Disease-free Survival In Group Research Articles

P4-09-25: Impact of Body Mass Index (BMI) for Clinical Outcomes in Japanese Breast Cancer Patients.

Abstract Background: Obesity is risk factor of breast cancer incidence in postmenopausal women including Japanese population. Currently, many clinical trials data were shown that obesity may be one of prognostic factors after primary treatment in postmenopausal breast cancer patients. However, the proportion of obesity is large different between Asain and Western populations in all breast cancer patients. There is a little paper about relationship between body mass index (BMI) and prognosis after surgery in Asian breast cancer population. Methods: We conducted retrospective analysis about BMI and outcome after primary treatment in Japanese breast cancer patients. We reviewed the clinical data (height, weight, BMI, ER status, HER status, and outcome) based on our medical reports in our single institution. This research object is 1,100 patients with primary breast cancer who operated between Jan 2003 and Jan 2006 in our institution. Median follow up was 59 months (1-97). All patients are categorized into four groups according to BMI. The range of BMI is less than 18.5 kg/m2, from 18.5 to 24.9 kg/m2, 25 to 29.9 kg/m2, more than 30 kg/m2 in underweight, normal, overweight and obesity groups, respectively. Patient's characteristics are well balanced excluding age and menopausal status. Nobody is obesity in young women (less than 35 years old). The correlation BMI with disease free survival (DFS) and overall survival (OS) were statistically analyzed by using the Cox hazard model. Results: 785 (71.3%), 88 (8%), 192 (17.5%), 35 (3.2%) patients were categorized into normal, underweight, overweight obesisty groups, respectively. Breast cancer recurrences including local and distant metastases were occurred in 126 patients (11.5%).66 (6%) patients died due to breast cancer recurrence (54 patients) and other disease (8 patients). The multivariate hazard ratio (HR) in obesity groups was tend to be high compared with normal groups in disease free survival and overall survival. HR for OS was 4.30 (95%CI, 1.79−10.3) in obesity group. However, there are no statistical significant differences among four groups. Especially, HR for DFS and OS was 2.90 (95% CI 1.15−7.30 p=0.024) and 7.05(95%CI 2.38−20.8 P<0.001) in obesity group compared with normal group in ER positive patients, respectively. However, there are no statistical significant difference for DFS and OS among four groups in ER negative patients. Conclusions: The proportion of obesity is very lower in Japanese population (3.2%) than Western population (about 25–30%). However, obesity might be risk factor for DFS and OS in Japanese breast cancer patients with ER positive similar with Western countries. The different proportion of BMI may be influenced the different overall survival rate in lymph node negative breast cancer patients between Japan and Western countries. This study is a first report of the association between obesity and clinical outcomes in Japanese breast cancer patients. However, a number of patients were limited and this study is retrospective analyses including heterogeneous subtypes in single institution. A large scale cohort study should be conducted based on the clinical trial in Japanese population. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-25.

Tumor size as a prognostic factor in resected small hepatocellular carcinoma: A controversy revisited

The widespread use of screening programs has resulted in an increase in detection of small hepatocellular carcinoma (HCC). Surgical resection generally leads to favorable outcomes in this group of patients; however, the prognostic significance of tumor size and the optimal cutoff point in resected specimens of small HCC have not been well defined. The aim of current study is to evaluate the prognostic significance of tumor size in small resected HCC. Patients who underwent surgical resection for small HCC at the Changhua Christian Hospital during January 2001 to June 2007 were enrolled. Small HCC was defined as a single HCC nodule with maximum diameter ≤ 5 cm. Cox regression hazard ratios for cancer-specific death were calculated to survey the prognostic significance of tumor size. We then determined the optimal cut-point for tumor size that could be used to stratify patients into 5-year disease-free survival (DFS) and cancer-specific survival (CSS) groups. A total of 140 patients who underwent resection of small HCC were enrolled. The mean tumor size was 2.9 cm (range 0.9-5.0) and the mean follow-up period was 43.4 months. The 5-year DFS and CSS rates were 46.6% and 81.6%, respectively. Cox regression analysis revealed that tumor size (hazard ratio = 2.973, 95% confidence interval: 1.073-8.239, P = 0.036) was an independent prognostic factor. Our analysis showed that a tumor size of 3 cm was the cut-point that could dichotomize patients into statistically different 5-year DFS and CSS risk groups. Tumor size is an independent prognostic factor in resected small HCC and the prognostic significance of tumor size may vary according to different cut-off points.

