Poor 5-year Disease-free Survival Research Articles

Breast Cancer Prognosis and Occult Lymph Node Metastases, Isolated Tumor Cells, and Micrometastases

The prognostic relevance of isolated tumor cells and micrometastases in lymph nodes from patients with breast cancer has become a major issue since the introduction of the sentinel lymph node procedure. We conducted a systematic review of this issue. Studies published from January 1, 1977, until August 11, 2008, were identified by use of MEDLINE, EMBASE, and the Cochrane Library. A total of 58 studies (total number of patients = 297,533) were included and divided into three categories according to the method for pathological assessment of the lymph nodes: cohort studies with single-section pathological examination of axillary lymph nodes (n = 285,638 patients), occult metastases studies with retrospective examination of negative lymph nodes by step sectioning and/or immunohistochemistry (n = 7740 patients), and sentinel lymph node biopsy studies with intensified work-up of the sentinel but not of the nonsentinel lymph nodes (n = 4155 patients). We used random-effects meta-analyses to calculate pooled estimates of the relative risks (RRs) of 5- and 10-year disease recurrence and death and the multivariably corrected pooled hazard ratio (HR) of overall survival of the cohort studies. In the cohort studies, the presence (vs the absence) of metastases of 2 mm or less in diameter in axillary lymph nodes was associated with poorer overall survival (pooled HR of death = 1.44, 95% confidence interval [CI] = 1.29 to 1.62). In the occult metastases studies, the presence (vs the absence) of occult metastases was associated with poorer 5-year disease-free survival (pooled RR = 1.55, 95% CI = 1.32 to 1.82) and overall survival (pooled RR = 1.45, 95% CI = 1.11 to 1.88), although these endpoints were not consistently assessed in multivariable analyses. Sentinel lymph node biopsy studies were limited by small patient groups and short follow-up. The presence (vs the absence) of metastases of 2 mm or less in diameter in axillary lymph nodes detected on single-section examination was associated with poorer disease-free and overall survival.

Exploiting Warburg's Effect for Clinical Gain: Pdk-3 is a Potential Target for Mitochondrial Modulation in Colorectal Cancer (CRC)

Exploiting Warburg's Effect for Clinical Gain: Pdk-3 is a Potential Target for Mitochondrial Modulation in Colorectal Cancer (CRC)

Prognostic Factors for Breast Cancer with 10 or More Lymph Nodes Metastasis.

Abstract Background: Although the proportion of early breast cancer has been increased, advanced breast cancers of N3 stage still compose about 10% of all breast cancers. The purpose of this study was to investigate factors associated with prognosis of breast cancers with extensive nodal metastasis.Patients and method: Of 3912 invasive breast cancer patients who underwent surgery between April 1986 and May 2006 at Severance Hospital, patients who had 10 or more metastatic lymph nodes without distant metastasis were 304 (7.8%). With 55 months of median follow-up period, their clinicopathologic characteristics, follow-up of survival and the factors associated with disease free survival (DFS) and overall survival (OS) were analyzed.Result: Median age was 46.5 years and median number of positive lymph node was 16 with metastases to supraclavicular lymph nodes in 14 patients (4.6%). Median 5-year DFS rate were 42.4% and OS rate was 47.5%. In the Kaplan-Meier survival analysis, age less than 35 years (19.4% vs. 45.9%; p=0.001), the history of NAC (13.1% vs. 48.8%; p<0.001), T4 stage (15.8% vs. 45.8%, excluding T4d; p<0.001), 20 or more positive lymph nodes (27.0% vs. 50.2%; p<0.001), lymphovascular invasion (20.2% vs. 48.4%; p=0.003), and negative progesterone receptor (32.8% vs. 49.3%; p=0.003) were significantly associated to poor 5-year DFS. For 5-year OS, age less than 35 years (43.8% vs. 59.7%; p=0.033), the history of NAC (28.0% VS. 63.8%; p<0.001), T4 stage (21.1% vs. 61.0%, excluding T4d; p=0.001), 20 or more positive lymph nodes (48.9% vs. 63.8%; p<0.001), and negative progesterone receptor (49.0% vs. 64.2%; p=0.013) were statistically significant. On the multivariate analysis, significant factors associated with poor DFS and OS were 20 or more metastatic lymph nodes (relative risk [RR] =1.598 and p=0.024 for DFS; RR=1.956 and p<0.001 for OS), the history of neoadjuvant chemotherapy (RR=3.163 and p<0.001 for DFS; RR=2.900 and p<0.001 for OS). The contribution of lymphovascular invasion was significant only to DFS on the multivariate analysis.Conclusion: The patients with the same N3 stage show various prognosis. Clinical trial using new therapeutic agents should be applied in advanced breast cancers with high risk, which are predicted to be refractory to conventional adjuvant therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4064.

