Nida Iqbal

Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. Dimerization of the receptor results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways leading to cell proliferation and tumorigenesis. Amplification or overexpression of HER2 occurs in approximately 15–30% of breast cancers and 10–30% of gastric/gastroesophageal cancers and serves as a prognostic and predictive biomarker. HER2 overexpression has also been seen in other cancers like ovary, endometrium, bladder, lung, colon, and head and neck. The introduction of HER2 directed therapies has dramatically influenced the outcome of patients with HER2 positive breast and gastric/gastroesophageal cancers; however, the results have been proved disappointing in other HER2 overexpressing cancers. This review discusses the role of HER2 in various cancers and therapeutic modalities available targeting HER2.

Imatinib: A Breakthrough of Targeted Therapy in Cancer

Deregulated protein tyrosine kinase activity is central to the pathogenesis of human cancers. Targeted therapy in the form of selective tyrosine kinase inhibitors (TKIs) has transformed the approach to management of various cancers and represents a therapeutic breakthrough. Imatinib was one of the first cancer therapies to show the potential for such targeted action. Imatinib, an oral targeted therapy, inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT. Imatinib has also been proven to be effective in steroid-refractory chronic graft-versus-host disease because of its anti-PDGFR action. This paper is a comprehensive review of the role of Imatinib in oncology.

Complete response after autologous stem cell transplant in multiple myeloma.

We evaluated long‐term outcome of patients achieving complete response (CR) after autologous stem cell transplantation (ASCT) for multiple myeloma. Between April 1990 and June 2012 191 patients underwent ASCT. The median age was 53 years (range, 26–68 years), 135 were men. Pretransplant, patients received induction therapy with VAD (vincristine, doxorubicin, dexamethasone; n = 77), novel agents (n = 92), or alkylating agent‐based, n = 22); 43% received more than one line of induction regimen. Response to transplant was defined as per EBMT criteria. The median follow‐up for the entire group was 85 months (range, 6–232.5 months). Following transplant 109 (57.1%) patients achieved CR. Median progression‐free survival (PFS) for patients with CR was higher compared to those with VGPR and PR, (107 vs. 18 vs. 18 months, P < 0.001). Number of lines of therapy pretransplant (one or two vs. more than two lines of therapy (P < 0.001), and absolute lymphocyte count of ≤3000/cmm were predictors of superior PFS. Median overall survival (OS) for patients with CR was higher, (204 months), compared to those with VGPR (71.5 months, P < 0.001) and PR (51.5 months, P < 0.001), respectively. On Cox regression analysis, patients who received one line of induction therapy pretransplant (hazard ratio, HR 2.154, P < 0.001) and those with absolute lymphocyte count of ≤3000/mm3 (HR 0.132, P < 0.001) had superior PFS. For overall survival, induction treatment up to one line (HR 2.403, P < 0.004) and Hb > 7.1 G/dL at diagnosis (HR 4.756, P < 0.01) were associated with superior outcome. On landmark analysis at 12 months, PFS and OS continued to remain superior for patients attaining CR. Achievement of CR post transplant is associated with longer OS and PFS. Among complete responders, those who receive one line of induction therapy pretransplant have superior outcome.

Successful Treatment of Disseminated Subcutaneous Panniculitis-Like T-Cell Lymphoma with Single Agent Oral Cyclosporine as a First Line Therapy

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare cutaneous neoplasm of mature cytotoxic T-cells. Currently there are no standardized therapies for SPTL; however good responses have been seen with chemotherapy regimens generally employed for B-cell lymphomas. Cyclosporine, an immunosuppressant, has shown good responses in relapsed/refractory SPTL; however its use in first line setting is not well established. We, herein, describe a 22-year-old girl with disseminated SPTL who attained complete clinical remission with single agent oral cyclosporine used as a first line therapy.

