Featured Articles from the EJCMO & APJOH

Role and Prognostic Significance of the Ki-67 Index in Non-Hodgkin's Lymphoma

Bairey O, Role and Prognostic Significance of the Ki-67 Index in Non-Hodgkin’s Lymphoma. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 109-116 

Review Article

Osnat Bairey

Affiliation: Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah Tiqwa, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel


ABSTRACT

The Ki‐67 monoclonal antibody recognizes a nuclear antigen that is present in all phases of the cell growth cycle but is absent in resting cells. The Ki‐67 proliferation index is used to measure the growth fraction of malignant cells. In the major types of lymphoma, its range is very wide. Mean Ki‐67 expression is low in indolent lymphomas and high in aggressive lymphomas; a cutoff index value of 45% can help clinicians to differentiate indolent from aggressive lymphoma. In follicular lymphoma, the Ki‐67 proliferation index increases with increased follicular grade. In diffuse large B‐cell lymphoma (DLBCL), most studies found that a high Ki‐67 proliferation index (>60–70%) was a predictor of poor survival. The most extensive data exist on mantle cell lymphoma, for which multivariate analyses confirmed the central prognostic role of cell proliferation and the superiority of the Ki‐67 proliferation index over all other histomorphological and clinical criteria. The stratification of patients with mantle cell lymphoma according to Ki‐67 expression can be expected to have a profound impact on therapeutic options in risk‐adapted strategies. For the prognostication of peripheral T‐cell lymphoma, the Ki‐67 proliferation index was integrated into a new predictive score. Thus, overall, the Ki‐67 proliferation index is an important tool for determining lymphoma grade, and in many subtypes, it has prognostic significance. At the same time, it should be borne in mind that Ki‐67 staining is still associated with poor reproducibility among laboratories, and each laboratory should determine its own cutoff values.

Keywords: Ki‐67, proliferation index, follicular lymphoma, diffuse large B‐cell lymphoma, mantle cell lymphoma, T‐cell lymphoma, prognostic index
Correspondence: Osnat Bairey, MD, Davidoff Cancer Center Rabin Medical Center, Institute of Hematology, Beilinson Hospital Petah Tiqwa 49100, Israel

Optimizing Prostate Intensity-Modulated Radiation Therapy (IMRT): Do Stricter Constraints Produce Better Dosimetric Results?

Buckey CR, Swanson GP, Stathaki S, Papanikolaou N, Optimizing Prostate Intensity-Modulated Radiation Therapy (IMRT): Do Stricter Constraints Produce Better Dosimetric Results?. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 139-144

Review Article

Courtney R Buckey^1, Gregory P Swanson^2, Sotirios Stathakis¹ and Nikos Papanikolaou¹

Affiliations: ¹Departments of Radiology and Radiation Oncology and ²Departments of Radiation Oncology and Urology,
The University of Texas Health Science Center at San Antonio, TX, USA


ABSTRACT

Purpose
Intensity Modulated Radiation Therapy (IMRT) is considered by many to be the standard of care in the delivery of external beam radiotherapy treatments to the prostate. The purpose of this study is to determine if using criteria stricter than that used in the current randomized trials will provide dosimetric improvement.

Materials and Methods
Treatment plans were produced for ten patients utilizing the dose constraints recommended by the large randomized RTOG 0415 protocol and more restrictive restraints similar to those employed by a large cancer center.

Results
The restrictive plans show consistently lower doses to the rectal and bladder volumes of interest. They also show a significant reduction in dose to the penile bulb. PTV coverage was more homogeneous for the protocol based plans.

Conclusions
It is clear from our analysis that general constraints, while easily met, don’t result in the maximal benefits of Intensity Modulated Radiation Therapy in sparing the rectum. The trade off is with more homogeneity in the target volume. Further research is needed to identify the ideal balance between reducing toxicity and sacrificing tumor coverage.

