Longer Disease-free Survival Time Research Articles

Clinical Analysis of Matched Sibling Donor Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Young Patients with Multiple Myeloma

To investigate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of young patients with multiple myeloma (MM). The clinical data of 8 young patients (median age：46 years) with MM who underwent allo-HSCT from HLA-indentical sibling donors in the First Affiliated Hospital of Chongqing Medical University from June 2013 to September 2021 were collected, and their survival and prognosis were retrospectively analyzed. All the patients were successfully transplanted, and 7 patients could be evaluated the efficacy after transplantation. The median follow-up time was 35.2 (2.5-84.70) months. The complete response (CR) rate was 2/8 before transplantation and 6/7 after transplantation. Acute GVHD developed in 2 cases and extensive chronic GVHD developed in 1 case. Within 100 days, 1 case died of non-recurrent events, and 1-year and 2-year disease-free survival were 6 and 5 cases, respectively. At the end of follow-up, all the 5 patients who survived for more than 2 years survived, and the longest disease-free survival time has reached 84 months. With the development of new drugs, HLA-matched sibling donor allo-HSCT may be a curable treatment for young patients with MM.

Identification of the Immune Subtype of Hepatocellular Carcinoma for the Prediction of Disease-Free Survival Time and Prevention of Recurrence by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.

BackgroundThe main factors affecting the long-term prognosis of hepatocellular carcinoma (HCC) patients undergoing radical surgery are recurrence and metastasis. However, the methods for predicting disease-free survival (DFS) time and preventing postoperative recurrence of HCC are still very limited.MethodsIn this study, immune cell abundances in HCC samples were analyzed by single-sample gene set enrichment analysis (ssGSEA), while the prognostic values of immune cells for DFS time prediction were evaluated by the least absolute shrinkage and selection operator (LASSO) and subsequent univariate and multivariate Cox analyses. Next, a risk score was constructed based on the most prognostic immune cells and their corresponding coefficients. Interactions among prognostic immune cells and the specific targets for the prevention of recurrence were further identified by single-cell RNA (scRNA) sequencing data and CellMiner.ResultsA novel efficient T cell risk score (TCRS) was constructed based on data from the three most prognostic immune cell types (effector memory CD8 T cells, regulatory T cells and follicular helper T cells) for identifying an immune subtype of HCC patients with longer DFS times and inflammatory immune characteristics. Functional differences between the high- and low-score groups separated by TCRS were clarified, and the cell-cell communication among these immune cells was elucidated. Finally, fifteen hub genes that may be potential therapeutic targets for the prevention of recurrence were identified.ConclusionsWe constructed and verified a useful model for the prediction of DFS time of HCC after surgery. In addition, fifteen hub genes were identified as candidates for the prevention of recurrence, and a preliminarily investigation of potential drugs targeting these hub genes was carried out.

Clinical Characteristics of Peripheral Hemogram and DNMT3A Gene Mutation in Patients with Primary AML Treated by FLT3-ITD-mt and FLT3-ITD-wt

To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL). The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed. All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months. allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.

Clinical Study of Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed or Refractory Peripheral T-Cell Lymphoma

To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL). The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed. All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months. allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.

Clinical Characteristics of Peripheral Hemogram and DNMT3A Gene Mutation in Patients with Primary AML Treated by FLT3-ITD-mt and FLT3-ITD-wt

To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL). The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed. All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months. allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.

Endometriosis-associated Ovarian Cancer is a Subset With a More Favorable Outcome and Distinct Clinical-pathologic Characteristics.

