Trastuzumab, Pertuzumab, and Docetaxel as the First Line for HER-2-Positive Metastatic Breast Cancer among Arabs.

INTRODUCTION: Human epidermal growth factor receptor 2 (HER-2) targeted therapy regimens can improve tumor response in HER-2-positive metastatic breast cancer (MBC), with overall survival benefits. OBJECTIVE: We evaluated the efficacy of dual HER-2 blockade combined with chemotherapy for HER-2-positive MBC patients as a first-line therapy in our patient population. PATIENTS AND METHODS: We identified 75 patients at King Faisal Specialist Hospital and Research Center that received trastuzumab, pertuzumab, and docetaxel as a first-line therapy in HER-2 positive MBC in 2013-2016. RESULTS: Median age at diagnosis was 45 years; 54.7% were estrogen receptor (ER)-positive. 10% of patients presented with only bone metastasis. The median follow-up time was 36 months with an objective response rate of 74.7% (complete response [CR] 18.7%; partial response [PR] 56%). The 5-year progression-free survival (PFS) and overall survival (OS) were 21% and 71.9% respectively, with a median PFS of 36 months (95% confidence interval [CI] 23.6-48.4). The 5-year OS for ER-negative and ER-positive patients was 93.9% and 59.4% respectively (p = 0.189); 23 patients experienced grade 1/2 toxicity and 2 patients had grade 3/4 toxicity. In terms of OS and PFS, the site of metastasis did not make any significant difference. CONCLUSIONS: First line pertuzumab, trastuzumab, and docetaxel for HER-2-positive MBC patients was found to be an effective and safe therapy in the Saudi population. This finding was consistent with the results seen in the CLEOPATRA trials.

"Tocilizumab-an option for patients with COVID-19 associated cytokine release syndrome: A single center experience", a retrospective study-original article.

BACKGROUND: The first case of Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was diagnosed in Wuhan, China in 2019. In the first half of 2020, this disease has already converted into a global pandemic. This study aimed to find that treatment of patients with COVID-19 pneumonia with Tocilizumab or steroids was associated with better outcomes. Objectives: To analyze the effectiveness of Tocilizumab in moderate to severe Covid-19 patients based on predefined assessment criteria . Study Settings: Single-center, Fatima Memorial Hospital, Lahore. STUDY DESIGN: Quasi-experimental. DURATION OF STUDY: From May 12, 2020 to June 12, 2020. PATIENTS & METHODS SAMPLE SIZE AND TECHNIQUE: Sample size was 93; 33 patients were kept in the experimental group, given Tocilizumab, 8 mg/kg intravenously or 162 mg subcutaneously, and the rest of the 60 patients were given corticosteroids, methylprednisolone 80 mg/day. Consecutive sampling. Failure of therapy was labeled when patients were intubated or died, and the endpoints were failure-free survival which was the primary endpoint, and overall survival secondary at the time of discharge. RESULTS: A total of 93 patients were enrolled, the Tocilizumab (TCZ) group (case) and Corticosteroid (CS) group (Control). The median age was 58 years (IQR-21), 37 (39.8%) patients with diabetes mellitus, 11 (11.8%) in the TCZ group, and 26 (28%) in the CS group. On the whole, the total median hospital stay in days was 7 with IQR (4), a total of 83 (89.2%) patients recovered successfully and discharged, 27 (29%) in the TCZ group and 56 (60.2%) in the CS group. Total 10 (10.8%) patients died, out of which 6 (6.5%) belonged to the TCZ group and 4 (4.3%) belonged to the CS group The median Oxygen requirement with IQR was 8 (9) in both the groups and in total as well, p-value (0.714). CONCLUSIONS: Tocilizumab is a quite effective treatment option for critically sick patients of Covid-19 by reducing their oxygen requirement drastically and so the ICU stay, median hospital stay and so the mortality as well. CLINICALS TRIALS REGISTRATION: UIN # NCT04730323.

Adrenal Insufficiency In Pakistani Hiv Infected Patients.

