Favorable Prognostic Factor For Overall Survival Research Articles

Chinese medicine herbal treatment based on syndrome differentiation improves the overall survival of patients with unresectable hepatocellular carcinoma.

To investigate the effects of Chinese medicine (CM) herbal treatment based on syndrome differentiation on patients with unresectable hepatocellular carcinoma (HCC). A total of 94 patients with unresectable HCC were reviewed between June 2008 and June 2011. Survival analysis was performed between patients who received CM with/without non-curative antitumor treatments of Western medicine (WM) (CM group, 30 cases) and patients who were not treated with CM but with non-curative antitumor treatments of WM or supportive treatment alone (non-CM group, 64 cases). Then, survival analysis was performed between patients treated with CM combined with non-curative antitumor treatments of WM (combination therapy group, 25 cases) and patients with non-curative antitumor treatments of WM alone (non-curative antitumor treatments group of WM, 52 cases). The survival analysis was performed by Kaplan-Meier method and prognostic factors for overall survival (OS) were assessed by the Cox proportional hazards regression model. The median survival time (MST), 1- and 2-year survival rates of the CM group and the non-CM group were 36 months, 76.7%, 56.1% and 12 months, 48.4%, 26.6%, respectively. The Log-rank test revealed significant difference between the two groups in OS (P<0.01). Cox proportional multivariate analysis revealed that CM was an independent favorable prognostic factor for OS. The MST, 1- and 2-year survival rates of combination therapy group and non-curative antitumor treatments group of WM were 36 months, 76.0%, 55.5% and 13 months, 55.8%, 30.8%, respectively. There was significant difference in OS between the two groups (P=0.004). CM herbs based on syndrome differentiation have positive effects on survival of patients with unresectable HCC. Furthermore, combination therapy of CM and WM are recommended in HCC treatment.

Post Transplant Lymphoproliferative Disorders (PTLD) after Solid Organ Transplant: Cleveland Clinic Experience

Background: Post transplant lymphoproliferative disorders (PTLD) are rare pathologically and clinically heterogeneous diseases arising in the setting of immunosuppression following hematopoietic stem cell and solid organ transplants (SOT). Our understanding of PTLD is restricted by its low incidence and heterogeneous treatment approaches, resulting in paucity of data. We sought to further describe characteristics and outcomes in PTLD patients who underwent treatment at our institution.Methods and Patients: We performed a retrospective study to describe our institutional experience in a relatively large cohort of PTLD patients after SOT. Patient and disease characteristics were examined and prognostic factors for survival were determined using univariate and multivariate Cox analysis.Results: Between May 1987 to January 2014, 98 patients with a confirmed diagnosis of PTLD underwent treatment at our institution. Median time from SOT to PTLD diagnosis was 60 months with median follow of 68 months from PTLD diagnosis. Baseline characteristics include male gender 77%, ECOG performance status (PS) 0-1 in 61%, and stage III-IV 69% with a median age at diagnosis of 47 years. Most common transplanted organ included heart 30%, lung 24%, kidney 20% and liver 19% and median time from SOT to PTLD diagnosis was 60 months. Most cases had monomorphic histology (81%) and were EBV+ (82%). Graft involvement and rejection were observed in 32% and 43% respectively. Of the 84% with extranodal (EN) involvement, gastrointestinal tract (37%) and lung (27%) were the common sites, while 3.2% had bone marrow (BM) involvement. Central nervous system (CNS) was involved in 11% of the cases. Only 58% received rituximab as part of the initial therapy, as significant part of our cohort was treated prior to rituximab era. Reduction in immunosuppression (73%), chemotherapy (40%), radiation (11%) and surgery (8%) were utilized either as single modality or in combination for treatment. Of the 66 patients with response data, 59% had complete response (CR) and 14% had progressive disease (PD). Relapse occurred in 23% of cases. Median overall survival (OS) from diagnosis of PTLD was 6 years (Figure 1), but in rituximab treated patients it was 8 years. On univariate analysis, higher age at diagnosis (HR 1.19, 95% CI 1.01-1.40, p=0.033), lung transplant (HR 2.42, 95% CI 1.36-4.33, p=0.003), higher IPI (HR 1.83, 95% CI 1.40-2.39, p=<0.001), decreased PS (HR 2.43, 95% CI 1.70-3.48, p=<0.001), and platelet count <200,000 (HR 2.84, 95% CI 1.27-6.33, p=0.011) were associated with lower OS, whereas liver transplant (HR 0.24, 95% CI 0.09-0.68, p=0.007) and GI involvement (HR 0.47, 95% CI 0.24-0.95, p=0.036) predicted better OS. Rituximab treatment (Figure 2) and achieving CR were associated with better OS. Histology, EN involvement, and EBV status were not significant predictors for survival. On multivariate analysis only lung transplant, IPI, and PS were predictive for OS. Lung transplant patients had a higher risk of mortality compared to other SOT (HR 2.63, 95% CI 1.39-4.95, p=0.003). Both higher IPI (HR 1.66, 95% CI 1.18-2.32, p=0.003) and poor PS (HR 1.94, 95% CI 1.27-2.96, p=0.002) were associated with inferior OS.Conclusions: In this large cohort of PTLD patients after SOT, lung transplants, higher IPI and poor PS were identified as poor prognostic factors for OS on both univariate and multivariate analysis. Rituximab treatment was a favorable prognostic factor for OS that resulted in prolonged survival observed in this cohort. [Display omitted] [Display omitted] DisclosuresHill:Millenium: Research Funding; Novartis: Research Funding.

