Median Disease-free Survival Duration Research Articles

Creation of a Novel Nomogram Based on the Direct Bilirubin-To-Indirect Bilirubin Ratio and Lactate Dehydrogenase Levels in Resectable Colorectal Cancer

Background: Recently, many studies have suggested that bilirubin is associated with the prognosis of colorectal cancer (CRC). Conversely, there is substantial evidence that lactate dehydrogenase (LDH) levels are associated with the prognosis of cancer. Therefore, we sought to find a novel marker based on the above to predict prognosis in patients with resectable CRC. Methods: A total of 702 patients from Hubei Cancer Hospital were included. The whole population was randomly divided into training (n = 491) and testing (n = 211) cohorts. Next, we established a new index based on direct bilirubin, indirect bilirubin and LDH levels. Chi-square tests, Kaplan-Meier survival analyses, and Cox regression analyses were used to evaluate prognosis. The prediction accuracies of models for overall survival (OS) and disease-free survival (DFS) were estimated through Harrell’s concordance index (C-index) and the Brier score. Results: The median DFS duration was 32 months (range: 0–72.6 months), whereas the median OS duration was 35 months (range: 0 months–73.8 months). In addition, a new indicator, (DIR.LDH) (HR: 1.433; 95% CI, 1.069–1.920) could independently predict outcomes in CRC patients. Moreover, the module based on DIR. LDH was found to have exceptional performance for predicting OS and DFS. The C-index of the nomogram for OS was 0.802 (95% CI, 0.76–0.85) in the training cohort and 0.829 (95% CI, 0.77–0.89) in the testing cohort. The C-index of the nomogram for DFS was 0.774 (95% CI, 0.74–0.81) in the training cohort and 0.775 (95% CI, 0.71–0.84) in the testing cohort. Conclusion: We successfully established a novel module to guide clinical decision-making for CRC.

Transarterial chemoembolization combined with radiofrequency ablation for solitary large hepatocellular carcinoma ranging from 5 to 7cm: an 8-year prospective study.

This prospective study was performed to investigate long-term (8-year) survival in patients with solitary large hepatocellular carcinoma (HCC) ranging from 5 to 7cm who underwent transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) and identify factors that significantly affected outcomes. Forty-eight patients with large HCC (36 men, 12 women; mean age, 57.0 ± 11.2 [range, 37-82] years) without fever or signs of infection were enrolled. All patients were treated with TACE + RFA. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. Prognostic factors were assessed using the Cox hazards regression method. The median OS duration was 47.0months, and the 1-, 3-, 5-, and 8-year OS rates were 73%, 57%, 53%, and 27%, respectively. The median DFS duration was 9.05 (3.99-12.01) months, and the 1-, 3-, and 5-year DFS rates were 35%, 9%, and 0%, respectively. Cox hazards regression analysis revealed that the Child-Pugh class, platelet count, lymphocyte-to-monocyte ratio (LMR), and DFS were independent predictive factors of OS (p = 0.000, 0.003, 0.020, and 0.000, respectively). The LMR and platelet-to-lymphocyte ratio (PLR) were independent predictive factors of recurrence (p = 0.046 and 0.016, respectively). TACE + RFA may be a safe and effective treatment for selected solitary large HCC ranging from 5 to 7cm. Measurement of the LMR (> 4) and PLR (≤ 100) in peripheral blood before the intervention might help to identify which patients with solitary large HCC are suitable for TACE + RFA. Registration number: ChiCTR-TRC-12002768 ( https://www.chictr.org.cn ).