HLA-A, -B, -C Expression in Colon Carcinoma Mimics That of the Normal Colonic Mucosa and is Prognostically Relevant

Whether human leukocyte antigen (HLA)-A, -B, -C expression has any predictive value on the prognosis of human malignancies remains controversial. Herein, monoclonal antibodies with preferential reactivity for HLA-A, HLA-B, and HLA-C (HCA2, HC10, and L31) were used to stain an archival collection of 291 formalin-fixed/paraffin-embedded tissues, comprising neoplastic lesions from stages II and III colon carcinoma patients (n=165), and the uninvolved, morphologically normal mucosae from a subset (n=126) of these patients. Marked staining variability was detected not only in the tumors as in previous studies, but also in the normal paired mucosae. HLA-A, -B, -C expression was similar in approximately two thirds of the available 126 normal/neoplastic pairs, confirming in vivo our previous observation that most tumor cells mimic the HLA phenotypes of their normal counterparts. Both up and down-regulation occurred in the remaining third of the pairs, but did not coincide with high and low expression, respectively, conventionally evaluated on the tumor lesion only. Remarkably, a "paired" evaluation, but not high or low expression in the tumor, was predictive of the clinical outcome. Deviations from the expression in the normal paired mucosa (both increases and decreases) of HCA2-reactive class I molecules (possibly HLA-A), and down-regulation of L31-reactive class I molecules (possibly HLA-C), particularly in tumors from stage II patients, correlated with poor 5-year overall and disease-free survival, hazard risk ranging from 2 to 6, approximately. Thus, a paired immunohistochemical comparison reveals a novel immune evasion strategy that may impact on the prognosis of colon carcinoma.

2438: Relationship Between Primary Tumor Volume and Radiotherapeutic Outcome in Nasopharyngeal Carcinoma