Does early PET/CT assesment of response to chemotherapy predicts survival in patients with advanced stage non-small-cell lung cancer?

The aim of this study is to determine the prognostic role and the timing of metabolic response to chemotherapy, based on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET), in patients with metastatic non-small-cell lung cancer (NSCLC).The study included 55 patients with metastatic NSCLC that were analyzed in terms of prognostic factors and survival. 18F-FDG-PET/CT findings were evaluated in patients separated into 3 groups, before and after 1st, 2nd, 3rd cycle of the first line chemotherapy. Metabolic response was assessed according to PET Response Criteria in Solid Tumors (PERCIST 1.0).Among the 55 patients, 34 (62%) died, and 21 (38%) remained alive during a mean follow-up of 13.5 months. Median overall survival (OS) was 11.69 months (range 2–26.80 months) and median progression-free survival (PFS) was 6.27 months (range 1.37–20.43 months). Univariate analysis showed that the only favorable prognostic factor for OS in all the patients was the achievement of metabolic response. Metabolic response according to PERCIST, and weight lose ≤ 5% were also independent favorable prognostic factors predictive of survival in all patients based on multivariet analysis (metabolic response: P = 0.002, OR; 1.90, 95% CI 1.26–2.89, and weight lose ≤ 5%: P = 0.022, OR; 2.24, 95% CI 1.12–4.47). Median OS in all patients with partial response (PR)-according to the PERCIST 1.0- was significantly longer than in those with progressive disease (PD) (16.36 months vs 8.14 months, P = 0.008). Median OS in the patients with PR was significantly longer than in those with PD based on PET/CT performed after 2nd and 3rd cycles of chemotherapy (18.35 months vs 7.54 months, P = 0.012 and 18.04 months vs 7.43 months, P < 0.001, respectively), whereas, median OS did not differ significantly between patients with PR and those with PD based on PET/CT performed after the 1st cycle of chemotherapy (8.01 months vs 5.08 months, P = 0.290).Metabolic response according to PERCIST and weight loss are independent factors predictive of OS. PET/CT performed after second cycle of chemotherapy may be the earliest predictor of treatment response in patients with advanced stage NSCLC.

Clinical outcome of advanced and metastatic renal cell carcinoma treated with targeted therapy: is there a difference between young and old patients?

BackgroundTo assess whether the clinical outcome of advanced and metastatic renal cell carcinoma (mRCC) treated with targeted therapy differs between young and old patients.Patients and methodsA total of 327 patients with advanced renal cell carcinoma and mRCC who received targeted therapy in two Chinese clinical centers were analyzed retrospectively. The patients were stratified into three groups: young (aged <45 years), middle-aged (aged 45–64 years), and old (aged ≥65 years). Overall survival (OS) and progression-free survival (PFS) curves were drawn using the Kaplan–Meier method, and Cox’s proportional hazard regression model was used to compare OS and PFS within age groups.ResultsThere were no significant differences among young, middle-aged, and old groups in terms of OS (P=0.087), whereas PFS in the old group was significantly better than in the young and middle-aged groups (P=0.043). Both OS and PFS in the younger groups (aged <65 years) were significantly worse than in the old group (age ≥65 years; median OS, 28.1 vs 28.7 months [P=0.029]; median PFS, 11.4 vs 14 months [P=0.015]). No difference in OS or PFS was found between the young and middle-aged groups. After adjusting for sex, body mass index, smoking status, hypertension, diabetes mellitus, Eastern Cooperative Oncology Group score, history of cytokines, and Fuhrman grade, old age was an independent favorable prognostic factor for OS and PFS compared with younger age (<65 years) (OS, hazard ratio, 0.552 [95% confidence interval, 0.329–0.828; P=0.006]; PFS, hazard ratio, 0.584 [95% confidence interval, 0.401–0.850; P=0.005]).ConclusionYounger patients with advanced renal cell carcinoma and mRCC receiving targeted therapy have a poorer prognosis compared with old patients. These results remain to be examined in prospective cohorts.

Role of thoracic conformal radiotherapy in patients with extensive-stage small cell lung cancer

