Background: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the developing central and peripheral nervous systems during embryogenesis. Human telomerase reverse transcriptase (h-TERT) protein resumption is the main process of preservation of telomeres that maintains DNA integrity. The present study aims to evaluate the prognostic role of ALK-1 and h-TERT protein expression and their correlation with ALK gene alterations in glioblastoma multiforme (GBM). Methods: The current study is a retrospective study on a cohort of patients with GBM (n = 53) that attempted to detect ALK gene alterations using fluorescence in situ hybridization. ALK-1 and h-TERT proteins were evaluated using immunohistochemistry. Results: Score 3 ALK-1 expression was significantly associated with male sex, tumor multiplicity, Ki labeling index (Ki LI), and type of therapeutic modality. Score 3 h-TERT expression exhibited a significant association with Ki LI. ALK gene amplifications (ALK-A) were significantly associated with increased Ki LI and therapeutic modalities. Score 3 ALK-1 protein expression, score 3 h-TERT protein expression, and ALK-A were associated with poor overall survival (OS) and progression-free survival (PFS). Multivariate analysis for OS revealed that ALK gene alterations were an independent prognostic factor for OS and PFS. Conclusions: High protein expression of both ALK-1 and h-TERT, as well as ALK-A had a poor impact on the prognosis of GBM. Further studies are needed to establish the underlying mechanisms.
Background and aimColorectal cancer is one of the most common malignant tumors worldwide. As CD133 and CD44 are notable markers of cancer stem cells (CSCs) identity, it is thought to be a predictive indicator for colorectal cancer. The aim of this study was to investigate the cell cycle state of CD133+ CD44+ and CD133− CD44−cells, isolated from primary human colorectal tumors, and to assess the clinical impact of CD133+ CD44+ CSCs on patients’ outcome regarding disease-free survival (DFS) and overall survival (OS).Materials and methodsTissue samples were collected from 50 primary colorectal cancer patients. Flow cytometric analysis was performed to isolate tissue CD133+ CD44+ CSCs and CD133− CD44− tumor cells from primary colorectal cancer tissue to compare the cell cycle of both types of cells. Also circulating CSCs were assessed by flow cytometry.ResultsHigher percentage of tissue CD133+ CD44+ CSCs isolated from colorectal cancer patients was found in G0/G1 phase. However, tissue CD133− CD44− tumor cells were predominantly found in the S phase; there were significant negative correlations between tissue CD133+ CD44+ CSCs and DFS and OS (r=−0.470, P<0.001, respectively and r=−0.487, P<0.001, respectively), also significant negative correlations between tissue CSCs and DFS and OS (r=−0.548, P<0.001, respectively and r=−0.497, P<0.001, respectively). Only the pathological grade (P<0.004) and T stage (P<0.004) had a significant effect on circulating CSC counts.ConclusionTissue CD133+ CD44+ CSCs were more quiescent than tissue CD133− CD44− tumor cells and both circulating CSCs and tissue CSCs were considered independent negative prognostic factors on OS and DFS.
Background: In patients with advanced non-small cell lung cancer the priority should be given to controlling symptoms of the disease and thoracic radiotherapy remains an important treatment modality for these patients. The use of shorter radiotherapy schedules has an economic and logistic advantage for radiotherapy departments, as well as a high degree of patient convenience. However there is still no consensus on which fractionation scheme should be used.The aim of the study is to evaluate the effect of hypofractionated regimen (36Gy/12 fractions versus 17Gy/2 weekly fractions regimen) on symptoms relief, assessment of treatment related toxicity and its impact on overall survival (OS) in patients with locally advanced stage III and stage IV non-small cell lung cancer (NSCLC). Patients and methods:Patients were randomly assigned into two treatment groups: 1, receive 36 Gy per 12 fractions and group 2, receive 17 Gy per two fractions. Assessments by clinician for improvement of symptoms and toxicity were done weekly during radiotherapy, one month, 3 months and every 3 months thereafter. Symptomatic response was assessed by comparing the initial score for each symptom with the best score during follow-up period. A total symptom score (TSS) was produced for each patient, by adding the scores of each individual symptom. Results:The total symptom scores before radiotherapy was significantly higher to that after radiotherapy (Wilcoxon signed-rank test Z=-6.434, P=.0001). The degree and duration of symptom relief were equivalent in the treatment groups. There were no reported cases of grade 3 or 4 esophagitis or pulmonary toxicity. Grade 2 acute esophagitis was greater among patients received 36 Gy/ 12 fractions compared to those received 17 Gy/ 2 fractions (26.3% vs 14%, P = .177) but did not reach statistical significance. Two patients (3.5%) experienced grade 2 acute pneumonitis. No significant difference in survival among treatment groups was found (one year OS for group 1, was 22.3% and for group 2, was 20.4%, P = .434).Conclusion: 17Gy/2 weekly fractions regimen, provide good symptomatic relief with comparable survival to 36Gy/12 fractions regimen and should be used for patients requesting a shorter treatment course especially in which palliative chemotherapy is planned.
