Cumulative Recurrence-free Survival Rates Research Articles

Clinical outcome of medium-sized hepatocellular carcinoma treated with microwave ablation.

To evaluate the outcomes of patients with medium-sized hepatocellular carcinoma (HCC) who underwent percutaneous microwave ablation (MWA). We retrospectively reviewed all patients with a single medium-sized HCC who underwent percutaneous MWA from January 2010 to January 2013. Technical success, technical effectiveness and complications were subsequently observed. Survival curves were constructed using the Kaplan-Meier method. The Cox proportional hazards model was fitted to each variable. The relative prognostic significance of the variables for predicting overall survival rate, recurrence-free survival rate and local tumor recurrence(s) was assessed using univariate analysis. All variables with a P value < 0.20 were subjected to multivariate analysis. The study included 182 patients (mean age, 58 years; age range: 22-86 years) with a single HCC (mean size, 3.72 ± 0.54 cm; range: 3.02-5.00 cm). The estimated technical effectiveness rate was 93% in 182 patients. The major complication rate was 2.7% (5/182), including liver abscess in 4 cases, and abdominal bleeding at the puncture site in 1 case. Thirty-day mortality rate was 0.5% (1/182). One patient died due to liver abscess-related septicemia. Cumulative recurrence-free survival and overall survival (OS) rates were 51%, 36%, 27% and 89%, 74%, 60% at 1, 2, and 3 years, respectively. Age (P = 0.017) and tumor diameter (P = 0.029) were independent factors associated with local tumor recurrence. None of the factors had a statistically significant impact on recurrence-free survival. Serum albumin level (P = 0.009) and new lesion(s) (P = 0.029) were independently associated with OS. Percutaneous MWA is a relatively safe and effective treatment for patients with medium-sized HCC.

Role of radiofrequency ablation in patients with hepatocellular carcinoma who undergo prior transarterial chemoembolization: long-term outcomes and predictive factors.

Background/AimsThe role of radiofrequency ablation (RFA) remains uncertain in patients with viable hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE).MethodsA total of 101 patients (April 2007 to August 2010) underwent RFA for residual or recurrent HCC after TACE. We analyzed their long-term outcomes and predictive factors.ResultsThe overall survival rates after RFA were 93.1%, 65.4%, and 61.0% at 1, 3, and 5 years, respectively. Predictive factors for favorable overall survival were Child-Pugh class A (hazard ratio [HR], 3.45; p=0.001), serum α-fetoprotein (AFP) level <20 ng/mL (HR, 2.90; p=0.02), and recurrent tumors after the last TACE (HR, 3.14; p=0.007). The cumulative recurrence-free survival rate after RFA at 6 months was 50.1%. Predictive factors for early recurrence (within 6 months) were serum AFP level 20 ng/mL (HR, 3.02; p<0.001), tumor size 30 mm at RFA (HR, 2.90; p=0.005), and nonresponse to the last TACE (HR, 2.13; p=0.013).ConclusionsPatients with recurrent or residual HCC who undergo prior TACE show a favorable overall survival, although their tumors seem to recur early and frequently. While good liver function, a low serum AFP level, and recurrent tumors were independent predictive factors for a favorable overall survival, poor response to TACE, a high serum AFP level, and large tumors are associated with early recurrence.

Transarterial chemoembolization using drug eluting beads and subsequent percutaneous MR-guided radiofrequency ablation in the therapy of intermediate sized hepatocellular carcinoma

