Event Free Interval Research Articles

Acute lymphoblastic leukemia in children with Down syndrome: Comparative analysis versus patients without Down syndrome.

Children with Down syndrome (DS) more commonly have acute lymphoblastic leukemia (ALL) and a lower survival rate than those without Down syndrome (WDS). We analyzed the clinical, demographic, and biological characteristics and treatment response of children with DS-ALL versus those WDS-ALL. Patients and methods: Patients with ALL between January 1990 and November 2016. The demographic and biologic characteristics and treatment response were compared using the χ² and Wilcoxon rank-sum tests. The overall survival and event-free interval (EFI) were analyzed using the Kaplan-Meier and log-rank tests. 1795 patients were included; 54 had DS. Patients with DS-ALL were older (p= 0.0189). All had B-cell precursor immunophenotype and a lower incidence of recurrent abnormalities (p < 0.0001). They showed a better response rate to prednisone (p= 0.09) and a higher mortality in induction and complete remission (p < 0.0001). All deaths of patients with DS-ALL were treatment-related. The event-free survival (EFS) was 47% (± 8%) versus 73% (± 1%) (p= 0.006) and the EFI was 54% (± 9%) versus 75% (± 1%) (p= 0.0297) among patients with DS-ALL versus those WDS-ALL, respectively. The rate of relapse was similar in both groups (p= 0.6894). The EFI of patients with DS-ALL was lower in the group aged 6-9 years: 39% (± 19%) (p= 0.7885). A lower survival was observed among children aged 6-9 years with DS-ALL. Although these children showed a better early response, their EFS and EFI were lower due to treatment-related mortality.

Study of Management of Retinoblastoma with Vitreous Seeds (Retrospective Study)

AbstractBackground: The response of retinoblastoma with vitreous seeds to the different modalities of treatment as regards tumor regression, vitreous seeds regression and eye salvage.Aim of the Work: Study of the response of Rb with vitreous seeds to the different modalities of treatment as regards tumor regression, vitreous seeds regression and eye salvage.Patients and methods: This is a retrospective observational study in which we collected the data from medical records of cases of retinoblastoma with vitreous seeds who were managed over ten years at Ocular Oncology Unit, Ophthalmology Department, Ain Shams University Hospitals in the period from January 2004 to June 2015 and followed-up for at least 12 months after the completion of treatment. Our study included 37 patients. Fourty-two eyes affected with retino-blastoma with vitreous seeds were divided into four groups according to the modality of treatment: Group (1): 15 eyes treated with chemoreduction±focal therapy (diode laser ther-motherapy or cryotherapy), Group (2): 8 eyes treated with intravitreal chemotherapy, Group (3): 2 eyes treated with intra-arterial chemotherapy and Group (4): 17 eyes of treated with subTenon's Carboplatin. All eyes had received systemic chemotherapy as a primary treatment before these modalities of treatment.Results: Our study showed that the rate of ocular salvage was the highest in group 4 (52.9%) followed by group 1 (40%), group 2 (20%) and group 3 (0.0%). There was a statistically significant difference between group 1 and group 4 as regards tumor number, tumor location, tumor base diam-eter, number of thermotherapy sessions as primary treatment, mean duration of follow-up and event free interval from last treatment.Conclusion: Subtenon's Carboplatin, chemoreduction plus focal therapy, intravitreal chemotherapy and intra-arterial chemotherapy may be effective supplementary modalities of treatment that help in ocular salvage.

Abstract P2-01-22: The long term outcomes of Metasin RTqPCR intra-operative sentinel node analysis in early breast cancer

