Metastatic Esophageal Carcinoma: Prognostic Factors and Survival.

BACKGROUND: Worldwide, esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer-related death. At initial diagnosis, about 50% of esophageal cancer patients present with metastasis. The prognosis of metastatic esophageal cancer is poor with 5-year survival rate of less than 5%. METHODS: This is a retrospective study of stage IV esophageal cancer patients registered at Clinical Oncology and Nuclear Medicine department and Oncology Center Mansoura University in the period from 2009 to 2018 inclusive. Eligibility criteria were all pathologically proven stage IV esophageal cancer patients. The medical files of patients were reviewed. RESULTS: Most patients were ≥ 50 years (67.8%) with male predominance (76.7%). Middle third was the most common site of primary tumor (38.9%). Squamous cell carcinoma was more common with incidence of grade 3 (40%). T3-4 lesion was recorded in 61.1% and node positive in 66.7%. As regards metastasis; liver was the most common one (45.5%) followed by lung (30%). One-year survival rate was 25.6% with median survival time of 8 months. Multivariate analysis indicated that age (p = 0.03), site (p = 0.04), grade of primary tumor (p = 0.049), T classification (p = 0.0038), ECOG PS (p = 0.046), site (p = 0.026), and number of metastasis (p = 0.04) significantly affect prognosis while sex (p = 0.74) and histologic type (p = 0.94) do not. CONCLUSION: Metastatic esophageal carcinoma is a disease of poor prognosis especially in patients with the following criteria: old age, lower third location, high grade and large tumors, poor performance status, multiple sites of metastasis and presence of bone secondaries.

Pathophysiology, Mechanism, and Outcome of Ischemic Stroke in Cancer Patients.

OBJECTIVES: The purpose of this study is to assess the risk factors, biomarkers of stroke, mechanism, and outcomes of cerebral infarction among cancerous diseases. MATERIALS & METHODS: 156 patients presented by acute ischemic stroke were divided into two groups: the first group included 78 ischemic stroke patients associated with different types of cancer and the second group (control group) included 78 ischemic stroke patients not associated with cancer. Both groups were compared regarding the risk factors, previous thrombotic activity, subtypes, biomarkers of stroke, and outcomes. RESULTS: Cancer patients presented by acute ischemic stroke were accompanied by a significantly less incidence of diabetes mellitus, hypertension, dyslipidemia, and coronary heart disease, and atrial fibrillation than non-cancer patients (P < 0.001). While, levels of biomarkers of inflammation like erythrocyte sedimentation rate and C-reactive protein, and stroke biomarkers like fibrinogen, and D-dimer, all together were highly elevated in cancerous disease group of patients (P < 0.01). The prevalence of deep vein thrombosis, pulmonary embolism, and myocardial infarction was significantly higher in patients with cancer than in control patients without cancer (P = 0.008, P < 0.01 and P < 0.01 respectively). The most common stroke etiologies were atherosclerosis of large arteries and stroke of undetermined cause in a cancerous group of patients. Cancer patients were accompanied by significant higher mortality rate (P = 0.005), and more disability as determined by mRS (P < 0.005) CONCLUSIONS: Pathophysiology and mechanism of ischemic stroke in cancerous disease patients were due to different risk factors, biomarkers of stroke, and subtypes in comparison with non- cancerous cases.

Current approaches in treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is diagnosed more frequently in younger and premenopausal women and is highly prevalent in African American women. TNBC is a term derived from tumors that are characterized by the absence of ER, PgR, and HER2. So patients with TNBC do not benefit from hormonal or trastuzumab-based therapies. TNBCs are biologically aggressive, although some reports suggest that they respond to chemotherapy better than other types of breast cancer, prognosis remains poor. This is due to: shortened disease-free interval in the adjuvant and neoadjuvant setting and a more aggressive course in the metastatic setting.

Concomitant chemoradiotherapy with Cisplatin plus 5-Fluorouracil for anal squamous cell carcinoma.

