Prognostic value of lymph node ratio in poor prognosis node-positive breast cancer patients in Saudi Arabia.

AIM: Women in Saudi Arabia develop breast cancer at a young age with high prevalence of poor prognostic features. Because of such features, it is necessary to examine prognostic factors in this population. One such factor is the prognostic role of lymph node ratio (LNR). METHODS: We performed retrospective analyses of patients with invasive non-metastatic breast cancer who underwent axillary lymph node dissection and had one or more positive axillary lymph nodes. RESULTS: Two hundred and seventeen patients were considered eligible for the analysis. The median age was 46 years. At a median follow-up of 39.8 months, the median disease-free survival (DFS) was 67.3 months (95% CI, 50.4 to 84.3 months). Neither the classification of patients based on positive lymph node (pN) staging system, nor the absolute number of pN prognosticated DFS. Conversely, age 0.20 to 0.65) LNR categories were the only variables that were independently associated with adverse DFS. Using these variables in a prognostic model allowed the classification of patients into three distinctive risk strata. The overall survival (OS) in this series was 92.5 months (95% CI, 92.1-92.6). Only ER negative tumor adversely influenced OS. CONCLUSION: Analysis of survival outcome of mostly young patients with early breast cancer identified adverse prognostic variables affecting DFS. If the utility of the derived model including LNR is proven in a larger patient population, it may replace the use of absolute number of positive axillary lymph nodes.

Cetuximab-based therapy for metastatic colorectal cancer: a meta-analysis of the effect of K-ras mutations.

BACKGROUND: Cetuximab has a favorable effect on patients with metastatic colorectal cancer harboring wild K-ras gene. This meta-analysis was planned to quantify the benefit. METHODS: A meta-analysis of clinical studies that have used cetuximab-based therapy (CBT) for patients with known K-ras status. RESULTS: There were four randomized studies (RS) that compared CBT versus non-cetuximab control (NCC) in 2,292 patients, and six non-randomized studies (NRS) included patients received cetuximab after failure of prior chemotherapy (411 patients). Patients in RS with wild K-ras tumor gained more benefit from CBT vs. NCC. For response rate (RR), the odds ratio was 2.10 (p = 0.0002), while the hazard ratio (HR) for progression-free survival (PFS) was 0.64 (p = 0.04). On the other hand, CBT was associated with an adverse effect on RR and no effect on PFS in mutated K-ras. In all patients who received CBT in RS and NRS, those with wild vs. mutated K-ras demonstrated higher RR (odds ratio 3.72; p < 0.0001). Compared with NCC in three RS, CBT showed significant overall survival (OS) advantage in patients with wild K-ras (HR = 0.68; p = 0.01). CONCLUSIONS: The significant clinical benefit of CBT concerning RR, PFS, and OS was restricted to patients with wild-type K-ras. There is a need to better define potential responders to CBT.

Folic acid supplementation for the prevention of recurrence of colorectal adenomas: metaanalysis of interventional trials.

Conflicting data have emerged from preclinical and clinical studies that examined the relationship between folic acid and the risk of recurrence of colorectal adenomas. To determine precisely that relation, we planned this metaanalysis. We searched literature to identify interventional randomized, placebo-controlled studies where folic acid in specific dose and for specific duration was administered to evaluate its effect on the recurrence of adenomatous colorectal polyps. Five eligible trials were identified. The total number of patients with history of colorectal adenomas in the folate and the placebo groups was 805 and 775 patients, respectively. Our analysis showed that folate supplementation had no protective effects on the recurrence of colorectal adenomas [odds ratio = 1.08 (95% CI; 0.87, 1.33; P = 0.49)], nor has a positive outcome on the number of recurrent polyps per patient (P = 0.41). Examination of folic acid dose effect showed that the two studies that have used folic acid as 1 mg/day favored folic acid over placebo with an odds ratio of 0.62 (95% CI; 0.48, 0.80). However, the overall effect for all included studies was not significant [odds ratio = 0.78 (95% CI; 0.49, 1.24; P = 0.30)]. We found significant heterogeneity between trials, moreover, included trials exhibit inconsistency in methodological quality. The present metaanalysis has failed to show potential benefit for folate supplementation. Future trials should examine the effect of different dosage and duration. Moreover, the confounding effect of dietary and life style habits should be carefully controlled.

Basal vs. luminal A breast cancer subtypes: a matched case-control study using estrogen receptor, progesterone receptor, and HER-2 as surrogate markers.