Keywords: Prostate cancer, IMRT, Radiotherapy, Dose constraints, Normal tissue
Correspondence: Sotirios Stathakis, Cancer Therapy and Research Center at the University of Texas Health Science Center, MC 7889/Radiation Oncology, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Tel: (1)‐210‐450‐1010; e‐mail: stathakis@uthscsa.edu

Novel Strategies for Diagnosis of Glioblastoma Multiforme

Sonabend AM,Yun J,Canoll P,Bruce JN, Novel Strategies for Diagnosis of Glioblastoma Multiforme. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 125-134


Review Article

Adam M Sonabend, Jonathan Yun, Peter Canoll and Jeffrey N Bruce

Affiliation: Gabriele Bartoli Brain Tumor Research Laboratory, Department of Neurological Surgery, Neurological Institute, Columbia University Medical Center,
New York NY, USA


ABSTRACT

Glioblastoma multiforme (GBM) is the most common of all primary brain tumors and has the worst prognosis. Increased understanding of glioma biology and pathophysiology has translated into interesting advances in the diagnostic approach for patients bearing these tumors. This review explores the clinical, radiographic, and histological features of GBM that aid in its identification, with an emphasis on the application of emerging technologies. The use of novel imaging modalities including magnetic resonance imaging (MRI) spectroscopy, positron emission tomography, and perfusion MRI are discussed along with a review of tumor genetics and epigenetics from the perspective of their diagnostic and prognostic relevance.

Keywords: glioblastoma multiforme, glioma, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), genetics,diagnosis
Correspondence: Jeffrey N Bruce, MD, Neurological Institute, Room 434, 710 West 168th St., New York, NY 10032. Tel: 212-305-7346; Fax:212-305-2026; e-mail: jnb2@columbia.edu

Autologous Stem Cell Transplantation as First-Line Therapy in Peripheral T-Cell Lymphomas

Reimer P, Autologous Stem Cell Transplantation as First-Line Therapy in Peripheral T-Cell Lymphomas. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 117-124

Review Article

Peter Reimer

Affiliation: Klinik fu¨r Ha¨matologie, Internistische Onkologie und Stammzelltransplantation, Kliniken Essen Su¨d, Evangelisches Krankenhaus Essen-Werden gGmbH,
Essen, Germany


ABSTRACT

Peripheral T/NK‐cell lymphomas (PTCL) comprise a rare and heterogeneous group of malignancies that are characterized by an aggressive course. So far, no standard therapy has been defined. With the exception of anaplastic large cell lymphoma (ALCL) expressing the anaplastic lymphoma kinase (ALK), conventional (anthracycline‐based) polychemotherapy leads to dismal outcome, with sustaining complete remissions achievable in only a minority of patients. High‐dose therapy supported by autologous stem cell transplantation (HDT‐ASCT) is a well‐defined and widely used therapeutic approach in different hematological malignancies (e.g., relapsed aggressive B‐cell lymphomas, relapsed Hodgkin’s disease, multiple myeloma), and has also shown efficacy in relapsed PTCL. However, on account of the lack of randomized PTCL‐restricted studies, the impact of HDT‐ASCT as first‐line therapy in PTCL is unclear. Retrospective studies in this setting have shown good feasibility with a low therapy‐associated morbidity and mortality not exceeding toxicity in high‐dose studies on aggressive B‐cell lymphomas. To date, five larger prospective PTCL‐restricted trials have addressed this strategy, varying in terms of inclusion criteria, induction therapy, high‐dose protocols, etc. The outcome shows promising results with an overall survival of about 50% at 3 years. Patients achieving complete remission (CR) at transplantation seem to benefit most from this strategy. Therefore, induction therapy needs to be further improved to increase the transplantation rate. With the limited data available, upfront HDT‐ASCT seems a reasonable approach in eligible patients, especially in patients achieving CR after induction therapy. This approach should be urgently evaluated in randomized trials, as planned by the German High‐Grade Non‐Hodgkin Lymphoma Study Group.