There is a controversy about whether endometriosis-associated ovarian cancer (EAOC) might represent a different entity from the corresponding ovarian cancer occurring de novo, in the absence of endometriosis. This study investigated the clinical-pathologic characteristics and outcome of EAOC compared with other ovarian carcinomas that are not associated with endometriosis (non-EAOC) in a large cohort. Seven hundred two patients meeting the inclusion criteria were further subclassified as group I when patients had ovarian carcinoma associated with or arising within endometriosis (EAOC) and group II when patients had non-EAOC. Age, gross features, histologic type, International Federation of Gynecology and Obstetrics stage, and disease-free survival (DFS) were compared between the groups. One hundred sixty-eight (23.9%) patients had EAOC, whereas 534 (76.1%) patients had non-EAOC. EAOCs were mostly endometrioid and clear cell type. Patients with EAOC were younger, present early, and had a lower rate of recurrence when compared with patients with non-EAOC, P<0.001. Patients with EAOC had longer DFS time, 51.9 mo (95% confidence interval, 44.9-58.8) versus 30.5 mo (95% confidence interval, 27.7-33.3) in non-EAOC patients. The 5 yr Kaplan-Meier estimate of DFS rate was 70% in 166 patients of group I and was 39.3% in 532 patients of group II, P<0.001. On multivariate analysis, International Federation of Gynecology and Obstetrics staging, histologic type, and treatment were the only significant factors affecting the hazards of recurrence. Patients with tumors associated with endometriosis are usually, younger, present early, have lower rate of recurrence, longer DFS, and their tumors are of lower grade and are more likely endometrioid or clear cell carcinoma.

Prognostic significance of inflammatory cell response in patients with colorectal cancer.

Cancer cells are characterized by a low antigenic immunogenicity, a rapid growth and an immunosuppressive effect on the extracellular matrix. These properties induce a weak immune response in colorectal cancer (CRC) carcinogenesis. It is therefore crucial to determine the composition of the inflammatory mass, including neutrophils, macrophages and eosinophils in the tumor tissue of patients with CRC, and to analyze other clinicopathological parameters. The present study included 144 patients diagnosed with CRC. Tissue samples obtained from routine histopathological diagnosis were stained with hematoxylin and eosin. Inflammatory cells were assessed in the invasive front and in the center of the tumor by light microscopy under a high-power magnification. The percentage of neutrophils in the invasive front was significantly higher compared with that in the center of the tumor mass (P<0.01). Macrophages and eosinophils were present in the invasive front and in the center of tumor mass in most cases. The presence of neutrophils, macrophages and eosinophils was correlated with various clinicopathological features. Patients with macrophages present in the center of tumor mass had longer disease-free survival time (P=0.041). In conclusion, the present study demonstrated that the inflammatory cell infiltrate served a significant role in the immune response of patients with CRC. It should be noted that the presence of macrophages localized in the stroma of the central part of the primary tumor mass was associated with the survival time of patients with CRC.

CAR-T bridging to allo-HSCT as a treatment strategy for relapsed adult acute B-lymphoblastic leukemia: a case report

BackgroundAdults with relapsed acute lymphoblastic leukemia (ALL) have a poor prognosis, especially in patients who relapsed within 6 months of complete remission 1 (CR1). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice. However, this can only be considered after complete remission 2 (CR2) is achieved. Therefore, bridging treatment is urgently needed.Case presentationIn the present study, we report a relapsed adult B-cell ALL case that achieved CR2 after treatment with CD19-directed chimeric antigen receptor (CAR)-modified T cell (CAR-T) therapy. After subsequent allo-HSCT, the patient acquired 21 months of disease-free survival.ConclusionThe present results confirm that both CAR-T and allo-HSCT are effective for treating refractory or relapsed B-ALL. However, a novel sequential treatment strategy with these two therapeutic methods may achieve longer disease-free survival time.

Primary hepatic neuroendocrine tumors: retrospective analysis of seven cases and literature review