Objective To evaluate the role of thoracic three-dimensional conformal radiotherapy (3DCRT) in patients with extensive-stage small cell lung cancer (ES-SCLC).Methods A total of 171 patients with ES-SCLC admitted from 2004 to 2009 were included in the study.Eighty-six patients received thoracic 3DCRT and systemic chemotherapy (CT),while 85 patients received systemic CT alone.3DCRT was delivered at 1.5 Gy/fraction twice daily or 2.0 Gy/fraction once daily,with a total dose ranging from 40 to 62 Gy.The CT regimen consisted of carboplatin/cisplatin and etoposide.The survival time and survival rate were calculated by the Kaplan-Meier method,and the log-rank test was used for univariate prognostic analysis;the Cox model was used for multivariate prognostic analysis.Results The follow-up rate was 100％.The median overall survival (OS) time and the 2-and 5-year OS rates were 15 months,31.5％,and 2.4％,respectively,for all patients;they were 18 months,35.3％,and 2.4％,respectively,for the CT/3DCRT group,versus 12 months,14.5％,and 2.4％ for the CT group (P =0.023).The median progression-free survival (PFS) time and the 1-and 2-year PFS rates were 8 months,27.5％,and 2.4％,respectively,for all patients;they were 9 months,35.4％,and 6.0％,respectively,for the CT/3DCRT group,versus 6 months,20.5％,and 6.0％ for the CT group (P =0.004).In the CT/3DCRT group,the 22 patients who received 45 Gy at 1.5 Gy/fraction twice daily had a median PFS time of 11 months,versus 9 months for the 26 patients who received 60 Gy at 2.0 Gy/fraction once daily (P =0.037).Multivariate analysis revealed that receiving ≥ 4 cycles of CT (P =0.001) and 3DCRT (P =0.008) were favorable prognostic factors for OS.Conclusions Thoracic 3DCRT can improve the OS and PFS in patients with EDSCLC,and it has good efficacy when delivered with a total dose of 45 Gy at 1.5 Gy/fraction twice daily.Thoracic 3DCRT and receiving ≥4 cycles of CT are independent favorable prognostic factors for OS. Key words: Lung neoplasms/radiotherapy; Radiotherapy, three-dimensional conformal; Radiotherapy, hyperfraction; Prognosis

Treatment of Patients with Adult T Cell Leukemia/Lymphoma with Cord Blood Transplantation: A Japanese Nationwide Retrospective Survey

Allogeneic bone marrow and peripheral blood stem cell transplantations are curative treatment modalities for adult T cell leukemia/lymphoma (ATLL) because of the intrinsic graft-versus-ATLL effect. However, limited information is available regarding whether cord blood transplantation (CBT) induces a curative graft-versus-ATLL effect against aggressive ATLL. To evaluate the effect of CBT against ATLL, we retrospectively analyzed data from 175 patients with ATLL who initially underwent single-unit CBT. The 2-year overall survival (OS) rate was 20.6% (95% confidence interval [CI], 13.8% to 27.4%). A multivariate analysis revealed that the development of graft-versus-host disease (GVHD) was a favorable prognostic factor for OS (hazard ratio, .10; 95% CI, .01 to .94; P = .044). Furthermore, the 2-year OS (42.7%; 95% CI, 28.1% to 56.6%) of patients with grade 1 to 2 acute GVHD was higher than that of patients without acute GVHD (24.2%; 95% CI, 11.2% to 39.8%; P = .048). However, the cumulative incidence of treatment-related mortality (TRM) was high (46.1%; 95% CI, 38.2% to 53.7%), and early death was particularly problematic. In conclusion, CBT cures patients with ATLL partly through a graft-versus-ATLL effect. However, novel interventions will be required, particularly in the early phase, to reduce TRM and optimize GVHD.

Primary intrathoracic liposarcoma: a clinicopathologic study and prognostic analysis of 23 cases.

BackgroundPrimary intrathoracic liposarcoma is an extremely rare malignancy as well as a rare histologic subtype of intrathoracic sarcoma. Relatively few reports appear in the world literatures. We explored the clinicopathologic features and prognostic factors of this tumor in this study.MethodsWe retrospectively analyzed the clinicopathological data of 23 patients with primary intrathoracic liposarcoma who were treated in Shanghai chest Hospital affiliated to Jiao Tong University, from January 2003 to March 2013. These patients were classified into three groups according to the distinct tumor locations, including mediastinum, pleura and lung liposarcoma. Also, these patients could be divided into four types, including well-differentiated, myxoid, dedifferentiated and pleomorphic liposarcoma. The influences of age, sex, tumor size, tumor location, tumor histologic type and therapy on the prognosis of the patients were analyzed.ResultsThere were no significant difference for survival among distinct liposarcoma locations. However, significant difference for survival among distinct liposarcoma types were observed. Poor disease-free survival (DFS) was observed in the myxoid, pleomorphic and dedifferentiated types as compared to well-differentiated type (P = 0.038). Inferior overall-survival (OS) was observed in dedifferentiated, pleomorphic and myxoid types relative to well-differentiated type (P = 0.027). The radical surgery was a favorable prognostic factor for OS, as demonstrated by the better OS of the radical surgery group as compared to that of the non-radical surgery group ( P = 0.029). Notably, there were no significant differences for DFS and OS in other clinical parameters including tumor size, gender and age. In addition, radiotherapy and/or chemotherapy could not improve the prognosis of the patients receiving non-radical surgery or suffering from relapse.ConclusionsThe histological type and the radical surgery are the factors that influence the behavior and prognosis of liposarcoma. In general, radiotherapy and chemotherapy are believed to be ineffective therapeutic modalities for survival. So it is essential to completely resect the primary intrathoracic liposarcoma as radical cure of the disease.