Keywords: peripheral T-cell lymphoma, autologous stem cell transplantation, high-dose therapy
Correspondence: Peter Reimer, Klinik fu¨r Ha¨matologie, Internistische Onkologie und Stammzelltransplantation, Kliniken Essen Su¨d,
Evangelisches Krankenhaus Essen-Werden gGmbH, Pattbergstr. 1–3, D-45239 Essen, Germany. Tel: (49)-201–4089–2230; Fax: (49)-201–4089–2297; e-mail: p.reimer@kliniken-essen-sued.de

Prognostic Value of Minimal Residual Disease Monitoring in the Context of Allogeneic Stem Cell Transplantation in Childhood Acute Lymphoblastic Leukemia

Willasch A, Kreyenberg H, Klingebiel T, Bader P, Prognostic Value of Minimal Residual Disease Monitoring in the Context of Allogeneic Stem Cell Transplantation in Childhood Acute Lymphoblastic Leukemia. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 101-108

Review article

Andre Willasch, Hermann Kreyenberg, Thomas Klingebiel and Peter Bader

Affiliation: Goethe University Frankfurt, Department of Pediatric Hematology, Oncology and Hemostaseology, Frankfurt am Main, Germany


ABSTRACT

Relapse is still the principal cause of treatment failure after allogeneic stem cell transplantation (SCT) for high‐risk childhood acute lymphoblastic leukemia (ALL). Specific methods aimed at preventing relapse comprise the use of intensive treatment prior to transplant, optimal transplant preparative regimens, and post‐transplant interventions with targeted or immunological therapies. Diagnostic tools such as minimal residual disease (MRD) and chimerism monitoring peritransplant can identify patients facing the highest risk for relapse, and provide a basis for therapeutic intervention to prevent relapse. Patients with increasing mixed chimerism or MRD burden have been shown to benefit from pre‐emptive therapy. A variety of targeted immunological therapies are emerging, which could have an impact on relapse and improve the survival of children with ALL after transplantation.

Keywords: minimal residual disease (MRD), chimerism, peritransplant monitoring, acute leukemia, stem cell transplantation
Correspondence: Peter Bader and Andre Willasch, Goethe University Frankfurt, Hospital for Children and Adolescents III, Department of Pediatric Hematology, Oncology and Hemostaseology, Theodor‐Stern‐Kai 7, D‐60590 Frankfurt am Main, Germany. Tel: (49)‐69‐6301‐7542; Fax: (49)‐69‐6301‐4202; e‐mail: peter.bader@kgu.de, andre.willasch@kgu.de

Thrombocytopenia in Solid Tumors

Khasraw M, Faraj H, Sheikha A, Thrombocytopenia in Solid Tumors. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 89-92

Review Article

Mustafa Khasraw, Heewa Faraj and Anwar Sheikha

Affiliation: Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia


ABSTRACT

Thrombocytopenia in patients with solid malignancy can be caused by bone marrow involvement or toxicity from anticancer therapy; however, it could rarely be the first presentation of a tumor such as breast cancer or lymphoma. Hematological paraneoplastic syndromes such as paraneoplastic thrombocytopenia and/or immune thrombocytopenic purpura (ITP) are well described as secondary findings simultaneously with malignancies such as breast cancer and lymphoma. Other hematological conditions such as severe amegakaryocytic thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), and myelodysplastic syndromes (MDS) have also rarely been described as a possible paraneoplastic process complicating solid tumors. On the one hand, occult disseminated malignancy may mimic ITP and TTP, leading to diagnostic and therapeutic problems. On the other hand, thrombocytopenia could be the first manifestation of cancer.