BACKGROUND: Adrenal insufficiency (AI) is the most common endocrine complication among patients with AIDS/HIV infection and there are number of causes of AI in HIV patients. Human immunodeficiency virus directly as well as indirectly destroys adrenal glands. The estimates of its prevalence and severity vary. AI is the most life threatening but readily correctable endocrine complication that occurs in persons with HIV infection. This study was carried out to determine the frequency of Adrenal Insufficiency in HIV patients and their clinical features as proper diagnosis and timely treatment have been shown to improve quality of life and long-term mortality in AIDS patients. METHODS: It was a cross sectional survey conducted at HIV clinic and Jinnah Allama Iqbal Institute of Diabetes and Endocrinology, Jinnah Hospital Lahore. Sixty-four HIV positive patients, both male and female, aged above 15 years were included in the study. HIV patients who had recently taken steroids, ketoconazole or rifampicin, determined on history, were excluded from the study. The data was collected on a structured proforma and analysis was performed in SPSS-21.0. Frequency and percentages for adrenal insufficiency and its characteristics were calculated. Chi-square test was used with p<0.05 as statistically significant. RESULTS: In this study, 9 (14.06%) HIV patients were diagnosed with adrenal insufficiency, male to female ratio was 3.5:1 and AI was found statistically significantly associated with fatigue (p<0.008) and weight loss (p<0.001). CONCLUSIONS: Adrenal insufficiency was high among the patients with HIV, it was not gender specific but it was found to be associated with fatigue and weight loss.

Frequency and Severity of Acute Toxicity of Pelvic Radiotherapy for Gynecological Cancer.

OBJECTIVE: To determine the frequency and severity of acute toxicity of pelvic radiotherapy for gynecological cancer. STUDY DESIGN: A case series. PLACE AND DURATION OF STUDY: Department of Oncology, The Aga Khan University Hospital, Karachi, from March 2011 to June 2012. METHODOLOGY: A total of 99 patients with histologically proven uterine and cervical cancer, receiving radiation therapy, were enrolled into the study after informed consent on justification of inclusion and exclusion criteria. Patients were evaluated for the frequency and severity of pelvic radiotherapy's side effects according to toxicity criteria based on RTOG/EORTC and CTC version 2 criteria at the start, during and at the end of treatment. The data was analyzed by using SPSS version 16. RESULTS: Out of the 99 enrolled patients, 58 (58.6%) had uterine and 41 (41.4%) had cervical cancer. Mean age was 54.54 ± 10.29 years. Thirty-five (35.4%) patients received chemotherapy with RT. Mean RT dose was 60.72 ± 7.15 Gy. The most common gastrointestinal adverse effect was diarrhea in 64 (64.6%) followed by proctitis in 55 (55.5%), nausea in 33 (33.3%) and vomiting in 16 (16.2%) patients. Grade (G) 1 was the most frequently observed severity. The most common hematological toxicity was anemia in 37.8% (n=31/82) {(G1=18 (21.9%), G2=11 (13.4%), G3=2 (2.4%)} followed by thrombocytopenia in 22.8% (21/92) {(G1=16 (17.3%), G2=2 (2.1%), G3=3 (3.2%)} and neutropenia in 21 (21.2%) {(G1=12 (12.1%), G2=5 (5%), G3=3 (3%), G4=1 (1%)}. Urinary toxicity was observed in 49 (49.5%) patients. On stratification, chemotherapy and higher RT dose were strong predictor of increased hematological and upper gastrointestinal toxicity (p < 0.05) and age > 60 years for diarrhea (p < 0.05). CONCLUSION: The frequency and severity of acute toxicity of pelvic radiotherapy in women with gynecologic cancers was found intermediate to high.

Treatment updates regarding anaplastic oligodendroglioma and anaplastic oligoastrocytoma.