Nonrhabdomyosarcomatous abdominopelvic sarcomas: Analysis of prognostic factors

Background: Data concerning treatment outcome and prognostic factors in sarcomas of abdomen and pelvis are sparse in literature.Methods and Results: Of 696 patients with nonrhabdomyosarcomatous soft tissue sarcoma registered at our center between June 2003 and December 2012, 112 (16%) patients of sarcomas arising from abdomen and pelvis were identified, of which 88 patients were analyzed for treatment outcome and prognostic factors. The median age was 40 years (range: 1–78 years) with a male: female ratio of 0.7:1. Twenty-one (24%) patients were metastatic at baseline. The most common tumor sites were retroperitoneum in 70% patients and abdominal wall in 18% patients. Leiomyosarcoma was the most common histological subtype in 36% patients followed by liposarcoma in 17% patients. Thirty-five (40%) patients had Grade III tumors. Forty-six (52%) patients underwent surgical resection. At a median follow-up of 43 months (range: 2–94 months), the 5-year event-free survival (EFS) and overall survival (OS) were 35% and 42%, with a median of 22 months and 43 months, respectively. Multivariate analysis identified male gender (P - 0.03, hazard ratio [HR] - 0.46, 95% confidence interval [CI] - 0.23–0.92), baseline metastatic disease (P - 0.01, HR - 2.98, 95% CI - 1.27–6.98) and Grade III tumors (P - 0.02, HR - 1.84, 95% CI - 1.08–3.13) as factors associated with poor EFS, whereas baseline metastatic disease (P < 0.001, HR - 5.45, 95% CI - 2.31–12.87) and unresectability (P - 0.01, HR - 2.72, 95% CI - 1.27–5.83) were associated with poor OS. Conclusion: This is a single-institutional study of patients with abdominopelvic sarcomas where gender was identified as a new factor affecting survival apart from baseline presentation, histologic grade, and surgical resection.

Update on Salvage Options in Relapsed/Refractory Hodgkin Lymphoma after Autotransplant

Despite a high clinical success, relapse in Hodgkin lymphoma occurs in 10–30% of cases and 5–10% patients are nonresponsive to initial chemotherapy. The standard management of these patients includes high-dose chemotherapy followed by autologous stem cell transplant. However, 50% of patients ultimately relapse after autotransplant which poses a big challenge. Allogeneic stem cell transplantation offers the only chance of cure in these patients. For patients who are not candidates for allogeneic stem cell transplantation, achieving cure with other possible options is highly unlikely, and thus the treatment plan becomes noncurative. Various novel agents have shown promising results but the duration of response is short lived. A standard approach to deliver the most effective treatment for these patients is still lacking. This review focuses on the treatment options currently available for relapsed and refractory disease after autotransplant.

Spontaneous tumor lysis syndrome in a patient of chronic lymphocytic leukemia.

Sir, Spontaneous tumor lysis syndrome (TLS) describes electrolyte abnormalities and renal dysfunction occurring in the presence of rapid cellular turnover before the administration of cytoreductive therapies.[1] Spontaneous TLS is well-described in Burkitts’s lymphoma, acute lymphoid leukemia, diffuse large B-cell lymphoma and in solid malignancies such as breast cancer, lung cancer, prostate cancer and malignant melanoma.[2-4] Spontaneous TLS is exceedingly rare in patients with the chronic lymphocytic leukemia (CLL).

Cerebral Venous Thrombosis: A Mimic of Brain Metastases in Colorectal Cancer Associated with a Better Prognosis

Malignancy is known to be one of the predisposing factors of cerebral venous thrombosis (CVT) due to its hypercoagulable state. CVT is a rare disorder which can lead to frequent misdiagnoses of brain metastases in such cases. We report here the case of a 35-year-old female with metastatic colon adenocarcinoma presenting with sudden neurological symptoms. Brain MRI and magnetic resonance venography confirmed the presence of CVT. She was treated with low molecular weight heparin followed by warfarin. She recovered and is doing well on warfarin after 5 months of diagnosis of CVT. CVT should be strongly suspected as a cause of neurological dysfunction in any case of disseminated malignancy including colon adenocarcinoma. Rapid diagnosis and initiation of therapy should be considered because of its favourable outcome.

Poor Response to Standard Chemotherapy in Early T-precursor (ETP)-ALL: A Subtype of T-ALL Associated with Unfavourable Outcome: A Brief Report

Early T-precursor (ETP)-ALL, a type of T-ALL, is a new pathobiologic entity with distinct immunophenotype (CD1a−, CD8−, CD5weak/absent with stem-cell/myeloid markers) and genetic expression, poor response to standard intensive chemotherapy and very high risk of relapse. The genetic mutations typically associated with the pathogenesis of acute myeloid leukemia are seen with increased prevalence in ETP-ALL. No Indian data exists regarding this rare entity. Recently we have seen six cases of ETP-ALL and hereby reporting their clinical characteristics and treatment outcome. All patients were given induction chemotherapy according to standard protocols. Only one out of six patients could achieve remission after induction therapy. Rest five patients died because of their leukemia. This reflects the aggressive biology of this disease and its poor response to standard chemotherapy regimens generally used in T-ALL. The limited experience with ETP-ALL reflects whether rarity of this condition or failure to recognize this is not clear at this time. More studies are required to understand the basic biology of this disease and new therapeutic strategies need to be devised.