Breast cancer is a heterogeneous disease that encompasses several distinct entities with different biological characteristics and clinical behavior. Basal subtype is considered as a prognostically unfavorable subset. The purpose of this study is to compare the clinico-pathological characteristics and outcome of basal vs. luminal A subtype, as approximated by ER, PR, and HER-2. Sixty-four patients with basal breast cancer were matched for age, stage, and year of diagnosis with 64 patients having luminal A disease. Basal tumors were immunohistochemically defined by a lack of expression of estrogen receptor (ER), progesterone receptor (PR), and HER-2, while luminal A cancers were ER+ or PR+, and HER-2-. As compared with luminal A, basal subtype patients had significantly larger primary tumor size, higher percentage of grade III tumor, more tumor that showed lymphovascular invasion, less presence of non-invasive disease, and higher proportion of extranodal extension. There was no statistically significant difference in metastatic sites, pathology type, or in the axillary lymph nodal status. A few patients received neoadjuvant chemotherapy--13 and 9 patients in basal and luminal A groups, respectively). The complete pathological response was 20% and 14%, respectively (not significant). At a median follow-up of approximately 2 years, there was no statistically significant difference in the overall survival rate between basal and luminal A patients. Analysis of disease-free survival (DFS) for stage I-III (53 patients in each group) showed that the median DFS for basal patients was 41.4 months (95% CI, 26.5-55.3 months), whereas the DFS for the luminal A patients was not reached (P = 0.014). After adjusting for several significant prognostics variables identified in a univariate analysis, a multivariate conditional logistic regression analysis identified the negative effect of lymphovascular invasion and the favorable influence of the use of neoadjuvant and/or adjuvant chemotherapy. This matched case-control study confirmed the poor clinical and pathological characteristics of patients with basal subtype and their unfavorable outcome compared with luminal A disease. Management of basal tumors remains a challenging task, and new therapeutic strategies are warranted.

Relative hypocalcaemia and muscle cramps in patients receiving imatinib for gastrointestinal stromal tumour.

Purpose. Imatinib treatment causes muscle cramps in up to 40% of patients, but their pathogenesis is unknown. We present a case series illustrating an association between imatinib, relative hypocalcaemia, and the development of cramps. Patients. The index patient developed muscle spasms and cramps after receiving imatinib for gastrointestinal stromal tumour (GIST) for 5 months. The adjusted serum calcium had dropped to the lower limit of normal. The low serum calcium and muscle cramps improved on stopping imatinib and recurred on rechallenge. We reviewed the medical records of 16 further patients. Results. Two patients reported muscle cramps (12%). There was a rapid and sustained reduction in adjusted serum calcium in the first 6 months from 2.45 +/- 0.11 mmol/L (mean +/- SD) to 2.30 +/- 0.08 mmol/L (p = 0.025). Conclusion. Imatinib treatment of GIST is associated with reduction in serum calcium which may explain the development of neuromuscular symptoms. In patients receiving imatinib, serum electrolytes should be monitored and muscle cramps treated by correction of serum calcium, or an empirical trial of quinine sulphate.

Trials in advanced Hodgkin's disease: more than 30 years experience of the British National Lymphoma Investigation.

Hodgkin's disease demonstrates an exquisite sensitivity to chemotherapy and radiation therapy. This necessitates investigation of modes of delivering these modalities in the best possible fashion to improve outcomes. The British National Lymphoma Investigation (BNLI) has conducted randomized trials in advanced Hodgkin's disease for > 30 years. The results of BNLI studies have demonstrated that MOPP (mechlorethamine/vincristine/procarbazine/prednisone) chemotherapy is superior to MOP (mechlorethamine/vincristine/procarbazine) chemotherapy; that there are no significant differences between MOPP and B-MOPP (MOPP plus bleomycin); that there is no significant benefit from maintenance therapy with lomustine/vinblastine/bleomycin; that LOPP (chlorambucil/vincristine/procarbazine/prednisone) is as effective as MOPP and has less acute toxicity; that alternating therapy with LOPP and EVAP (etoposide/vinblastine/doxorubicin/prednisolone) is superior to EVAP alone or hybrid LOPP and EVA (etoposide/vinblastine/doxorubicin); that alternating therapy with ChlVPP (a substitute for MOPP) and prednisolone/doxorubicin/bleomycin/vincristine/etoposide regimens is superior to the latter regimen alone; that the Stanford V regimen (doxorubicin/vinblastine/mechlorethamine/vincristine/bleomycin/etoposide/prednisone) combined with disciplined radiation therapy is safe and effective; that hybrid therapy with ChlVPP and EVA and alternating therapy with ChlVPP and prednisolone/doxorubicin/bleomycin/vincristine/etoposide are as effective as ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) alone; and that there is no additional benefit from total nodal irradiation or combined-modality therapy compared with MOPP; and that treatment with high-dose BEAM (carmustine/etoposide/cytarabine/melphalan) and autologous bone marrow transplantation is superior to mini-BEAM (lower-dose BEAM not requiring bone marrow rescue) for poor-risk relapsed and refractory disease.