Fertility-sparing surgery for patients with stage IC2 or IC3 epithelial ovarian carcinoma: any evidence of safety?

ObjectiveInvestigate the overall survival of patients with stage IC2/IC3 epithelial ovarian carcinoma undergoing fertility-sparing surgery.MethodsPatients aged <45 years diagnosed between January 2004 and December 2015 with epithelial ovarian carcinoma, who underwent surgical staging and had tumor involving the ovarian surface (IC2), malignant ascites or positive cytology (IC3), were identified in the National Cancer Database. The fertility-sparing surgery group included patients who had preservation of the uterus and the contralateral ovary while the radical surgery group included patients who had hysterectomy with bilateral salpingo-oophorectomy. Overall survival was evaluated following generation of Kaplan–Meier curves while a Cox model was constructed to control for tumor grade and performance of lymphadenectomy. A systematic review of the literature was performed and cumulative relapse rate among patients with IC2/IC3 disease who underwent fertility-sparing surgery was calculated.ResultsA total of 235 cases were identified; 105 (44.7%) patients underwent fertility-sparing surgery. There was no difference in overall survival between the fertility-sparing and radical surgery groups (p=0.37; 5- year overall survival rates 90.2% and 85%, respectively). After controlling for tumor grade and performance of lymphadenectomy, fertility-sparing surgery was not associated with worse overall survival (HR 1.22, 95% CI 0.56, 2.62). A systematic review identified 151 patients with stage IC2/IC3 disease who underwent fertility-sparing surgery. Cumulative relapse rate was 19.3% (n=29) while 12 (6.7%) deaths were reported. Median time to recurrence was 19 (range 1–128.5) months. Tumor recurrence involved the ovary exclusively in 42% (11/26) of patients, while 15% (4/26) had a lymph node, 35% (9/26) a pelvic/abdominal, and 8% (2/26) a distant tumor relapse.ConclusionsIn a large cohort of patients with stage IC2/IC3 epithelial ovarian carcinoma, fertility-sparing surgery was not associated with worse overall survival. However, based on a literature review, relapse rate is approximately 20%.

Response and relapse rates after treatment with long-acting somatostatin analogs in multifocal or recurrent type-1 gastric carcinoids: A systematic review and meta-analysis

Background Type-1 gastric neuroendocrine tumors represent a recurring disease and long-acting somatostatin analogs can inhibit both gastrin release and endocrine cell proliferation. The efficacy and timing of this treatment are still unclear. We performed a systematic review of the literature to clarify the role of somatostatin analog treatment in type-1 gastric neuroendocrine tumors. Methods A computerized literature search was performed using relevant keywords to identify all the pertinent articles published in the last 15 years. Results Eight studies were included in this systematic review on somatostatin analogs in type-1 gastric neuroendocrine tumors. A complete response rate ranged from 25–100%. When only the six prospective studies were considered, no significant heterogeneity was observed, and the pooled cumulative complete response rate was 84.5% (confidence interval 73.8–92.8). Three studies evaluated the type-1 gastric neuroendocrine tumor recurrence, with a cumulative relapse rate of 30.2% (confidence interval 13.1–50.6) after 34 months. Conclusion Somatostatin analogs, namely lanreotide and octreotide, have an excellent response rate, with a good safety profile in selected type-1 gastric neuroendocrine tumors, which cannot be safely managed by endoscopic follow-up or resection due to multiple or frequently recurring disease. After therapy discontinuation, the cumulative relapse rate observed after a median 34-month follow-up was relatively high (30.2%).

Combination of Low Rate of γδ T Cells and High Rate of Regulatory T Cells after Allogeneic Stem Cell Transplantation Is a Poor Prognostic Factor for Patients with Hematological Neoplasm

After allogeneic hematopoietic stem cell transplantation (HSCT), immune recovery is important to protect the patient from relapse and co-morbidities such as graft-versus-host disease (GVHD) and infection. Various numbers of low-frequency immunocompetent cells are known to exist among T cells and each subset shows different immunological action. Among them, γδ T cells were reported to facilitate a graft-versus-leukemia (GVL) effect and regulatory T cells (Tregs) were reported to prevent acute GVHD. In this study, we focused on the clinical relevance of γδ T cells and Tregs in peripheral blood (PB) after allogeneic HSCT in patients with hematological neoplasm to outcome. We retrospectively analyzed 33 adult patients with hematological neoplasms who underwent allogeneic HSCT between July 2011 and February 2015 at Niigata University Medical and Dental Hospital, including 17 with acute myeloid leukemia, 8 with acute lymphoblastic leukemia, 4 with myelodysplastic syndromes, 2 with Epstein-Barr virus-associated lymphoproliferative disorder, 1 with adult T-cell leukemia/lymphoma and 1 with primary myelofibrosis. Circulating γδ T cells and Tregs were analyzed by flow cytometry within 30-100 days after allogeneic HSCT. γδ T cells were identified as CD3+/γδTCR+ cells. Tregs were identified as CD4+/Foxp3+/CD25+ cells. The percentage of γδ T cells was calculated by dividing by CD3+ cells. The percentage of Tregs was calculated by dividing by CD4+ cells. The Kaplan-Meier method was used to estimate the probability of disease-free survival (DFS). The Mann-Whitney U test was used to compare the percentage of γδ T cells in PB or Tregs in PB and any grade of acute GVHD or grade II-IV acute GVHD. Cumulative relapse rate and non-relapse mortality (NRM) were based on Gray's estimates. Fine-Gray proportional hazards models were used for assessment by multivariate analysis of relapse rate. Factor adjustment was performed for age, conditioning regimen, disease status and HLA compatibility. The median percentage of γδ T cells divided by CD3+ cells in PB was 3.3% (0-28.4%). The median percentage of Tregs divided by CD4+ cells in PB was 1.9% (0-17.3%). The percentage of γδ T cells in PB was not associated with the incidence of acute GVHD. In addition, the percentage of Tregs in PB was not associated with the incidence of acute GVHD. Next, we established an immune scoring system according to the percentage of γδ T cells and Tregs in PB. Less than 4% of γδ T cells as a proportion of CD3+ cells in PB was scored as 1 point and more than 4% of Tregs as a proportion of CD4+ cells in PB was scored as 1 point. The patients with 1 point for γδ T cells did not show a significant difference to the patients with 0 points in terms of cumulative relapse rate or NRM. In addition, the patients with 1 point for Tregs did not show a significant difference to the patients with 0 points in terms of cumulative relapse rate or NRM. We classified the patients into score 0-1 and score 2 upon adding the points. Patients with score 2 showed a higher relapse rate in univariate analysis (p=0.002) and multivariate analysis (hazard ratio 3.65, p=0.017) than patients with score 0-1. Moreover, patients with score 2 showed higher DFS in univariate analysis (p=0.001) and multivariate analysis (hazard ratio 3.50, p=0.027) than patients with score 0-1. Our study suggests that the combination of a low rate of γδ T cells and a high rate of Tregs in PB after allogeneic HSCT is a poor prognostic factor for patients with hematological neoplasm. In addition, it suggests that the balance of immunosuppression and immunoactivation may be important for the outcome of patients after allogeneic HSCT. Disclosures No relevant conflicts of interest to declare.