Keywords: paraneoplastic immune thrombocytopenia, thrombotic thrombocytopenia, solid tumors
Correspondence: Mustafa Khasraw, Department of Medical Oncology, Royal North Shore Hospital, St Leonards, 2065 NSW Australia. Tel:(61)-2-9926-5020; Fax: (61)-2-9906-4150; e-mail: mkhasraw@med.usyd.edu.au

Treatment of Recurrent Platinum-Sensitive Epithelial Ovarian Cancer

Liu JF, Matulonis UA, Treatment of Recurrent Platinum-Sensitive Epithelial Ovarian Cancer. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 71-78

Review Article

Joyce F Liu and Ursula A Matulonis

Affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA


ABSTRACT

Ovarian cancer remains a leading cause of cancer death among women, with an estimated 125000 deaths worldwide. Newly diagnosed ovarian cancer is very responsive to first‐line platinum‐based therapy, but the majority of patients will have disease recurrence. Patients in whom disease recurs more than 6 months after completing prior platinum‐based treatment are considered to have platinum‐sensitive disease, and questions remain regarding the optimal management of their disease. Many options exist for these patients, including systemic chemotherapy, and in specific circumstances, secondary cytoreductive surgery or radioablative techniques can be considered for patients with localized recurrences and long disease‐free intervals. For patients receiving systemic chemotherapy, data from clinical trials suggest that combination platinum‐based chemotherapy should be considered in this setting for patients in whom the toxicities would be acceptable, although the optimal regimen remains unclear. Ongoing investigations seek to address the role of secondary cytoreductive surgery, the optimal therapy for recurrent platinum‐sensitive disease, the therapeutic potential of non‐platinum‐based therapies, and the role of biological therapy in this setting.

Keywords: ovarian cancer, recurrent disease, cytotoxic chemotherapy, secondary cytoreductive surgery, platinum sensitive
Correspondence: Joyce F Liu, Department of Medical Oncology, Dana‐Farber Cancer Institute, 44 Binney Street, Boston, MA 02115

Treating Locally Advanced, Recurrent or Metastatic Endometrial Cancer: A Focus on Ixabepilone

Kilfoyle K, Dizon DS, Treating Locally Advanced, Recurrent or Metastatic Endometrial Cancer: A Focus on Ixabepilone. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 65-70

Review Article

Kimberly Kilfoyle¹ and Don S Dizon²

Affiliations: ¹The University of Medicine and Dentistry of New Jersey, NJ, USA and ²The Program in Women’s Oncology, Women & Infants’ Hospital/The Warren
Alpert Medical School of Brown University, Providence, RI, USA


ABSTRACT

Endometrial cancer is a common malignancy affecting women. The majority of patients are diagnosed with endometrial cancer early and treated curatively with surgery and adjuvant therapy. The platinums, taxanes, and anthracyclines are the most active agents in endometrial cancer and therefore form the basis of first‐line chemotherapy regimens. Challenges arise in the context of women who suffer from disease that is refractory to first‐line chemotherapy or recurrent after receiving treatment. Second‐line therapies are currently being investigated. The most effective to date is paclitaxel; however, the response is temporary, patients ultimately progress, and survival is poor. Other therapies have failed to show improved response or survival compared with paclitaxel in the second‐line setting. Because paclitaxel is part of first‐line therapy, there are many patients who are paclitaxel resistant but require second‐line therapy. Ixabepilone is a novel semi‐synthetic member of the epothilones that acts as a microtubule‐stabilizing drug similar to paclitaxel. However, ixabepilone has shown activity in cell lines that are paclitaxel resistant, and has shown activity in clinical trials against a variety of malignancies. Current investigations into ixabepilone for endometrial cancer are ongoing and will further define ixabepilone’s role in treatment for endometrial cancer.

Keywords: endometrial cancer, chemotherapy, biologic therapy, clinical trials
Correspondence: Don S Dizon, Program in Women’s Oncology, Women & Infants’ Hospital, 101 Dudley Street, Providence, RI 02905, USA

Adjuvant Cisplatin-Based Chemotherapy for Elderly Patients with Completely Resected Non-Small Cell Lung Cancer: Review of Current Evidence

Fruh M, Shepherd FA, Adjuvant Cisplatin-Based Chemotherapy for Elderly Patients with Completely Resected Non-Small Cell Lung Cancer: Review of Current Evidence. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 59-64

Review Article

Martin Fruh¹ and Frances A Shepherd²

Affiliations: ¹Department of Medical Oncology, Kantonsspital St Gallen, St Gallen, Switzerland and ²Department of Medical Oncology, Princess Margaret Hospital,Toronto, ON, Canada