The Impact of the Introduction of Total Mesorectal Excision on Local Recurrence Rate and Survival in Rectal Cancer: Long-Term Results

To investigate the influence of the introduction of total mesorectal excision (TME) on local recurrence rate and survival in patients with rectal cancer. A total of 171 consecutive patients underwent anterior or abdominoperineal resection for primary rectal cancer. When the TME technique was introduced, the clinical setting, including the surgeons, remained the same. Group 1 (1993-95, n =53) underwent conventional surgery and group 2 (1995-2001, n = 118) underwent TME. All patients were followed for 7 years or until death. Between the two groups, no statistically significant differences were present with regards to patient-, treatment-, or tumor-related characteristics apart from the time point of radiotherapy. The total local recurrence rates were 11 of 53 (20.8%) in group 1 and 7 of 118 (5.9%) in group 2, and the rates of isolated local recurrences were 6 of 53 (11.3%) in group 1 and 2 of 118 (1.7%) in group 2. Both differences were highly statistically significant. The disease-free survival in groups 1 and 2 was 60.4 and 65.3% at 5 years, and 58.5 and 65.3% at 7 years, respectively. Excluding patients with synchronous or metachronous distant metastasis from the analysis, both the disease-free survival and the cancer-specific survival were statistically significantly better in group 2 than in group 1. No statistically significant difference between the two groups was detected regarding the overall survival. The introduction of TME led to an impressive reduction of the local recurrence rate. Survival is mainly determined by the occurrence of distant metastasis, but TME seems to improve survival in patients without systemic disease.

The Prognosis of Tumors with only Microscopic Skin Involvement without Clinical T4b Signs is Significantly Better than T4b Tumors in Breast Carcinoma

The number of studies forming a base for tumor (T)-node (N)-metastasis (M) classification by comparing T4b tumors with only histological skin involvement in breast carcinoma is limited and results are contradictory. In this study, the survival of patients with T4b tumor and patients whose tumor had only microscopic skin involvement without clinical T4b signs were compared. The file records of 101 patients with T4b tumor (group A) and 79 patients whose tumor had only microscopic skin involvement (group B) were reviewed. The endpoint was disease recurrence. For the whole series, disease-free survival (DFS) of group B patients was significantly better compared with group A patients treated with either adjuvant (p<0.001) or neoadjuvant (p<0.001) therapies. When patients were subgrouped according to tumor size, DFS of group B patients was significantly better than group A patients receiving either adjuvant or neoadjuvant therapy for all tumor size subgroups of ≤3, >3, ≤5, and >5cm. Presence of T4b clinical signs had independent prognostic value in multivariate Cox analysis. In conclusion, tumors with only histological skin involvement without clinical T4b signs should be classified as T1-T3 according to their size instead of T4 as stated in the TNM classification.

Outcomes of a Prospective Phase II Study of Reduced-Intensity Stem Cell Transplantation for Acute Myeloid Leukemia with t(8;21)- In Comparison with Autologous and Myeloablative Allogeneic Stem Cell Transplantation.

AbstractAbstract 4559Patients with acute myeloid leukemia (AML) and t(8;21) generally have a favorable prognosis with a higher rate of first complete remission (CR1) and higher rate of cure with high-dose cytarabine (HDARA-C). However, some studies comparing stem cell transplantation (SCT) and conventional consolidation chemotherapy raised questions regarding improved survival with autologous SCT (ASCT) in these patients. Moreover, there has been some concern that the rate of relapse after HDARA-C is higher than previously reported and resultingly, only 50 – 60% of these patients are cured with contemporary treatment. Role of reduced intensity conditioning (RIC)-SCT has not been determined in this population. To date, few studies have analyzed the outcome of RIC-SCT for this population specifically. From this point of view, we performed a prospective phase II study to evaluate the efficacy of RIC-SCT for AML with t(8;21) and also compared the results with those of the historical cohort who treated with ASCT or myeloablative conditioning (MC)-SCT in our institution.We included adult patients aged between 16 and 65 with AML who had t(8;21) with or without additional aberration at the time of diagnosis. Since Mar 2007, we transplanted 19 consecutive adult patients with AML and t(8;21) after RIC from matched sibling (n = 12) or unrelated (n = 7) donor. Patients in RIC-SCT group were given a RIC regimen consisting of fludarabine (30 mg/m2/d, days –6, –5, –4, –3, and –2), busulfan (3.2 mg/kg/d, days –6 and –5) and low dose total body irradiation (400 cGy). Their clinical features were compared with historical patients who were transplanted with autografting (n = 47) or MC (n = 38) in our institution from 2001. The pretransplant characteristics among the three groups were well balanced except for patient age and time to SCT. For recipients of RIC, probability of overall survival (OS) and disease free survival (DFS) was 77.5 ± 9.9% and 78.2 ± 9.7%, respectively, with a median follow-up of 30 months (range: 9.5+ – 41.2+ months) for surviving patients (Fig 1a and b). 2-year cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM) was 11.9 ± 7.9%, respectively (Fig. 1c and d). OS and DFS in this group were not different from those of ASCT and MC-SCT group. CIR appears to be lower than that of ASCT, but failing to demonstrate statistical difference. Patients in ASCT group showed clearly lower NRM (P = .049). By univariate analysis, age (£ 50 vs > 50 years) seems to be a dominant factor affecting DFS and OS in RIC-SCT and ASCT group (P = 0.25 and 0.29, respectively, for RIC-SCT group, and P = 0.36 and 0.13, respectively, for ASCT group). In ASCT group, presence of –Y was associated with inferior DFS (p = 0.049, Fig. 2a), whereas this difference disappeared when RIC or MC was applied for these patients (Fig. 2b and c). CIR was significantly lower in patients without –Y than with –Y (P = 0.012, Fig. 2d), while there was no difference in NRM between the two subgroups. Of 41 male patients with –Y, probability of DFS of allogeneic SCT recipients was slightly better than that of ASCT, although failing to demonstrate a statistical difference (Fig. 2e).RIC-SCT is effective treatment modality in terms of relapse and survival, judging from no difference in CIR and survival in comparison with those of MC-SCT, but greater effort should be put to reduce NRM further. Because ASCT was associated with extremely low NRM and demonstrated comparable efficacy to those of allo-SCT, this modality might be a preferable treatment option for this disease except for the subgroup of patients with –Y. Several previous studies reported that –Y was associated with shorter survival. In our study, patients with –Y demonstrated inferior survival only in the setting of ASCT, and these differences disappeared in allo-SCT groups, justifying that allo-SCT should be considered in this subgroup of patients. Superior survival in patients without –Y seems to be result of lowered CIR rather than improved NRM. Finally, MC-SCT is not recommended in patients with t(8;21) in CR1 because it has no advantages in terms of relapse and NRM. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

