following treatment of childhood hepatoblastoma with two different regimens of multi-agent chemotherapy. Methodology: This was a comparative observational study conducted at Bangabandhu Sheikh Mujib Medical university in 24 childhood hepatoblastoma patients who received either cisplatin/carboplatin /doxorubicin (Group A; n=14) or cisplatin/ vincristine/5- fluorouracil (Group B; n= 10) to between March 2010 and July 2014. Results: Grade 3 or 4 anaemia and thrombocytopenia, and Grade 4 neutropenia were observed in 64.3% vs 60%, 35.7% vs 20% and 57.1% vs 20% respectively in group A and Group B. Febrile neutropenia occurred in 100% vs 70% and septicaemia developed in 92.9% vs 70%. Red cell concentrates and Platelet transfusions were required in 35.7% vs 50% and 14.3% vs 10% respectively in two groups. Deaths due to haematological toxicities occurred in 21.4% in Group A and 21% in Group B. Conclusion: We found similar toxicity profiles for two chemotherapy regimens except for higher rates of febrile neutropenia and septicaemia in patients treated with cisplatin/carboplatin /doxorubicin compared to cisplatin/ vincristine/5- fluorouracil.

Impact of Postoperative Complications on Recurrence in Patients With Stage II/III Gastric Cancer Who Received Adjuvant Chemotherapy With S-1.

This study aimed to investigate the impact of postoperative complications (PCs) in patients with pathological stage (pStage) II or III gastric cancer (GC) who received adjuvant chemotherapy with S-1 after curative surgery. Altogether, data for 226 patients were examined retrospectively. The relationship between PCs and clinicopathological features and survival were examined. Recurrence-free survival was significantly worse in the group with PCs than in the PC-negative group. On multivariate analysis, having PCs of grade 2 or more was an independent risk factor for recurrence (hazard ratio=1.721; 95% confidence intervaI=1.014-2.920; p=0.044). In addition, for each pStage analysis, having PCs of grade 2 or more was a risk factor for recurrence even in patients with pStage II GC. PC of grade 2 or more was an independent risk factor for recurrence in patients with pStage II GC who received adjuvant chemotherapy with S-1 after curative gastrectomy. Thus, for patients with PCs, even for those with pStage II GC, more effective adjuvant chemotherapy, such as S-1 plus docetaxel, may be needed.

Clinical status and prognostic factors in Japanese patients with uterine leiomyosarcoma

ObjectiveUterine leiomyosarcoma (uLMS) is a rare gynecologic malignancy for which the currently available treatments do not consistently provide long-term disease control. This study aimed to reveal the current clinical status of uLMS to support future clinical trials. MethodsThis study enrolled patients with uLMS treated at 53 Japanese institutions from 2000 to 2012. Central pathological review (CPR) was performed. All cases were confirmed by CPR, and epidemiological features, treatment, and prognosis were analyzed statistically. ResultsA total of 307 patients were enrolled. A diagnosis of uLMS was confirmed in 266 patients (86.6%) of patients after CPR, of whom data for 259 were analyzed. Of these, 186 (71.8%) patients underwent complete gross resection as primary therapy. Ninety-eight patients received no additional adjuvant therapy, while docetaxel and gemcitabine was the most frequent regimen among 155 patients treated with adjuvant chemotherapy. In all cases, the median overall survival (OS) was 44.2 months. Multivariate analyses of prognostic factors in all cases identified stage III and IV disease, high serum lactate dehydrogenase level, and menopausal status as poor prognostic factors. However, in stage I cases, high serum lactate dehydrogenase level and no adjuvant treatment were identified as poor prognostic factors. The 5-year OS of patients with stage I uLMS treated with adjuvant chemotherapy was significantly better than that of those without adjuvant treatment (67.8% vs 46.7%, P = 0.0461). ConclusionsDespite complete removal of the primary lesion, the clinical course of patients with uLMS was poor due to recurrence of distant metastasis. The application of a suitable biomarker and effective adjuvant chemotherapy are required to improve the prognosis of patients with uLMS.