Improved survival among oral cancer patients: findings from a retrospective study at a tertiary care cancer centre in rural Kerala, India

BackgroundOral cancer is very common in India. The reported 5-year survival of such patients is around 50% after treatment with surgery and radiotherapy, much lower than most of the developed countries.MethodsA retrospective study of a prospective database of oral cancer patients undergoing surgery from June 2009 to June 2013 was conducted. Follow-up details were updated from case records and by phone calls. Data were double entered in EpiData Entry version 3.1 and were analysed using EpiData Analysis software 2.1.0.73.ResultsTwo-hundred and twenty patients were analysed (136 males); 85% were consuming tobacco, mainly in chewable form. The majority (51.1%) had tongue cancer, of whom 75 patients (34.1%) had T4 tumours. Postoperative radiotherapy was given to 108 patients (49.1%). Forty had recurrence, of which 23 were in early stage. Of these, 19 showed node positivity (p < 0.01). Node-negative patients had 79% 5-year survival while node positive had 59% which is comparable to that reported in developed countries. Median disease-free survival duration was 48.2 months.ConclusionsNode positivity is the single factor affecting recurrence and survival. The overall survival and disease-free survival is better in patients without lymph node involvement and in patients with early stage of cancer as compared to the patients with node involvement and in advanced stages.

Pregnancy and oncologic outcomes after fertility-sparing management for early stage endometrioid endometrial cancer.

Hormonal management is an alternative treatment for preserving fertility in patients with presumed early stage endometrioid endometrial cancer. This study aimed to define the pregnancy and oncologic outcomes and factors of successful conception after hormone therapy for endometrioid endometrial cancer. We retrospectively analyzed patients presumed to have stage IA, grade 1-2 endometrioid endometrial cancer who underwent fertility-sparing treatment. Concurrent medroxyprogesterone and levonorgestrel-release intra-uterine devices were used for treatment. The pregnancy outcomes and oncologic outcomes were compared between the pregnant and non-pregnant groups. Seventy-one patients presumed to have stage IA, grade 1-2 endometrioid endometrial cancer had complete remission, and 49 of them tried to conceive. Twenty-two (44.9%) patients became pregnant; the total number of pregnancies was 30. These pregnancies resulted in seven abortions (23.3%), one pre-term birth (3.3%), and 20 full-term births (66.6%). The total live birth rate was 66.6 % (20/30). The median duration of hormonal treatment was 11.9 months (range 4-49) and 12.0 months (range 3-35) in the pregnant and non-pregnant groups, respectively. On multivariate analysis, age, body mass index, treatment duration, medroxyprogesterone dose, and number of dilatation and curettage biopsies were not significantly associated with pregnancy failure, but the association with grade (OR 6.2, 95% CI 1.0 to 38.9; P<0.05) was statistically significant. The median disease-free survival duration was 26 months (range 20-38) and 12 months (range 4-48) in the pregnant and non-pregnant groups, respectively (P<0.05, log-rank test). A lower grade might be a positive factor for future pregnancy. Moreover, successful pregnancy might be a factor in preventing recurrence.

CD56 and CD11b Positivity with Low Smac/DIABLO Expression as Predictors of Chemoresistance in Acute Myeloid Leukaemia: Flow Cytometric Analysis

Background:Resistance to chemotherapy is a major obstacle to curing acute myeloid leukaemia (AML), and several antigens are claimed to play primary roles in this resistance.Purpose:The aim of this study was to evaluate the roles of CD56, CD11b and Smac/DIABLO gene expression levels as prognostic markers of the clinical outcome, response to chemotherapy and survival of AML patients.Materials and Methods:A cross-sectional observational study was conducted on 60 naïve-AML patients who received induction therapy with mitoxantrone and cytarabine combined with a high dose of cytarabine. The CD56,CD11b and Smac/DIABLO expression levels were assessed using flow cytometry at diagnosis and were analysed for correlation with the possible associated risk factors, response to chemotherapy, and median duration of disease-free survival (DFS) and overall survival (OS).Results:The overall results revealed that AML patients who exhibited positive expression for CD56 and CD11b had short median durations of DFS and OS.(P = 0.019, 0.006, 0.029 and 0.024, respectively). Additionally, low Smac/DIABLO expression had a negative impact on treatment outcome in terms of CR rate (p=0.012) and reduced DFS (p=0.000) and OS(p=0.000) values.Conclusions:CD56 and CD11b positivity and low Smac/DIABLO expression are important predictive factors for the occurrence of chemoresistance, in addition to other risk factors, among AML patients.

