The benefit of consolidation high-dose chemotherapy (HDC) for high-risk primary breast cancer is controversial. We evaluated the efficacy and safety of consolidation HDC with cyclophosphamide, thiotepa and carboplatin (CTCb) followed by autologous stem-cell transplantation (ASCT) in resected breast cancer patients with 10 or more positive lymph nodes.
Between December 1994 and April 2000, 22 patients were enrolled. All patients received 2 to 6 cycles of adjuvant chemotherapy after surgery for breast cancer. The HDC regimen consisted of cyclophosphamide 1,500 mg/m2/day, thiotepa 125 mg/m2/day and carboplatin 200 mg/m2/day intravenous for 4 consecutive days.
With a median follow-up of 58 months, 11 patients recurred and died. The median disease-free survival (DFS) and median overall survival (OS) were 49 and 69 months, respectively. The 5-year DFS and OS rates were 50% and 58%, respectively. The 12 patients with 10 to 18 involved nodes had better 5-year DFS (67%) and OS (75%) than 10 patients with more than 18 involved nodes (30% and 38%, respectively). The most common grade 3 or 4 nonhematologic toxicity was diarrhea, which occurred in 5 patients (23%). No treatment-related death was observed.
Consolidation HDC with CTCb followed by ASCT for resected breast cancer with more than 10 positive nodes had an acceptable toxicity but does not show promising survival.
Citations
The surgical caseload or duration of practice of a surgeon may influence the outcomes of gastric cancer surgery. This study aimed to clarify the surgical quality provided by specialized gastric cancer surgeons.
The postoperative courses of 1,877 patients who underwent surgery for gastric cancer were retrospectively reviewed. For classification of the surgeon's expertise, the number of yearly resections performed by, and consecutive years of practice of, the surgeons were used. The outcome measures used were the 30-day mortality and long-term survival.
Surgical mortalities of patients who underwent surgery by a specialized surgeon and those by a general surgeon revealed no statistically significant difference. A significant difference in the five-year survival rates was found with surgeons with at least two consecutive years of practice compared to those with less than two years, when 50 or more cases had been conducted per year (63.9% and 59.7%; p=0.0380). In cases of four-years of consecutive practice, the five-year survival rate was significantly improved, even if only 10 cases were performed annually (64.9% and 58.3%; p=0.0023), although the best survival rate was found with surgeons that had performed 50 or more surgeries per year.
Improved survival rates, with acceptable surgical mortality, can be achieved for gastric cancer when the surgery is performed by a specialized surgeon. A specialized gastric cancer surgeon can be defined as one who has operated on more than 50 new cases per year, with 2 or more consecutive years of surgical practice.
Citations
The aim of this study was to evaluate the multidimensional constructs of the EORTC Quality of Life Questionnaire (QLQ-C30) in patients with cancer, employing not only the commonly used multitrait scaling analysis and interscale correlations, but also the factorial and multidimensional scaling (MDS) analyses.
A total of 334 Korean cancer patients participated in this cross-sectional study. All patients completed the QLQ-C30.
With the multitrait scaling analysis, the cognitive functioning scale did not meet item convergent and divergent validities. With the interscale correlations, the physical and role functioning scales were found to be highly correlated; this was also evident in the factorial analysis. The MDS showed that each item within the social, emotional, global health status/quality of life, and nausea/vomiting scales were clustered close together, but far from those of the other scales.
The authors conclude that the four way evaluation of the QLQ-C30 produced results that supported the original hypothesized constructs. However, the physical and role functioning scales were not distinctive, and that of the cognitive functioning was somewhat problematic in the Korean population with cancer.
Citations
Reliability and Validity of the Arabic Version of the EORTC QLQ-C30 and QLQ-BR23 Questionnaires
To assess tumor regression, as determined by pelvic magnetic resonance imaging (MRI), and evaluate the efficacies and toxicities of the interim brachytherapy (BT) modification method, according to tumor regression during multi-fractionated high-dose-rate (HDR) BT for uterine cervical cancer.
Consecutive MRI studies were performed pre-radiotherapy (RT), pre-BT and during interfraction of BT (inter-BT) in 69 patients with cervical cancer. External beam radiotherapy (EBRT) was performed, using a 10 MV X-ray, in daily fraction of 1.8 Gy with 4-fields, 5 d/wk. Radiation was delivered up to 50.4 Gy, with midline shielding at around 30.6 Gy. Of all 69 patients, 50 received modified interim BT after checking the inter-BT MRI. The BT was delivered in two sessions; the first was composed of several 5 Gy fractions to point A, twice weekly, using three channel applicators. According to the three measured orthogonal diameters of the regressed tumor, based on inter-BT MR images, the initial BT plan was modified, with the second session consisting of a few fractions of less than 5 Gy to point A, using a cervical cylinder applicator.