Background: Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare. Their clinical features, diagnosis and effective treatment strategies are not well understood. Methods: We aimed to investigate them by combining retrospectively analyzing the clinical data of seven patients with PHNETs who were admitted to our hospital from April 2009 to November 2017 with literature review. Results: PHNET patients without medical history of hepatitis or liver cirrhosis presented no specific symptom, and hepatic tumor markers such as alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were all within the normal range. Imaging of PHNET patients was found to be with a dominant hypervascular hepatic mass accompanied by a lower cystic signal and a higher hemorrhagic signal area on T1-weighted magnetic resonance imaging (MRI), with rapid washout and capsular enhancement on dynamic MR imaging or computed tomography (CT) imaging and restricted diffusion on diffusion-weighted (DW)-MRI. All patients underwent preoperative and postoperative CT examination or MRI examination which identified no extrahepatic tumors. All patients underwent surgery-centered comprehensive individualized treatment. Postoperative pathology confirmed that all patients had NETs. On immunohistochemistry all of the tumors were chromogranin A (CgA) positive, six were synaptophysin (Syn) positive. At the end of the follow-up period ranging from 9 to 87 months, six patients survive without recurrence. The longest postoperative survival time and the longest disease-free survival (DFS) time were all 87 months. Conclusions: Our findings suggest PHNET patients have unique clinical characteristics. The diagnosis of PHNETs relies on pathology and imaging examination MRI or CT to exclude primary extrahepatic tumors. Surgery-centered individualized comprehensive treatment leads to a good prognosis of patients with PHNETs.

A single institution report of 19 hepatocellular carcinoma patients with bile duct tumor thrombus.

BackgroundObstructive jaundice caused due to bile duct tumor thrombus (BDTT) in a hepatocellular carcinoma (HCC) patient is an uncommon event. This study reports our clinical experiences and evaluates the outcomes of HCC patients with BDTT in a single institution.MethodsA retrospective review of 19 HCC patients with secondary obstructive jaundice caused due to BDTT during a 15-year period was conducted.ResultsAt the time of diagnosis, 14 (73.7%) patients had obstructive jaundice. Eighteen (94.7%) patients were preoperatively suspected of “obstruction of the bile duct”. Sixteen patients (84.2%) underwent a hepatectomy with curative intent, while two patients underwent removal of BDTT combined with biliary decompression and another patient received only palliative care as his liver reserve and general condition could not tolerate the primary tumor resection. The overall early recurrence (within 1 year) after hepatectomy occurred in more than half (9/16, 56.3%) of our patients. The 1-year survival rate of patients was 75% (12/16). The longest disease-free survival time was >11 years.ConclusionIdentification of HCC patients with obstructive jaundice is clinically important because proper treatment can offer an opportunity for a cure and favorable long-term survival.

Disscussion and analysis of the effect of adjuvant radiotherapy after neoadjuvant chemotherapy for stage T1-2N1M0 breast cancer

Objective To evaluate the effects and significance of adjuvant radiotherapy after neoadjuvant chemotherapy on local recurrence (LR) rate in patients with stage T1-2N1M0 breast cancer. Methods Clinical data were collected from patients with stage T1-2N1M0 breast cancer who were admitted to our hospital and treated with neoadjuvant chemotherapy from 2005 to 2010. The clinical outcomes in those patients were analyzed after treatment with adjuvant radiotherapy. A total of 144 patients with a median age of 45 years (23-72 years) were enrolled as subjects. Results In the 144 patients, 30 patients (21%) who had pathological complete response (pCR) in primary breast tumor and axillary lymph node received adjuvant radiotherapy; 10 out of 45 patients who had pCR in axillary lymph node alone did not receive adjuvant radiotherapy; 6 out of 69 patients who still had axillary lymph node metastasis after treatment did not receive adjuvant radiotherapy; all of the rest received adjuvant radiotherapy. In all patients, the median follow-up time was 88 months; 46 patients (32%) had relapse and metastasis. The 5-year LR rate was 3.0% in patients with pCR. In patients with pCR in axillary lymph node metastasis after neoadjuvant chemotherapy, there was no significant difference in the 5-year LR rate between patients treated with and without radiotherapy (7% vs. 16%, P=0.181). In patients with axillary lymph node metastasis after neoadjuvant chemotherapy, there was also no significant difference in the 5-year LR rate between patients treated with and without radiotherapy (15.9% vs. 33.3%, P=0.267). In all patients, those with pCR had significantly longer disease-free survival (DFS) time than those without pCR (P=0.017). Conclusions Patients with pCR to neoadjuvant chemotherapy have longer DFS time than those without pCR. The LR rate is relatively lower in patients with pCR undergoing adjuvant radiotherapy. Patients with pCR in axillary lymph node metastasis do not benefit from postoperative adjuvant radiotherapy. However, adjuvant radiotherapy is helpful in patients with axillary lymph metastasis after neoadjuvant chemotherapy who have high LR rates Key words: Breast neoplasms/neoadjuvant chemotherapy; Pathological complete response; Breast neoplasms/adjuvant radiotherapy

