Improving outcomes in advanced lung cancer. Maintenance therapy in non-small-cell lung carcinoma

Systemic chemotherapy has remained the traditional treatment for metastatic non-small-cell lung carcinoma [NSCLC], enhancing survival rate at 1 year to 29%. The median survival had plateaued at around 10 months until early 2008, and in an attempt to enhance survival in advanced disease, maintenance chemotherapy trials were initiated which had recently demonstrated prolongation of survival by an additional 2-3 months in patients who had performance status [PS] 0-1 and well-preserved organ functions. Suitable patients with any degree of clinical benefit are treated with 4-6 cycles, and then one of the active agents is continued until best response, or toxicity [continued maintenance], or changed to a cross non-resistant single agent [switch maintenance]. The article briefly reviews the evolution of systemic therapy and describes key randomised trials of maintenance therapy instituting chemotherapy and targeted agents in an attempt to improve outcomes in advanced metastatic NSCLC, based on certain clinical features, histology, and genetics

Solid pseudopapillary neoplasm of the pancreas: a case report with review of the diagnostic dilemmas and tumor behavior

Solid pseudopapillary neoplasm of the pancreas is a rare tumor of the pancreas often detected initially on imaging. Of uncertain histogenesis, it has a low-grade malignant potential with excellent post-surgical curative rates and rare metastasis. Despite advances in imaging, pseudocysts and other cystic neoplasms feature in the differential diagnosis. Pathological and/or cytological evaluation remains the gold standard in reaching a definitive diagnosis. On morphology alone, other primary pancreatic tumors and metastatic tumors pose a diagnostic challenge. Recent advances in immunohistochemical characterization have made the histopathologic diagnosis more specific and, in turn, shed light on the likely histogenesis of this rare tumor. We report a case of solid pseudopapillary neoplasm of the pancreas that was suspected on radiology and diagnosed intraoperatively on imprint cytology guiding definitive surgery. The diagnostic dilemmas are reviewed.

Metastatic malignant melanoma during pregnancy: case report and a review of the literature

Malignant melanoma is one of the most rapidly increasing cancers and, when it occurs during pregnancy, it can frequently metastasise to the placenta and the foetus. Earlier reports suggested a rapid progress of the disease during pregnancy with a poor prognosis; however, recent controlled studies found that stage for stage, the prognosis of melanoma during pregnancy is similar to that in a non-pregnant state. Early diagnosis and prompt treatment can avoid a tragic outcome

Outcome as a measure of quality of care in oncology: experience at Sultan Qaboos University Hospital, Oman

Measurement of outcomes is increasingly employed as an indicator of the quality of clinical care. The most commonly measured outcome in many clinical studies, especially in oncology, still remains the overall survival rate. Sultan Qaboos University Hospital [SQUH], Oman, is striving for excellence through quality management. In seeking continual improvement, quality measurement exercises have been initiated throughout the Hospital. We present the overall survival rate of four of the ten most common cancers diagnosed in Oman. The cancers included non-Hodgkin's lymphoma [NHL], Hodgkin's lymphoma [HL], breast cancer, and stomach cancer. The studies were all retrospective and had been conducted previously. For present purposes, only the overall survival was compared with studies both from the region, and with bench-mark studies. For NHL, with a median follow-up of 8 months, the 2-year overall survival rate was 64%; 90% for low risk, 55% for intermediate risk, and 15% for high risk groups. For HL, the 5-year overall survival rate was 64%; 76% for low risk and 42% for high risk. For breast cancer, the 5-year survival rate was 67%; percentages were 88%, 75% and 59% for Groups I, II, and III respectively. For gastric cancer, the 5-year survival rate was 16.5%; 24% for the non-metastatic group. The outcome of patients with early stages and fewer adverse prognostic factors is comparable to what has been reported in the international literature; however, the outcome is inferior for patients presenting withadvanced stage disease and several adverse prognostic factors

Major advances in the treatment of cancer. What does a non-oncologist need to know?