Disparity in clinical outcomes between pure and combined pulmonary large-cell neuroendocrine carcinoma: A multi-center retrospective study

ObjectivesThe 2015 World Health Organization classification defines pulmonary large-cell neuroendocrine carcinoma (LCNEC) as a high-grade neuroendocrine carcinoma. However, the clinical characteristics and prognostic factors of pure LCNEC and combined LCNEC remain unclear. Hence, we performed a multi-center retrospective study to compare the clinical outcomes of pure versus combined LCNEC. Materials and methodsData from 381 patients with pulmonary LCNEC admitted to 17 Chinese institutes between 2009 and 2016 were collected retrospectively. Clinical characteristics and prognosis were analyzed among patients receiving adjuvant (adjuvant group; n = 56) and first-line (first-line group; n = 146) chemotherapy, as well as among patients receiving small cell lung cancer (SCLC) and non-SCLC (NSCLC) chemotherapy regimens. The Kaplan-Meier method and multivariable Cox regression were used to identify clinicopathological variables that might influence patient outcomes. ResultsExpression levels of neuroendocrine markers (synaptophysin, chromogranin-A, CD56) were associated with patients’ prognosis in the total study cohort. In the adjuvant group, median disease-free survival was non-significantly longer for SCLC-based regimens than for NSCLC-based regimens (P = 0.112). In the first-line group, median progression-free survival was significantly longer for SCLC-based regimens than for NSCLC-based regimens (11.5 vs. 7.2 months, P = 0.003). Among patients with combined LCNEC, adenocarcinoma was the most common combined component, accounting for 70.0 % of cases. Additionally, median overall survival was non-significantly shorter for combined LCNEC than for pure LCNEC (P = 0.083). ConclusionThe SCLC regimen is a more effective choice, as either first-line or adjuvant chemotherapy, when compared to the NSCLC regimen for LCNEC treatment. Further studies are needed to clarify the survival differences between patients with pure-, and combined LCNEC.

Treating osteosarcoma with CAR T cells.

Novel therapies to treat patients with solid cancers that have developed resistance to chemotherapy represent unmet needs of considerable dimensions. In the present review, we will address the attempts to develop chimeric antigen receptor (CAR) targeted immunotherapy against osteosarcoma (OS). This aggressive cancer displays its peak incidence in children and young adults. The main cause of patient death is lung metastases with a 5-year survival as low as 5%-10% in the primary metastatic setting and 30% in the relapse situation, respectively. Effective adjuvant combination chemotherapy introduced more than 40years ago improved the survival rates from below 20% to around 60% in patients; however, since then, no major breakthroughs have been made. The use of immune checkpoint inhibitors has been disappointing in OS, while other types of immunotherapies such as CAR T cells remain largely unexplored. Indeed, for CAR T-cell therapy to be efficacious, two main criteria need to be fulfilled: (a) CAR T cells should target an epitope selectively expressed on the cell surface of OS in order to prevent toxicities in normal tissues and (b) the target should also be widely expressed on OS metastases. These challenges have already been undertaken in OS and illustrate the difficulties in developing tomorrow's CAR-T treatment in a solid tumour. We will discuss the experiences with CAR-T therapy development and efficacy to combat the clinical challenges in OS.

Lobaplatin inhibits breast cancer progression, cell proliferation while it induces cell apoptosis by downregulating MTDH expression.

ObjectiveLobaplatin shows antitumor activity against a wide range of tumors, including metastatic breast cancer (BCa). The overexpression of metadherin (MTDH) is associated with poor prognosis of BCa patients. This study was designed to investigate the effect of lobaplatin on MCF-7 cell proliferation and its association with MTDH expression.Patients and methodsClinical treatment for BCa using lobaplatin, in combination with other general chemotherapy drugs, was administered to 32 BCa patients. The safety, effectiveness, and prognosis in lobaplatin-treated BCa patients were compared with those in controls (n=32). In vitro experiments were performed in MCF-7 cells to investigate the effect of lobaplatin on cell proliferation, apoptosis, and MTDH expression.ResultsWe found the intraoperative local chemotherapy using lobaplatin was safe and effective for BCa treatment, in comparison with the patients administered general chemotherapy drugs. Treatment of MCF-7 cell cultures with lobaplatin significantly reduced cell proliferation and increased cell apoptotic percentage. The expression of MTDH and Bcl-2 was inhibited by lobaplatin and that of Bax was increased by lobaplatin. Moreover, we observed the inhibition of MTDH by shRNA reduced cell proliferation and enhanced cell apoptosis.ConclusionLobaplatin was a safe and effective adjuvant chemotherapy for BCa. The effect of lobaplatin on inhibiting MCF-7 cell proliferation and inducing cell apoptosis might be, as least in part, mediated by suppressing the expression of oncogene MTDH.

Outcomes of surgery for hepatocellular carcinoma with tumor thrombus in the inferior vena cava or right atrium.