AML Patients In First CR with Intermediate Risk Cytogenetic and High Level of CD34+ Mobilization Have Better DFS After Allogeneic Transplantation.

AbstractAbstract 4563AML patients having a high apheretic yield in CD34+ cells during mobilization have a poor prognosis, independently from cytogenetic risk (Feller 2004, Keating 2004). It is however not known if prognostic value of PBSC mobilization is retained after different post remissional treatment and clinical usefullness of this prognostic information in dealing with intermediate cytogenetic group patients, the more represented AML subgroup in which post remissional therapy is still a controversial issue. METHODSA group of 64 AML adult patients in 1st CR was prospectively studied. PBSC mobilization was attempted following first consolidation course. Cytogenetic assessment at diagnosis was available in 95% of patients. Post remissional treatment was chosen based on cytogenetic risk, sibling donor availability and presence of others prognostic factors, MUD transplants were proposed in cytogenetic high risk patients or in selected young patients with intermediate cytogenetic, Autologous HSC Transplantation was proposed when allogeneic transplant was felt not indicated, no further therapy was administered in patients deemed ineligible for any kind of transplantation. Prognostic significance of CD34+ cells was evaluated measuring DFS in groups of patients identified from value of CD34+ peak in respect to 50th percentile (CD34 peak: 65×10e6/L) and 75th percentile (197×10e6/L). Those patients having a CD34+ cell peak below median value (65×10e6/L) were categorised as LOW MOBILIZER, those having a CD34+ peak between 65 and 197 ×10e6/L were categorised as GOOD MOBILIZER, and those having a CD34+ peak over 75th percentiles (197 ×10e6/L) were categorised as SUPERMOBILIZER. RESULTSIn our serie 40% of patients received an Allogeneic transplant after a myeloablative treatment, 49% an autologous transplant while 11% no further chemotherapy. Disease Free Survival (DFS) was 60%. CD34+ peak during mobilization, evaluated as a continuous variable, in a Cox regression model resulted important for DFS (hazard ratio:1.001; p=0.01). Importance of CD34+ peak was maintained also when the stratum of patients with intermediate cytogenetic risk was analysed (DFS: p=0.002). POOR MOBILIZER, GOOD MOBILIZER and SUPERMOBILIZER patients had statistically different DFS when cases were analysed as a whole (DFS: POOR M.: 70%; GOOD M. 50%; SUPER M: 30%; log rank: p=0.05); mobilizing efficiency was important for DFS also in intermediate cytogenetic group (DFS: POOR M. 70%; GOOD M. 40% DFS; SUPER M. 28%; log rank p= 0.02), importance was maintained also in patients treated by allogeneic transplantation or with autologous transplantation (fig.1).When allogeneic transplantation was compared to the group of patients receiving autologous transplantation or other post remissional strategies both in the cases as a whole and in the stratum of intermediate cytogenetic (table 1), the group of POOR mobilizer had after autologous transplants results non different from patients receiving allogeneic transplantation, however, the group of GOOD mobilizer patients had after allogeneic transplants a DFS significantly better compared to other treatment while SUPER mobilizer patients had poor results also when allogeneic transplantation was employed.In conclusion in AML in 1st CR, evaluation of CD34 peak during mobilization is a parameter providing prognostic informations useful also within intermediate cytogenetic group.INTERMEDIATE CYTOGENETIC RISK (n.42)DFS (All patients) (n.42)DFS (Autologous Tx Group) (n.16) or no Tx (n.6)Log rankDFS (Allogeneic Tx Group) (n.20)CD34+ LOW MOBILIZER70%65%NS80%CD34+ GOOD MOBILIZER40%0%p=0.0275%CD34+ SUPER MOBILIZER28%0%NS30%Log rankp=0.02p=0.005p=0.04 [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Tumor Invasion of Extralobar Soft Tissue Beyond the Hilar Region Does Not Affect the Prognosis of Surgically Resected Lung Cancer Patients