Interval between neoadjuvant treatment and definitive surgery in locally advanced rectal cancer: impact on response and oncologic outcomes

The optimal waiting period between neoadjuvant treatment completion and surgery in locally advanced rectal cancer (LARC) is controversial. The specific purpose of this study was to evaluate the effect of prolonging this interval on the pathologic response, postoperative morbidity, and long-term oncologic outcomes. Retrospective data analysis is reported from LARC patients who had been treated with chemoradiation followed by surgery and intra-operative radiotherapy, between February 1995 and December 2012. In total, two groups were studied, according to the time elapsed between neoadjuvant treatment and surgery: conventional interval (CI; <6 weeks) and delayed interval (DI; ≥6 weeks). Clinicopathological data related to tumor response, postoperative morbidity, and oncologic outcomes were compared. This study included 335 consecutive LARC patients. There was a higher proportion of patients with clinical staging nodal involvement (cN+) in the DI group (76.6 vs. 64.1 %; p = 0.01). The pathologic complete response (pCR) was not significantly different among groups (8.8 vs. 12.1 %; p = 0.34). Longer intervals did not affect complication incidence or severity or hospital admission length. Certain postneoadjuvant tumor effect parameters were significantly increased in the DI group, including N-downstaging and T-downsizing. After a median follow-up of 71 months, patients in the DI group presented with superior 5-year overall survival (OS) (55.9 vs. 70.4 %, p = 0.014); however, no statistically significant differences were observed in 5-year disease-free survival (DFS) or 5-year local control (LC) (69.9 vs. 74.9 %, p = 0.223; 90.4 vs. 94.5 %, p = 0.123, respectively). A modest surgical interval delay (≥6 weeks) did not increase postoperative complications and was identified as a favorable prognostic factor for OS, although no differences were observed in pCR, LC, or DFS. Innovative multidisciplinary strategies incorporating further time extension of the surgical interval can be safely explored.

Improving trends in survival of patients who receive chemotherapy for metastatic or recurrent gastric cancer: 12 years of experience at a single institution

The aim of this retrospective study was to evaluate the changes in clinical features and treatment outcomes of the patients with metastatic or recurrent gastric cancer (MRGC) treated in the past 12 years. A total of 3888 patients who received chemotherapy for MRGC between January 2000 and December 2011 were analyzed via a prospectively collected registry. The analysis focused on the comparison among three periods: 2000-2003 (period 1), 2004-2007 (period 2) and 2008-2011 (period 3). There were 880 patients (23%) in period 1, 1573 (40%) in period 2 and 1435 (37%) in period 3. The most commonly used first-line chemotherapy regimen was fluoropyrimidine with/without platinum (72%) for all periods. The use of second- and third-line chemotherapy was slightly but significantly more common in the two recent periods: 46 and 19 % in period 1, 54 and 26% in period 2, and 53 and 27% in period 3, respectively. Overall, 3494 patients (89.9%) died with a median overall survival (OS) of 10.6 months (95% CI 10.2-11.0). The OS was statistically significantly improved over the study period: 9.6 months (95% CI 9.0-10.2) in period 1, 10.3 months (95% CI 9.8-10.9) in period 2 and 11.7 months (95% CI 11.0-12.4) in period 3 (p for trend <0.001). Multivariate analysis including eight prognostic factors (performance, gastrectomy, peritoneal/bone/lung metastasis, abnormal alkaline phosphatase/albumin/total bilirubin) showed that the more recent treatment period was an independent favorable prognostic factor for OS (p < 0.001). The OS of patients who receive chemotherapy for MRGC has been shown to improve over time.

Prognostic factors in adult soft tissue sarcoma treated with surgery combined with radiotherapy: a retrospective single-center study on 164 patients.

The aim of the present study is to assess the disease profile, outcome and prognostic factors in patients treated with surgery combined with radiotherapy (RT), with or without chemotherapy (CXT), for soft-tissue sarcoma (STS) in a multidisciplinary setting. One hundred and sixty-four patients with STS treated between 1980 and 2010 at the Centre Hospitalier Universitaire Vaudois were enrolled in this retrospective study. Seventy-six percent of patients underwent postoperative RT with (24%), or without (52%) CXT, 15% preoperative RT with (5%), or without (10%) CXT, surgery alone (7%), or RT alone (2%) with or without CXT. The median follow-up was 60 months (range 6-292). Local failure was observed in 18%, and distant failure in 21% of the patients. Overall survival (OS), diseasefree survival (DFS), local control (LC) and distant metastases-free survival (DMFS) were 88%, 68%, 83%, and 79% at 5 years, and 80%, 56%, 76%, and 69% at 10 years, respectively. In univariate analyses, favorable prognostic factors for OS, DFS, and DMFS were tumor size 6 cm or less, World Health Organization (WHO)/Zubrod score 0, and stage 2 or less. Age and superficial tumors were favorable only for OS and DMFS respectively. STS involving the extremities had a better outcome regarding DFS and LC. Histological grade 2 or less was favorable for DFS, DMFS, and LC. Radical surgery was associated with better LC and DMFS. RT dose more than 60 Gy was favorable for OS, DFS, and LC. In multivariate analyses, independent factors were age for OS; tumor size for OS, DFS and DMFS; WHO/Zubrod score for OS, DFS and LC; hemoglobin level for DFS; site for DFS and LC; tumor depth for DMFS; histological grade for DFS and LC; surgical procedure for LC and DMFS; and RT dose for OS.This study confirms that in a multidisciplinary setting, STS have a fairly good prognosis. A number of prognostic and predictive factors, including the role of surgery combined with RT, were identified. Regarding RT, a dose of more than 60 Gy was associated with a better outcome, at the price of a higher toxicity. We could not demonstrate a superiority of preoperative RT over postoperative RT.