The numbers of patients in FIGO stages Ib, IIa, IIb and IIIb+IVa were 19 (27.5%), 18 (26.1%), 27 (39.2%) and 5 (7.2%), respectively. Our treatment characteristics were comparable to those from the literatures with respect to the biologically effective dose (BED) to point A, rectum and bladder as reference points. In the regression analysis a significant correlation was observed between tumor regression and the cumulative dose to point A on the follow-up MRI. Nearly 80% regression of the initial tumor volume occurred after 30.6 Gy of EBRT, and this increased to 90% after an additional 25 Gy in 5 fractions of BT, which corresponds to 73.6 Gy of cumulative BED10 to point A. The median total fraction number, and those at the first and second sessions of BT were 8 (5~10), 5 (3~7) and 3 (1~5), respectively. The median follow-up time was 53 months (range, 9~66 months). The 4-year disease-free survival rate of all patients was 86.8%. Six (8.7%) patients developed pelvic failures, but major late complications developed in only two (2.9%).
Our study shows that effective tumor control, equivalent survival and low rates of major complications can be achieved by modifying the fraction size during BT according to tumor regression, as determined by consecutive MR images. We recommend checking the follow-up MRI at a cumulative BED10 of around 65 Gy to point A, with the initial BT modified at a final booster BT session.
Citations
Previous epidemiologic studies have demonstrated that nonsteroidal anti-inflammatory drugs can reduce the risk of breast cancer, and this possibly happens via cyclooxygenase (COX) inhibition. Moreover, growth factor-inducible COX-2, which is overexpressed in neoplastic tissue, is an attractive therapeutic target. Thus, we evaluated the expression of COX-2 in breast cancer tissues, and we assessed the association between COX-2 expression and HER-2/neu expression and also with several clinicopathological features.
We analyzed the surgical specimens from 112 women with breast cancer who had undergone lumpectomy or mastectomy. The expressions of COX-2, HER-2/neu, MMP-2 and TIMP-2 were determined immunohistochemically. The correlations between COX-2 expression and several variables, including clinicopathological factors, HER-2/neu expression, MMP-2 expression and TIMP-2 expression were analyzed. Survival analysis was also performed with respect to COX-2 overexpression.
The overexpression of COX-2 protein was observed in 28.6% of the breast cancer tissues. Tumors with lymph node metastasis more frequently showed COX-2 overexpression than did those tumors without metastasis (p=0.039), and the increased COX-2 expression correlated positively with HER-2/neu overexpression (p=0.000). No significant differences were found for the MMP-2 or TIMP-2 expression rates in the COX-2 positive and negative groups. The survival analysis revealed no significant differences according to the COX-2 expression.
This study results suggest that increased COX-2 expression is related with the progression of breast cancer, e.g., with lymph node invasion. COX-2 overexpression found to be related with HER-2/neu overexpression, but not with MMP-2 or TIMP-2 expression. These results support the potential use of selective agents that inhibit COX-2 or HER-2/neu for the management of breast cancer.
Citations
Gallbladder cancer is a malignancy with poor prognosis, predominantly resulting from invasion and metastasis. Our previous studies have demonstrated that prostaglandin E2 (PGE2), generated by cyclooxygenase 2 (Cox-2), transactivates epidermal growth factor receptor (EGFR), c-Met and β-catenin; thus, enhancing colon cancer cell growth and invasiveness
Thirty-five specimens of invasive gallbladder cancer, 8
Cox-2, c-Met, β-catenin, c-erbB2 and EGFR were over-expressed in 80, 74, 71, 62 and 11% of invasive gallbladder cancers, respectively. β-catenin was expressed in 80% of non-malignant specimens, exclusively in the cell membrane, while the cancer specimens showed cytoplasmic and/or nuclear staining. Significantly higher Cox-2, c-Met and β-catenin expressions were present in cancer cells of the invasive front than in the tumor central areas (p<0.001), and these expressions were significantly (p=0.01) associated with the invasion depth. Co-expressions of Cox-2, c-Met, β-catenin and c-erbB2 were present in 42% of the specimens in cancer cells forming the invasive front.
The overexpressions, and often co-localizations, of Cox-2, c-Met and β-catenin in cancer cells forming the invasive front indicate their local interactions and important roles in invasion.
Citations
The aim of this study was to quantitatively assess the intensity of tumor budding in rectal carcinoma and to determine how it correlates with the malignant potential.