The last few years have seen major advances in the management of cancers. Since it is not possible for the non-oncologist to keep abreast with the latest developments in the field of oncology, this review summarises the most significant advances in the area of treatment of various cancers over the past four years. In some areas, a paradigm shift has occurred setting new standards of care, for example, the use of targeted therapy [trastuzumab] in adjuvant treatment of breast cancer; the use of monoclonal antibodies[rituximab], with or without chemotherapy, in the treatment and maintenance of indolent lymphoma; the use of the tyrosine kinaseinhibitor, imatinib, in the adjuvant setting in resected gastrointestinal stromal tumours. In other areas, new treatments have emerged,such as, the use of targeted therapies in hepatocellular carcinoma [sorafenib] and renal cell carcinoma [sunitinib, sorafenib, temsirolimus, bevacizumab]. In some other cancers, the addition of targeted therapies has improved survival rates, for example, in colon cancer [bevacizumab, cetuximb, panitumumab], head and neck cancers [cetuximab], and pancreatic adenocarcinoma [erlotinib]. In yet another group, new targeted therapies have emerged where resistance was previously observed with the existing targeted therapies, for example, breast cancer [lapatinib], chronic myeloid leukemia [dasatinib]. Finally, the addition of chemotherapeutic agents has improved survival in some forms of cancer, for example, oxaliplatin in adjuvant treatment of colon cancer, temozolamide in glioblastoma multiforme, and adjuvant chemotherapy in non-small cell lung cancer. The information summarized here may provide useful for the busy physician needing an update in the field of oncology

Nodular lymphocyte predominant Hodgkin's lymphoma presenting as severe hypercalcaemia: a case report

Nodular lymphocyte predominant Hodgkin's lymphoma [NLPHL] is a recently described type of Hodgkin's lymphoma [HL] and accounts for 5-6% of all the cases of HL. Here we report the case of an elderly man who presented to Sultan Qaboos University Hospital, Oman, with severe hypercalcemia, and was diagnosed to have stage IV NLPHL. Although the incidence of hypercalcemia is estimated to be between 1-5% in classical HL, to our knowledge this is the first report of NLPHL presenting with severe hypercalcemia. The patient responded to the anti-CD20 monoclonal antibody, Rituximab, and has been in clinical remission for more than 3 years

Acute myeloid leukemia following regression of sarcoidosis: a case report

This report describes Acute Myeloid Leukemia [AML] occurring in a 46 years old woman previously diagnosed to have Sarcoidosis. There was no evidence of Sarcoidosis at the time of diagnosis of AML. Although the association is well recognized, a cause and effect relationship between the two diseases is not fully established. A brief review of the literature is presented. Case Reports: A 46 years old lady presented to the emergency room with a history of high grade fever, exertional dyspnoea and generalized weakness for the past 4 weeks. She had undergone coronary artery bypass grafting [CABG] five years back. A year before the current presentation, she had presented with a history of fever, dry cough and anorexia. Examination had been unremarkable, except for an ESR of 32 mm/hr and bilateral hilar lymphadenopathy on chest X-ray. She was treated with standard anti-tuberculosis therapy [ATT] empirically. Subsequent to a lack of response to ATT and cultures for Acid Fast Bacilli remaining negative, Angiotensin Converting Enzyme [ACE] levels were found to be elevated to 59 IU/L [normal 8-52 IU/L]. A lymph node had also appeared in the left supraclavicular region by this time; excisional biopsy of which revealed non-caseating granuloma. ATT was discontinued and the patient was started on oral steroids. Within the next two months she became asymptomatic and the chest X-ray showed a complete regression of hilar Lymph nodes. During her current admission, she was found to be febrile, pale, icteric with hepatosplenomegaly, but no lymphadenopathy Examination of the cardiovascular, respiratory and the central nervous system were unremarkable. Her laboratory data revealed a haemoglobin of 6.3 g/dl, total leukocyte count of 121x 109/L with 88% blast cells, and a platelet count of 24x109/L. Bone marrow aspirate revealed Auerrod containing blast cells which constituted 90% of the total nucleated cells. 80% of the cells showed reactivity to Sudan Black. The patient was diagnosed to have AML. The chromosomal analysis revealed a 46 XX karyotype. Serum chemistries revealed a BUN of 7 mg/dl; creatinine 1mg/dl; Na 140 mEq/L; K 2mEq/L; total bilirubin 3.6 mg/dl; ALT 11 IU/L; alkaline phosphate 52 IU/L; LDH 5487 IU/L; and uric acid 7.2 mg/dl. The ACE levels were within normal limits. The chest Xray showed evidence of previous sternotomy and no lymphadenopathy. She was started on induction chemotherapy consisting of cytosine arabinoside 100 mg/m2 for 7 days and mitoxantrone 12 mg/m2 for three days. Hematological remission was documented on the 29th day of induction treatment. Bone marrow biopsy did not reveal a granuloma or fibrosis