The prognosis of hepatocellular carcinoma (HCC) patients with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA) is extremely poor. We reviewed the recent surgical treatments and outcomes of this form of advanced HCC. TT is classified into three types according to its anatomic location relative to the heart: the inferior hepatic type (type I), where the TT is in the IVC below the diaphragm; the superior hepatic type (type II), where the TT is in the IVC above the diaphragm, but still outside the RA; and the intracardiac type (type III), where the TT is above the diaphragm and has entered the RA. Type I can be treated relatively easily by standard radical hepatectomy. For type II, the intrathoracic IVC is approached via the abdominal cavity and an incision in the diaphragm with total hepatic vascular exclusion (THVE). For type III, hepatectomy plus thrombectomy is generally performed under cardiopulmonary bypass. If the TT is only just inside the RA, THVE can be performed by mobilizing the liver caudally. The median overall survival of HCC patients with TT in the IVC or RA, who undergo curative resection, is 19.0-30.8months. As postoperative recurrence is likely to develop, even after curative surgery, effective postoperative adjuvant chemotherapy is required.

SY9-1 - Standard Therapy for Localized Soft Tissue Sarcomas

Soft tissue sarcomas (STS) are very rare malignant tumors. Because of the rareness, it is difficult to develop new standard therapies for STS. According to the Soft Tissue Tumor Registry by the Japanese Orthopaedic Association, approximately 75% of the patients with STS exhibit the localized disease at first presentation. All localized STS should be treated by definitive surgery with appropriate margin as standard treatment. The low-grade, superficial or small STS can be cured by surgery alone. Insufficient surgical margin, including marginal or intra-lesional resection, may require adjuvant radiation therapy. On the other hand, high-grade, deep-seated and large, i.e., high-risk STS result in poor prognosis when they are treated by surgery alone. To establish the effective adjuvant chemotherapy for high-risk STS, a number of randomized clinical trials have been carried out. All the randomized studies, except one, failed to demonstrate the superiority of adjuvant chemotherapy in overall survival (OS) of the patients with localized STS in comparison with surgery alone. However, meta-analyses of the randomized trials have confirmed the significant improvement of OS by adjuvant chemotherapy for STS. Recently, a randomized study comparing neo-adjuvant full-dose epirubicin (EPI)+ifosfamide (IFM) and histology-tailored chemotherapy for high-risk STS conducted by the Italian Sarcoma Group has clearly showed the significantly better OS in EPI+IFM group. The result was comparable with that in a phase II trial, JCOG0304, using neo-adjuvant chemotherapy with doxorubicin (DOX)+IFM carried out by the Japan Clinical Oncology Group (JCOG). Thus, the current standard therapy for high-grade, deep-seated and large STS is the neo-adjuvant chemotherapy with full-dose DOX+IFM. We are currently conducting a randomized phase II/III study comparing the efficacy of neo-adjuvant DOX+IFM and gemcitabine+docetaxel for high-risk localized STS, JCOG1306.

Impact of in vitro chemosensitivity test-guided platinum-based adjuvant chemotherapy on the surgical outcomes of patients with p-stage IIIA non-small cell lung cancer that underwent complete resection.

The impact of in vitro chemosensitivity test-guided platinum-based adjuvant chemotherapy on the surgical outcomes of patients undergoing complete resection for locally advanced non-small cell lung cancer (NSCLC) has yet to be elucidated. In the present study, the utility of adjuvant chemotherapy based on the collagen gel droplet embedded culture drug sensitivity test (CD-DST) in patients with p (pathology)-stage IIIA NSCLC was retrospectively analyzed. A series of 39 patients that had received platinum-based adjuvant chemotherapy following complete resection between 2007 and 2012 were enrolled. Their surgical specimens were subjected to the CD-DST. The patients were subsequently classified into two groups on the basis of in vitro anti-cancer drug sensitivity data obtained using the CD-DST: The sensitive group (25 patients) were treated with regimens including one or two of the anti-cancer drug(s) that were indicated to be effective by the CD-DST, whereas the non-sensitive group (14 patients) were treated with chemotherapy regimens that did not include any CD-DST-selected anti-cancer drugs. There were no significant differences in the background characteristics of the two groups [including in respect of the pathological TN (tumor-lymph node) stage, tumor histology, epidermal growth factor receptor mutation status, the frequency of each chemotherapy regimen, and the number of administered cycles]. The 5-year disease-free survival (DFS) rate of the sensitive group was 32.3%, whereas that of the non-sensitive group was 14.3% (P=0.037). In contrast, no difference in overall survival (OS) was observed (P=0.76). Multivariate analysis revealed that adjuvant chemotherapy based on the CD-DST had a significant favorable effect on the DFS (P=0.01). Therefore, the present study has demonstrated that CD-DST data obtained from surgical specimens aid the selection of effective platinum-based adjuvant chemotherapy regimens for patients undergoing complete resection for p-stage IIIA NSCLC. The use of CD-DST-guided platinum-based regimens may have a beneficial impact on the DFS of such patients.