Intensities of the tumor budding at the invasive front of the surgical specimens from 90 patients (male, 51) with well- or moderately-differentiated rectal carcinoma were investigated. Differences in the budding intensity among pathologic variables were compared, and recurrences and survivals were analyzed in accordance with degree of the budding intensity. The patients ranged in age from 33 to 75 years (mean, 55.4) with the median follow-up being 43 months (range, 12~108).
Tumor budding was identified in 89 patients (98.9%) with a mean intensity of 7.5±5.3. The budding intensity was significantly higher in tumors with lymphatic invasion (p=0.0081), blood vessel invasion (p<0.0001), and perineural invasion (p=0.0013) than in those tumor without these findings. It became significantly higher with the increase in nodal stage (p<0.0001). The intensity of tumor budding in patients with relapse (29 patients) was significantly higher than that in patients without relapse (6.2±5.0 vs. 10.2±4.9; p=0.0005), but this difference in the intensity was observed only for the node-positive patients (8.0±3.4 vs. 11.9±5.1; p=0.0064). When the patients were stratified into two groups on either side of the mean of the intensity, the higher intensity group showed a significantly less favorable disease-free (DFS) and overall survival (OS) (p=0.0026 and 0.0205, respectively). Based on the multivariate analysis, the nodal stage and the intensity of budding proved to be the independent variables associated with DFS (p=0.023 and 0.03, respectively).
Tumor budding at the invasive margin is a reliable pathologic index that indicates a higher malignant potential and a less favorable prognosis for patients with advanced rectal carcinoma.
Citations
To reveal the interaction between β-Lapachone (β-lap) and ionizing radiation in causing cell death in RKO human colon adenocarcinoma cells, and to elucidate the potential usefulness of combined β-lap treatment and radiotherapy for cancer treatment.
The cytotoxicities of various treatments were determined
β-lap caused clonogenic cell death and rapid apoptosis in RKO cells
β-lap is cytotoxic against RKO cells, both
Citations
To determine the effects of combinations of radiation and flavopiridol, an inhibitor of cyclin-dependent kinases and global transcription, in a human uterine cervix cancer cell line.
Human uterine cervix cancer cells (HeLa), cultured to the mid-log phase, were exposed to X-rays, flavopiridol, and combinations of X-rays and flavopiridol in various sequences. The end point in this study was the clonogenic survival, which was measured via clonogenic assays. In order to determine the intrinsic cytotoxicity of flavopiridol, 0, 5, 12.5, 25, 37.5, 50 and 100 nM of flavopiridol were added to cell culture media. In the combination treatment, four different schedules of flavopiridol and irradiation combinations were tested: treatment of flavopiridol for 24 hours followed by irradiation, simultaneous administration of flavopiridol and irradiation, and irradiation followed by flavopiridol (for 24 hours) at intervals of 6 and 24 hours. The fraction of cells surviving after the combination treatment with 2 Gy of radiation (SF2) was compared with that of the fraction of cells surviving after treatment with irradiation alone.
The cytotoxicity of flavopiridol was found to be dose-dependent, with an IC50 of 80 nM. No cytotoxic enhancements were observed when flavopiridol and radiation were administered simultaneously. Flavopiridol, administered either 24 hours before or 6 hours after irradiation, exerted no sensitizing effects on the cells. Only one protocol resulted in a radiosensitizing effect: the administration of flavopiridol 24 hours after irradiation.
Flavopiridol enhanced the effects of radiation on a uterine cervix cancer cell line
Citations
This study was carried out to assess the usage of an
The assay systems used were the hollow fiber and xenografts assays. The hollow fiber assay was carried out with the following steps; preparation of fibers, preparation of cells, loading and implanting fibers, treatment with drugs, removal of fibers and assaying for the cell viability by the MTT assay. For the xenografts assay, cell suspensions were subcutaneously transplanted into the mice. Therapy was started when the tumor volume reached 100~200 mm3. The tumor volumes were calculated using the formula V=[length+(width)2]/2, and used for evaluating the efficacy of the drugs. The drug treatment doses used were adriamycin 2.1 mg/kg, mitomycin-C 0.25 mg/kg, 5-fluorouracil 24.5 mg/kg and paclitaxel 2.5 mg/kg, and administrated intravenously five times daily.
The correlation between the xenografts and hollow fiber assays was evaluated in 20 tumor cell lines and 4 anti-cancer agents. In the 20 tumor cell lines, the overall predictive accuracy of the hollow fiber assay for sensitivity was 83%, with a predictive accuracy for resistance of 92%.
The hollow fiber assay was assessed as effective in drug efficacy evaluation, and found to be compatible with that of the xenografts assay.
Citations