Purpose: Palliative treatment techniques for advanced stage rectal cancer should be designed according to the patients' major symptoms. Combined chemo-radiation therapy is effective choice for symptomatic patients with good performance status. In this study, we reviewed our patients' stage IV rectal carcinoma in regard to most common presentation, outcome and possible prognostic features. Methods Medical chart of twenty patients who were diagnosed with stage IV rectal carcinoma, were reviewed based on the hospital database information, which included images, radiotherapy charts, and their follow up notes. Results: All patients were young with age less than 40 years. Bleeding per rectum, pain, and symptoms of obstruction were the most common presentation. Seven patients had solitary lesion and 13 patients had multiple lesions. Eleven patients with multiple metastases were treated with palliative chemotherapy and radiotherapy. Patients who had solitary metastases to liver had a median survival time of 49 months versus 13.5 months for other patients (p = 0.001). Conclusion: Patients who presented with solitary liver metastases could be treated with a course of neoadjuvant chemo-radiotherapy similar to the curative one.
Background: Although concurrent radio-chemotherapy and adjuvant temozolomide (TMZ) treatment for six cycles has been established as a standard of care for newly diagnosed glioblastoma multiforme (GBM) patients, the recommended duration of adjuvant TMZ remains a matter of debate. Methods: We conducted this historical cohort study to evaluate the survival benefit and toxicity profile of administration of 12 cycles of adjuvant TMZ in patients with newly diagnosed histologically confirmed GBM and compared this data with that of patients who completed the standard 6 cycles without disease progression. After concurrent radio-chemotherapy, TMZ was administered for 6 cycles (group 1) and for 12 cycles (group 2). Univariate and multivariate analysis (using the Cox proportional hazards model) were performed to identify factors affecting progression free survival (PFS) and overall survival (OS). Results: Between June 2016 and February 2018, 55 patients were eligible. Patients in Group 1 (n=29) had a median PFS of 15 months (95% CI: 10.215-19.785), while those in Group 2 (n=26) had a median PFS of 18 months (95% CI: 16.611-19.389). After a median follow up duration of 20 months (range: 12-41), the median OS was 18 months (95% CI: 13.420-22.580) in Group 1 and 22 months (95% CI: 18.777-25.223) in Group 2. There was no statistically significant correlation between the number of chemotherapy cycles and PFS (P = 0.513) or OS (P = 0.867). The extent of surgical resection was the only independent prognostic factor for both PFS (P = 0.015) and OS (P = 0.028) by multivariate analysis. Three grade ≥3 hematologic toxicity were encountered in three patients. One in the six-cycle group (neutropenia), and two in the 12-cycle group (one had neutropenia and the other one developed thrombocytopenia). No statistically significant difference in the toxicity profile between both groups.Conclusions: Although extending adjuvant TMZ to 12 cycles was not associated with increased toxicities, it did not significantly improve PFS or OS. So we do not recommend any modifications in the six months protocol until further studies are performed. It should be weighed against the compromised quality of life and the cost to the health care system.
Purpose: Our prospective phase II trial aims to show the feasibility of adjuvant paclitaxel-based concurrent chemoradiotherapy (CCRT) following doxorubicin and cyclophosphamide (AC) to get the survival benefit of taxanes addition and avoid delay of radiotherapy. Patients and Methods: A total of 63 patients with pT1-2, and pN1-3, M0 breast cancer underwent conservative surgery followed by adjuvant 4 cycles AC followed by 4 cycles Paclitaxel 175 mg/m 2 every 3 weeks. Adjuvant radiotherapy started during the first and second cycle of paclitaxel (CCRT). Toxicities evaluated at the base time, weekly during radiation therapy and every 3 months for 24 months for skin, pulmonary, cardiac, lymphedema, subcutaneous fibrosis and cosmoses. Survival reported at 2-year median follow-up. Results: At median follow up time of 24 months (6 -30), we did not report any toxicity postpone or stop treatment and only two patients had grade III acute dermatitis. Fifty-two patients (82.5%) had satisfactory cosmoses and none of the patients developed local recurrence. Conclusion: Three-weekly paclitaxel during radiotherapy is considered safe without significant complications and acceptable cosmoses with excellent local control and could be considered to avoid radiotherapy delay.
Background: Triple-negative breast cancer (TNBC) is considered an aggressive breast cancer subtype despite giving standard therapies, these patients have high metastatic and relapse rates in addition to short survival. Therefore, we conducted this trial to study the validity of giving adjuvant Capecitabine, after receiving standard neoadjuvant /adjuvant chemotherapy in operable TNBC patients. The primary end point was disease-free survival (DFS) and secondary end points were overall survival (OS) and safety profile. Material and Methods: The 89 eligible patients were randomly assigned into two groups (A "Capecitabine arm" and B "observation arm") after receiving neo/adjuvant anthracycline and/or taxanescontaining chemotherapy. Results: 78.7% were invasive duct carcinoma (IDC), and a median age was 48 years. 50.6% were node positive patients. 79.5% received adjuvant anthracyclines and taxanes chemotherapy protocol for group A and (75.6%) for group B. (56.2%) underwent breast-conservative surgery. regarding 4year disease free survival (DFS), there was statistically significant difference between both groups (P = 0.032) and 4-y overall survival (OS) (P = 0.050)) with an acceptable toxicity profile in the Capecitabine arm. Conclusions: Our study showed statistically significant increase in DFS and OS after giving adjuvant Capecitabine to standard Neo-/Adjuvant chemotherapy in early TNBC patients with acceptable toxicity of Capecitabine arm. However, a larger study with more number of patients is recommended to give more statistical powered results.
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