ABSTRACT

Based on results from randomized phase III studies adjuvant cisplatin‐based chemotherapy represents the current standard of care in patients with resected stage IB‐III non‐small cell lung cancer. A pooled analysis of the five largest cisplatin‐based adjuvant chemotherapy trials conducted after 1995 showed an absolute overall survival benefit of 5.4% at five years. Even though almost 50 % of non‐small cell lung cancers occur in patients older than 70, this group of patients were under‐represented in these studies with less than 10 % falling into this category. We herein review the studies which investigated this subgroup of patients.

Keywords: non‐small cell lung cancer (NSCLC), elderly, adjuvant, chemotherapy
Correspondence: Martin Früh, Department of Medical Oncology, Kantonsspital St Gallen, 9007 St Gallen, Switzerland. Tel: (41)‐71‐494‐11‐11; Fax: (41)‐71‐494‐63‐25; e‐mail: martin.frueh@kssg.ch

Lung Cancer Incidence in Never Smokers

Clement-Duchene C, Wakelee H, Lung Cancer Incidence in Never Smokers. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 49-58

Review Article

Christelle Clement-Duchene¹ and Heather Wakelee¹

Affiliation: ¹Department of Medicine, Division of Oncology, Stanford University, Stanford Cancer Center, Stanford, CA, USA


ABSTRACT

Although lung cancer is predominantly caused by tobacco consumption, lung cancer among never smokers is an important health problem that is rapidly gaining recognition. The main causes of lung cancer in never smokers are still unknown, but second hand smoke exposure, radon exposure, occupational or environmental exposures, and viruses have been implicated. Lung cancer in never smokers has specific epidemiological and clinical characteristics; specifically, the disease occurs more frequently in women, particularly of Asian descent, and the main histology is adenocarcinoma. Specific molecular characteristics of the disease, compared with lung cancer in smokers, have also been identified including mutations in epidermal growth factor receptor (EGFR), EML4‐ALK, K‐ras, p53, and certain chromosomal abnormalities. Never smokers with lung cancer also have a better response to many treatments and a better survival than smokers. All these characteristics suggest that lung cancer in never smokers is distinct from lung cancer in smokers. This article will review the epidemiological and molecular findings, and the possible risk factors for lung cancer in never smokers.

Keywords: lung cancer, never smokers, epidermal growth factor receptor (EGFR) mutations, adenocarcinoma, second hand smoke exposure
Correspondence: Heather Wakelee, Department of Medicine, Division of Oncology, Stanford Cancer Center, 875 Blake Wilbur Drive,Stanford, CA 94305-5826, USA. Tel: (1)-650-736-7221; Fax: (1)-650-724-3697; e-mail: hwakelee@stanford.edu

Analysis of Adjuvant Chemotherapy in Non-Small Cell Lung Cancer

Cuffe S, Leighl NB, Analysis of Adjuvant Chemotherapy in Non-Small Cell Lung Cancer. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 37-48

Review Article

Sinead Cuffe and Natasha B Leighl

Affiliation: Department of Medical Oncology and Hematology of the University Health Network, Princess Margaret Hospital and the University of Toronto,
Toronto, Ontario, Canada


ABSTRACT

Lung cancer is the leading cause of cancer‐related mortality in the developed world. The majority of patients with non‐small cell lung cancer (NSCLC) present with advanced disease. Even in the one‐third of patients presenting with early‐stage disease, there is a high rate of relapse despite complete surgical resection. As most patients recur with distant metastases, it is hypothesized that micrometastases may be present at the time of surgery, suggesting a potential role for adjuvant chemotherapy. Postoperative cisplatin‐based chemotherapy has been established as the standard of care in resected stage II–III NSCLC, improving 5‐year survival by 8–15%. This review explores the evolution of adjuvant chemotherapy trials since the 1970s, charts what progress has been made to date, and analyzes the evidence leading to current standards of care. We also review some of the retrospective studies evaluating potential biomarkers in NSCLC and evaluate whether these may contribute to the heterogeneity of the chemotherapy response and assist in tailoring treatment. In addition, we review current studies of targeted therapy in the adjuvant setting and offer potential future directions for research.