Visceral pleural invasion, which is defined as tumor extension beyond the elastic lamina, is one of the most important prognostic factors in patients who have undergone curative resection for non-small cell lung cancer. However, in pathologic slides, pleural elastic lamina could not be found in the hilar region in which the pleura is reflected. Till date, when cancer cells are seen in this region, a basical agreement dealing with T factor is controversial among pathologists. The purpose of this study is to evaluate the significance of tumor invasion of that region as a prognostic factor. We reviewed 91 cases of surgically resected lung cancer in which invasion of the hilar region was visible macroscopically. By microscopic examination, we divided them into three groups: a group in which no cancer cells are seen in the soft tissue beyond the hilar region (group A), a group in which cancer cells are seen in the soft tissue beyond the hilar region (group B), and a group in which cancer cells could not be seen in the soft tissue beyond the hilar region but invade into the mediastinal visceral pleura at some other site (group C). We then evaluated the clinicopathologic characteristics of the patients and their outcome. There was no statistically significant difference in the 5-year overall survival rate or disease-free survival rate between group A and group B (overall: 55 versus 48%; disease free: 43 versus 42%), but disease-free survival of group C was significantly lesser than that of group A and group B (A versus C: p = 0.022; B versus C: p = 0.040). Tumor invasion of the soft tissue beyond hilar region would not be a prognostic factor in patients who have undergone curative resection for primary lung cancer, although investigation of larger number of cases will be needed to confirm the validity of our conclusion.

The presence of central nervous system disease at diagnosis in pediatric acute myeloid leukemia does not affect survival: A Children's Oncology Group study

The presence of central nervous system (CNS) disease in pediatric acute myeloid leukemia (AML) is often thought to confer a worse prognosis. This study examined the outcome of children with AML who had CNS disease at diagnosis. Patients enrolled on Children's Cancer Group protocols 2861, 2891, 2941, and 2961 being treated for de novo AML were classified for the presence of CNS disease at diagnosis as CNS1 (<5 WBC in the CSF without blasts), CNS2 (<5 WBC in the CSF with blasts), or CNS3 (> or =5 WBC in the CSF with blasts). CNS disease at diagnosis was then analyzed regarding patient characteristics and outcome. There was an incidence of CNS disease (i.e., CNS3 status) of 11% in the 1,459 patients analyzed in this study. The risk factors found are young age, high white cell count, hepatomegaly or splenomegaly at diagnosis, M4 subtype, chromosome 16 abnormalities, and hyperdiploid cytogenetics. There were no significant differences in overall survival, event free survival, or remission rates between the groups; however, a significant difference was seen between the CNS1 and CNS3 groups in disease free survival and isolated CNS relapse risk. Patients with CNS disease at diagnosis have similar survival to those without CNS disease, although they have an increased incidence of isolated CNS relapse. Patients with CNS disease at diagnosis may warrant more aggressive CNS directed therapy.

Primary outcome results of NSABP B-32, a randomized phase III clinical trial to compare sentinel node resection (SNR) to conventional axillary dissection (AD) in clinically node-negative breast cancer patients.

LBA505 Background: NSABP B-32 is the largest prospective randomized phase III trial designed to determine in SN negative patients that SNR alone results in the same survival and regional control as SNR + AD while reducing morbidity. It was designed to detect a survival difference of 2% between the 2 groups at 5 years. Methods: 5,611 women with operable, clinically N0, invasive breast cancer were randomized to SNR + AD (Group 1) or to SNR alone with AD only if SNs were positive (Group 2). 3,989 (71.1%) of the 5,611 patients were SN negative and followed for events. 99.9% of these SN negative patients had follow-up information: 1,975 in Group 1 and 2,011 in Group 2. Median time on study was 95.3 months. Patients were well balanced across clinical strata. Log-rank tests for unadjusted analyses and Cox proportional hazard models adjusting for study stratification variables were used to compare overall survival (OS) and disease-free survival (DFS) between the two groups. Two-sided p-values were used. HR values &gt; 1 indicate a more favorable outcome in Group 1 (SNR + AD). Results: Comparisons of OS (Group 1 vs. Group 2) yielded an unadjusted HR of 1.20 (p = 0.12) and an adjusted HR of 1.19 (p=0.13). Five-year Kaplan-Meier estimates for OS are 96.4% in Group 1 and 95.0% in Group 2 and the 8-year estimates are 91.8% and 90.3%, respectively. Comparisons of DFS (Group 1 vs. Group 2) yielded an unadjusted HR of 1.05 (p=0.54) and an adjusted HR of1.07 (p=0.57). No substantial differences could be seen across sites for first treatment failure. Five-year Kaplan-Meier estimates for DFS are 89.0% in Group 1, and 88.6% in Group 2 and the 8-year estimates are 82.4% and 81.5%, respectively. Local and Regional Recurrences: There were 54 local recurrences in Group 1 and 49 in Group 2 (p=0.55). There were 8 regional node recurrences as first events in Group 1 and 14 in Group 2 (p=0.22). Conclusions: No significant differences were observed in OS, DFS, or regional control between the trial groups. Within the limits of this trial, SNR without AD is validated as a safe and effective method for regional node treatment of SN negative breast cancer patients. [Table: see text]