Paired Samples Analyses Of GATA2 mutations During Clinical Follow-Ups In 138 Patients With Acute Myeloid Leukemia-The Mutation Is Unstable During Disease Evolution

▪ BackgroundHeritable mutation in GATA2, a zinc-finger (ZF) transcription factor crucial for hematopoietic stem cell proliferation and differentiation, was identified in the families with myelodysplastic syndrome related acute myeloid leukemia (MDS-AML). Recently, GATA2 mutations were found to be strongly associated with CEBPA double mutations (CEBPAdouble-mut) in AML, which define a distinct genetic entity of AML. However, the stability of the mutation during the clinical course remains unclear. In this study, we evaluated the clinical and biological features of AML with GATA2 mutation and analyze its sequential changes during the clinical follow-ups. Materials and MethodsMutation analysis of GATA2 exons 3-7 was performed by polymerase chain reaction and direct sequencing in 192 de novo AML patients. The association between GATA2 mutations and clinical features, chromosomal changes and genetic mutations were analyzed. Furthermore, sequential analyses of GATA2 mutation during the clinical course were performed in 375 samples from 138 patients. ResultsGATA2 mutations were seen in 27.4%, 6.7% and 1% of patients with CEBPAdouble-mut, CEBPA single mutation and CEBPA-wild type, respectively. Fourteen different missense GATA2 mutations, which were all clustered in the highly conserved N-terminal ZF-1 domain, were identified in 20 patients, most commonly A318V (n=4), followed by L321F (n=3) and A318T (n=2).GATA2 mutations were detected much more frequently in younger patients, and were closely associated with FAB M1 subtype, intermediate-risk cytogenetics, and expression of HLA-DR, CD7, CD15 or CD34 on leukemic cells. In contrast, GATA2 mutations were negatively associated with FAB M4 subtype and favorable-risk cytogenetics.A thorough mutation screening in 166 patients, including 15 GATA2-mutated ones, was performed to investigate the association between mutations of GATA2 and 17 other genes. The most common additional genetic aberrations in 15 GATA2-mutated patients at initial diagnosis were CEBPA mutation (n=14), followed by TET2 mutation (n=3) and NRAS mutation (n=2). Patients with GATA2 mutations had a significantly higher incidence of CEBPA mutation than those with GATA2-wild type (93.3% versus 34.4%, P<0.0001). Of note, CEBPA mutations concurrent with GATA2 mutations were mostly CEBPAdouble-mut.Of the 154 AML patients undergoing conventional intensive induction chemotherapy, 124 (81%) patients achieved a complete remission (CR). Patients with GATA2 mutation had a higher CR rate and a trend of lower relapse rate compared with those with GATA2 wild-type (CR rate: 95% versus. 78.5%; relapse rate: 21% versus. 44.8%). With a median follow-up of 24.3 months (ranges, 0.1 to 150), patients with GATA2 mutation had significantly better overall survival (OS) and relapse-free survival (RFS) than those without GATA2 mutation (P=0.010 and P=0.033, respectively). Interestingly, among the subgroup of CEBPAdouble-mut patients, GATA2-mutated patients still had a trend of better OS and RFS than GATA2-wild type (median, not reached versus. 61 months, P=0.068 and not reached versus. 17 months, P=0.066, respectively). Multivariate analysis demonstrated that GATA2 mutation was an independent favorable prognostic factor for OS irrespective of age, white blood cell counts, cytogenetics and NPM1/FLT-ITD (HR: 0.0133, 95% CI: 0.018-0.978, P=0.047).In the serial studies of GATA2 mutations in 375 samples from 138 patients, including 14 GATA2-mutated and 124 GATA2-wild patients, all 14 GATA2-mutated patients lost the original mutations when first CR was achieved. Among them, four patients relapsed; two regained the original mutations and the other two lost them. On the other hand, two of the 124 GATA2-wild patients acquired a novel GATA2 mutation at first relapse and lost it at second CR. Interestingly, one of them regained the same GATA2 mutation at the second relapse. ConclusionAML patients with GATA2 mutations presented distinct clinical and biological features and a favorable prognosis in the total cohort. In the subgroup of patients with CEBPAdouble-mut, those with GATA2 mutations also had a trend of better OS and RFS compared with GATA2-wild patients. Sequential studies showed GATA2 mutation was not stable during disease evolution; it might be lost or acquired at disease progression, implying it was a second hit in the leukemogenesis of AML with CEBPA mutation. Disclosures:No relevant conflicts of interest to declare.