Keywords: Adjuvant chemotherapy, lung cancer, non‐small cell lung cancer, cisplatin, molecular markers
Correspondence: Natasha Leighl, Department of Medical Oncology and Hematology, Princess Margaret Hospital, 6‐105, 610 University Avenue, Toronto, Ontario, Canada, M5G 2M9. Tel: (1)‐416‐946‐4645; Fax: (1)‐416‐946‐6546; e‐mail: Natasha.Leighl@uhn.on.ca

Secondary Causes of Low Bone Mineral Density in Breast Cancer Patients: An Update

Kang YC, Miller JA, Mann GB, Secondary Causes of Low Bone Mineral Density in Breast Cancer Patients: An Update. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 31-36

Review Article

Y Chiu Kang^1, Julie A Miller^1,2 and G Bruce Mann^1,2,3

Affiliations: ¹The University of Melbourne, Melbourne, Australia; ²The Royal Melbourne Hospital, Melbourne, Australia and ³The Royal Women’s Hospital,Parkville, Australia


ABSTRACT

Bone health has become increasingly important in the management of early breast cancer. The reasons for this include the general recognition of post‐menopausal osteoporosis as an important health issue, the long survival of most women diagnosed with breast cancer, and the impact of treatments, especially the aromatase inhibitors, on bone density. Algorithms and guidelines for managing these issues have mainly focused on detecting low bone mineral density and treating it. New evidence has emerged suggesting that secondary causes of low bone mineral density are common and a significant problem for breast cancer survivors. This article reviews recent studies and suggests ways of incorporating these new data into practice.

Keywords: breast cancer, bone mineral density, aromatase inhibitor, vitamin D, hyperparathyroidism
Correspondence: G Bruce Mann, Suite 12, The Royal Women’s Hospital, Parkville, Victoria, 3052, Australia. Tel: (61)‐3‐93476301; Fax: (61)‐3‐93478799; e‐mail: bruce.mann@mh.org.au

The Prevalence of Lymphedema and Changes in Practice to Reduce its Occurrence in Women with Breast Cancer

McLaughlin SA, Van Zee KJ, The Prevalence of Lymphedema and Changes in Practice to Reduce its Occurrence in Women with Breast Cancer. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 23-30

Review Article

Sarah A McLaughlin and Kimberly J Van Zee

Affiliation: Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, Evelyn H Lauder Breast Center, New York, NY, USA


ABSTRACT

Lymphedema is a chronic debilitating condition affecting many long‐term breast cancer survivors. The incidence of lymphedema is reported to range from 6% to 70% after axillary surgery for breast cancer; however, its true incidence has been difficult to quantify because of the lack of standard diagnostic and universal assessment criteria. Extent of nodal dissection, axillary radiation, injury, and infection in the ipsilateral upper extremity remain significant risk factors for the development of lymphedema. Current changes in axillary management, including the adoption of sentinel node biopsy, the selective omission of completion axillary dissection after a positive sentinel node, and the elimination of axillary staging, have been proposed to further reduce axillary morbidity. Early research on lymphedema risk reduction focuses on supervised weight training after axillary surgery, axillary reverse mapping to avoid removal of lymph nodes draining the upper extremity, and incorporation of fused single photon emission computed tomography (SPECT)‐CT axillary nodal images to better plan adjuvant radiation treatments.