Re: Adjuvant Sunitinib in High-risk Renal-cell Carcinoma After Nephrectomy

BackgroundSunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. MethodsIn this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. ResultsThe median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo gr...

Effect of non-alcoholic liver disease on recurrence rate and liver regeneration after liver resection for colorectal liver metastases.

Resection of metastases is the only potential cure for patients with liver metastasis from colorectal cancer (crc-lm). But despite an improved overall 5-year survival, the recurrence rate is still as high as 60%. Non-alcoholic fatty liver disease (nafld) can decrease the liver's capacity to regenerate after resection and might also affect cancer recurrence, potentially by elevating transforming growth factor β, levels of specific metalloproteinases, and oxidative stress. The objective of the present work was to determine the effect of the histologic features of nafld on cancer recurrence and liver regeneration. This retrospective analysis considered 60 patients who underwent an R0 hepatectomy for crc-lm. Volumetric analysis of the liver was calculated using axial view, portovenous phase, 2.5 mm thickness, multiphasic computed tomography images taken before and after surgery. The histologic features of nafld (steatosis, inflammation, and ballooning) were scored using the nafld activity score, and the degree of fibrosis was determined. The hepatic recurrence rate was 38.33%. Median overall survival duration was 56 months. Median disease-free survival duration was 14 months, and median hepatic disease-free survival duration was 56 months. Multivariate analysis revealed significant correlations of hepatic disease-free survival with hepatocyte ballooning (p = 0.0009), lesion diameter (p = 0.014), and synchronous disease (p = 0.006). Univariate and multivariate analyses did not reveal any correlation with degree of steatosis or recurrence rate. This study reveals an important potential negative effect of hepatocyte ballooning on hepatic disease-free survival.

Prediction of Recurrence by Preoperative Intratumoral FDG Uptake Heterogeneity in Endometrioid Endometrial Cancer

PURPOSE: To investigate the prognostic value of preoperative intratumoral 18F-FDG uptake heterogeneity (IFH) derived from positron emission tomography (PET)/computed tomography (CT) in patients with endometrioid endometrial cancer. METHODS: We retrospectively evaluated clinicopathological data from patients with pathologically proven endometrioid endometrial cancer who had undergone 18F-FDG PET/CT scans before surgery. Patients were divided into two groups according to their IFH. The main outcome measure was disease-free survival (DFS). RESULTS: Between January 2010 and January 2015, data from 72 patients were available for analysis. The median duration of DFS was 23 months (range, 6 to 57 months), and 4 (5.6%) patients experienced recurrence. There were significant differences in tumor size, IFH, and DFS between patients with and without recurrence. In regression analysis, high IFH value [P = .007, hazard ratio (HR) 2.545, 95% confidence interval (CI) 1.468-8.674] was the only independent risk factor for recurrence. The Kaplan-Meier survival graphs showed that DFS significantly differed in groups categorized based on IFH (P < .001, log-rank test). CONCLUSIONS: Preoperative IFH measured by 18F-FDG PET/CT was associated with recurrence of endometrioid endometrial cancer. The finding supports evidence that FDG-based heterogeneity can be a novel and useful predictor of endometrioid endometrial cancer recurrence.

Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy

BackgroundSunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy.MethodsIn this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety.ResultsThe median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects.ConclusionsAmong patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number, NCT00375674.)