Purpose/Objective(s)To investigate the correlation of primary tumor volume of nasopharyngeal carcinoma with the clinical result of radiotherapy.Materials/MethodsOne hundred and fifty-four patients with nasopharyngeal carcinoma were treated with late-course accelerated hyperfractionated radiotherapy alone to a total dose of 78Gy/60Fx/6w. The primary tumor volume (PTV) was obtained by outlining the tumor contour on CT images, followed by the summation of area technique. The median follow-up time was 49.5 months. Kaplan Meier method was used to calculate survival and local control rates.ResultsEvident volume disparity with different T stage and the volume data overlap between continuous T stages was found. The mean primary tumor volume was as follows (cm3): T1 18.90(0.55∼59.33), T2 25.80(2.22∼80.64), T3 40.07(13.97∼87.97) and T4 56.04(19.18∼115.00). Univariant analysis showed that the poor 5-year local control, disease-free survival and distant relapse-free survival rates in patients with large tumor volume(>60cm3). Primary tumor volume was found to be an independent prognostic factor of local control in multivariant analysis without statistical significance to predict the disease-free survival or distant relapse-free survival rates.ConclusionsThe greater volume disparity with the same T stage and the data extension overlap with different T stage are demonstrated and the primary tumor volume may be considered as a prognostic factor in the treatment of nasopharyngeal carcinoma.Nasopharyngeal neoplasm, Radiotherapy, Computed tomography, Primary tumor volume. Purpose/Objective(s)To investigate the correlation of primary tumor volume of nasopharyngeal carcinoma with the clinical result of radiotherapy. To investigate the correlation of primary tumor volume of nasopharyngeal carcinoma with the clinical result of radiotherapy. Materials/MethodsOne hundred and fifty-four patients with nasopharyngeal carcinoma were treated with late-course accelerated hyperfractionated radiotherapy alone to a total dose of 78Gy/60Fx/6w. The primary tumor volume (PTV) was obtained by outlining the tumor contour on CT images, followed by the summation of area technique. The median follow-up time was 49.5 months. Kaplan Meier method was used to calculate survival and local control rates. One hundred and fifty-four patients with nasopharyngeal carcinoma were treated with late-course accelerated hyperfractionated radiotherapy alone to a total dose of 78Gy/60Fx/6w. The primary tumor volume (PTV) was obtained by outlining the tumor contour on CT images, followed by the summation of area technique. The median follow-up time was 49.5 months. Kaplan Meier method was used to calculate survival and local control rates. ResultsEvident volume disparity with different T stage and the volume data overlap between continuous T stages was found. The mean primary tumor volume was as follows (cm3): T1 18.90(0.55∼59.33), T2 25.80(2.22∼80.64), T3 40.07(13.97∼87.97) and T4 56.04(19.18∼115.00). Univariant analysis showed that the poor 5-year local control, disease-free survival and distant relapse-free survival rates in patients with large tumor volume(>60cm3). Primary tumor volume was found to be an independent prognostic factor of local control in multivariant analysis without statistical significance to predict the disease-free survival or distant relapse-free survival rates. Evident volume disparity with different T stage and the volume data overlap between continuous T stages was found. The mean primary tumor volume was as follows (cm3): T1 18.90(0.55∼59.33), T2 25.80(2.22∼80.64), T3 40.07(13.97∼87.97) and T4 56.04(19.18∼115.00). Univariant analysis showed that the poor 5-year local control, disease-free survival and distant relapse-free survival rates in patients with large tumor volume(>60cm3). Primary tumor volume was found to be an independent prognostic factor of local control in multivariant analysis without statistical significance to predict the disease-free survival or distant relapse-free survival rates. ConclusionsThe greater volume disparity with the same T stage and the data extension overlap with different T stage are demonstrated and the primary tumor volume may be considered as a prognostic factor in the treatment of nasopharyngeal carcinoma.Nasopharyngeal neoplasm, Radiotherapy, Computed tomography, Primary tumor volume. The greater volume disparity with the same T stage and the data extension overlap with different T stage are demonstrated and the primary tumor volume may be considered as a prognostic factor in the treatment of nasopharyngeal carcinoma.

Coexpression of cyclooxygenase-2 and thymidine phosphorylase as a prognostic indicator in patients with FIGO stage IIB squamous cell carcinoma of uterine cervix treated with radiotherapy and concurrent chemotherapy

To evaluate the prognostic significance of thymidine phosphorylase (TP) and coexpression of cyclooxygenase-2 (COX-2)/TP, and to investigate the relationship between COX-2 and TP expression in squamous cell carcinoma of the uterine cervix. Cancer specimens from 75 patients with International Federation of Gynecology and Obstetrics Stage IIB squamous cell carcinoma of the uterine cervix who had undergone radiotherapy and concurrent chemotherapy were immunohistochemically stained with COX-2 and TP antibodies and scored. The prognostic significance of their expression status, and the relationship between COX-2 and TP was investigated. TP predominantly stained cytoplasm and the cell membrane of the tumor cells mainly in a diffuse and intense manner. TP was negative (<10% distribution) in 17%, 1+ (10-50%) in 25%, and 2+ (>50%) in 57% of patients. TP overexpression was related to a marginal prognostic significance of a poor 5-year overall survival (p = 0.082, log-rank test) and a high locoregional recurrence rate (p < 0.1, chi-square test). COX-2 and TP coexpression was observed in 24% of patients and was significantly related to poor 5-year disease-free and overall survival rates (p = 0.0083 and p = 0.025, respectively), a high pelvic lymph node involvement rate, a poor response to treatment, and a greater incidence of locoregional recurrence (p < 0.05). By multivariate analyses, only COX-2, TP, and coexpression of COX-2/TP were significant independent prognostic indicators of patient survival. All tumors showed 1+ or 2+ TP expression when COX-2 was positive, and no tumor expressed COX-2 when TP was negative (p = 0.03). In contrast, 77% of tumors expressed 1+ or 2+ TP without the synchronous expression of COX-2. Thymidine phosphorylase expression or COX-2/TP coexpression may be used as a molecular prognostic marker for squamous cell carcinoma of the uterine cervix. TP appears to be an important downstream molecule of COX-2 during angiogenesis and may be a new target for the treatment of uterine cervical cancer.