Abstract 1930: Early post-operative adoptive multiple-cellular immunotherapy in gastric cancer: A 3-year follow-up report

Abstract Objective Adoptive immunotherapy is an active approach, but efficacy is limited in the clinic for most solid tumor. We hypothesized that there are three factors might lead to improved clinical outcome in the patients with gastric cancer that include: 1) the combination of multiple immune cells, 2) more effector cells reaching at the site of the tumor by infusion in peritoneal cavity, 3) performing of immunotherapy as soon as possible after operation. Patients &amp; Methods 51 gastric cancer patients (stage III-IV 42/51) who underwent operation from September 2005 to March 2008 were retrospectively analyzed. Data were censored in 39 months (January 2009),Group A patients (n=22) received a course of immunotherapy which included autologous tumor lysate-pulsed dendritic cell (DC) via intradermic injection, cytokine induced killer cells (CIK) by iv, as well as DC-CIK by intraperitoneal injection in 11-14 days after operation, then a standard chemotherapy (18/22) and immunotherapy again. Group B patients (n=29) only received postoperative chemotherapy. Overall survival (OS) and disease-free survival (DFS) were calculated by the Kaplan-Meier method. Results In total, 24 patients died, giving a median survival time of 25 months. The estimated 2-year OS and DFS of group A were 63.6% and 67.3%, while that of group B were 25.2% and 33.2%, respectively. Both of the estimated 3-year OS and DFS were significantly superior in group A (log-rank test, P&amp;lt;0.01). Conclusions Early post-operative adoptive multiple-cellular immunotherapy with infusion in peritoneal cavity significantly improved overall survival and disease-free survival in gastric cancer patients. Key words gastric cancer; early; postoperative; adoptive cellular immunotherapy Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1930.

Lymph Node Sampling and Taking of Blind Biopsies Are Important Elements of the Surgical Staging of Early Ovarian Cancer

The purpose of this study was to determine the effect of lymph node sampling and taking of blind biopsies as part of the surgical staging procedure for early ovarian cancer on disease-free survival (DFS) and overall survival (OS) in patients who received no adjuvant chemotherapy. In the EORTC ACTION Trial, 448 patients with early ovarian carcinoma were randomized between November 1990 and March 2000-224 patients to observation and 224 to adjuvant platin-based chemotherapy. Only patients allocated to observation were included for the current study. Analyses were performed in a subgroup of 75 optimally staged patients (group A), 46 patients in whom all staging steps were performed except para-aortic or pelvic lymph node sampling (group B), and 14 patients who fulfilled all staging criteria but in whom no blind peritoneal biopsies were taken (group C). The study group did not differ in stage distribution, cell type, or tumor grade. Significantly improved 5-year DFS (P = 0.03) and 5-year OS (P = 0.01) were found in group A (optimally staged) versus group B (no lymph node sampling). A significant difference was also shown in 5-year DFS (P = 0.02) and 5-year OS (P = 0.003) between group A and group C (no blind biopsies). Recurrences occurred in 11 (14.6%) of 75 patients in group A, 16 (34.8%) of 46 patients in group B, and 5 (35.7%) of 14 in group C. The 5-year DFS in group A was 79% versus 61% and 64% in groups B and C, respectively. The 5-year OS decreased from 89% in group A to 71% in group B and 65% in group C. In this study, statistically significant differences were found in patients in whom para-aortic and pelvic lymph node sampling and taking of blind peritoneal biopsies were undertaken compared with patients in whom these staging steps had been omitted. These findings support the relevance of lymph node sampling and the taking of blind peritoneal biopsies in the surgical staging of early ovarian cancer.

Prognostic relevance of hypoxia inducible factor-1α expression in patients with melanoma

Overexpression of hypoxia inducible factor (HIF)-1alpha has been found in several human cancers and is thought to correlate with aggressive disease and poor response. A retrospective analysis was carried out on 89 patients with primary cutaneous melanoma. HIF-1alpha expression was assessed by immunohistochemistry in formalin-fixed, paraffin wax-embedded tumour sections. Overall survival (OS) and disease-free survival (DFS) were determined using univariate and multivariate analyses. Of the 89 patients, 78 (87.6%) expressed HIF-1alpha, and the remaining 11 patients (12.4%) did not. HIF-1alpha expression correlated with age (P = 0.002), but not with the main predictive factors in melanoma. Survival analysis disclosed no difference between the groups for OS and DFS. In multivariate analysis, only Breslow Index and ulceration were significantly associated with poor OS. Our results indicate that HIF-1alpha overexpression is present in most primary melanomas, but is not associated with clinicopathological variables, patient prognosis or survival.