OBJECTIVE: The objective of this study was to evaluate the results of combined chemoradiotherapy using 5-fluorouracil and cisplatin with radiation in treatment of anal squamous cell carcinoma in terms of local control, survival, and toxicity. PATIENTS AND METHODS: This study included 32 patients with histologically confirmed locally advanced anal squamous cell carcinoma (T1-4 with any N). They received chemotherapy consisted of 5-fluorouracil 1000 mg/m(2)/day on the first 5 and last 5 days of RT, cisplatin 75 mg/m(2) on days 2 and 30. External beam RT consisted of 45Gy/f/25 sessions/5 sessions per week. A boost of 9Gy/5 sessions was given to those who developed complete or partial response. RESULTS: Median age was 55 years with female to male ratio 2.2:1. Fifty-six percent of them had ECOGPS of 1; moderately differentiated pathology was the most common one (53 %). Thirteen patients (40.6 %) presented with N0 and 56 % presented with T2. None of the patients died of acute complications and none developed grade 4 toxicity. Non-hematological complications were more common than hematological ones. Dermatitis was the most common toxicity (59.3 %) than diarrhea and neurologic one (40.7 %). Anemia was the most frequent hematological adverse event (37.5 %). Complete response was reported in 81.2 %. After median follow-up of 25 months, local recurrence was observed in five patients (15.6 %) as the following: three in the anal canal and two in the inguinal lymph nodes. Three patients (9.4 %) developed distant metastasis (two in the liver and one in the lung), while one patient (3 %) had both local and distant metastases. Three-year overall survival rate (OS) was 81.3 %, while 3-year progression-free survival (PFS) rate was 72 %, and colostomy-free survival was 90 %. CONCLUSION: Concomitant chemoradiotherapy of 5-fluorouracil and cisplatin with radiotherapy is a highly effective and well-tolerated treatment of anal cancer. But further studies with larger number of patients are needed to support the indication to treat anal cancer using this regimen.

Immunohistochemical expression and prognostic relevance of Bmi-1, a stem cell factor, in epithelial ovarian cancer.

Ovarian cancer is the fourth most common cause of cancer-related death in women. Bmi-1 is a stem cell factor implicated in many human malignancies with poor outcome. Few published reports on the expression of Bmi-1 in epithelial ovarian cancer were either experimental or performed on cell lines. This study evaluates the immunohistochemical expression of Bmi-1 protein in epithelial ovarian cancer tissue specimens and its relevance to the clinicopathologic prognostic variables and patient survival. Forty cases of epithelial ovarian cancer were selected according to the availability of paraffin-embedded tissue and the clinicopathologic and survival data. Immunohistochemistry was performed for anti-Bmi-1 antibody. Low and high Bmi-1 expression groups were compared with age, tumor stage, laterality, grade, histology, and patient survival. Bmi-1 expression was detected in 72.5% of cases, of which 42.5% had high expression. High Bmi-1 expression strongly associated with advanced International Federation of Gynecology and Obstetrics stages (P = .007), bilaterality (P = .01), and higher Gynecologic Oncology Group grades (P = .031) and carcinomas of serous histology (P = .027). It had no association with patient age. Bmi-1 expression displayed a significant inverse association with patient overall and mean survival (P = .006, P < .001). These observations suggested correlation between increased Bmi-1 expression and clinical progression in ovarian epithelial cancer.

Oxaliplatin plus 5-fluorouracil and folinic acid (OFF) in gemcitabine-pretreated advanced pancreatic cancer: a phase II study.

BACKGROUND: Despite median survival of less than 6 months, there is a significant proportion of advanced pancreatic cancer patients who progress on gemcitabine that remains fit, and these patients are candidates for second-line treatment. OBJECTIVE: The objective of this study is to evaluate the efficacy and safety of oxaliplatin plus 5-fluorouracil and folinic acid in patients with gemcitabine-pretreated advanced pancreatic cancer. PATIENTS AND METHODS: Thirty patients with advanced pancreatic cancer who were pretreated with gemcitabine received oxaliplatin (85 mg/m(2)) on days 1 and 15 followed by leucovorin (20 mg/m(2)) and 5-fluorouracil (500 mg/m(2)) on days 1, 8, and 15. The cycle was repeated every 3 weeks. RESULTS: The majority of patients (80 %) had locally advanced disease. Median age was 63 years, and 60 % were males. The liver was the most common site of metastasis. Partial response was observed in 2 patients (6.7 %) and stable disease in 6 patients (20 %), while 12 patients progressed (40 %). Improved performance status was reported in 10 patients (33.3 %). The median duration of response was 13 weeks, and median overall survival was 22 weeks. There was no grade 4 toxicity apart from grade 4 neutropenia in 6.6 % of patients. Neutropenia (46.5 %) and neuropathy (43.2 %) were the most common toxicities, while hand-foot syndrome was the least frequent one (20 %). There were no treatment-related deaths. The 6-month survival rate was 30 %. CONCLUSION: This regimen is feasible and active with an acceptable toxicity; however, further investigation in phase III trial is needed.

