Survival In Intermediate-risk Patients Research Articles

Risk-adapted local therapy and intensive chemotherapy in patients with high-risk rhabdomyosarcoma.

10031 Background: Outcomes for patients with metastatic RMS remain poor. Dose escalation of radiation may reduce risk of local failure, and maintenance therapy has prolonged survival in intermediate risk patients. We investigated a multimodal chemotherapeutic regimen with risk adapted local therapy and the addition of maintenance therapy following intensive chemotherapy to improve the outcome for patients with high-risk RMS. Methods: We conducted a phase 2 multi-center trial for patients with newly diagnosed high-risk (stage 4) RMS. Patients received 54 weeks of chemotherapy (vincristine/irinotecan, interval compressed vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide, and vincristine/dactinomycin/cyclophosphamide) followed by 4 cycles of anti-angiogenic maintenance therapy (bevacizumab, sorafenib, cyclophosphamide). Primary tumor local control consisted of surgery and photon/proton radiation therapy (RT) dependent on the degree of resection (negative margin – no RT, positive margin – 36 GyRBE, unresected ≤5cm – 50.4 GyRBE, unresected > 5cm – 59.4 GyRBE). RT was administered at Week 4 or 20 based on size/location, and to radiographically visible (non-CR) sites of metastatic disease at end of treatment. Results: Thirty-nine eligible patients with high-risk RMS (64% FOXO1 fusion positive, 74% with nodal disease, 67% Oberlin score > 1) were enrolled. Two of 13 patients with Oberlin score ≤ 1 were FOXO1 fusion positive whereas 23 of 26 patients with Oberlin score > 1 were fusion positive. Seventeen patients received maintenance therapy as planned (progression, n = 12; received alternate maintenance regimen, n = 4; other, n = 6) with a median of 4 cycles (range 1-4). Common toxicities of maintenance included palmar-plantar erythrodysesthesia (n = 9), rash (n = 7), and cystitis (n = 6). At a median follow-up of 43.5 months for survivors, 3-year EFS was 29.5% (95% CI 15.4-45.1%). Fusion positive status significantly predicted EFS (negative, 60.6% vs. positive, 9.6%, p = 0.019), whereas low Oberlin score approached significance for EFS (≤1, 56.6% vs. > 1, 16.4%, p = 0.064). The cumulative incidence of local failure was 17.5% (95% CI 6.9-32.2%). Twenty-one patients achieved CR of all metastatic sites and did not receive metastatic site RT. Of those, 7 experienced disease recurrence in a pre-existing metastatic soft tissue site. Among 4 patients who received metastatic site RT at the end of treatment, one patient experienced disease recurrence in a pre-existing metastatic site. Conclusions: The addition of maintenance therapy to intensive chemotherapy and risk adapted radiotherapy did not improve EFS in this population. Consolidative radiation should be considered for soft tissue metastatic sites regardless of radiographic response. Clinical trial information: NCT01871766.

Comparison of adenocarcinoma and adenosquamous carcinoma prognoses in Chinese patients with FIGO stage IB-IIA cervical cancer following radical surgery

BackgroundTo compare adenocarcinoma (AC) and adenosquamous carcinoma (ASC) prognoses in patients with FIGO stage IB–IIA cervical cancer who underwent radical hysterectomy.MethodsWe performed a retrospective analysis of 240 patients with AC and 130 patients with ASC. Kaplan–Meier curves, Cox regression models, and log-rank tests were used for statistical analysis.ResultsPatients with ASC had higher frequencies of lymphovascular space invasion (LVSI) and serum squamous cell carcinoma antigen (SCC-Ag) > 5 ng/ml (p = 0.049 and p = 0.013, respectively); moreover, they were much older (P = 0.029) than patients with AC. There were no clinically significant differences in overall survival (OS) between the groups. When stratified into three risk groups based on clinicopathological features, survival outcomes did not differ between patients with AC and those with ASC in any risk group. Multivariate analysis showed that lymph node metastasis (LNM) was an independent risk factor for recurrence-free survival (RFS) and OS in patients with AC and in patients with ASC. Carcinoembryonic antigen (CEA) > 5 ng/ml and SCC-Ag > 5 ng/ml were independent predictors of RFS and OS in patients with AC. In addition, among those stratified as intermediate-risk, patients with ASC who received concurrent chemoradiotherapy (CCRT) had significantly better RFS and OS (P = 0.036 and P = 0.047, respectively).ConclusionsWe did not find evidence to suggest that AC and ASC subtypes of cervical cancer were associated with different survival outcomes. CCRT is beneficial for survival in intermediate-risk patients with ASC, but not in those with AC. Serum tumour markers can assist in evaluating prognosis and in providing additional information for patient-tailored therapy for cervical AC.