Resected colorectal liver metastases: Does the survival differ according to postoperative chemotherapy regimen?

We compared clinical outcomes in patients who were treated with different chemotherapeutic regimens after resection of hepatic metastases from colorectal cancer (CRC). Between August 2001 and June 2008, 156 patients who entered into chemotherapy of adjuvant intent after hepatic metastasectomy were reviewed retrospectively. Of the 156 patients, 58 patients were treated with oxaliplatin/fluoropyrimidines (group I), 48 with irinotecan/fluoropyrimidines (group II), and 50 with fluoropyrimidines alone (group III). In the univariate analysis, there was a marginally significant difference among the three groups with respect to the disease-free survival (DFS); 23.4 months in group I, 14.1 months in group II, and 16.3 months in group III, P = 0.088). Group I showed better DFS when compared to the other two groups combined (group II and III) (P = 0.03). Multivariable analysis showed a marginally significant gain in the DFS for group I (P = 0.068). Multiple metastases (P = 0.045) and positive resection margin (P = 0.003) were significantly associated with poorer DFS. Postoperative combination chemotherapy of oxaliplatin/fluoropyrimidines seemed to show better DFS when compared to fluoropyrimidine monotherapy or irinotecan-based combination in patients who underwent liver metastasectomy.

Impact of Neoadjuvant Chemotherapy with FOLFOX/FOLFIRI on Disease-Free and Overall Survival of Patients with Colorectal Metastases

Study AimsTo determine if neoadjuvant FOLFOX/FOLFIRI is associated with improved disease-free survival (DFS) or overall survival (OS) in patients with colorectal metastases (CRM) to the liver. MethodsNinety-nine patients (from 457 eligible) with CRM that underwent hepatic resection during 2000 to 2005 were included. Group 1 (n = 44) patients received neoadjuvant FOLFOX/FOLFIRI, and Group 2 (n = 55) did not receive neoadjuvant therapy. ResultsThere were 58% men. The median age for Group 1 was 58 and Group 2, 64 (p = 0.03). OS for Group 1 at 1, 3, and 5 years was 93%, 62%, and 51%, respectively, with a median OS of 5.8 years. In Group 2 survival at 1l, 3, and 5 years was 90%, 63%, and 45%, respectively, with a median OS of 3.7 years (HR 1.06, p = 0.87). The DFS for Group 1 at 1, 3, and 5 years was 51%, 20%, and 20%, with a median DFS of 1.1 years and Group 2 at 1, 3, and 5 years was 58%, 32%, and 32% (median DFS—1.2 years; HR = 1.24, p = 0.45). ConclusionsNeoadjuvant FOLFOX/FOLFIRI was employed more frequently in younger patients with CRM; however, neoadjuvant chemotherapy for CRM was not significantly associated with an increase in OS or DFS, despite additional adjuvant therapy.

Outcome after curative resection for a huge (≥10 cm) hepatocellular carcinoma and prognostic significance of gross tumor classification

Background and objectives The purpose of this study was to investigate the surgical outcomes in patients with huge (≥10 cm) hepatocellular carcinoma (HCC). Methods Clinicopathological features and surgical outcomes of 50 patients with huge HCC who underwent curative resection (group A) were compared with 447 patients with smaller tumors (group B). In group A, we investigated prognostic factors. Results Group A patients had a higher incidence of α-fetoprotein at more than 1,000 IU/mL, microscopic vascular invasion, and advanced stage tumors. The disease-free survival of group A was significantly worse than group B. The rates of initial extrahepatic recurrence and early recurrence were higher in group A. The 5 year-overall survival of group A was 40.2%, significantly lower than that of group B (65.9% at 5 years). In group A, multivariate analysis revealed that the presence of single nodular type tumors was the only good prognostic factor for survival. Conclusions Huge HCCs exhibit a more aggressive clinical behavior and worse survival. However, because the outcome of surgical treatment is far better than that of nonsurgical treatment, resection should be actively considered for patients with huge HCC. A single nodular type tumor is the best candidate for surgical resection.

Impact of CYP2D6 polymorphisms in tamoxifen adjuvant breast cancer treatment

The aim of this study is to evaluate the impact of CYP2D6 genotyping in predicting disease-free survival and toxicity in breast cancer patients treated with adjuvant tamoxifen. DNA from 91 patients was genotyped using the AmpliChip CYP450 GeneChip, Roche that facilitates the classification of individuals by testing 27 alleles. When patients were grouped into group 1 (*4/*4, *4/*41, *1/*5 and *2/*5) and group 2 (the remaining genotypes), a significant difference in disease-free survival (DFS) was observed between groups (P = 0.016). The mean DFS in group 1 was 95 months in contrast with 119 months in group 2. No significant relationship was found between the CYP2D6 genotype classification and severe, mild or no toxicity (P = 0.2). Nevertheless, severe, and mild toxicity was more frequent among poor metabolizer patients than in patients with a normal metabolizer pattern (18.8 and 43.8% vs. 10.7 and 36%, respectively). In breast cancer, patients treated with adjuvant tamoxifen, non-functional and severely impaired CYP2D6 variants are associated with a worse DFS and with a higher frequency of severe and mild toxicities. Larger studies of the CYP2D6 genotype-clinical outcomes association are needed to complement initial results.