Clinical research of reduced intensity allogeneic hematopoietic stem cell transplantation for relapsed or refractory lymphoma

Objective To explore the efficacy and safety of reduced intensity allogeneic stem cell transplantation(allo-HSCT)in the treatment of relapsed or refractory lymphoma. Methods 5 patients with relapsed or refractory lymphoma received reduced intensity allo-HSCT from January 2012 to December 2013 of Beijing Military General Hospital, including 4 males and 1 female, aged from 20 to 39 years old, with the mean age 28.7 years old. 3 cases were HLA-identical matching and the other two cases were HLA-haploidentical. Donors received granulocyte colony-stimulating factor mobilization, and stem cells were collected from both peripheral blood and bone marrow. Pretreatment scheme reduced the strength of pretreatment for fludarabine combined with busulfex and ATG. Combined immunosuppressive agents were used for graft-versus-host disease(GVHD)prophylaxis, including cyclosporine A, methotrexate, mycophenolate mofetil and soon. The toxicity, GVHD and disease-free survival in patients were observed after transplantation. Results All of the patients acquired hematopoietic reconstitution. The average time of the neutrophils count ≥ 0.5 × 109/L and platelets ≥ 20×109/L were 18.8 d and 24.5 d, respectively. Implantation was confirmed by the evidence of 100 % of donor hematopoiesis. As of follow-up to December 2014 with the median 19.2 months(6-35 months), 2 cases died of recurrence, the other 3 patients remained disease-free survival, and the longest disease-free survival time was up to 35 months. Conclusions Reduced intensity allogeneic hematopoietic stem cell transplantation is an effective and safe method for relapsed or refractory lymphoma, which could be chosen as a salvage treatment method for relapsed or refractory lymphoma. Key words: Allogeneic hematopoietic stem cell transplantation; Rducing strength; Rlapsed; Refractory; Lymphoma

Clinical analysis of reduced conditioning intensity allo-HSCT treatment for relapsed ETO-positive AML

This study was aimed to explore the effect and feasibility of reduced conditioning intensity allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed ETO positive acute myeloid leukemia (AML) patients. Fifteen cases of relapsed AML received the reducing conditioning intensity allo-HSCT from January 2011 to January 2013 in Beijing Military Command General Hospital. All patients were high-risk type of relapsed or refractory AML, including 10 males and 5 females, aged from 16 to 48 years old with mean age of 32.5 years. Ten cases are HLA-identical matching and other 5 cases are HLA-haploidentical.donors received granulocyte colony-stimulating factor (G-CSF) to mobilize the peripheral blood stem cell for transplantation. Conditioning regimen was fludarabine combined with busulfex, cytarabine and cyclophosphamide. The preventive donor's peripheral blood stem cell infusion were performed after 3 months of transplantation, and the toxicity, GVHD and disease-free survival were observed in patients after transplantation. The results showed that all patients achieved hematopoietic reconstitution, the average time of neutrophils ≥ 0.5 × 10⁹/L and platelets ≥ 20 × 10⁹/L were 15.5 d and 16.8 d respectively. Implantation was confirmed by the evidence of 100% donor hematopoiesis. Follow-up to June 2014, with a median follow-up duration of 27.5 months (18-54 months), GVHD occurred in 8 cases of all patients, one died of complication, the other 4 cases died of relapse and the other three patients remained in disease-free survival. The disease-free survival rate of 2-year was 66.7%,the longest disease-free survival time was up to 54 months. It is concluded that the reduced conditioning intensity allo-HSCT is the effective and safe method for relapsed AML with ETO-positive, and it may be chosen as a treatment method for relapsed ETO positive AML patients.