Prognostic significance of tumor deposits in patients with stage Ⅲ colon cancer

Objective: To investigate the prognostic significance of tumor deposits (TD) in patients with stage Ⅲ colorectal cancer who underwent radical resection. Methods: We retrospectively analyzed the clinicopathological data, and the impact of tumor deposits on the disease free survival (DFS) and overall survival (OS) in 206 patients with stage Ⅲ colorectal cancer using Kaplan-Meier and Cox regression analyses. Results: Among the 206 patients with stage Ⅲ colorectal cancer, there were 112 (54.4%) tumor deposit-positive (TD+ ) cases and 94 (45.6%) tumor deposit-negative (TD-) cases. The TD- and TD+ cases accounted for 10.6% and 21.4% of patients aged <50 years, 22.3% and 36.6% of patients with poorly differentiated carcinoma, and 16% and 29.5% of patients with neural invasion, respectively (P<0.05 for all). In addition, the neural invasion was more often found along with the increasing number of TD. However, multivariate analysis showed that TD was not significantly associated with DFS and OS of the patients. Among the patients with N1 stage cancer, the 3-year DFS rates of TD+ and TD- groups were 23.0% and 58.8%, and the median disease-free survival durations were 26 months and 43 months, respectively (P=0.002). Meanwhile, in the TD- group, the 3-year DFS rates in the patients with stage N1a~1b without tumor deposit and N1c cancer were 63.5% and 21.2%, and the median disease-free survival durations were 41 and 25 months, respectively (P=0.004). Conclusions: Tumor deposit is an independent unfavorable prognostic factor affecting the DFS. The number of tumor deposits may be an important factor affecting prognosis in stage Ⅲ colorectal cancer patients. Tumor deposits after radical resection are associated with neural invasion, and can be used as an independent factor of poor prognostic evaluation in patients with stage N1 colorectal cancer.

Prognostic value of preoperative intratumoral FDG uptake heterogeneity in patients with epithelial ovarian cancer.

To investigate the prognostic value of intratumoral FDG uptake heterogeneity (IFH) derived from PET/CT in patients with epithelial ovarian cancer (EOC). We retrospectively reviewed patients with pathologically proven epithelial ovarian cancer who underwent preoperative 18F-FDG PET/CT scans. PET/CT parameters such as maximum and average standardized uptake values (SUVmax and SUVavg), sum of all metabolic tumour volume (MTV), cumulative total lesion glycolysis (TLG) and IFH were assessed. Regression analyses were used to identify clinicopathological and imaging variables associated with disease-free survival (DFS). Clinicopathological data were reviewed for 61 eligible patients. The median duration of DFS was 13 months (range, 6-26months), and 18 (29.5%) patients experienced recurrence. High IFH values were associated with tumour recurrence (P = 0.005, hazard ratio 4.504, 95% CI 1.572-12.902). The Kaplan-Meier survival graphs showed that DFS significantly differed in groups categorized based on IFH (P = 0.002, log-rank test). Moreover, there were significant differences in DFS (P = 0.009) and IFH (P = 0.040) between patients with and without recurrence. Preoperative IFH measured by 18F-FDG PET/CT was significantly associated with EOC recurrence. FDG-based heterogeneity could be a useful and potential predicator of EOC recurrence before treatment. • Preoperative IFH was significantly associated with recurrence of EOC • Disease-free survival significantly differed in groups categorized by IFH • FDG-based heterogeneity could be a potential predicator of EOC recurrence before treatment.