Abstract Background: Axillary lymph node involvement is a prognostic factor in breast cancer and it is used to guide adjuvant therapy. Axillary clearance remains the standard of care in lymph node positive disease in most parts of the world. Usually this is performed as second procedure but immediate intra-operative node analysis allows clearance to be performed as part of the initial procedure where necessary. The Metasin assay targets the breast epithelial cell markers CK19 and mammaglobin mRNA and detects the presence of breast tissue (metastatic disease) in the sentinel nodes. Evidence shows the Metasin assay to be fast (average assay time 41.2min) and accurate with a discordance rate below 4% compared with histology. The cost effectiveness of the assay has been reported in our previous studies. Aim: The aim of this study is to assess the risk of axillary recurrence following the use of the Metasin assay to guide axillary management. Method: This is a single centre retrospective study which included all patients presenting to a district general hospital with early clinically node negative breast cancer undergoing sentinel node biopsy between Oct 2011 and Dec 2014. Alternate 2 mm slices of the node were examined intraoperatively using the Metasin assay and the remainder sent for histological examination. The results of the Metasin assay and histology were compared. The risk of axillary recurrence using the Metasin test to select patients for immediate axillary clearance was assessed. Results: 1073 sentinel nodes from 545 patients were analysed during this three-year period. 2 patients were lost to follow up. 94 patients were node positive and underwent axillary clearance as part of their primary surgery. 449 patients had sentinel node biopsy with no further axillary procedure. There were 36 nodes (3.34%) with discordant results. Median follow up was 32 months (range 18 to 55 months). Fourteen patients presented with recurrences (2.56%). The mean event free interval was 15 months. Of the 14 patients, 5 patients tested with Metasin had macrometastases and underwent immediate axillary clearance during the primary surgery. 7 patients were node negative and 2 patients were shown to have micrometastases. 11 patients recurred with distant metastases, 3 patients with local recurrence and 2 patients (0.36%) with axillary recurrences. The two axillary recurrences occurred at 3 and 5 months after primary surgery. Both patients underwent Metasin intraoperative analyses of sentinel nodes which were negative. Subsequent histological examination confirmed no metastatic node involvement in one patient but micro-metastases in the other. Both of these patients had aggressive disease with local, axillary and distant metastasis and subsequently died of their disease. Conclusions: The Metasin assay is a reliable intraoperative test for sentinel node involvement and when used to guide surgical axillary management is associated with very low axillary recurrences (0.36% with a median follow up of 32 months). Citation Format: Udayasankar S, Ashley E, Jenkins KS, Huws A, Sharaiha Y, Sai-Giridhar P, Thomas D, Munir A, Holt S, Khawaja S. The long term outcomes of Metasin RTqPCR intra-operative sentinel node analysis in early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-22.

The impact of a prior history of cardiovascular events on outcomes in patients on renal replacement therapy

Renal transplant centers have evolved extensive cardiovascular evaluation protocols to screen potential candidates prior to initiation of dialysis. The risk of new cardiac events remains high even among patients initiating hemodialysis with no previous cardiac symptoms [1]. A key unanswered question remains whether prior thromboembolic events themselves have a role in prognosis for patients undergoing renal replacement therapy (RRT). We followed stable diabetic patients on RRT to determine whether a history of previous cardiovascular events (PCVE) could predict subsequent cardiovascular events (SCVE) and all cause mortality. After approval by Institutional Review Boards, clinically stable patients undergoing RRT in participating dialysis units were consecutively enrolled. PCVE included myocardial infarction, coronary artery intervention, peripheral bypass or amputation surgery, cerebrovascular accident, or carotid artery intervention and the occurrence of subsequent events until July 15, 2010. Subjects lost to follow up were censored at last documented clinic visit. For patients receiving a transplant during the study, follow up was concluded at surgery. Information retrieved from the Social Security Death Index was considered valid for end-point with cause of death “unknown.” Dialysis patients were considered under entry mode of treatment with either hemodialysis (HD) or peritoneal dialysis (PD) throughout the entire course of study. The Kaplan–Meier function was utilized to estimate years of event free interval (EFI); medians and 95% confidence limits are reported. Comparisons between function curves and medians were tested for significance using the log-rank test [2].