Clinical Study of Allo-HSCT with Conditioning Regimen Containing Decitabine in the Treatment of advanced Acute Myloid Leukemia and Myelodysplastic Syndrom

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment options to hematologic malignancies. However, majority of patients with refractory or resistant hematologic malignancies can not achieve remission before transplantation. And the relapse rate of these patients after transplantation remains high obviously. Therefore, it is necessary to design a safe and effective conditioning regimen to improve the remission rate of these patients and disease-free survival (DFS), but to reduce transplantation related mortality (TRM). The optimal conditioning regimen not only can reduce tumor burden and eradicate minimal residual disease but also can make immunosuppressive state to ensure engraftment. As well as, it does not increase the TRM. One of the promising drugs of epigenetics is decitabine (DAC), which has a significant effect on a variety of hematologic malignancies. It is widely used in myelodysplastic syndromes(MDS) even for relapsed and refractory acute myelocytic leukaemia (AML). Because decitabine can not only up-modulate the tumor-associated antigen express on surface of leukemia cells to increase graft-versus-leukemia (GVL) effect but also can reduce the incidence of graft-versus-host disease (GVHD) by increase the number of regulatory T Cells（Tregs）. Aims: This clinical study will investigate the security and efficacy of conditioning regimen containing decitabine. Further to explore the role in advanced malignant hematologic disease. Methods: We retrospectively studied 20 cases of patients with hematologic malignancies, who underwent allo-HSCT with decitabine combined with conditioning regimens in the Department of Hematology, the First Affiliated Hospital of Soochow University during May 1, 2012 to April 30, 2014. Results: 19 patients achieved complete remission and hematopoietic reconstitution after transplantation. Only 1 NR case died on day +27 post transplant. The median time of neutrophil and platelet reconstitution were 12 (10-22) and 14.5 (12-35) days respectively. The median time of archiving full donor chimerism [short tandem repeat (STR)STR>95%] was 18(13-62) days. The median follow-up post transplant was 246 (19-582) days. 3 cases relapsed. 2 cases were dead due to relapse.1 case achieved complete remission again after donor lymphocyte infusion (DLI). 1 CR case was dead due to hemorrhage of digestive tract. The other 15 CR cases were survival with continued remission. The estimated 2-year overall survival (2yr-OS) rate was 78%.The 2 year disease-free survival (2yr-DFS) rate was 62.6%. The cumulative relapse rate was 26.7%. The transplantation-related mortality (TRM) rate was 0. Furthermore, the estimated 2-yr OS and DFS of patients with DNMT3A mutations or abnormalities of chromosome 7 and complex chromosomal karyotype were 72.9% and 60.6% respectively. Concerning about transplant related toxicity, except one case has grade III gastrointestinal toxicity, all the other toxicities were mild (grade I-II). The cumulative rate of aGVHD and cGVHD were 20.5% and 48.3%.And the cumulative rate of aGVHD for grade I-II and grade II-IV were 15% and 10.5%. Conclusions Allo-HSCT is an effective treatment for refractory and relapsed AML and high- risk MDS. It is feasible to use conditioning regimen containing decitabine before allo-HSCT. The treatment were well tolerated. 92.3% of the patiants achieved CR, and were well engraftment. Because of decitabine can promote megakaryocytic maturation and accelerate the release of platelet, so hematopoietic was reconstructed rapidly, especially for the megakaryocyte. The 2yr-DFS rate was 62.6%, the cumulative relapse rate was 26.7%. The conditioning regimen containing decitabine before allo-HSCT seems to reduce the incidence of aGVHD. The prognosis and survival of the patients with complex chromosomal karyotype or chromosome 7 abnormalities or DNMT3A mutation may be improved by treating with decitabine containing conditioning regimen. Disclosures No relevant conflicts of interest to declare.