ObjectiveTo evaluate safety, efficacy, survival and recurrence-free survival of transarterial chemoembolization (TACE) with drug eluting (DC) beads combined with MR-guided radiofrequency (RF) ablation for the treatment of hepatocellular carcinomas (HCC) larger than 3cm. Materials and methodsThis retrospective study was approved by the institutional review board. 20 patients (69.6 years ±SD 8.8) with HCC underwent DC Bead TACE and subsequent MR-guided RF ablation. Treatment interval varied between 5 and 15 days. Mean HCC diameter was 39mm ±SD 7mm (range 31–50mm). Rates of recurrence-free survival and overall survival were estimated using the Kaplan–Meier method. ResultsTechnical success rate, primary and secondary technical effectiveness rate were 100%, 90% and 95%, respectively. Local tumour progression developed in one patient. Cumulative survival rates at 1, 3 and 5 years were 90% (Confidence Interval [CI]: 67%–97%), 50% (CI: 29%–70%), 27% (CI: 11%–51%) respectively. Median survival time was 37.4 months. During follow up (mean: 39.1 months ±SD 22.4; range 5–84 months), tumour progression in untreated liver developed in 14 cases. Cumulative recurrence-free survival rates at 1, 3 and 5 years were 48% (CI: 27–69%), 16% (5–39%), 16% (5–39%) respectively. Median recurrence-free survival time was 10.7 months. One major complication occurred due to misdiagnosed local recurrence. ConclusionIn conclusion, we demonstrated that MR-guided RF ablation with subsequent DC Bead TACE is safe and effective in local tumour control in patients with intermediate sized HCC.

Fertility-Preserving Treatment in Young Women With Endometrial Adenocarcinoma: A Long-Term Cohort Study

Growing evidence suggests that fertility-preserving treatment is feasible for young women with early-stage, low-grade endometrial carcinoma. However, published data on their long-term outcomes and prognostic factors remain scanty. We aimed to investigate the outcomes of young women receiving fertility-preserving treatment. Between 1991 and 2010, the outcomes of young women with grade 1 endometrioid endometrial carcinoma at presumed stage IA (without myometrial invasion) who underwent fertility-preserving treatment of megestrol acetate 160 mg/d with or without other hormonal agents were retrospectively analyzed. We identified 37 eligible patients (median age, 32 years; range, 18-40 years). The median follow-up time was 78.6 months (range, 19.1-252.8 months). Complete response (CR) lasting more than 6 months was achieved in 30 (81.1%) women. Responders were significantly younger than nonresponders (P = 0.032). Of the 30 women who had a CR, 15 (50.0%) had disease recurrence. The 5-, 10-, and 15-year cumulative recurrence-free survival rates were 51.0%, 51.0%, and 34.0%, respectively. Notably, those recurred were significantly older (P = 0.003), and the time to CR was significantly longer (P = 0.043) than those without recurrence. One patient developed late recurrences at 156 months, and 2 patients developed ovarian metastasis (6 and 137 months from diagnosis). All the patients are currently alive. This study demonstrates the feasibility of high-dose megestrol acetate-based therapy for fertility preservation. The substantial risk of late recurrences highlights the need for long-term follow-up studies of large sample sizes with in-depth tumor and host molecular signatures.

Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution's experience with 398 consecutive patients

Surgical resection is an important curative treatment for hepatocellular carcinoma (HCC); however, some patients experience an unexpected recurrence even after hepatectomy. The present study aimed to investigate risk factors and predictive criteria for early and late recurrence of HCC after resection. A retrospective analysis of 398 Chinese patients who received curative resection for HCC was conducted. Patients were divided into three groups: without recurrence, early recurrence, and late recurrence. Prognostic factors and predictive criteria for early and late recurrence were statistically analyzed. The cumulative recurrence-free survival rates at 1, 2, 3, 4, and 5 years were 75.5%, 58.2%, 54.1%, 40.5%, and 28.7%, respectively. The distribution of the time to recurrence suggested that recurrence could be divided into early phase (before 2 years; n=164) and late phase (after 2 years; n=83). Cox's multivariate proportional hazard model analysis revealed that multiplicity of tumors (P=0.004) and venous infiltration (P=0.002) were independent risk factors associated with early recurrence. In contrast, indocyanine green retention rate at 15 minutes (P=0.007), serum albumin level (P=0.045), and HBeAg status (P=0.028) proved to be significant independent adverse prognostic factors for late recurrence. Patients with at least 1 of the 2 early recurrence risk factors (multiplicity of tumors ≥ 2 and venous infiltration) or with 2 or more late recurrence risk factors are often susceptible to recurrence (P=1.36e-4 and 1.0e-6, respectively). Early and late recurrences correlate with different risk factors and predictive criteria. Early recurrence primarily results from intrahepatic metastases, while late recurrence may be multicentric in origin.