The clinical significance of tumor cells in bone marrow or apheresis product and the efficacy of CD34+ selection and high‐dose chemotherapy in patients with Stage III breast cancer

The purpose of this study is to determine the presence of disseminated tumor cells in bone marrow or apheresis product, and also to evaluate the clinical significance of contaminated products and the efficacy of CD34(+) selection and high-dose chemotherapy in patients with Stage III breast cancer. Fifty-five patients were enrolled in this prospective cohort study. Whereas CD34(+) positive selection was not carried out in the first group (unselected group, n:31), CD34(+) positive selection was performed in the second group (CD34 selected group, n:24). Tumor cells were detected with anticytokeratin monoclonal antibody in the bone marrow, apheresis product and positive fraction. Tumor cells were found in six (19.3%) patients in unselected group and four patients (16.6%) in CD34 selected group (P = 0.76). The percentages of distant metastases were found higher in unselected group (51.6% vs. 25%, P < 0.01). Although there were no differences between the two groups for disease free survival (DFS; 44% vs. 74%, P = 0.24) or overall survival (54% vs. 68%, P = 0.84), DFS was significantly lower in patients with tumor cells than in patients without tumor cells (21% vs. 62%, P = 0.02). In conclusion, the presence of tumor cells in bone marrow or apheresis product decreases DFS in patients with Stage III breast cancer who underwent high-dose chemotherapy. CD34(+) selection does not change survivals, but it may decrease the distant metastases.

Solitary Large Hepatocellular Carcinoma

To evaluate and compare the clinical and pathologic characteristics and outcomes after hepatic resection of large hepatocellular carcinoma (SLHCC), small HCC (SHCC), and nodular HCC (NHCC). Traditional viewpoint insists that the classification and prognosis of HCC are determined by the size of HCC. As a result, large HCC is often considered as advanced and unresectable. However, we have observed a unique type of HCC-SLHCC, which is large in size but exhibits good clinical, pathologic, and molecular biologic characteristics as well as prognosis. From January 1992 to December 2002, a total of 481 consecutive patients were diagnosed with HCC and received hepatic resection. In this series of patients, the clinical and pathologic data, surgical outcome, and long-term survival of patients with SLHCC (group A, n = 260) were analyzed retrospectively and compared with patients who had SHCC (group B, n = 135) or NHCC (group C, n = 86). Postresection prognostic factors of HCC were also evaluated by univariate and multivariate analysis using Cox's proportional hazards model. The clinical and pathologic characteristics of SLHCC and SHCC were similar except for tumor necrosis and tumor size. Patients of SLHCC had significantly longer operative time, higher intraoperative blood loss, higher intraoperative blood transfusion, and higher postoperative morbidity than SHCC. However, the 2 groups were similar in duration of hospital stay and overall morbidity. Overall survival and disease-free survival in group A and group B were similar and significantly better than those in group C. Multivariate analysis revealed that large amount of intraoperative blood transfusion and vein invasion were independently significant factors for overall survival of patients with HCC. The clinical and pathologic characteristics and the outcome after hepatic resection of SLHCC are similar to that of SHCC, but significantly better than NHCC. We propose SLHCC as a specific subtype of HCC and hepatic resection as its choice of standard treatment.

Reduction of Immunosuppression and Subsequent Rituximab Monotherapy or CHOP-Based Chemotherapy +/− Rituximab as a Treatment for PTLD Does No Impair the Renal Graft Function: A Matched Pair Control Analysis in 55 Renal Transplant Recipients with PTLD and 1075 Renal Transplant Controls