Anaplastic Oligodendroglioma / Anaplastic Oligoastrocytoma (AO/AOA) is a WHO Grade-III primary brain tumor. These tumors comprise about 5 - 10% of all gliomas, which make them the third most common primary brain tumors after glioblastoma multiforme and astrocytomas. For many years standard of treatment remained Maximum Safe Resection (MSR) followed by Radiotherapy (RT). These tumors have also been known to be sensitive to alkylator-based chemotherapy particularly the subset having 1p/19q co-deletion signature. There is robust data showing that these tumors are responsive to chemotherapy in recurrent or progressive setting. Recently, up front chemotherapy has been added to standard post-surgery RT. It has been found that subset of AO/AOA having 1p/19q co-deletion responded very well to the addition of chemotherapy. This substantial benefit in terms of median Overall Survival (OS) and median Progression Free Survival (PFS) have intrigued the personalized treatment of AO/AOA on the basis of molecular signature markers.

Plan dose evaluation of three dimensional conformal radiotherapy planning (3D-CRT) of nasopharyngeal carcinoma (NPC): experience of a tertiary care University Hospital in Pakistan.

BACKGROUND: Radiation therapy is the mainstay of treatment for nasopharyngeal carcinoma. Importance of tumor coverage and challenges posed by its unique and critical location are well evident. Therefore we aimed to evaluate our radiation treatment plan through dose volume histograms (DVHs) to find planning target volume (PTV) dose coverage and factors affecting it. MATERIALS AND METHODS: This retrospective study covered 45 histologically proven nasopharyngeal cancer patients who were treated with definitive 3D-CRT and chemotherapy between Feb 2006 to March 2013 at the Department of Oncology, Section Radiation Oncology ,Aga Khan University Hospital, Karachi, Pakistan. DVH was evaluated to find numbers of shrinking field (phases), PTV volume in different phases and its coverage by the 95% isodose lines, along with influencing factors. RESULTS: There were 36 males (80%) and 9 females (20%) in the age range of 12-84 years. Stage IVA (46.7%) was the most common stage followed by stage III (31.1). Eighty six point six-percent received induction, 95.5% received concurrent and 22.2% received adjuvant chemotherapy. The prescribed median radiation dose was 70Gy to primary, 60Gy to clinically positive neck nodes and 50Gy to clinically negative neck regions. Mean dose to spinal cord was 44.2Gy and to optic chiasma was 52Gy. Thirty seven point eight-percent patients completed their treatment in three phases while 62.2% required four to five phases. Mean volume for PTV3 was 247.8 cm3 (50-644.3), PTV4 173.8 cm3 (26.5-345.1) and PTV5 119.6 cm3 (18.9-246.1) and PTV volume coverage by 95% isodose lines were 74.4%, 85.7% and 100% respectively. Advanced T stage, intracranial extension and tumor volume >200 cm3 were found to be important factors associated with decreased PTV coverage by 95% isodose line. CONCLUSIONS: 3D CRT results in adequate PTV dose coverage by 95% isodose line. However advanced T stage, intracranial extension and large target volume require more advanced techniques like IMRT for appropriate PTV coverage.

Carcinosarcoma of the breast.

Carcinosarcoma of the breast is an extremely rare and aggressive tumour with two distinct cell lines comprising epithelial and mesenchymal components, with few cases reported in the literature. The prognosis of carcinosarcoma breast is less favourable compared to more common types of breast cancers such as infiltrating ductal or lobular carcinomas. These tumours form a diagnostic and therapeutic challenge. A case of carcinosarcoma breast in a 36 years old woman is presented here.

Non-secretory myeloma: a rare variant of multiple myeloma.

The spectrum of plasma cell neoplasm represents indolent conditions like Monoclonal Gammopathy of Undetermined Significance (MGUS) to more aggressive multiple myeloma and plasma cell leukemia. Non-secretory myeloma comprises less than 01% of this spectrum where serum protein electrophoresis and quantitative immunoglobulins remain essentially normal. We are presenting a case report of this rare variant involving the sternum of an adult male.

Imatinib-related bone marrow aplasia after complete cytogenetic response in chronic myeloid leukemia.

Imatinib mesylate is a BCR-ABL tyrosine kinase inhibitor used in the management of chronic myeloid leukemia. It is a safe and well-tolerated agent with a few manageable side effects. We are reporting a case of imatinib-related fatal bone marrow aplasia after complete cytogenetic response.