Efficacy of sorafenib as adjuvant therapy to prevent early recurrence of hepatocellular carcinoma after curative surgery: A pilot study

Until now, no effective adjuvant therapy to prevent early recurrence of hepatocellular carcinoma (HCC) after curative treatment has been reported. The aim of this study is to evaluate the clinical benefit of sorafenib as adjuvant treatment in subjects with HCC after hepatic resection. The pilot study was undertaken involving HCC patients who had undergone curative liver surgery with high recurrence risk factors. Time to recurrence and disease recurrence rate were assessed. Sorafenib 400 mg q.d. was administrated continuously for 4 months after hepatic resection. A total of 31 patients were enrolled and eligible for final data analysis. The median follow-up time was 19 months (range, 9.5-30.2). Time to recurrence in the sorafenib arm was 21.45 ± 1.98 months (mean ± standard deviation), compared to 13.44 ± 2.66 months in the control arm (P = 0.006). The median recurrence-free survival in the sorafenib arm did not reach the data cut-off date compared to 8 months in the control arm (P = 0.006). The recurrence rate between the two groups was significantly different (29.4% vs 70.7%, P = 0.032). Cox regression analysis showed that taking study medicine was the only prognostic variable associated with HCC recurrence (hazard ratio = 0.24, 95% confidence interval = 0.08-0.75, P = 0.014). This study showed that setting sorafenib as adjuvant therapy for HCC to prevent early recurrence after hepatic resection could be a potential indication. The cumulative recurrence-free survival rate also demonstrated the preventive effectiveness of sorafenib.

CT with hepatic arterioportography as a pretreatment examination for hepatocellular carcinoma patients: a randomized controlled trial.

OBJECTIVES:The combination of computed tomography with hepatic arteriography and arterial portography (CTHA/CTAP) can detect additional hepatocellular carcinoma (HCC) nodules undetected by conventional dynamic CT.METHODS:In this single-center, randomized, open-label, controlled trial, we randomly assigned 280 patients who were diagnosed as having HCC by conventional dynamic CT, and eligible for radiofrequency ablation (RFA), to undergo CTHA/CTAP before treatment, or to the control group. Newly detected HCC nodules by CTHA/CTAP were intended to be ablated completely. The primary end point was recurrence-free survival and the key secondary end point was overall survival. The analysis was conducted on an intention-to-treat basis. Those with nonablated nodules were treated as for recurrence.RESULTS:A total of 75 nodules were newly diagnosed as HCC by CTHA/CTAP in 45 patients. Three patients (one in the CTHA/CTAP group and two in the control group) who refused treatment were excluded from all analyses. The cumulative recurrence-free survival rates at 1, 2, and 3 years were 60.1, 29.0, and 18.9% in the CTHA/CTAP group and 52.2, 29.7, and 23.1% in the control group, respectively (P=0.66 by log-rank test; hazard ratio, 0.94 for CTHA/CTAP vs. control; 95% confidence interval (CI), 0.73–1.22). The cumulative overall survival rates at 3 and 5 years were 79.7 and 56.4% in the CTHA/CTAP group and 86.8 and 60.1% in the control group, respectively (P=0.50; hazard ratio, 1.15, 95% CI, 0.77–1.71).CONCLUSIONS:CTHA/CTAP may detect recurrent lesions earlier. However, CTHA/CTAP before RFA did not improve cumulative recurrence-free survival or overall survival.

Risk Factors for Hepatic Steatosis After Pancreatectomy

The occurrence of hepatic steatosis after pancreatectomy has been previously known. However, this condition has been neglected because its clinical course has been considered benign. The aims of this study were to identify the risk factors for hepatic steatosis after pancreatectomy, to clarify the impact of this condition on long-term prognosis, and to suggest methods for preventing hepatic steatosis. One hundred two patients, who were diagnosed with postoperative computed tomography, were enrolled. The severity of hepatic steatosis was determined by using unenhanced computed tomography. The variables that might influence the development of hepatic steatosis were compared between the groups with and without hepatic steatosis. The incidence of postoperative hepatic steatosis was 31.4%. Multivariate analysis showed that absence of postoperative insulin use (P < 0.01) and decrease in postoperative body mass index of greater than 3 kg/m(2) (P < 0.01) were independent risk factors for hepatic steatosis. The cumulative recurrence-free survival rate of the group with hepatic steatosis was poorer than that of the group without (P = 0.053). Postoperative hepatic steatosis may affect long-term prognosis after pancreatectomy. Surgeons should take care of nutritional management including insulin therapy for patients with hepatic steatosis after pancreatectomy.