Allo-HSCT From Unrelated Donors Improves The Outcome Of Elderly AML Patients In CR1

BackgroundRecent reports have suggested that allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched related donors improves the outcome of elderly acute myeloid leukemia (AML) patients in first complete remission (CR1) (Kurosawa et al BBMT 2011). However, the efficacy of allo-HSCT from alternative donors for the management of elderly AML patients in CR1 remains to be clarified. In this study, we examined the efficacy of allo-HCST for the management of elderly AML patients. MethodsWe retrospectively collected the data of consecutive AML patients who were aged 50-70 years and diagnosed in our hospital between January 1, 2000 and May 31, 2013. Patients with acute promyelocytic leukemia (APL) and patients who could not receive intensive therapy or died within 60 days after diagnosis were excluded. The primary endpoint of this study was overall survival (OS), which was defined as the interval between diagnosis and the last follow up. The unadjusted probabilities of OS were estimated using the Kaplan-Meier method. To compare OS between the treatment groups, the log-rank test was used. Multivariate analysis were performed with Cox proportional hazard regression models and 95% confidence intervals (CIs) were calculated. ResultsA total of 131 elderly AML (non-APL) patients were identified. Except for 14 patents, all received chemotherapy. 12 patients who died within 60 days were excluded from the study. Among the remaining 105 patients, 41 could not be induced into complete remission (CR) and showed a dismal outcome; the probabilities of 2 years (2y)-OS were 0% and 4.4% for 5 patients who received allo-HSCT and 36 patients who did not, respectively. In contrast, the probability of 2y-OS of 64 patients who achieved CR1 was 48.5%. Of these 64 patients, 20 proceeded to allo-HSCT. 13 patients were transplanted in CR1, 3 in second CR (CR2), and 4 in relapse. The probabilities of 2y-OS were 56.1% and 45.0% for patients who received and who did not receive allo-HSCT, respectively (p=0.27). When the disease status at allo-HSCT was considered, the 2y-OS of patients who received allo-HSCT in CR1 reached 83.3%, whereas that of patients transplanted in CR2 or relapse reached only 14.3%. Next, we performed univariate and multivariate analysis of OS of patients who achieved CR1. In addition to whether allo-HSCT was performed in CR1 or not, the following factors were also considered as covariates: age and leukocyte counts at diagnosis, cytogenetic classification according to National Comprehensive Cancer Network guidelines, presence or absence of preceding hematological diseases, and the number of induction regimens required for achieving CR1. Univariate analysis showed that allo-HSCT in CR1 was associated with improved OS (2y-OS: 83.3% vs 40.6%, p=0.013) (figure1). Multivariate analysis also showed that allo-HSCT in CR1 was the only favorable prognostic factor for OS (Hazard ratio=0.25, 95%CI: 0.077-0.82, p=0.022). Stem cell sources of allo-HSCT done in CR1 were 1 HLA-matched related donor and 12 unrelated donors including umbilical cord blood from 1 donor. [Display omitted] ConclusionAllo-HSCT, even from an unrelated donor, improves the outcome of elderly AML patients in CR1. However, allo-HSCT for those with relapsed or refractory disease could hardly extend their survival. Disclosures:No relevant conflicts of interest to declare.

Prognostic analysis of chemotherapy with concurrent three-dimensional radiotherapy in non-small cell lung cancer patients with bone metastases

Objective To investigate the role of three-dimensional (3D) radiotherapy to the thoracic primary tumor in non-small cell lung cancer (NSCLC) patients with bone metastases during chemotherapy with concurrent 3D radiotherapy.Methods From 2003 to 2010,the clinical data of 95 stage Ⅳ NSCLC patients with bone metastases were collected.All patients received 3D radiotherapy to the thoracic primary tumor and at least 2 cycles of chemotherapy.Of the 95 patients,47 had only bone metastases,and 48 had metastases to bones and other organs.The Kaplan-Meier method was used to calculate overall survival (OS) rates.The log-rank test was used for survival difference analysis and univariate prognostic analysis.The Cox regression model was used for multivariate prognostic analysis.Results The follow-up rate was 95％.The 1-,2-,and 3-year OS rates were 44％,17％,and 9％,respectively.The univariate analysis showed that radiation dose to the planning target volume (PTV) of primary tumor of ≥ 63 Gy,response to treatment of primary tumor,and at least 4 cycles of chemotherapy were favorable prognostic factors for OS in all patients (P =0.001,0.037,and 0.009).Radiation dose to the PTV of primary tumor of ≥ 63 Gy remained the favorable prognostic factor for OS in patients with only bone metastases and those with metastases to bones and other organs (P =0.045 and 0.012).Among patients with only bone metastases,those with T1 + T2 primary tumors had longer OS than those with T3 + T4 primary tumors (P =0.048).The multivariate analysis showed that radiation dose to the PTV of primary tumor of ≥ 63 Gy and metastases to bones only were independent favorable prognostic factors for OS in all patients (P =0.036 and 0.035).Conclusions For NSCLC patients with bone metastases,3D radiotherapy to the thoracic primary tumor and its dose play an important role in improving OS during chemotherapy with concurrent 3D radiotherapy. Key words: Carcinoma, non-small cell lung/concurrent chemoradiotherapy; Radiotherapy,three-dimensional; Prognosis