Surgical Outcomes in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombosis

Different approaches to surgical treatment of portal vein tumor thrombosis (PVTT) have been advocated. This study investigated the outcomes of different surgical approaches in hepatocellular carcinoma (HCC) patients with PVTT. We reviewed prospectively collected data for all patients who underwent hepatectomy for HCC at our hospital between December 1989 and December 2010. Patients were excluded from analysis if they had extrahepatic disease, PVTT reaching the level of the superior mesenteric vein, or hepatectomy with a positive resection margin. The remaining patients were divided into three groups for comparison: group 1, with ipsilateral PVTT resected in a hepatectomy; group 2, with PVTT extending to or beyond the portal vein bifurcation, treated by en bloc resection followed by portal vein reconstruction; group 3, with PVTT extending to or beyond the portal vein bifurcation, treated by thrombectomy. A total of 88 patients, with a median age of 54 years, were included in the analysis. Group 2 patients were younger, with a median age of 43.5 years versus 57 in group 1 and 49 in group 3 (p = 0.017). Group 1 patients had higher preoperative serum alpha-fetoprotein levels, with a median of 8,493 ng/mL versus 63.25 in group 2 and 355 in group 3 (p = 0.004), and shorter operation time, with a median of 467.5 min versus 663.5 in group 2 and 753 in group 3 (p = 0.018). No patient had thrombus in the main portal vein. Two (2.8 %) hospital deaths occurred in group 1 and one (10 %) in group 2, but none in group 3 (p = 0.440). The rates of complication in groups 1, 2, and 3 were 31.9, 50.0, and 71.4 %, respectively (p = 0.079). The median overall survival durations were 10.91, 9.4, and 8.58 months, respectively (p = 0.962), and the median disease-free survival durations were 4.21, 3.78, and 1.51 months, respectively (p = 0.363). The groups also had similar patterns of disease recurrence (intrahepatic: 33.8 vs. 28.6 vs. 40.0 %; extrahepatic: 16.9 vs. 14.3 vs. 0 %; both: 28.2 vs. 42.9 vs. 40.0 %; no recurrence: 21.1 vs. 14.3 vs. 20.0 %; p = 0.836). The three approaches have similar outcomes in terms of survival, complication, and recurrence. Effective adjuvant treatments need to be developed to counteract the high incidence of recurrence.

Prognostic significance of WT1 expression at diagnosis and end of induction in Egyptian adult acute myeloid leukemia patients

BackgroundWilms' tumor (WT1) gene overexpression has been reported in the majority of acute myeloid leukemia (AML) patients at diagnosis and has been evaluated as prognostic and minimal residual disease (MRD) marker.Patients and methodsWT1 overexpression was evaluated in 68 adult AML patients at diagnosis and at the end of induction using quantitative real-time polymerase chain reaction (PCR).ResultsNo significant associations were encountered between WT1 overexpression at diagnosis and other prognostic factors. Complete remission (CR) was achieved in 74% of the patients with WT1 overexpresssion compared to 80% of patients with normal levels (P = 0.5). No significant associations were encountered between WT1 overexpression at diagnosis and disease-free survival (DFS) or overall survival (OS) (P = 0.6 and 0.3, respectively). At the end of induction, the median duration of DFS in patients achieving ≥2 log reduction was not reached compared to only 5 months (range: 2.1–7.9 months) in those attaining <2 log reduction (P = 0.2). The median duration of OS in patients achieving ≥2 log reduction was 13 months (range: 0–33.3 months) compared to 7.5 months (5.4–9.6 months) in those attaining <2 log reduction (P = 0.2). The survival at 1 year in patients achieving ≥2 log was double the group with <2 log reduction (67% compared to 33%).ConclusionOur results, although not reaching the level of significance, probably due to the small sample size, still suggest that the early assessment of WT1 transcript level at the end of induction in patients in CR may have a prognostic significance on clinical outcome and may thus be a useful marker for risk stratification especially in patients lacking disease-specific marker.

A single-institution study of stereotactic body radiotherapy for patients with unresectable visceral pulmonary or hepatic oligometastases