Resection of segment VIII for hepatocellular carcinoma

Anatomical resection of segment VIII (SVIII) is technically demanding. Only two small studies have published short-term outcomes. The aim of the present study was to evaluate short- and long-term outcomes after anatomical resection involving SVIII for hepatocellular carcinoma (HCC), and to compare long-term outcomes with those after non-anatomical resection of SVIII. Outcomes after anatomical resection of SVIII or its subsegments for HCC were compared with those in patients who underwent primary non-anatomical resection of SVIII during the same period. A total of 154 patients underwent anatomical resection involving SVIII and 122 had non-anatomical resection. In patients undergoing anatomical resection, the preoperative indocyanine green retention rate at 15 min ranged from 2·9 to 32·2 (median 13·6) per cent, and was 10 per cent or more in 109 patients (70·8 per cent). Median duration of operation and blood loss were 378 min and 705 ml respectively. There were no postoperative deaths, but major adverse events occurred in ten patients (6·5 per cent). The cumulative 5-year recurrence-free and overall survival rates were 28·5 and 79·6 per cent, which were significantly better than rates of 19·4 and 64·8 per cent respectively after non-anatomical resection (P = 0·036 and P < 0·001). Complete resection of SVIII or its subsegments can be performed safely and the long-term outcomes seem acceptable. This can be a curative procedure for HCC, especially in patients with limited liver function reserve, in whom right hepatectomy or right paramedian sectorectomy might otherwise be needed.

Clinical Outcomes of Breast-Conserving Surgery in Patients Using a Modified Method for Cavity Margin Assessment

This study describes a modified intraoperative method for cavity margin (CM) assessment in place of lumpectomy margin assessment in patients undergoing breast-conserving surgery (BCS). This is a retrospective review of 422 breast cancer patients undergoing BCS with intraoperative CM assessment. After an initial lumpectomy with intent to obtain ≥1-cm margins, separate specimens 1 × 1 cm, 0.5-cm thick were taken from the cavity margin circumferentially. These were frozen without reference to the side of the new margin as a time-saving measure, and parallel sections of the resected surface were evaluated. After a median follow-up of 55.5 months, a cumulative 5-year locoregional recurrence-free survival rate of 95.3%, metastasis-free survival rate of 97.8%, disease-free survival rate of 88.3%, and overall survival rate of 96.0%, was achieved. The CM positivity rates were of no statistical difference when <7, 7-8, and >8 CMs were assessed. The second operation rate was 3.5% because of the false-negative results of the frozen section analysis on CMs. Univariate and multivariate analysis revealed that a higher pN stage and cT stage as well as a lack of adjuvant chemotherapy or radiation demonstrated significantly worse clinical outcomes. Locoregional recurrences and metastasis are both correlated with worse overall survival. The number of the CMs assessed was not associated with clinical outcomes. The modified CM assessment presented here is a rapid, accurate, and oncologically safe approach for margin evaluation in BCS patients. Lumpectomy margin assessment might be spared when this method is used.

Long-Term Results of a Randomized, Observation-Controlled, Phase III Trial of Adjuvant Interferon Alfa-2b in Hepatocellular Carcinoma After Curative Resection