Radiotherapy versus stenting in treating malignant dysphagia.

The most commonly used treatments for maliganat dysphagia are stenting and radiotherapy (RT). A prospective data of 91 patients with locally advanced or metastatic esophageal cancer who has been treated with either palliative RT, stent or both. Group I had RT only, Group II had stent only and group III had both RT and stent. The median overall survival was 169, 119 and 237 in the three groups respectively. The difference between GI & III was statistically significant (P=0.01). Combinations of stent and RT may provide survival benefit in patients with malignant dysphagia. A randomized clinical trial is recommended.

Concomitant chemoradiotherapy using low-dose weekly gemcitabine versus low-dose weekly paclitaxel in locally advanced head and neck squamous cell carcinoma: a phase III study.

The objective of this study was to compare concomitant chemoradiotherapy based on weekly low-dose gemcitabine versus weekly low-dose paclitaxel in locally advanced head and neck squamous cell carcinoma. Previously, untreated patients with locally advanced squamous cell carcinoma of the head and neck were randomly assigned to one of the two concomitant chemoradiation regimens: (1) weekly gemcitabine at a dose of 100 mg/m(2) over 30 min 1-2 h before radiotherapy and (2) weekly paclitaxal at a dose of 20 mg/m(2) over 60 min 4-6 h before radiotherapy. The planned radiotherapy dose was 65 Gy over 6.5 weeks in 32 settings. Two hundred and sixteen patients were randomly divided into 2 groups: group A (110 patients) and group B (106 patients) who received concomitant weekly low-dose gemcitabine and low-dose paclitaxal, respectively, with the radiotherapy protocol. The hematological toxicity was generally mild. On the contrary, non-hematologic toxicities were severe. Grade III mucositis occurred in 36% in group A and in 24% in group B (P = 0.04). Moreover, grade III dermatitis were encountered in 24% in group A and 13% in group B (P = 0.049). Thirty-two (29%) of group A and 18(17%) of group B patients required enteral or parenteral feeding (P = 0.01). Sixteen (15%) of group A and 6 (6%) of group B required enteral or parenteral feeding that lasted for 6 months (P = 0.03). Regarding the late effect on swallowing, 8% of patients in group A and 2% of patients in group B required enteral or parenteral feeding for more than 6 months (P = 0.035). Response rates were 78 and 89% in groups A and B, respectively (P = 0.038). The 2-year progression-free survival figures were 54 and 64% of groups A and B, respectively; however, the 2-year overall survival figures were 56 and 67%, respectively. On the other hand, the 3-year progression-free survival figures were 39 and 48% for groups A and B, respectively, while the 3-year overall survival figures were 45 and 49%, respectively (P = 0.05). Both concomitant chemoradiotherapy regimens were easily given in the outpatient clinic. The regimen based on paclitaxel was significantly more tolerable and effective; however, the difference was not enormous.

Neoadjuvant concurrent chemoradiotherapy with capecitabine and oxaliplatin in patients with locally advanced esophegeal cancer.

Evaluation of the feasibility and efficacy of neoadjuvant concurrent chemoradiotherapy (CRT) with capecitabine and oxaliplatin in patients with locally advanced esophageal cancer. Forty-two patients were eligible for the study. The chemotherapy during CRT consisted of two cycles of intravenous oxaliplatin of 120 mg/m(2) on day 1 and oral capecitabine 825 mg/m(2) twice daily on days 1-14 at 3-week intervals. The radiotherapy (1.8 Gy/fraction/day to a total dose of 45 Gy) was delivered to the primary tumor site and regional lymph node. All patients completed the planned treatment. Overall clinical response rate was 54.8% with complete response in 16.7% while pathological response rate was 38%. Anemia was the commonest hematologic toxicity (52.3%) with grade 3 in 4.7%, and esophagitis was the commonest non-hematologic toxicity 59.5% with grade 3 and 4 in 9.5%. No treatment-related death was observed. After a median follow-up duration of 19 months, the 2-year survival rate was 42%, median survival time was 20 months (95%CI: 13.802-26.198), while 2-year progression-free survival (PFS) rate was 32.5% with median PFS time of 15 months (95%CI: 10.042-19.958). Neoadjuvant concurrent CRT with capecitabine and oxaliplatin was found to be well tolerated and effective in patients with locally advanced esophageal cancer; however, these results should be further evaluated in a phase III study.