PurposeThe purpose of this study is to evaluate the feasibility, efficacy and toxicity of SBRT for treatment of unresectable hepatic or lung metastases regardless of their primary tumor site for patients who received prior systemic chemotherapy.Methods and materialsBetween July 2007 and June 2010, 90 patients were treated with the CyberKnife® SBRT system for hepatic or pulmonary metastatic lesions. Medical records were retrospectively reviewed. The endpoints of this study were local control, overall survival (OS), disease-free survival (DFS), local relapse free-survival (LRFS), and treatment toxicity.ResultsA total of 113 liver and 26 lung metastatic lesions in 52 men (58%) and 38 women (42%) were treated. Median follow-up was 17 months. Median age at treatment was 65 years (range, 23–84 years). Primary cancers were 63 GI, three lung, eight breast, four melanoma, three neuro-endocrine tumors, and three sarcomas. Median diameter of the lesions was 28 mm (range, 7–110 mm) for liver and 12.5 mm (range, 5–63.5 mm) for lung. Local control rates at 1 and 2 years were 84.5% and 66.1%, respectively. Two-year overall survival rate was 70% (95% CI: 55–81%). The 1 and 2-year disease-free survival rates were 27% (95% CI: 18–37%) and 10% (95% CI: 4–20%), respectively. Median duration of disease-free survival was 6.7 months (95% CI: 5.1–9.5 months). Observed toxicities included grade 1–3 acute toxicities. One grade 3 and no grade 4 toxicity were reported.ConclusionHigh-dose SBRT for metastatic lesions is both feasible and effective with high local control rates. Overall survival is comparable with other available techniques. Treatment is well tolerated with low toxicity rates. It could represent an interesting treatment option for oligometastatic patients not amenable to surgery, even when patients had been pre-treated with chemotherapy.SummaryStereotactic body radiotherapy (SBRT) has previously been successfully used in the treatment of metastatic lesions. It could be considered as a curative option for oligometastatic patients. This retrospective study involved 90 patients, designed to test potential effectiveness of SBRT in the treatment of oligometastases irrespective of primary. Results suggest SBRT could be an effective treatment extending patients’ life span. This treatment appears to be more effective when used prior to multiple systemic treatment regimens.

Peritonectomy for Peritoneal Carcinomatosis: Long‐Term Outcomes from a Single Brazilian Institution

The objective of this study was to evaluate the long-term outcomes of a single institution, Hospital Sírio-Libanes in São Paulo, Brazil, regarding the treatment of peritoneal carcinomatosis. Between October 2002 and October 2006, 46 consecutive patients were treated with radical cytoreduction and hyperthermic peritoneal chemotherapy. There were 21 patients with peritoneal surface malignancy (PSM) from colorectal origin (among whom 8 had an appendiceal primary), 15 with ovarian carcinomas, 2 with primary peritoneal mesotheliomas, and 8 with other cancers. The median age was 49 years (range 18-77 years). All patients were followed for a median of 20 months. Demographic data, tumor histology, the peritoneal carcinomatosis index (PCI), operative procedures (extension of resection, lymphadenectomy), and hyperthermic intraperitoneal chemotherapy (HIPEC) characteristics (drugs, temperature, duration) were prospectively recorded. Perioperative mortality and morbidity and the long-term outcome were assessed. Complete cytoreduction was achieved in 45 patients. The median PCI was 11, and the mean operating time was 17 h. There were no procedure-related deaths, but major morbidity was observed in 52% and included fistulas, abscesses, and hematologic complications. The overall Kaplan-Meier 4-year estimated survival was 56%. Among patients with PSM from colorectal carcinoma, the estimated 3-year survival was 70%. Nine (42%) patients had a recurrence, three with peritoneal disease. The median disease-free-interval was 16 months. The ovarian cancer patients had an estimated 4-year survival rate of 75% and median disease-free survival duration of 21 months. Cytoreductive surgery with HIPEC may improve survival of selected patients with peritoneal carcinomatosis, with acceptable morbidity.

Predictable prognostic factor of CD56 expression in patients with acute myeloid leukemia with t(8:21) after high dose cytarabine or allogeneic hematopoietic stem cell transplantation

CD56 expression in acute myeloid leukemia (AML) has been associated with extramedullary leukemia and multidrug resistance, but its clinical and prognostic significance has not been clearly identified. This study examined CD56 expression in 37 adult de novo AML patients with t(8:21). CD56 was expressed in 25 cases (67.6%). Complete remission (CR) rates were similar in both groups (91.7% vs. 88.7%; P = 0.73), but the relapse rates differed considerably (60% vs. 25%; P = 0.02). The median duration of disease-free survival (DFS) was significantly shorter in the CD56+ (median, 12.2 +/- 6.4 months) than in the CD56- group (median, not reached) (P = 0.02). In addition, the median duration of survival differed significantly in the CD56+ group (median, 14.9 +/- 4.4 months) compared with the CD56- group (median, not reached) (P = 0.01). Of the fifteen transplanted patients who achieved CR, allogeneic HST was performed from their siblings. The median duration of DFS in the CD56+ patients was significantly shorter than the CD56- patients (median, 24.4 +/- 4.5 months vs. median, not reached; P = 0.02). We concluded that CD56 expression correlates to a reduced DFS and survival for AML patients with t(8:21), including those patients who underwent transplantation.