Clinical significance of the appearance of abnormal protein band in patients with multiple myeloma

Multiple myeloma (MM) is characterized by clonal expansion of malignant bone marrow cells producing a unique monoclonal immunoglobulin. The appearance of abnormal protein band (APB) in MM has been reported during follow-up. We aimed to evaluate the clinical characteristics and outcomes of patients with APB in a single center cohort. A total of 377 consecutive MM patients were treated at the Asan Medical Center between January 2002 and December 2012. We compared clinical characteristics and survival outcome between those with and without APB. Of the 377 patients, 34 (9 %) experienced APB. They comprised 18.2 % (27/148) of patients treated with autologous stem cell transplantation (ASCT) and 3.1 % (7/229) of those not receiving ASCT. APB occurred after a median of 7.9 months (range, 2.2-95.7 months) from diagnosis. Immunoglobulin isotypes at diagnosis were as follows: IgG (n = 10), IgA (n = 8), IgD (n = 5), free κ (n = 4), and free λ (n = 7). Nine patients experienced a second APB. With a median follow-up of 54.1 months, the median overall survival (OS) has not been reached in patients with APB and was 38.3 months in patients without (P < 0.001). Multivariate analysis indicated that the development of APB was a significant favorable prognostic factor for OS (hazard ratio 0.21; 95 % confidence interval 0.08-0.52). Serum β₂-microglobulin, albumin, creatinine, and ASCT were also independent prognostic factors for OS. Further investigation is required to establish the mechanisms underlying APB in MM.

Treatment modality selection and prognosis of early stage small cell lung cancer: retrospective analysis from a single cancer institute

We evaluated the role of surgery followed by either chemotherapy (ChT) alone or chemotherapy and thoracic radiotherapy (ChT/TRT) versus sequential ChT/TRT in patients with clinical stage I or stage II small cell lung cancer (SCLC). Ninety-six patients received surgery (complete resection) followed by either ChT alone or ChT/TRT (Group I), while 49 patients were treated exclusively with sequential ChT/TRT (Group II). The ChT regimens consisted of either carboplatin/etoposide or cisplatin/etoposide. The total TRT dose was 50-60 Gy. For the whole group (n = 145), the median survival time was 54 months, and the 5-year overall survival (OS) rate was 48%. The corresponding figures for Group I were 91 months and 57%, respectively, and for Group II, they were 34.6 months and 31.4% respectively (P = 0.004). Multivariate analysis revealed that a Karnofsky Performance Status score ≥ 80 [hazard ratio (HR), 0.281; P = 0.015] and the treatment modality including surgery (HR, 0.503; P = 0.004) were independent favourable prognostic factors for OS.

Clinical outcomes of treatment for spinal cord compression due to primary non-Hodgkin lymphoma

Background contextPrimary non-Hodgkin lymphoma of the spine (PNHLS) with spinal cord compression is an extremely rare disease in clinical practice. The optimal treatment options for this disease have been controversial and pose a challenge for the clinicians. PurposeTo provide some useful insight into the treatments, outcomes, and prognostic factors of PNHLS. Study designRetrospective analysis. Patient sampleThe authors collected 40 patients’ data with primary non-Hodgkin lymphoma at the mobile spine, and these patients presented with spinal cord compression as a first symptom between 1998 and 2010. Outcome measuresThe posttreatment neurologic status, general status, local recurrence, and survival were noted according to the telephone calls, letters, or follow-up visits in the outpatient department. MethodsMultidisciplinary treatments, including surgical intervention, chemotherapy, and radiotherapy, were performed in this series. Follow-ups regarding treatment outcomes, local recurrence, and survival rates were carried out and analyzed. The prognostic factors including age, neurologic status, general status, vertebrae involvement, and treatment outcomes were determined. ResultsThe median age of the patients was 52 years (range, 13–79 years). After treatments, 30 patients (75%) reached a complete remission (CR). The 5-year overall survival (OS) of all patients was 72.9%. Patients who were younger than 60 years, with single vertebra involvement, or had CR after treatment had higher 5-year OS (p<.05). In multivariate analysis, CR after treatment and involvement of a single vertebra were identified as favorable prognostic factors for OS. ConclusionsPatients with PNHLS with neurologic compression had distinct clinical features. Regarding treatment, the authors emphasized the importance of multidisciplinary management and the optimal operating juncture. Patients with excellent response to the treatment and single vertebra involvement had better survival.

Prognostic Value of Gross Tumor Volume for Definitive Radiation Therapy in Patients With Locoregionally Recurrent Non–Small-Cell Lung Cancer After Surgical Resection

