Hanan Ahmed Wahba

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.

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.

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.

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.

Locally Advanced Esophageal Cancer

Cancer of the esophagus is a highly lethal malignancy. There are approximately 16,980 people diagnosed with esophageal cancer each year in the United States and 14,710 deaths from the disease (Siegel et al., 2011). It currently ranks ninth among the most frequent cancers in the world (Lerut et al., 2001), and it is the sixth leading cause of death from cancer (Falk et al., 2007). Although the best treatment for locally advanced esophegeal cancer is still being debated, the use of neoadjuvant chemoradiotherapy has gained acceptance (Tepper et al., 2008). The rationale for chemoradiotherapy (CRT) followed by surgery has potential to downsize the tumor, thereby increasing the rate of tumor-free (RO) resections, reducing early relapses, and improving survival (Swisher et al., 2005; Brucher et al.,2006). Chemoradiotherapy (CRT) has proved effective against resectable/unresectable esophageal squamous cell carcinoma. The Radiation Therapy Oncology Group (RTOG) trial 85-01 demonstrated the superiority of CRT with cisplatin (CDDP), 5-fluorouracil (5-FU), and concurrent irradiation (50.4 Gy) over radiotherapy alone (64 Gy) in patients with T1–3N0– 1M0 esophageal cancer (Herskovic et al., 1992). Definitive chemoradiotherapy is appropriate for locally advanced cancer in patients who do not want surgery or in whom surgery is not possible as a result of technical or medical reasons. The higher doses of radiation administered with concurrent chemotherapy was explored in the protocol RTOG9504 which established 50.4 Gy as the standard dose of radiation to be administered concurrently with chemotherapy (Minsky et al., 2002). Three-dimensional conformal radiotherapy (3D-CRT) is an approach to the planning and delivery of radiation therapy and numerous investigators have demonstrated the benefits of this modality in a variety of cancers. These benefits include its normal tissue-sparing capabilities and its ability to deliver higher radiation doses compared with conventional radiotherapy (Oh et al., 1999).