Treatment for Acute Myelogenous Leukemia by Low Dose Irradiation Based Conditioning and Hematopoietic Cell Transplantation from Related and Unrelated Donors.

Conventional allogeneic hematopoietic cell transplantation (HCT) is effective treatment for AML, but its use has been restricted to younger patients in good medical condition. However, AML is increasingly common with advancing age, and older patients have more adverse prognostic features than younger patients. The vast majority of older patients who reach a CR with chemotherapy relapse within two years from diagnosis and die within three years. The situation is similar in patients with secondary AML or with AML in CR2, more advanced remission status or in partial remission, where median duration of disease-free survival (DFS) is generally <12 months. The use of low-dose irradiation-based preparative regimens has allowed extending allografting to, and exploring graft-versus-tumor effects in, older and medically infirm patients.The present study included 122 patients with AML ineligible for conventional transplants. Their disease stages ranged from CR1 to resistant disease, and their median age was 57.5 (range 17–74) years. The patients were given 2 Gy total body irradiation (TBI) on day 0 with and without preceding fludarabine (30 mg/m2/d from days -4 to -2). After HCT, cyclosporine, 6.25 mg/kg, was given twice daily from day -3, and mycophenolate mofetil, 15 mg/kg, twice daily from day 0. HLA-matched related donors were used in 58, and HLA-matched/partially matched unrelated donors in 64 patients. Among 121 (one died to early after transplant) evaluable patients, 116 (95.8%) had durable engraftment. Cumulative incidences of acute GvHD grade II-IV were 33 % after related and 42% after unrelated HCT. With a median observation time of 17 (range 4–57) months, 58 patients were alive, 53 of whom were in complete remissions. Cumulative non-relapse mortalities (NRM) were 12% and 27%, and the cumulative relapse mortalities were 47% and 34% at 2 years for related and unrelated recipients, respectively. Two-year overall survival (OS) was 41%, and DFS was 35%, with stages of the disease and cytogenetic risks being major determinants for outcomes. Patients transplanted in CR1 had a 2-year OS of 40% after related and 57% after unrelated HCT. We concluded that HCT from related and unrelated donors after low-dose TBI is promising therapy for elderly patients and medically infirm younger patients with AML not eligible for conventional HCT. Due to the lower relapse rates, results in patients with unrelated donors were better than results in patients with related donors. Results have encouraged studies of the role of low-dose irradiation-based conditioning and allogeneic HCT in the primary treatment of patients with AML ≥60 years.

Personal Experience in Surgical Management of Pulmonary Pleomorphic Carcinoma

Background Pleomorphic carcinoma is a rare epithelial malignant tumor. Pulmonary pleomorphic carcinoma was introduced by the 1999 World Health Organization classification as a new peculiar type of lung carcinoma showing concurrent malignant epithelial and sarcomatoid spindle cell elements. Few reports describe its clinical behavior. My colleagues and I report a series of patients surgically treated for pulmonary pleomorphic carcinoma to describe our experience with this malignant neoplasm. Methods Twenty cases of pleomorphic pulmonary carcinoma were collected and studied clinicopathologically. All patients underwent surgical resection. The cases were as follows: 6 stage I, 12 stage II, and 2 stage IIIA. Histologic diagnosis was established by using light microscopic examination and immunohistochemistry. Survival rates were calculated with the Kaplan-Meier method. Results We postoperatively diagnosed 20 cases of pleomorphic carcinoma: 14 cases were exclusively spindle and giant-cell carcinomas, 2 cases were spindle and giant-cell carcinoma combined with adenocarcinoma, 2 were combined with squamous cell carcinoma, and 2 were combined with large cell carcinoma. At last follow-up, 4 patients were still alive; they were postoperative T1 N0 and T2 N0. The remaining 16 patients died from early distant metastases. The median duration of disease-free survival was 5 months. The median duration of overall survival was 8 months. Conclusions The prognosis of patients with pleomorphic carcinoma was poor, despite surgery and adjuvant chemotherapy, because of early relapse of disease. Nodal involvement was a determinant prognostic variable, because advanced stages were related to worse prognosis. In case of preoperatively proven pulmonary pleomorphic carcinoma, surgery should be recommended to N0 patients.