Increased levels of multiple forms of dihydrofolate reductase in peripheral blood leucocytes of cancer patients receiving haematopoietic colony-stimulating factors: interim analysis

The precise mechanism whereby granulocytes proliferate when haematopoietic colony stimulating factors (CSFs) are used in neutropenic cancer patients is poorly understood. The purpose of this study was to investigate whether these cytokines bring about leucocyte proliferation by increasing the levels of multiple forms of dihydrofolate reductase (DHFR). Blood samples were collected from 36 cancer patients (25 males and 11 females) with chemotherapy-induced neutropenia. One sample of blood from each patient was obtained before therapy either with CSF, such as granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) or with placebo, and another one at the time of resolution of neutropenia. Peripheral blood leucocytes in these blood samples were counted, separated and lysed. From lysates, cytoplasmic samples were prepared and analyzed for active DHFR by a methotrexate-binding assay and for total immunoreactive DHFR by an enzyme linked immunosorbent assay. The increase in total leucocyte count (TLC) was most prominent (P < 0.005) in the CSF group and less so (P < 0.05) in the placebo group. The mean +/- SD concentration values of active DHFR before and after stimulation with GM-CSF found were to be 0.34 +/- 0.4 ng/mg protein and 0.99 +/- 0.82 ng/mg protein, respectively, and in the group treated with G-CSF, 0.24 +/- 0.32 ng/mg protein and 1.18 +/- 2.4 ng/mg protein, respectively. This increase in active DHFR after stimulation with CSF was statistically significant (P <0.05). Similarly, concentration values of immunoreactive but nonfunctional form of DHFR (IRE) were 110 +/- 97 ng/mg protein and 605 +/- 475 ng/mg protein before and after stimulation with GM-CSF, and 115 +/- 165 ng/mg protein and 1,054 +/- 1,095 ng/ mg protein before and after stimulation with G-CSF. This increase in concentration of IRE after stimulation with GM-CSF or G-CSF was statistically significant (P < 0.005). In the control group, there was an increase in the concentration of both active DHFR and IRE after treatment with placebo. However, this was not statistically significant. Resolution of neutropenia was quicker in the groups treated with CSF compared to the control group. Results of this study indicate that colony stimulating factors (G-CSF and GM-CSF) induce white cell proliferation by increasing the levels of multiple forms of DHFR.

All trans retinoic acid in acute promyelocytic leukemia: case series and review of literature

Over the past few years All Trans-Retinoic Acid [ATRA] has been increasingly used to induce remission in Acute Promyelocytic Leukaemia [APL]. ATRA is thought to restore the structural integrity of the nuclear bodies whic are disrupted by the transcribed chimeric protein [APL-RAR alpha] formed as a result of a specific non-random chromosomal translocation [15:17].Six patients of APL with ATRA were treated at a dose of 45 mg/m[2] orally. There were five female and one male patient. Five patients presented with pancytopenia while all had a picture of disseminated intravascular coagulation [Dic]. Four out of six patients entered into complete remission either on ATRA alone or with the addition of cytotoxic chemotherapy. The other two patients developed serious side effects and the treatment with ATRA had to be stopped. One of these patients subsequently entered into remission with standard chemotherapy. The mean time to remission was 39 days. Since ATRA does not induce cytotoxicity, the problem of marrow suppression and exacerbation of Dic were largely alleviated. The patients remained at home for the most part of their treatment. Relevant literature is reviewed