Locoregional recurrence after breast-conserving therapy remains an independent prognostic factor even after an event free interval of 10 years in early stage breast cancer

IntroductionLocoregional recurrence (LRR) after breast-conserving therapy is a well-known independent risk factor associated with unfavourable long-term outcome. Controversy exists concerning the prognostic impact of a LRR after a very long event-free interval. MethodPatients who underwent breast-conserving therapy for early stage breast cancer were pooled from four European Organisation for Research and Treatment of Cancer (EORTC) Breast Group trials. Only LRR as a first event was taken into account. Risk factors such as tumour size, nodal status, young age and chemotherapy were assessed in multivariate Cox regression analysis. LRR was used as a time-dependent variable in the landmark analysis for distant disease-free survival (DFS) and overall survival (OS). Patients were categorised as having at least 0, 5 or 10years event-free survival. ResultsIn total, 7751 early stage breast cancer patients were included with a median follow-up of 10.9years. Tumour size, nodal status, young age and chemotherapy are strong independent prognostic factors with a significant impact on long-term outcome, but lose their power and significance over time. Including all patients, LRR was the strongest prognostic factor for OS and distant DFS (resp. HR 5.01 and HR 5.31, p<0.001). In the subgroup of patients developing a LRR after at least 5 or 10years, LRR remained the strongest independent prognostic factor for OS (resp. HR 3.98, HR 4.96, p⩽0.001) and distant DFS (HR 4.42, HR 7.57 p<0.001). ConclusionThis is the first study which shows LRR after breast-conserving therapy is a very strong, time-independent prognostic factor for long term outcome in early stage breast cancer patients. These findings suggest that a LRR after a long event-free interval seems to be an indicator rather than an instigator of subsequent distant disease.

106 Locoregional recurrence after breast conserving therapy remains an independent prognostic factor even after an event free interval of ten years in early stage breast cancer

106 Locoregional recurrence after breast conserving therapy remains an independent prognostic factor even after an event free interval of ten years in early stage breast cancer

Vaginal brachytherapy alone: An alternative to adjuvant whole pelvis radiation for early stage endometrial cancer

Objective. Postoperative management of early stage adenocarcinoma of the endometrium remains controversial. The use of pelvic radiation therapy as shown by the Gynecologic Oncology Group (GOG)-99 trial improves the event free interval at the cost of increased toxicity. We reviewed and compared our results treating early stage endometrial adenocarcinoma using hypofractionated high dose rate (HDR) vaginal brachytherapy (VB) alone with the results of the GOG-99. Methods. From 1992 to 2002, 243 endometrial cancer patients were treated with TAH/BSO and selective lymph node dissection followed by adjuvant radiotherapy (RT). Of these, 50 FIGO stage I–II (occult) adenocarcinoma (no clear cell or serous papillary) of the endometrium were managed with HDR hypofractionated VB as monotherapy using Iridium-192 to a dose of 30 Gy in 6 fractions twice weekly prescribed to a depth of 5 mm and median length of 4 cm. The characteristics, toxicity rates, and outcomes of our patients were compared with the results of the GOG-99. The median follow up of our patients and the GOG-99 were 3.2 years and 5.8 years, respectively. Results. Patient characteristics including age, stage, and grade were similar in our study and the GOG-99. The local recurrence rate in our study, the pelvic RT arm of the GOG-99, and the no RT arm of the GOG-99 were 4% ( n = 2), 2% ( n = 3), and 9% ( n = 18), respectively. In our study, one patient failed in the vagina alone and a second patient failed in the vagina and pelvis. In the GOG-99, the vagina as a component of locoregional failure was also the most common failure site in the no RT arm 77.8% ( n = 14) and in the RT arm 100% ( n = 3). The 2-year cumulative recurrence rate in our study was 2%, which compares favorably with the GOG-99 pelvic RT arm (3%) and observation arm (12%). Four-year survival rates of the no RT arm of the GOG-99, the RT arm of the GOG-99, and our study with HDR VB were 86%, 92%, and 97%, respectively. Chronic grade 2 toxicity rates were reduced by the use of VB compared to pelvic RT, especially GI toxicity 0% vs. 34% ( P value < 0.001), and GI obstruction 0% vs. 7% ( P value = 0.08). Conclusion. Stage I–II (occult) endometrial adenocarcinoma treated with postoperative HDR vaginal brachytherapy has similar overall survival, locoregional failure rates, and cumulative recurrence rates to standard fractionation external beam pelvic RT with the benefit of much lower toxicity rates and shorter overall treatment time.