Adjuvant intraperitoneal cisplatin chemotherapy does not improve long-term survival after surgery for advanced gastric cancer.

The long-term survival probability of patients who undergo surgery for stage 3 and 4 gastric cancer is poor, predominantly due to metastatic spread of the tumor. Depending on the type of tumor histology, the pathway of metastases is mainly peritoneal or hepatic dissemination. Interruption of this mechanism may be possible by intraperitoneal chemotherapy (IPT). In a prospective randomized trial of 67 patients undergoing surgery for stage 3 and 4 gastric cancer, 33 patients underwent adjuvant postoperative IPT with cisplatin, while 34 control subjects remained untreated. Patients in the treatment group received a median of four IPT perfusions. Apart from frequent nausea, no adverse reactions or complications were noted. The median disease-free survival durations were 12.7 months and 9.7 months in treated patients and controls, respectively (P = .8). After a median follow-up duration of 72 months, 54 patients (80%) had died of primary disease or related complications. The median survival duration for IPT patients was 17.3 months as compared with 16.0 months for controls (P = .6). Autopsies were performed on 12 (18%) of 54 patients who died, and showed tumor spread to the peritoneal cavity and/or to the liver, irrespective of the application of IPT. IPT with cisplatin monotherapy does not improve survival probability after surgery for stage 3 and 4 gastric cancer. The reasons for ineffectiveness of IPT may be the choice of an unsuitable chemotherapeutic agent, an inefficient modus of application, or a lack of sufficient drug penetration into the serosa or peritoneal metastasis.

LOCALLY ADVANCED BREAST-CARCINOMA - RESULTS OF A MULTIMODAL THERAPY INCLUDING ALTERNATING NEOADJUVANT CHEMOTHERAPY, SURGERY AND RADIOTHERAPY

Thirty women with locally advanced breast cancer (LABC), but no evidence of distant metastases, were prospectively treated with four fixed cycles of neoadjuvant chemotherapy (CT). This regimen consisted of epidoxorubicin (Epi) alternated every 21 days with cyclophosphamide, methotrexate and 5-fluorouracil (CMF). After this induction CT, subsequent therapy was planned according to the response obtained as follows: (a) modified mastectomy with axillary dissection was performed in patients who had major objective response (complete or partial), followed by four doses of adjuvant CT and radiotherapy (RT); (b) debulking rescue surgery followed by RT and 2nd line CT with mitomycin C were given in patients with stable disease or minor response. The response rate to induction CT was 63% (19 of 30 patients) (95% confidence limits 46-80%). Overall, 43% of patients had no persistance of tumor at the end of the planned therapy. After a median follow-up time of 36 months, disease-free survival (DFS) and overall survival (OS) were 35% and 47%, respectively. The median duration of DFS was 16 + months (4-52+ months). A significantly better OS was observed in complete responders compared to the others (77% versus 23.5%; p=0.01). Compliance to treatment was high, gastrointestinal and hematological toxicities were the most common side-effects. Thus, this multimodal approach is effective in reducing primary tumor size with acceptable morbidity. Five of the 11 (45%) patients non responsive to induction CT obtained a transient local control of disease after debulking surgery, RT and mitomycin C. To assess the role of alternating non cross resistant regimens as induction therapy in LABC vs conventional schedules, phase III comparative studies are warrented.