Hend Ahmed El-Hadaad

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.

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.

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

ObjectiveTo 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 methodsBetween October 2006 and December 2009, 36 patients with non-metastatic rectal adenocarcinoma were treated with chemoradiotherapy of irinotecan (50 mg/m2 weekly), 5-fluorouracil (250 mg/m2 for 5 days/week) and pelvic radiation (45 Gy/1.8 Gy/fraction for 5 days/week) by 3D conformal radiotherapy.ResultsAll 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%.ConclusionCombined 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.

Safety and esthetic outcomes of therapeutic mammoplasty using medial pedicle for early breast cancer

Background Although therapeutic mammoplasty (TM) was introduced for treatment of localized ductal carcinoma in situ and invasive breast carcinoma (stages I and II) in females with large breast size, the suitability of medial pedicle TM for treatment of breast tumors at different locations has not been established. The objective of this study was to assess the safety and esthetic outcome of medial pedicle TM for breast tumors at different locations. Methods The study was conducted from February 2012 to July 2014. Consecutive patients with early breast carcinoma with medium- and large-sized breasts, with or without ptosis, who were offered medial pedicle TM were included in the study. Patients who were not candidates for breast-conserving surgery or those with tumors located along the medial pedicle were excluded. All patients received immediate postoperative adjuvant chemoradiotherapy. Results Thirty patients with a mean age of 48.5 years received medial pedicle TM in the breast harboring the tumor or, additionally, the other breast (N=14). The tumors were in the upper (60.0%), lower (26.7%), and lateral (13.3%) quadrants. Minor complications occurred in five cases (5/30, 16.7%) in the ipsilateral and in two (2/14, 14.3%) contralateral breasts. No wound dehiscence or areolar necrosis was recorded. A total of 22 (73.3%) patients were scored as excellent cosmesis. After a median follow-up of 20 months, no locoregional recurrence or distant metastases were observed. Conclusion TM using a medial pedicle is a safe and appealing technique among women with tumors at different locations.

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/m2) 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.

Impact of Thyroglobulin on Survival and Prognosis of Differentiated Thyroid Cancer

Proper assessment of risk factors contributes to the principle management of differentiated thyroid carcinoma post operatively. Aim of the study: to investigate the effect of Thyroglobulin (Tg) levels on prognosis together with other risk factors for Differentiated Thyroid Cancer (DTC). Patients and methods: Medical records of all patients with DTC presented to Clinical Oncology and Nuclear Medicine Department referred from Diabetes & Endocrine unit (Internal Medicine Hospital) and Surgery Department Mansoura University from 2011-2016 were retrospectively reviewed. Patients with distant metastasis or who lost follow-up were excluded. So data of 220 patients were analyzed. Data collected included pre-surgical assessment, also surgical interference either total or near total thyroidectomy with or without lymph node neck dissection were reviewed. Different prognostic factors that affect progression free survival (PFS) include age, umorsize, ymph node status, ex, multifocality, capsular infiltration, vascular invasion and Tg level were evaluated through multivariate analysis. Results: Most of the patients included were <45 years (69.1%). Incidence of the disease was higher in female (80%) with papillary type predominance (80.9%). About 59.5% of cases presented with tumor size ≤ 2 cm and multifocality was reported in 13.6%. While 30% had lymph node metastasis, 11% had vascular invasion. Capsular infiltration was observed in 15% and most of them showed Tg level ≤ 10 ng/ml (68.2%). About 70% received ablative radioiodine. The 5-year Progression Free Survival (PFS) was 85%. On multivariate analysis of variable prognostic factors on PFS, we found that tumor size, age, lymph node status, capsular infiltration, Tg level and vascular invasion significantly affected PFS (P = 0.01, 0.005, 0.004, 0.005, 0.02, 0.003) respectively. While sex, pathological type and multifocality were not (P = 0.9, 0.4, 0.6) respectively. Conclusion: Postoperative Tg level is a statistically significant prognostic factor together with other risk factors.

Advanced Non-Small Cell Lung Cancer: Retrospective Study of PrognosticFactors

Objective: The objective of the study is to investigate and improve our understanding of the impact of several potential prognostic factors on overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). Methods: Records of patients with advanced NSCLC (stage IIIB, IV) received first-line chemotherapy were reviewed. Age, gender, Eastern Cooperative Oncology Group performance status (ECOGPS), stage, histologic type, smoking status, leucocytic count, type of chemotherapy, albumin and hemoglobin level were evaluated for their prognostic significance in multivariate analysis. Results: A total of 140 patients with advanced NSCLC treated with first-line chemotherapy were identified. The median age was 54 (range from 35-83) years. The majority of patients were male (72%), had stage IIIB (67%) and were in PS 0or1 (75.7%). Forty-six percent had adenocarcinoma. Most patients were smokers (85%) and received platinum-based chemotherapy (78.6%).1-year OS was 39.3% with median survival time of 10 months (95% CI: 7.95-12).ECOGPS of 2(P=0.04), squamous histology (P=0.03), elevated leucocytic count (P=0.02),low hemoglobin level(P=0.02), smoking (P=0.03), low albumin level (P=0.05) and stage IV (P=0.01)were found to be independent prognostic factors for poor survival in multivariate analysis. While age (P=0.23), sex (P=1) and type of chemotherapy whether platinum-based or not (P=0.8) were insignificant factors for survival. Conclusion: From this study, we concluded that prognostic factors as smoking, ECOG PS of 2, squamous histology, stage IV, high leucocytic count, low hemoglobin level, low albumin level are found to have a significant impact on the survival while, gender, age, and type of chemotherapy are not. However, these results and additional information regarding prognostic factors in patients with advanced NSCLC in prospective studies should be validated.