Extracellular signal-regulated kinase (ERK) expression and activation in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival

Extracellular signal-regulated kinase (ERK) has been considered as a critical regulator of diverse cellular processes such as proliferation, survival and motility, being implicated in the malignant transformation in several tissue types. The present study aimed to evaluate the clinical significance of total ERK1 (t-ERK1) and phosphorylated ERK1/2 (p-ERK1/2) protein expression in mobile tongue squamous cell carcinoma (SCC). t-ERK1 and p-ERK1/2 protein expression in tumour cells and infiltrating the tumour microenvironment lymphoid cells was assessed immunohistochemically on 47 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients' survival. Enhanced nuclear t-ERK1 and p-ERK1/2 expression in tumour cells was associated with the absence of perineural invasion (p = 0.043) and shorter overall patients' survival (log-rank test, p = 0.028), respectively. Enhanced t-ERK1 expression in infiltrating lymphoid cells was significantly associated with female gender, absence of vascular and perineural invasion, lymph node metastases and early depth of invasion (p = 0.008, p = 0.019, p = 0.011, p = 0.036 and p = 0.001, respectively), as well as with longer disease-free survival times (log-rank test, p = 0.038). Enhanced p-ERK1/2 expression in infiltrating lymphoid cells was significantly associated with the presence of vascular invasion and lymph node metastases (p = 0.019 and p = 0.004, respectively) and shorter overall patients' survival (log-rank test, p = 0.013). In multivariate analysis, p-ERK1/2 expression in tumour cells and infiltrating lymphoid cells was identified as independent prognostic factors of overall survival (Cox regression analysis, p = 0.045 and p = 0.032, respectively). The present study supported evidence that ERK signalling pathway may exert a potential role in the pathophysiological aspects of the mobile tongue SCC, presenting also potential utility as a biomarker for patients' survival and reinforcing the development of novel anti-cancer therapies targeting ERK signalling cascade in this type of human malignancy.

Abstract 2383: Clinical significance of intratumoral HER2 heterogeneity in gastric cancer.

Abstract Aim: To evaluate the clinical significance of intratumoral HER2 heterogeneity in gastric cancer (GC). Methods: A total of 322 GC tissues were evaluated by HER2 immunohistochemistry (IHC), of which 73 with IHC 2+ or 3+ were subjected to fluorescence in situ hybridization (FISH). Also, 3-5 distinct spots in each case showing different HER2 staining intensity were evaluated individually for comparing IHC staining intensity with gene copy number (GCN). Minimum, average, and maximum FISH scores were generated for each case. Results: Intratumoral heterogeneity of HER2 overexpression and gene amplification were 54 and 30 of 73 cases with IHC 2+ or 3+, respectively. These cases were characterised by diffuse or mixed Lauren type, HER2 IHC 2+, and low-level amplification. Kaplan-Meier survival analysis revealed that the heterogeneous overexpression was significantly associated with longer disease-free survival times than the homogeneous, and the high average GCN was most associated with poor outcome. Also, there was a strong correlation between the IHC and FISH results for each spot. Quantitative PCR analysis of the cancer tissues and the cell-free plasma showed that HER2 gene copy by quantitative PCR on tissue correlated well with those by FISH, but plasma HER2 level was not.Conclusions: Considering the high incidence of intratumoral HER2 heterogeneity in GC, accurate HER2 assessment would require larger tissues and more detailed guidelines. The guidelines should include the recommendation that FISH-scoring areas be selected with reference to a corresponding IHC slide. Also, the definition of HER2-positive tumours should be reassessed considering the intratumoral heterogeneity. Citation Format: Hye Seung Seung Lee, Hee Eun Lee, Kyoung Un Park, Soo Kyung Nam, Do Joong Park, Hyung-Ho Kim. Clinical significance of intratumoral HER2 heterogeneity in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2383. doi:10.1158/1538-7445.AM2013-2383

Clinical research of reduced-intensity allogeneic hematopoietic stem cell transplantation for multiple myeloma