To investigate the clinical efficacy of adjuvant interferon alfa-2b (IFNα-2b) therapy on recurrence-free survival (RFS) of patients with postoperative viral hepatitis-related hepatocellular carcinoma (HCC). Despite most individual trials have failed to meet their primary endpoint, recent pooled-data meta-analyses suggest that adjuvant IFN therapy may significantly reduce the incidence of recurrence in curatively ablated HCC. Patients with curative resection of viral hepatitis-related HCC were eligible, and were stratified by underlying viral etiology and randomly allocated to receive either 53 weeks of adjuvant IFNα-2b treatment or observation alone. The primary endpoint of this study was RFS. A total of 268 patients were enrolled with 133 in the IFNα-2b arm and 135 in the control arm. Eighty percent of them were hepatitis B surface antigen seropositive. At a median follow-up of 63.8 months, 154 (57.5%) patients had tumor recurrence and 84 (31.3%) were deceased. The cumulative 5-year recurrence-free and overall survival rates of intent-to-treat cohort were 44.2% and 73.9%, respectively. The median RFS in the IFNα-2b and control arms were 42.2 (95% confidence interval [CI], 28.1-87.1) and 48.6 (95% CI, 25.5 to infinity) months, respectively (P = 0.828, log-rank test). Adjuvant IFNα-2b treatment was associated with a significantly higher incidence of leucopenia and thrombocytopenia. Thirty-four (24.8%) of treated patients required dose reduction, and 5 (3.8%) of these patients subsequently withdrew from therapy because of excessive toxicity. Adjuvant IFNα-2b only temporarily suppressed viral replication during treatment period. In this study, adjuvant IFNα-2b did not reduce the postoperative recurrence of viral hepatitis-related HCC. More potent antiviral therapy deserves to be explored for this patient population. This study is registered at ClinicalTrials.gov and carries the identifier NCT00149565.

Monthly intravesical bacillus Calmette-Guérin maintenance therapy for non-muscle-invasive bladder cancer: 10-year experience in a single institute

Intravesical bacillus Calmette-Guérin (BCG) therapy is the standard prophylaxis for recurrence of non-muscle-invasive bladder cancer (NMIBC). The aim of this study was to confirm the recurrence- and progression-preventing efficacy and safety of 12 times monthly BCG maintenance therapy for NMIBC. This study included 126 patients diagnosed with Ta, T1 and carcinoma in situ bladder cancer between January 2000 and December 2009. Thirty-four patients in the no maintenance group received a single 6-week course of intravesical immunotherapy after transurethral resection of the bladder tumor (TUR-BT). Ninety-two patients in the maintenance group received a 12-month course after a single 6-week course of intravesical immunotherapy. Recurrence, progression and side effects were assessed. End-points were recurrence-free survival (RFS), progression-free survival (PFS) and disease-specific survival (DSS). The estimated median RFS was 87 months (95% CI 53.0-120.9) in the maintenance group and 48 months (95% CI 0-96.8) in the no maintenance group (log-rank test; P=0.002). The 2-year cumulative RFS rates were 77.3% in the maintenance group and 52.6% in the no maintenance group. Median PFS and DSS were not estimable in both groups. The 2-year cumulative PFS rates were 91.1% in the maintenance group and 80.5% in the no maintenance group (log-rank test; P=0.178). The 2-year cumulative DSS rates were 97.7% in the maintenance group and 91.4% in the no maintenance group (log-rank test; P=0.111). The overall side effects were 40.2% in the maintenance group and 44.1% in the no maintenance group. Monthly maintenance immunotherapy appears to increase RFS rates in high-risk NMIBC. Further study is required to evaluate the efficacy of BCG monthly maintenence for increasing the PFS rate.

Clinical benefit of peretinoin for the suppression of hepatocellular carcinoma (HCC) recurrence in patients with Child-Pugh grade A (CP-A) and small tumor: A subgroup analysis in a phase II/III randomized, placebo-controlled trial.

165 Background: HCC has a high recurrence rate and poor prognosis; however, no effective treatment has been established for preventing recurrence after resection or ablation. Peretinoin, an acyclic retinoid, of 600 mg/day reduced HCC recurrence and a strong effect after two years suggested that it mainly suppressed de novo carcinogenesis (ASCO2010). Liver impairment causes non- HCC-related deaths or adverse events, and can potentially mask drug efficacy. The size of the main HCC nodule associates vascular invasion and intrametastasis. To evaluate peretinoin efficacy and assess its mechanism of action, we performed subgroup analysis in CP-A patients who had undergone curative therapy for a small tumor. Methods: Eligibility criteria included HCV positive, CP-A or B, and prior curative resection or ablation for conventional HCC. The patients were randomized into groups to receive peretinoin 600 mg/day (high dose, H), peretinoin 300 mg/day (low dose, L), or placebo (P). The patients were grouped according to the CP grade and the size of the major tumor &lt;20mm at the time of diagnosis. Cumulative recurrence-free survival rates were calculated. Hazard ratio (HR) was calculated using Cox regression analysis. Results: Of the 401 patients, 310 showed CP-A, and 144 showed CP-A and tumor size &lt;20 mm. In the CP-A subgroup, the HR of H group (100) vs. P group (106) was 0.603 (95% CI, 0.408-0.891); in the CP-A and tumor size &lt;20 mm subgroup, the HR of H group (49) vs. P group (49) was 0.376 (95% CI, 0.200-0.705). The common treatment-related adverse events in the CP-A subgroup were albuminuria, hypertension, and headache, which were tolerated. Conclusions: Subgroup analysis with CP-A reinforced the peretinoin efficacy in preventing HCC recurrence. In addition, the CP-A and tumor size &lt;20mm subgroup results strongly suggested that peretinoin inhibited de novo carcinogenesis. The subgroup analyses results of our phase II/II study supported the efficacy and safety of peretinoin and showed that it has early benefits for patients with well-preserved liver function and undergone curative therapy for a small tumor. [Table: see text]