Vaginal brachytherapy alone: An alternative to whole pelvis radiation for early stage endometrial cancer

Vaginal brachytherapy alone: An alternative to whole pelvis radiation for early stage endometrial cancer

Treating childhood acute myeloid leukaemia with the AML-BFM-83 protocol: experience in a developing country.

Treatment for childhood acute myeloid leukaemia (AML) consists of remission induction chemotherapy followed by postremission chemotherapy with or without bone marrow transplantation. The AML Berlin-Frankfurt-Munster (BFM)-83 protocol with induction-consolidation-maintenance chemotherapy for 2 years has been reported to result in a 6-year event-free survival (EFS) and event-free interval (EFI) of 49% and 61% respectively. A total of 174 Malaysian children were treated with this protocol between 1985 and 1999. The 5-year EFS and EFI was 30.7% and 48.0% respectively. The overall mortality from sepsis was 24%, which needs urgent address. The 5-year EFS for patients treated before 1993 and after 1993 was 18.6% and 41.3%, respectively (P = 0.04), while the EFI was 32% and 60.6% respectively (P = 0.034). The improvement seen after 1993 was related to a reduction in induction deaths for that period and probably reflected increased capability and familiarity to cope with the demands of the AML-BFM-83 protocol and accompanying complications in the treatment of AML.

Clinical study on effect of Fuzheng Kangbai Granule"Equation missing" on long-term survival of patients with acute leukemia) on long-term survival of patients with acute leukemia

Objective: To observe the effect of Fuzheng Kangbai Granule (FZKBG) on long-term survival of patients with acute leukemia, and to study its mechanism in treating minimal residual leukemia.Methods: FZKBG was used to treat 90 cases of completely remitted acute leukemia to observe the effect of treatment on 5-year event free interval (EFI), over survival (OS) and the immune function of patients.Results: Five-year EFI and OS of the 90 cases were 62.4% and 77.2% respectively, and the immune functions after FZKBG therapy were improved significantly.Conclusion: FZKBG could increase the 5-year EFI and 5-year OS, which might be reached through improving immune function of patients.

Results of treatment with an intensive induction regimen using idarubicin in combination with cytarabine and etoposide in children with acute myeloblastic leukemia

We report results achieved in our institution with a study opened in July 1990 (similar to the German AML-BFM-87 in which daunorubicin was replaced by idarubicin in the induction phase and cranial preventive radiotherapy was omitted) and closed in December 1994, for the treatment of newly diagnosed acute myeloblastic leukemia (AML), without prior malignancies except for myelodysplasia. This evaluation included 68 patients, whose mean age was 6 years (range: 1 month–16 years). Thirty-nine were boys and 29 were girls. Complete remission rate was 80.9% ( 55 68 ), death on induction rate was 14.7% and induction failure rate was 4.4%. At median follow up of 38 months (range: 12–66 months), the 4-year event-free survival (EFS) estimate was 0.428 (S.E.: 0.062), event-free interval (EFI) estimate was 0.529 (S.E.: 0.07) and overall survival (OS) estimate was 0.44 (S.E.: 0.071). We conclude that idarubicin in combination with cytarabine and etoposide is a highly effective regimen for induction in children with AML. Although preventive cranial irradiation was not delivered, we have observed only one combined CNS relapse. Finally, we corroborate that in this setting two definite risk groups may be identified in children with AML.

Acute Myeloid Leukemia in Children Less Than Two Years Old: Clinical, Cytologic and Cytogenetic Correlations Comparison with other age categories. A clinical survey of 39 cases