Adjuvant Pelvic Radiotherapy vs. Sequential Chemoradiotherapy for High-Risk Stage I-II Endometrial Carcinoma.

OBJECTIVE: To explore if the addition of adjuvant chemotherapy with paclitaxel and carboplatin to radiotherapy confers an advantage for overall survival (OAS), and progression free survival (PFS); to assess the incidence of relapses over standard pelvic radiotherapy; and to evaluate the related toxicity in high-risk stage I-II endometrial carcinoma. METHODS: Medical records were reviewed to identify high-risk stage I-II endometrial carcinoma cases treated in the Clinical Oncology and Nuclear Medicine department between 2002 and 2008 with adjuvant radiotherapy alone (arm I) (57 patients) or with sequential carboplatin (AUC5-6) and paclitaxel (135-175 mg/m(2)) with radiotherapy (arm II) (51 patients). Radiotherapy was performed through the four-field box technique at doses of 45-50 Gy (1.8 Gy/day × 5 days/week). RESULTS: The toxicity was manageable and predominantly hematologic with a grade 3 neutropenia and thrombocytopenia in 9.8% and 6% of the patients in arm I and arm II, respectively, without febrile neutropenia. All patients experienced hair loss. Chemoradiotherapy arm was associated with a lower incidence rate of relapse (9.8% vs. 22.7%). After a median follow-up period of 48 months, the 5-year OAS and PFS rates for chemoradiotherapy-treated patients were significantly more favorable than those who did not receive chemotherapy (P=0.02 and 0.03, respectively). In arm I, the OAS and PFS rates were 73.7% and 66.7% compared with those in arm II, whose rates were 90.2% and 84.3%. CONCLUSIONS: Adjuvant chemoradiation with paclitaxel and carboplatin improved the survival rates and decreased the recurrence rates in patients with high-risk stage I-II endometrial carcinoma. Chemotherapy was associated with an acceptable rate of toxicity. However, a prospective study with a larger number of patients is needed to define a standard adjuvant treatment for high-risk stage I-II endometrial carcinoma.

Combination of irinotecan and 5-fluorouracil with radiation in locally advanced rectal adenocarcinoma.

OBJECTIVE: To evaluate toxicity and efficacy of addition of weekly irinotecan to a regimen of chemoradiotherapy of 5-fluorouracil with concurrent pelvic radiation in patients with locally advanced rectal cancer. PATIENTS AND METHODS: Between October 2006 and December 2009, 36 patients with non-metastatic rectal adenocarcinoma were treated with chemoradiotherapy of irinotecan (50 mg/m(2) weekly), 5-fluorouracil (250 mg/m(2) for 5 days/week) and pelvic radiation (45 Gy/1.8 Gy/fraction for 5 days/week) by 3D conformal radiotherapy. RESULTS: All patients completed the planned treatment. After the chemoradiotherapy, overall clinical response rate was 55.5% and pathological complete was 16.7%. Neutropenia was the most common hematologic toxicity (58.3%) with grade III in 5.5% while among non hematologic toxicity, diarrhea was the most common reported one (63.9%) with grade III in 13.9% followed by nausea and vomiting (47.2%). After a median follow-up of 23 months, progression-free and overall survival estimates at 2 years were 72% and 91.7%, respectively. Distant relapses were recoded in 16.7%, the main distant failure sites were lung and liver, and local relapse was found in 5.6%. CONCLUSION: Combined chemoradiotherapy of irinotecan, 5-fluorouracil and radiotherapy for locally advanced non metastatic rectal adenocarcinoma is effective and safe. A prospective, randomized trial is needed to confirm these results in larger numbers and to compare this regimen with other non-irinotecan-based chemoradiotherapy regimens.