Low Platelet Counts at Diagnosis Predict Better Survival for Patients with Intermediate-Risk Acute Myeloid Leukemia

Background: Aggressive growth of primitive and immature cells in the bone marrow results in reductions in megakaryocyte and platelet (PLT) counts, leading to thrombocytopenia in acute myeloid leukemia (AML). However, not all AML patients show thrombocytopenia at the time of diagnosis, and the association of PLT count with patient survival is largely unknown. Methods: A retrospective study was performed to determine PLT counts at diagnosis in the peripheral blood in 291 newly diagnosed AML patients and assess the association of PLT counts with the overall survival (OS) and disease-free survival (DFS) of these patients. Results: Low PLT counts (≤40 × 10⁹/L) were associated with better outcomes for the whole cohort (5-year OS, 55.1 ± 3.8 vs. 35.3 ± 3.5%, p < 0.001; 5-year DFS, 49.1 ± 3.8 vs. 25.7 ± 4.0%, p < 0.001) and intermediate-risk patients (5-year OS, 64.5 ± 5.4 vs. 41.0 ± 4.8%, p < 0.001; 5-year DFS, 60.8 ± 5.6 vs. 28.6 ± 5.6%, p < 0.001). Moreover, low PLT counts were related to deeper molecular remission. Low PLT counts correlated with better survival of intermediate-risk AML patients treated with chemotherapy only. Allogeneic hematopoietic stem cell transplantation attenuated the negative impact of high PLT counts on the survival of intermediate-risk patients. Furthermore, univariate and multivariate analyses demonstrated that PLT count at diagnosis was an independent prognostic factor for intermediate-risk AML. Conclusion: PLT count at diagnosis predicts survival for patients with intermediate-risk AML.

Impact of guideline-based use of uPA/PAI-1 on patient outcome in intermediate-risk early breast cancer.

The purpose of this study was to evaluate the influence of guideline-based prospective use of uPA/PAI-1 on clinical outcome in an intermediate-risk cohort of breast cancer patients. We analyzed 381 consecutive primary breast cancer patients (2003-2011) at the breast center Ostbayern meeting the following criteria: M0/N0/estrogen receptor (ER)+/G2. Clinical-pathological data, uPA/PAI-1, and follow-up data were collected. Decisions for adjuvant chemotherapy were made upon consideration of prospectively measured uPA/PAI-1. Observed disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier estimates. Using guideline-based analysis of uPA/PAI-1, treatment with adjuvant chemotherapy was avoided in 86.5% of patients with low uPA/PAI-1, i.e., 38.8% of the total patient collective. Median follow-up was 52.5months. Five-year relapse-free survival in intermediate-risk patients (N0, G2) without chemotherapy was 99%. Five-year overall survival including all causes of death was 95%. By using uPA/PAI-1, adjuvant chemotherapy can be avoided in a major part of patients with intermediate-risk breast cancer. Nevertheless, DFS and OS of these patients at 5years remain excellent. The potential, but hardly measurable, benefit of adjuvant chemotherapy has to be set in contrast with its associated side effects and increased morbidity. Patients with high uPA/PAI-1 show benefit from chemotherapy. In this subgroup, a very good OS was observed as well. These findings strongly support the use of uPA/PAI-1 together with clinic-pathological parameters as an evidence-based, clinically relevant and inexpensive decision tool in the routine of a breast center.

Impact of Post-Remission Consolidation Modalities in the Clinical Outcomes of Acute Myeloid Leukemia Patients in First Remission - Is There a Role for Autologous Hematopoietic Stem Cell Transplant?