Maintenance therapy with bacillus Calmette‐Guérin Connaught strain clearly prolongs recurrence‐free survival following transurethral resection of bladder tumour for non‐muscle‐invasive bladder cancer

• To confirm the recurrence-preventing efficacy and safety of 18-month bacillus Calmette-Guérin (BCG) maintenance therapy for non-muscle-invasive bladder cancer. • The enrolled patients had been diagnosed with recurrent or multiple non-muscle-invasive bladder cancer (stage Ta or T1) after complete transurethral resection of bladder tumours (TURBT). • The patients were randomized into three treatment groups: a maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks as induction therapy, followed by three once-weekly instillations at 3, 6, 12 and 18 months after initiation of the induction therapy), a non-maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks) and an epirubicin group (epirubicin, 40 mg, intravesically instilled nine times). The primary endpoint was recurrence-free survival (RFS). • Efficacy analysis was performed for 115 of the full-analysis-set population of 116 eligible patients, including 41 maintenance group patients, 42 non-maintenance group patients and 32 epirubicin group patients. • At the 2-year median point of the overall actual follow-up period, the final cumulative RFS rates in the maintenance, non-maintenance and epirubicin groups were 84.6%, 65.4% and 27.7%, respectively. • The RFS following TURBT was significantly prolonged in the maintenance group compared with the non-maintenance group (generalized Wilcoxon test, P= 0.0190). • BCG maintenance therapy significantly prolonged the post-TURBT RFS compared with BCG induction therapy alone or epirubicin intravesical therapy.

Triple negativity and young age as prognostic factors in lymph node-negative invasive ductal carcinoma of 1 cm or less

BackgroundWhether a systemic adjuvant treatment is needed is an area of controversy in patients with node-negative early breast cancer with tumor size of ≤1 cm, including T1mic.MethodsWe performed a retrospective analysis of clinical and pathology data of all consecutive patients with node-negative T1mic, T1a, and T1b invasive ductal carcinoma who received surgery between Jan 2000 and Dec 2006. The recurrence free survival (RFS) and risk factors for recurrence were identified.ResultsOut of 3889 patients diagnosed with breast cancer, 375 patients were enrolled (T1mic:120, T1a:93, T1b:162). Median age at diagnosis was 49. After a median follow up of 60.8 months, 12 patients developed recurrences (T1mic:4 (3.3%), T1a:2 (2.2%), T1b:6 (3.7%)), with a five-year cumulative RFS rate of 97.2%. Distant recurrence was identified in three patients. Age younger than 35 years (HR 4.91; 95% CI 1.014-23.763, p = 0.048) and triple negative disease (HR 4.93; 95% CI 1.312-18.519, p = 0.018) were significantly associated with a higher rate of recurrence. HER2 overexpression, Ki-67, and p53 status did not affect RFS.ConclusionsPrognosis of node-negative breast cancer with T1mic, T1a and T1b is excellent, but patients under 35 years of age or with triple negative disease have a relatively high risk of recurrence.