Purpose: Post transplant lymphoproliferative disorder (PTLD) is a serious and often devastating complication after solid organ transplantation. The initial therapeutic action is reduction of immunosuppression (IR). Patients not responding to IR usually are treated with rituximab monotherapy and/or CHOP-based chemotherapy. The impact of treatment on the renal graft function is to be analyzed.Methods: A retrospective data analysis was performed on adult renal transplant recipients with PTLD requiring further therapy after failing to respond to IR. All patients gave their informed consent to this study and all had been treated within one of the prospective German PTLD Study Group protocols: PT-LPD-1 (rituximab monotherapy), PTLD-1 (sequential treatment with rituximab and CHOP chemotherapy) or PTLD D2006–2012 (different treatment protocols). Renal graft function was analyzed 6 months (6m) before, during and up to 2 years after treatment of PTLD. From our renal transplant database altogether 1075 transplant recipients that had transplantation between January 1998 and June 2008 served as a control. Controls were matched for sex, patient age, transplant age and transplant function at time of diagnosis of PTLD.Results: Median age at diagnosis of PTLD was 49 years. 38/55 pts. were male, 43/55 had late onset PTLD. 53/55 had B-cell PTLD: 2 polymorphic, 37 aggressive B-cell, 3 Hodgkin or Hodgkin-like PTLD and 11 others. 2/55 had T-cell PTLD. 34/55 had an advanced stage of disease and 26/51 had elevated LDH levels. 1 patient had renal graft involvement. Renal transplantation for endstage renal disease was either due to autoimmune disorders (26/55), to diabetes (4/55), to cystic renal degeneration (5/55) or to metabolic dysfunction (1/55, 19 others). At diagnosis of PTLD 10 patients were on calcineurin-inhibitor (CNI) therapy only, 16 were on CNI plus mycophenolate mofetil (MMF), 13 were on CNI plus azathioprin (AZA), 4 were on CNI plus mTor-inhibitor, 4 were on mTor-inhibitor plus MMF or AZA and 7 were on single agent immunosuppression with MMF, AZA or prednisone. Immunosuppression was reduced in all patients immediately after diagnosis of PTLD. 15/55 patients received further therapy with single agent rituximab, 40/55 patients received CHOP or CHOP-like chemotherapy +/− rituximab. 36/53 (68%) patients reached a complete remission (CR). At a median follow up of >2 years 4 patients relapsed and 17 died: 5 from PTLD, 7 from infections, 1 from myocardial infarction and 3 of unknown reason. Matching criteria were equally distributed in the patient and control group. After successful treatment of PTLD 4 of 38 PTLD survivors (10%) had failed renal allografts and recommenced hemodialysis: 1 due to a haemolytic uremic syndrom, 1 due to acute renal failure after a septic complication, 2 due to chronic transplant dysfunction. With a mean transplant age of 6.2 years transplant survival at 1 year after diagnosis of PTLD is 92% in the stable CR group. In a longitudinal analysis in 27 and 44 patient pairs evaluable not requiring hemodialysis we found a drop in eGFR values from 50.9 ml/min 6m before diagnosis of PTLD to 46.8 ml/min at time of diagnosis of PTLD that was statistically significant (p=0.04) suggesting a negative impact of the lymphoma (and/or of IR) to the graft function. With treatment of PTLD the graft function improved up to a mean eGFR of 56.3 ml/min 4 weeks after completing therapy (p=0.014). In subsequent subgroup analyses we found this effect to be restricted to and more durable in patients that had been treated with chemotherapy resulting in an eGFR of 57.6 ml/min, 55.7 ml/min and 58.6 ml/min 4 weeks, 6 months and 12 months after therapy, respectively. The graft function in this subgroup of patients was even superior to controls (p=0.012 at 6m, p=0.004 at 12m), which may result from the immunosuppressive effect of chemotherapy.Conclusion: PTLD may be associated with a worsening of graft function in renal transplant recipients but the graft often ameliorates during therapy. Beside rare acute complications like acute renal failure during septic complications there is no evident negative impact of therapy on renal graft function with rituximab and chemotherapy based 1st-line protocols in PTLD. Transplant survival in the disease free survival group is excellent.

Clinical outcomes of ethnic minority women in MA.17: a trial of letrozole after 5 years of tamoxifen in postmenopausal women with early stage breast cancer

Aromatase inhibitors are widely employed in the adjuvant treatment of early stage breast cancer. The impact of aromatase inhibitors has not been established in ethnic minority women. The purpose of this study was to evaluate the impact of letrozole on minority women in MA.17, a placebo-controlled trial of letrozole following 5 years of tamoxifen in postmenopausal women with early stage breast cancer. Retrospective comparison of disease-free survival (DFS), side effects, and mean changes in quality of life (QOL) scores from baseline between Caucasian and minority women was performed. Minority (n = 352) and Caucasian (n = 4708) women were analyzed. There was no difference between these groups in DFS (91.6% versus 92.4% respectively for 4 year DFS). Letrozole, compared with placebo, significantly improved DFS for Caucasians (HR = 0.55; P < 0.0001) but not for minorities (HR = 1.39; P = 0.53). Among women who received letrozole, minorities had a significantly lower incidence of hot flashes (49% versus 58%; P = 0.02), fatigue (29% versus 39%; P = 0.005), and arthritis (2% versus 7%; P = 0.006) compared with Caucasians. Mean change in QOL scores for minority women who received letrozole demonstrated improved mental health at the 6-month assessment (P = 0.02) and less bodily pain at the 12-month assessment (P = 0.046). Letrozole improved DFS in Caucasians but a definite benefit in minority women has not yet been demonstrated. Minority women tolerated letrozole better than Caucasians in terms of toxicity. These results need confirmation in other trials of aromatase inhibitors.