Neurocognitive Effects of Primary Brain Tumors

Cognitive impairment, a common finding with the brain tumors, may result from the tumor itself or the treatment used: surgery, chemotherapy, or radiotherapy. Surgery for brain tumors improves the cognitive function due to reduction of compression as in case of removal of noninvasive tumors. Stability of cognitive function also was observed after tumor resection, such as tumors of third ventricle. Postoperative cognitive worsening was observed. Postoperative worsening of executive functions may correlate to volume of the operated area. Cognitive deficits may follow radiotherapy by several months to many years. These deficits may be due to vascular injury, local radionecrosis, and cerebral atrophy. This usually involves multiple domains, including memory, attention, executive function, and intelligence. The irradiated volume of brain tissue has great impact on cognition. Intensity-modulated radiotherapy (IMRT) and proton beam therapy result in greater sparing of healthy brain tissue and allow for a more-targeted delivery of radiation and smaller penetration of tissue beyond the tumor consequently reduce the risk of cognitive deficit after radiotherapy. Chemotherapy treatment in brain tumor seems to have a role in cognitive dysfunction deficits. The toxicity of chemotherapy increased when was given during or after radiotherapy. Chemotherapeutic agents, such as BCNU, CDDP, cytosine arabinoside, and intrathecal or intravenous methotrexate, have toxic effect to the CNS. Glioblastoma patients undergoing radiotherapy with concomitant and adjuvant temozolomide treatment do not develop cognitive deterioration. Patients with brain tumors face the challenge of cognitive impairment due to the tumor itself or treatments. Cognitive deficits in processing speed, memory, attention, and executive functions interfere with patients’ daily life activities. Cognitive rehabilitation program has proven to be effective in patients with primary brain tumors. Cognitive impairments have a large impact on self-care, social and professional functioning, and consequently on quality of life. Preventing these late effects is a challenge for the medical team, psychologists, and rehabilitation specialists. Prevention depends in part on being able to predict those at greatest risk. Advances in neurosurgery, chemotherapy, and radiotherapy techniques are helping to a great extent, but may not be totally successful at preventing these late effects.

Metastatic Renal Cell Carcinoma: Sunitinib as First-Line Treatment; Results of a Retrospective Study

Abstract Background: Targeted agents were introduced over past years because of better understanding of oncogenetic mechanisms in metastatic renal cell carcinoma (mRCC). These agents include tyrosine kinase inhibitors (TKIs) such as sorafenib, sunitinib, pazopanib and axitinib. Methods: Review of recorded data from patients’ files with mRCC were analysed during the period from August 2008 to December 2014. Those patients were treated by sunitinib as first-line therapy. The data included patients characteristics such as age, sex, ECOG performance status (ECOG PS), number and sites of metastasis and pathological type. Also, we reviewed response to sunitinib therapy, its adverse events and progression-free survival (PFS). Results: This study included 26 patients; median age was 56 years with male predominance (76.9%) and 61.5% of patients were of ECOG PS0. Lymph nodes were the most common site of metastasis (38.5%) and 46.2% presented with ≥3 sites of disease. Clear cell pathology was reported in 96.2%. No grade IV adverse events to sunitinib reactions were observed. Thrombocytopenia was the most predominant haematological reaction (46%) followed by neutropenia (38.6%), whilst fatigue was the most reported non-haematological one (50%) followed by diarrhoea (42.3%). Partial response (PR) was found in 30.8% and stable disease (SD) in 46.2%. One-year PFS was 57.7% with median PFS time of 12 months. Conclusion: This study proved effectiveness and safety of sunitinib as first-line treatment for mRCC. However, this is a retrospective study and relatively small numbers of patients were included, so prospective studies with larger number of patients are needed for further evaluation.

Retro-Molar Trigonal Reconstruction and Oncologic Outcomes after Resection of Large Malignant Ulcers in Elderly Patients

Background: Buccal mucosa carcinoma represents 3 to 5% of oral-cavity cancer. Retromolar buccal trigon affected in one third of patients with buccal mucosal cancers. Squamous cell carcinoma is the commonest pathological finding.