Postmastectomy locoregional recurrence and recurrence-free survival in breast cancer patients

BackgroundOne essential outcome after breast cancer treatment is recurrence of the disease. Treatment decision is based on assessment of prognostic factors of breast cancer recurrence. This study was to investigate the prognostic factors for postmastectomy locoregional recurrence (LRR) and survival in those patients.Methods114 patients undergoing mastectomy and adjuvant radiotherapy in Cancer Institute of Tehran University of Medical Sciences were retrospectively reviewed between 1996 and 2008. All cases were followed up after initial treatment of patients with breast cancer via regular visit (annually) for discovering the LRR. Cumulative recurrence free survival (RFS) was determined using the Kaplan-Meier method, with univariate comparisons between groups through the log-rank test. The Cox proportional hazards model was used for multivariate analysis.ResultThe median follow up time was 84 months (range 2-140). Twenty-three (20.2%) patients developed LRR. Cumulative RFS rate at 2.5 years and 5 years were 86% (95%CI, 81-91) and 82.5% (95%CI, 77-87) respectively. Mean RFS was 116.50 ± 4.43 months (range, 107.82 - 125.12 months, 95%CI). At univariate and multivariate analysis, factors had not any influence on the LRR.ConclusionDespite use of adjuvant therapies during the study, we found a LRR rate after mastectomy of 20.2%. Therefore, for patients with LRR without evidence of distant disease, aggressive multimodality therapy is warranted.

18F-FDG PET in the assessment of tumor grade and prediction of tumor recurrence in intracranial meningioma

The purpose of this study was to investigate the role of (18)F-fluorodeoxyglucose (FDG) PET in detecting high-grade meningioma and predicting the recurrence in patients with meningioma after surgical resection. Fifty-nine patients (27 men and 32 women) with intracranial meningioma who underwent preoperative FDG PET and subsequent surgical resection were enrolled. All patients underwent clinical follow-up for tumor recurrence with a mean duration of 34+/-20 months. The tumor to gray matter ratio (TGR) of FDG uptake was calculated and a receiver-operating characteristic (ROC) curve of the TGR was drawn to determine the cutoff value of the TGR for detection of high-grade meningioma. Further, univariate analysis with the log-rank test was performed to assess the predictive factors of meningioma recurrence. The TGR in high-grade meningioma (WHO grade II and III) was significantly higher than that in low-grade ones (WHO grade I) (p=0.002) and significantly correlated with the MIB-1 labeling index (r=0.338, p=0.009) and mitotic count of the tumor (r=0.284, p=0.03). The ROC analysis revealed that the TGR of 1.0 was the best cutoff value for detecting high-grade meningioma with a sensitivity of 43%, specificity of 95%, and accuracy of 81%. Of 59 patients, 5 (9%) had a recurrent event. In the log-rank test, the TGR, MIB-1 labeling index, presence of brain invasion, and WHO grade were significantly associated with tumor recurrence. The cumulative recurrence-free survival rate of patients with a TGR of 1.0 or less was significantly higher than that of patients with a TGR of more than 1.0 (p=0.0003) FDG uptake in meningioma was the significant predictive factor of tumor recurrence and significantly correlated with the proliferative potential of the tumor.

PIVKA-II Is the Best Prognostic Predictor in Patients with Hepatocellular Carcinoma after Radiofrequency Ablation Therapy

Objective: This study was undertaken to assess the prognostic predictor in patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). Methods: This study retrospectively evaluated clinical outcomes in a cohort of 179 Child-Pugh stage A cirrhotic patients who received curative RFA for naive HCC within Milan criteria. The median follow-up period was 40.5 months. Results: The cumulative survival rate was significantly lower in patients with prothrombin induced by vitamin K absence or antagonist II (PIVKA-II) ≥100 mAU/ml compared with PIVKA-II <100 mAU/ml (58.0 vs. 84.0% at 5 years; p < 0.001). The cumulative recurrence-free survival rates were significantly lower in patients with PIVKA-II ≥100 mAU/ml compared with PIVKA-II <100 mAU/ml (12.1 vs. 16.9% at 5 years; p < 0.032). The cumulative rate of maintaining period within Milan criteria was significantly lower in patients with PIVKA-II ≥100 mAU/ml compared with PIVKA-II <100 mAU/ml (34.1 vs. 55.6% at 5 years; p < 0.001). Cox regression analysis showed that low serum albumin (<3.5 g/dl; p = 0.002, RR 3.75, CI 1.64–8.56), a high level of PIVKA-II (≥100 mAU/ml; p = 0.04, RR 3.15, CI 1.45–6.87), and multiple nodules (p = 0.021, RR 2.61, CI 1.15–5.91) were independently significant mortality risk factors. Conclusion: In patients with Child-Pugh stage A HCC, the PIVKA-II level is the best prognostic predictor after curative RFA.