PurposeTo investigate the prognostic value of gross tumor volume (GTV) for predicting survival outcomes and to present the results of definitive radiation therapy (RT) in patients with postsurgical locoregionally recurrent non–small-cell lung cancer (NSCLC). Materials and MethodsBetween April 2001 and September 2009, 38 patients with postsurgical locoregionally recurrent NSCLC underwent definitive RT with curative intent. Median follow-up time for surviving patients was 54.9 months. The primary endpoint was postrecurrence overall survival (OS). The effect of tumor volume on clinical outcome was assessed by using 2 cutoff values of GTV, 20 and 80 cm3. ResultsMedian postrecurrence survival time was 27.9 months, and the 2-, 3-, and 5-year estimated OS rates were 56.0%, 39.8% and 33.2%, respectively. The median GTV was 26.8 cm3. Patients with a GTV <20 cm3 had significantly higher 2-year (69.0% vs. 28.6%) and 3-year (61.4% vs. 14.3%) OS rates than patients with a GTV ≥80 cm3 (P = .004). Patients with isolated local or regional recurrence had significantly better OS than patients with combined local and regional recurrence (P = .001). Multivariate analysis showed that smaller GTV and isolated local or regional recurrence were independent favorable prognostic factors for OS. ConclusionsPostrecurrence OS of patients with postsurgical locoregionally recurrent NSCLC treated with definitive RT was excellent compared with previous findings. The GTV as a continuous variable was a better predictor of OS than stage at recurrence and may be useful for stratifying the risk in patients with postsurgical recurrent NSCLC.

RASSF1A and ERCC1 Expression Levels Might Be Predictive of Prognosis in Advanced, Recurrent, and Metastatic Squamous Cell Carcinoma of the Head and Neck Treated with Docetaxel and Cisplatin

Background: The purpose of this study was to test the hypothesis that the immunohistochemical expression of ERCC1 and RASSF1A would predict both response to and survival after docetaxel and cisplatin combination chemotherapy in inoperable or recurrent head and neck squamous cell carcinoma. Patients and Methods: A total of 54 patients were treated with frontline systemic chemotherapy composed of docetaxel (60 mg/m²) and cisplatin (65 mg/m²), every 3 weeks for up to 6 cycles. The expression levels of ERCC1 and RASSF1A were evaluated in the available 36 prechemotherapy samples. Results: The overall objective response rate was 35% (complete remission 12% and partial remission 23%). The median progression-free survival and overall survival (OS) times were 5.0 months (95% confidence interval (CI), 3.7–6.4 months) and 24.2 months (95% CI, 3.5–45.0 months), respectively. The status of low ERCC1 and high RASSF1A expression was an independent favorable prognostic factor for OS in multivariate analysis (p = 0.043; hazard ratio, 7.224; 95% CI, 1.060–49.217). Toxicities were comparable with those of previously reported trials. Conclusions: Less intensive doses of cisplatin and docetaxel are active but not effective in reducing toxicity. Also, both ERCC1 and RASSF1A might be useful prognostic markers in this regimen.

Prognostic value of pathologic complete response to preoperative chemotherapy in early-stage non small cell lung cancer: Combined analysis of two IFCT randomized trials.

7057 Background: Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non-small cell lung cancer (NSCLC) following neoadjuvant chemotherapy resulted in improved outcome and to determine predictive factors for pCR. Methods: Eligible patients with stage IB or II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique (IFCT) phase III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen. Results: Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival (OS) was 80.0% compared to 55.8% in the non-pCR group (p=0.0007). In multivariate analyses, pCR was a favorable prognostic factor of OS (RR=0.34; 95% CI=0.18-0.64) in addition to squamous cell carcinoma (SCC), weight loss ≤5%, and stage IB disease. Five-year disease-free survival (DFS) was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p&lt;0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (OR=4.30; 95% CI=1.90-9.72). Conclusions: Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in Stage IB-II NSCLC. Our study is the largest published series evaluating pCRs following preoperative chemotherapy. The only factor predictive of pCR was SCC. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen.

Prognostic Factors and Treatment Efficacy in Patients with Primary Diffuse Large B-cell Lymphoma of the Bone: Single Institute Experience Over 11 Years

Primary bone lymphoma is a rare disorder, accounting for less than 1% of all cases of malignant lymphoma. Primary bony diffuse large B-cell lymphoma (PBDLBCL) is the most common histological type. In our study, a favorable response and lower risk of emergent surgery were observed following the administration of systemic chemotherapy with or without rituximab. Patients diagnosed with malignant lymphoma at our hospital between 2000 and 2011 were evaluated for PBDLBCL. Pertinent data, including the clinical presentation, histological type, treatment modalities, long-term outcome, survival curve and prognostic factors, were analyzed. Twenty-four patients with a median age of 63 years were diagnosed with PBDLBCL. A complete response (CR) was achieved in 58.4% (n=14) of the patients. With treatment of the disease, nine of 10 patients with initially impending pathological bone fractures ultimately did not undergo surgery. The median follow-up duration was 48 months. Two patients experienced disease relapse. In a Kaplan-Meier analysis, the 5-year overall survival (OS) and disease-free survival (DFS) rates were 66.7% and 77.8%, respectively. In the univariate analyses, the significantly favorable prognostic factors for OS were an International Prognostic Index (IPI) score of <3, an age of ≤60 years, a performance status with an Eastern Cooperative Oncology (ECOG) score of <2, a CR and chemotherapy ≥6 cycles. For DFS, a CR was the only favorable factor. In the multivariate analysis, a CR was the only independent factor for both OS and DFS. Our study confirms the good prognosis of this rare disorder. Once a CR is achieved, even elderly patients may exhibit long-term survival, possibly obviating the need for surgery for less severe bone lesions.