Intramammary lymph node metastases are an independent predictor in breast cancer outcomes

615 Background: Breast cancer patients with intramammary lymph node (intraMLN) metastases are treated as having stage II disease, even in the absence of axillary nodal involvement. However, little is known about the true clinical significance of these lymph nodes. The purpose of this study was to determine the clinical relevance of intraMLN and what role they play in breast cancer outcomes. Methods: Between 1983–2003, 196 intraMLN specimens were identified in our pathology database. 130 were found in association with a primary breast malignancy. Data on clinical and pathologic features were collected, and then evaluated by univariate and multivariate analysis for locoregional recurrence (LRR), distant recurrence (DR), disease-free survival (DFS), and disease-specific survival (DSS). The median follow-up was 36 months. Results: The median age of patients was 53 years (range: 27–84). 24 patients (18%) had intraMLN identified pre-operatively by either mammography or ultrasound. The remainder were found during the pathologic examination of breast specimens. The incidence of intraMLN metastasis was 28% (n=36) and these were distributed across all T stages (T1-T4). The majority (83%) of patients with intraMLN metastases had axillary metastases. However, isolated intraMLN metastases were seen in 6 patients (5%). Univariate analysis revealed the presence of intraMLN metastasis to be associated with a poorer 5-year DFS (54% vs. 89%, p = .001) and 5-year DSS (66% vs. 90%, p = .001). On multivariate analysis, intraMLN involvement remained an independent predictor of DFS (risk ratio 2.33, p = 0.03) and DSS (risk ratio 5.32, p = .002). Conclusions: Intramammary lymph node metastases appear to be an independent predictor of poor outcome. Identification of an intraMLN with pre-operative imaging should prompt further histologic work-up. In addition, the identification of a positive intraMLN by lymphatic mapping may help identify a high-risk group of patients who warrant further axillary lymph node evaluation, despite an otherwise clinically negative axilla. No significant financial relationships to disclose.

Treatment results of endometrial carcinoma with positive peritoneal washing, adnexal involvement and serosal involvement.

To review the treatment results of patients with endometrial carcinoma having positive peritoneal washing (PPW), adnexal involvement, uterine serosal involvement, or all three. The treatment records of patients who had undergone primary surgery for endometrial cancer without distant metastasis during 1990--2001 at the Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, were reviewed. Thirty-five patients were found to have involvement of positive PPW, adnexal involvement, uterine serosal involvement, or all three. Seven (20%) of them had gross or microscopic lymph-node metastasis. Thirty-three (94.3%) patients received adjuvant radiotherapy (28 whole-pelvic irradiation [WPI]; five abdominal radiotherapy [WART]). Two patients with solitary ovarian metastasis received chemotherapy, and one with isolated PPW also received adjuvant hormonal therapy. The median follow-up was 50.4 months (range 2.4-151.2 months). Multivariate analysis was carried out using the Cox regression proportional hazards model. Among the 28 patients with clinical or pathological node-negative disease (International Federation of Gynecology and Obstetrics [FIGO] stage IIIA), only two patients with solitary ovarian metastases developed recurrence. The 5-year actuarial disease-free survival (DFS) rates for the whole group and patients without lymph-node involvement were 77.9% and 91.7%, respectively. Five out of the seven patients with lymph-node involvement developed recurrences. Univariate analysis showed that lymph-node involvement (P < 0.0001) and high-grade disease (P = 0.011) were the significant poor prognostic factors. Multivariate analysis showed that lymph-node involvement was the only significant poor prognostic factor to predict poor 5-year DFS (P = 0.0001). Only one patient (3.7%) who had received WART developed grade 4 toxicity. This study showed that good treatment results could be obtained from patients with stage IIIA endometrial carcinoma without clinical or pathological lymph-node involvement after adjuvant radiotherapy, with acceptable late side-effects. The relative prognostic importance of individual IIIA involvement and the optimal adjuvant treatment remain to be determined.