This study was purposed to explore the efficacy and feasibility of reduced-intensity allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of multiple myeloma (MM). Three patients with MM from January 2011 to January 2012 in General Hospital of Beijing Military Area were treated by reduced-intensity allo-HSCT. All donors are compatriots and affinity HLA identical. Donors were mobilized with granulocyte colony-stimulating factor (G-CSF), the MM patients were given combined transplantation of bone marrow and peripheral blood stem cells. Preconditioning regimen consisted of fludarabine combined with melphalan and anti-human thymocyte globulin, and the classic cyclosporin A (CsA) combined with methotrexate (MTX) was used to prevent graft-versus-host disease (GVHD). The preventive donor peripheral blood stem cell infusion in dose 0.2×10(8)/kg mononuclear cells (MNC) was applied after 3 months of transplantation, then the toxicity, GVHD and disease-free survival (DFS) in patients were observed after transplantation. The results showed that 3 patients got hematopoietic reconstitution, the average time of neutrophils ≥ 0.5×10(9)/L and platelets ≥ 20×10(9)/L was 14.3 d and 15.3 d respectively, the detection of implanting efficacy displayed 100% complete donor hematopoiesis. Follow-up to January 2013, the median follow-up time was 13 months (12 to 15 months), As a result, none of the patients got GVHD, infection and other serious complications, all patients are still in complete remission (CR), the longest DFS time has reached to 15 months. It is concluded that the reduced-intensity allogeneic hematopoietic stem cell transplantation is the effective method for MM, this method has the high safety and efficacy, as well as high complete remission rate in early transplantation, the MM patients may get a long-term survival. This method can be used as a key technology in clinic for treating MM.

Radiotherapy Can Improve the Disease-Free Survival Rate in Triple-Negative Breast Cancer Patients with T1–T2 Disease and One to Three Positive Lymph Nodes After Mastectomy

Several studies have demonstrated poor locoregional control in patients with triple-negative breast cancer (TNBC), compared with other molecular subtypes of breast cancer. We sought to evaluate whether or not postmastectomy radiotherapy (PMRT) improves locoregional recurrence-free survival (LRFS) and disease-free survival (DFS) outcomes in TNBC patients. Between January 2000 and July 2007, 553 TNBC patients treated with modified radical mastectomy from a single institution were analyzed retrospectively. Patients were categorized into three groups: low risk (stage T1-T2N0), intermediate risk (stage T1-T2N1), and high risk (stage T3-T4 and/or N2-N3). Cox proportional hazards models were used to evaluate the association between PMRT and LRFS and DFS times after adjusting for other clinicopathologic covariates. With a median follow-up of 65 months (range, 1-140 months), 51 patients (9.2%) developed locoregional recurrence and 135 patients (24.4%) experienced disease recurrence. On multivariate analysis, PMRT was associated with significantly longer LRFS and DFS times in the entire cohort. In the intermediate-risk group, PMRT was associated with a longer DFS time but not with the LRFS interval. In the high-risk group, PMRT was associated with significantly longer LRFS and DFS times. PMRT is associated with longer LRFS and DFS times in high-risk TNBC patients and a longer DFS time in intermediate-risk TNBC patients. Prospective randomized studies are needed to investigate the best locoregional treatment approaches for patients with this molecular subtype of breast cancer.

Clinical significance of intratumoral HER2 heterogeneity in gastric cancer

AimTo evaluate the clinical significance of intratumoral HER2 heterogeneity in gastric cancer (GC). MethodsA total of 322 GC tissues were evaluated by HER2 immunohistochemistry (IHC), of which 73 with IHC 2+ or 3+ were subjected to fluorescence in situ hybridisation (FISH). Also, 3–5 distinct spots in each case showing different HER2 staining intensities were evaluated individually by comparing IHC staining intensity with gene copy number (GCN). Minimum, average and maximum FISH scores were generated for each case. ResultsIntratumoral heterogeneity of HER2 overexpression and gene amplification were 54 and 30 of 73 cases with IHC 2+ or 3+, respectively. These cases were characterised by diffuse or mixed Lauren type, HER2 IHC 2+, and low-level amplification. Kaplan–Meier survival analysis revealed that the heterogeneous overexpression was significantly associated with longer disease-free survival times than the homogeneous, and the high average GCN was most associated with poor outcome. Also, there was a strong correlation between the IHC and FISH results for each spot. Quantitative polymerase chain reaction (PCR) analysis of the cancer tissues and the cell-free plasma showed that HER2 gene copy by quantitative PCR on tissue correlated well with those by FISH, but plasma HER2 level was not. ConclusionsConsidering the high incidence of intratumoral HER2 heterogeneity in GC, accurate HER2 assessment would require larger tissues and more detailed guidelines. The guidelines should include the recommendation that FISH-scoring areas be selected with reference to a corresponding IHC slide. Also, the definition of HER2-positive tumours should be reassessed considering the intratumoral heterogeneity.