Optimal indications of endocrine therapy alone as adjuvant systemic treatment of breast cancer

We examined the validity of the St Gallen algorithm for Japanese breast cancer patients and sought the optimal indications of endocrine monotherapy as adjuvant systemic treatment. According to the 2005 St Gallen algorithm, endocrine responsiveness (responsive, uncertain, or non-responsive) and recurrence risk (low, intermediate, or high) were assessed in 436 invasive breast cancer patients, who underwent surgery and adjuvant therapy of tamoxifen alone in 1982–1993. Furthermore, intermediate-risk patients were divided into three groups based on lymph node metastasis and number of risk factors as follows: Group A, negative lymph node metastasis and one risk factor; Group B, negative lymph node metastasis and two to five risk factors; and Group C, positive lymph node metastasis. Cumulative 10-year recurrence-free survival (RFS) rates of each type were calculated. Recurrence-free survival was as follows: endocrine responsiveness; responsive: 86.0%, uncertain: 79.5%, non-responsive: 72.4%, risk category; low: 93.3%, intermediate: 84.0%, high: 59.6%, intermediate-risk patients; Group A: 93.5%, Group B: 88.2%, and Group C: 75.0%. In conclusion, patient classification based on St Gallen algorithm appears valid in Japanese breast cancer patients. Endocrine monotherapy may be sufficient as adjuvant treatment in the intermediate-risk patients, in which only one risk factor was present without any metastatic involvement in lymph node.

Management of rectal cancer – is adjuvant radiotherapy safe for the elderly?

Sirs, We read with interest Bouvier's paper, ‘Trends in the Management and Survival of Digestive Tract Cancers among Patients Aged over 80 years’, in the recent issue of Alimentary Pharmacology and Therapeutics.1 They showed the trends in the treatment of digestive tract cancers among patients aged ≥80 years. They examined time trends in three age classes and in five 4-year time intervals. Analysing postoperative survival rates for various cancers in the digestive tract, they concluded that surgery should not be restricted on the basis of age alone and further improvements can be made in particular to enhance adjuvant therapy whenever possible. In their analysis, the proportion of patients with rectal cancer receiving adjuvant radiotherapy slightly increased without reaching 20% during the last time period. They stated that comorbidity and advanced age are the more commonly cited reasons for not administering adjuvant therapies in patients with rectal cancer aged ≥75 years than patient refusal. However, although Bouvier et al. 1 addressed the importance of adjuvant therapy to improve surgical outcome, their study did not provide any specific data concerning complications related with adjuvant therapy in the treatment of rectal cancer. In the treatment of rectal cancer, we have a similar study and agree with their conclusion supporting the application of the surgical treatment for elderly patients. Furthermore, concerning adjuvant radiotherapy, we recently demonstrated that neoadjuvant radiotherapy is a safe modality for elderly patients.2 We examined a total of 230 patients with T3/T4 rectal cancer who underwent preoperative radiotherapy. According to age, patients were divided into elderly group (≥70 years: n = 44) or younger group (<70 years old: n = 186). Between two groups, there was no significant difference in curative resection rate, sphincter-preserving rate, 5-year cumulative relapse-free survival rate or 5-year cumulative local recurrence-free survival rate. Furthermore, as for adverse effects, the frequency of grade 4 radiation toxicity or grade l–3 toxicity, including nausea, fatigue, diarrhoea and dermatitis, showed no statistical difference between two groups. Postoperative mortality was 0% in both groups and postoperative morbidity rate was 58.5% in the elderly group and 50.8% in the younger group (N.S.). Postoperative major complications occurred in 9.8% in elderly group and 7.7% in younger group (N.S.). All these results showed no significant disadvantage by adjuvant radiotherapy in elderly patients. Considering that the incidence of adverse events in relation with radiotherapy did not increase in elderly patients, together with Bouvier's results, it is suggested that adjuvant radiotherapy is a safe modality for rectal cancer in elderly patients.