Thirty-nine children under two years of age with newly diagnosed Acute Myeloid Leukemia (AML) were consecutively admitted to the Hôpital Saint-Louis (Paris) over a ten-year period (1978-1987). Nineteen were under one year of age at diagnosis and 3 had congenital leukemia. Comparison of FAB sub-classes among the different age categories showed that AML with a monocytic component (M4 and M5) (44%), and AML with megakaryocytic elements (M7) (21%), were much more frequent in children before the age of two years. This comparison was made on a series of 1409 AML and 859 ALL diagnosed in the same hospital during a twelve years period of time. During this period of observation, the compared incidence of ALL and AML showed 50% for each category for children under 2 years, 73% ALL versus 27% AML for children under 15 years, and 18% ALL versus 82% AML for adults. Of the 29 cases subjected to cytogenetic study, 62% had clonal chromosomal abnormalities, the most frequent being a translocation involving the long arm of chromosome 11. With a 72 months median follow-up for patients who are still alive, the 6-year actuarial survival was 23%, while the event free interval for Complete Remission (CR) patients was 35%. For the M4-M5 subgroup, these results were 37% and 50% respectively with a plateau reached at 27 months. M4-M5 FAB types represented the most common leukemia at this age, and these usually correlated with translocation of the long arm of chromosome 11. We obtained an unexpectedly high rate of survival, with acceptable sequellae, for children treated with intensive chemotherapy.

Identification of two risk groups in childhood acute myelogenous leukemia after therapy intensification in study AML-BFM-83 as compared with study AML-BFM-78. AML-BFM Study Group

The main difference between the two cooperative studies on therapy of childhood acute myelogenous leukemia AML-BFM-78 and AML-BFM-83 was the addition of an 8-day ADE (cytosine arabinoside, daunorubicin, etoposide) induction treatment in the second study. Due to this intensification, the relapse rate, but not the rate of induction failures, was reduced. The probability of a 6-year event-free survival increased from 38%, SD 4%, in study AML-BFM-78 to 49%, SD 4%, in study AML-BFM-83, P = .08. The improvement of the 6-year event-free interval (EFI) was significant in the second study (61%, SD 4%, versus 47%, SD 5%, P less than .05); it was restricted to the FAB types M1 through M4 (EFI: 67%, SD 5%, versus 45%, SD 5%, P less than .01). The difference in EFI seen in FAB M5 was not statistically significant (EFI: 40%, SD 10%, versus 63%, SD 11%, NS). According to the results of the second study, two different risk groups (low and high) could be identified by combinations of predominantly pretherapeutic parameters. The low risk group, comprising 37% of the patients who achieved complete remission, included the FAB types with granulocytic differentiation and specific additional features: FAB M1 with Auer rods, FAB M2 with white blood cell count of less than 20,000/microL, FAB M3 all patients, and FAB M4 with eosinophilia. The 6-year Kaplan-Meier estimation of EFI is 91%, SD 4%, compared with 42%, SD 6% in the high risk group. In future studies based on the AML-BFM-83 treatment, bone marrow transplantation in first remission should be mandatory only for children of the high risk group.

Identification of Two Risk Groups in Childhood Acute Myelogenous Leukemia After Therapy Intensification in Study AML-BFM-83 as Compared With Study AML-BFM-78

The main difference between the two cooperative studies on therapy of childhood acute myelogenous leukemia AML-BFM-78 and AML-BFM-83 was the addition of an 8-day ADE (cytosine arabinoside, daunorubicin, etoposide) induction treatment in the second study. Due to this intensification, the relapse rate, but not the rate of induction failures, was reduced. The probability of a 6-year event-free survival increased from 38%, SD 4%, in study AML-BFM-78 to 49%, SD 4%, in study AML-BFM-83, P = .08. The improvement of the 6-year event-free interval (EFI) was significant in the second study (61%, SD 4%, versus 47%, SD 5%, P less than .05); it was restricted to the FAB types M1 through M4 (EFI: 67%, SD 5%, versus 45%, SD 5%, P less than .01). The difference in EFI seen in FAB M5 was not statistically significant (EFI: 40%, SD 10%, versus 63%, SD 11%, NS). According to the results of the second study, two different risk groups (low and high) could be identified by combinations of predominantly pretherapeutic parameters. The low risk group, comprising 37% of the patients who achieved complete remission, included the FAB types with granulocytic differentiation and specific additional features: FAB M1 with Auer rods, FAB M2 with white blood cell count of less than 20,000/microL, FAB M3 all patients, and FAB M4 with eosinophilia. The 6-year Kaplan-Meier estimation of EFI is 91%, SD 4%, compared with 42%, SD 6% in the high risk group. In future studies based on the AML-BFM-83 treatment, bone marrow transplantation in first remission should be mandatory only for children of the high risk group.