The potential prognostic value of cathepsin D protein in serous ovarian cancer

Overexpression of a ubiquitous lysosomal aspartyl protease cathepsin D (cath-D) is involved in the progression of certain cancer types. This study investigated the prognostic value of the cath-D expression and its association with other known clinicopathological parameters in serous ovarian carcinoma. Cath-D was detected by immunohistochemistry in 49 serous ovarian carcinomas and compared to 50 benign serous ovarian tumors. The results were correlated with clinicopathological characteristics and survival outcomes. In both cath-D positive benign and malignant serous ovarian tumors, a specific granular cytoplasmic staining was observed in both epithelial and stromal cells. Cath-D expression levels were higher in serous ovarian carcinomas than in benign tumors (P < 0.01). Cath-D expression in tumor epithelial cells correlated with mesenchymal cell expression (P < 0.001). The cath-D expression levels of tumor epithelial cells correlated with residual tumor size (P = 0.027) and was not related to other factors (P > 0.05). Patients with higher cath-D expression in epithelial cells had longer disease-free survival time (DFST; P = 0.025) and overall survival time (OST; P = 0.030). Through the Cox regression test, we found that the response to treatment (P < 0.001), pathological stage (P < 0.001), and peritoneal cytology results (P = 0.018) were independent effect factors for DFST. The expression level of cath-D in epithelial cells (P = 0.025), response to treatment (P < 0.001), pathological stage (P = 0.001), and peritoneal cytology results (P = 0.002) were independent effect factors for OST. This showed that cath-D was an indicator of malignancy in serous ovarian carcinoma. It was expressed more highly in serous ovarian carcinoma than benign serous ovarian tumor. Additionally, our results suggested that high expression of cath-D in tumor epithelial cells was a favorable survival prognostic factor for serous ovarian carcinoma.

Neoadjuvant Treatment of Locally Advanced Soft Tissue Sarcoma of the Limbs: Which Treatment to Choose?

Soft tissue sarcomas (STSs) form a heterogeneous group of malignant neoplasms arising in the mesenchymal connective tissues. They can develop at any anatomic site but 60% occur in the extremities. Initially, treatment of STS relied solely on excision. In the 1970s, Enneking et al. developed the concept of compartmental resection to reduce the local failure rate. Later, Rosenberg et al. demonstrated, in a randomized study, that there was no difference in local tumor control and disease-free survival (DFS) in patients treated with amputation versus limb-saving surgery followed by 50-70 Gy external-beam radiotherapy (EBRT). A considerable proportion of patients present with locally advanced tumors as a primary or recurrent disease and cannot be resected with adequate clearance margins. These patients are threatened with amputation for complete tumor removal. Improvements in surgical techniques, such as microvascular muscle flaps, allow for the avoidance of limb loss in the majority of cases. However, the use of frozen sections to determine intraoperatively whether clear margins have been achieved is limited by the multiplanarity of resection specimens. Thus, local failure rates are 15%-25%, and preoperative measures to sterilize the invasive margin of sarcomas have been explored. High-dose preoperative EBRT for high-grade STS was developed, and its combination with intra-arterial or i.v. chemotherapy was reported to be effective. Recently, systemic chemotherapy combined with deep wave hyperthermia was shown to result in a longer DFS time in a large, randomized, phase III study. Treatment concepts differ significantly among centers and are influenced more by availability of technical equipment than by data. It is the aim of this review to elucidate the rationale of different regimens and analyze their potentials as well as weaknesses.