The optimal post-remission consolidation in Acute Myeloid Leukemia (AML) remains a topic of some debate, especially in the intermediate risk group of patients. We undertook a retrospective analysis of newly diagnosed AML patients treated in Singapore General Hospital from 1999 to 2012. Patients with M3 AML and patients who did not receive treatment of curative intent were excluded.286 patients were identified for analysis, median age was 48 (range 15 to 79), ELN risk grouping: Favorable (FR) (n=84), Intermediate-1 (IR1) (n=120), Intermediate-2 (IR2) (n=57), and High risk (HR) (n=25). Post-remission therapy was administered as follows, 107 received high dose cytarabine (HiDAC) consolidation, 67 received autologous hematopoietic stem cell transplant (HCT), and 112 received allogeneic HSCT. Conditioning for allogeneic HCT was administered according to widely accepted protocols: bulsuphan and cyclophosphamide (Bu/Cy) for patients 50 years and younger while reduced intensity or non-myeloablative protocol was administered for older patients or the physically unfit. Patients for Autologous HCT were mobilized with VP16 and cytarabine and conditioned with Bu/Cy. HiDAC was administered at 3g/m2 q12h on days 1, 3 and 5; the dose was reduced to 1 to 1.5g/m2 for those above 60 years old, median number of HiDAC cycles was 4 (range 1 - 4).After a median follow up of 110 months, 5 year overall survival (OS) between patients who received HiDAC, autologous HCT and allogeneic HCT was 43.2 %, 63% and 48.3% (p =.04), 5 year leukemia free survival (LFS) was 40.3%, 61% and 43.2% and (p = .01). The apparent difference between autologous and allogeneic HSCT (p=.119) disappeared when we excluded HR patients, in which only 1 received autologous HSCT. However, the OS difference between autologous HSCT and HiDAC remained significant (p=.03). When patients were stratified according to ELN risk, OS and LFS were similar in FR patients regardless of consolidation modalities (p = .67 and p = .18) while IR1 and 2 patients receiving HiDAC had poorer outcomes when compared with autologous and allogeneic HSCT (OS: 26.9%, 57.6%, 54.1%; LFS: 23.4%, 56.3%, 45.9% respectively, p < .0001 for OS and LFS), this remained significant when patients who did not complete at least 3 cycles of HiDAC consolidation were excluded (p = .02 for OS and LFS).In those who underwent autologous HSCT, predictors of better survival were age < 40 years (5yr OS 74.2% vs 56.7% p = .04, 5yr LFS 70% vs 56.7% p = .09), ELN favorable risk (5yr OS 80% vs 55% p = .03, 5 yr LFS 70% vs 55% p = .08) and bone marrow (BM) blast percentage of less than 70% in conjunction with a diagnostic white blood count (WBC) of less than 30 x 109 (5yr OS 75.7% vs 40% p = .007, 5yr LFS 70.9% vs 40% p = .01). On multivariate analysis, only BM blast of < 70% and diagnostic WBC of less than 30 x 109 remained predictive of OS (p = .048) and LFS (p = .049).Long term outcomes of patients who remained disease free 2 years post consolidation were excellent, with 84.5% alive and disease free 10 years after diagnosis. 4 (9.3%) patients relapsed in the HiDAC group, 6 (14.3%) in autologous HSCT and 2 (4%) in allogeneic HCT group. There is a tendency towards late AML relapse (> 4 yrs) in patients receiving HiDAC and autologous HCT (4/43 and 4/42 respectively) compared with those receiving allogeneic HSCT 1/49, although the differences were not statistically significant (p = .36). 8 patients in both HiDAC and autologous HSCT group developed a secondary malignancy while 3 in the allogeneic HCT group had a second cancer. 10yr OS in those who were alive and disease free 2 years post consolidation was 88.7% in the HiDAC group, 82.6% in the autologous group and 85.6% in the allogeneic group.In conclusion autologous HCT remains a viable post-remission treatment modality for AML in first complete remission, with acceptable short and long term outcomes compared with allogeneic HCT and HiDAC consolidation. The benefit of autologous HCT appears to be most pronounced in the IR group and patients with low BM blast and WBC at diagnosis. We recommend that autologous HCT be considered in these groups of patients without a matched donor.Overall Survival for intermediate risk patients. P = < 0.001 Leukemia Free Survival for intermediate risk patients. P = < 0.001 [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.