Keywords: lymphedema, axillary dissection, sentinel node biopsy, breast cancer, survivorship, patient perceptions
Correspondence: Kimberly J Van Zee, Breast Service, Department of Surgery, Memorial Sloan‐Kettering Cancer Center, and Weill Medical College of Cornell University, Evelyn H Lauder Breast Center, 300 E. 66th St., New York, NY, 10065, USA. Tel: (1)‐646‐888‐5362; Fax: (1)‐646‐888‐4920; e‐mail: vanzeek@mskcc.org

Genes Discriminating between Breast Cancers Responsive or Resistant to the Aromatase Inhibitor, Letrozole

Miller MR, Krause A, Larionov A, Evans DB, Anderson TJ, Dixon JM, Genes Discriminating between Breast Cancers Responsive or Resistant to the Aromatase Inhibitor, Letrozole. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 17-22

Review Article


William R Miller^1*, Andreas Krause^2, Alexey Larionov^1**, Dean B Evans^3, Thomas J Anderson¹ and J Michael Dixon^1**

Affiliations: ¹Breast Research Group, University of Edinburgh, Western General Hospital, Edinburgh, UK; ²Actelion Pharmaceuticals Ltd., Clinical Pharmacology,
Allschwil BL, Switzerland; ³Novartis Institutes for BioMedical Research, Oncology Research, Basel, Switzerland
Present addresses: ^*2 Stoneycroft Road, South Queensferry EH30 9HX, UK; ^**Edinburgh Breakthrough Research Unit, Western General Hospital, Edinburgh EH4
2XU, UK


ABSTRACT

RNA expression profiles from breast cancer biopsies taken before and after 10–14 days of neoadjuvant treatment with the aromatase inhibitor, letrozole, together with change in expression between the time points were compared in tumors classified as clinically responsive or resistant to treatment. Statistical analysis for microarrays identified 31 expression variables (six pretreatment, four on‐treatment, and 21 change parameters) that were significantly different (P<0.001) between 37 responsive tumors and 15 resistant cases. Notably, 18 of 21 change variables coded for ribosomal proteins. Gene ontology terms corresponding to the 31total variables were highly statistically enriched for “translation” and “structural components of ribosomes”. These data highlight the importance of changes in the expression of ribosomal proteins as early markers distinguishing between breast cancers clinically responsive and resistant to neoadjuvant letrozole.

Keywords: breast cancer, aromatase inhibitors, gene expression, letrozole
Correspondence: Professor W.R. Miller, 2 Stoneycroft Road, South Queensferry, EH30 9HX, UK. Tel: +44(0) 131 331 4609; Fax: +44(0) 131 331 5736; e-mail: w.r.miller@ed.ac.uk

Breast Intensity‐Modulated Radiation Therapy to Reduce Radiation Dermatitis

Pignol JP, Olivotto I, Breast Intensity-Modulated Radiation Therapy to Reduce Radiation Dermatitis. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 93-100


Review Article


Jean-Philippe Pignol¹ and Ivo Olivotto²

Affiliations: ¹Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada and ²British Columbia Cancer Agency-Vancouver Island Centre, Vancouver, BC, Canada


ABSTRACT

The majority of early‐stage breast cancers are treated with breast‐conserving surgery followed by adjuvant radiation treatment on the whole breast. Acute dermatitis is a frequent side‐effect of adjuvant breast radiotherapy, and this treatment can also impair the long‐term cosmetic result. Breast intensity‐modulated radiation therapy (IMRT) is a technique that improves the radiation dose distribution in the breast, allowing the avoidance of “hotspots”. To review current evidence that breast IMRT provides a patient benefit, a MedLine search was done to identify articles reporting on this technique. A total of 63 manuscripts reporting on breast IMRT were identified. Fifty‐six articles present original research data; the majority (80%) reported on physics or dosimetry, a smaller number on clinical outcomes (15%), and on health sciences or radiobiology (5%). Eight articles reported clinical outcomes, with six being single‐institution retrospective or prospective cohort from three centers in the USA, and two reporting prospective randomized controlled trials were from the UK and Canada. Combining all these data, the clinical outcomes of nearly 780 patients receiving breast IMRT have been reported and compared with 767 patients receiving standard wedged radiotherapy. There is level 1 evidence that breast IMRT reduces acute dermatitis from a Canadian, multicenter, randomized, double‐blinded, clinical trial, and there is level 1 evidence that breast IMRT improves the long‐term cosmetic results from a UK randomized clinical trial.

Keywords: breast cancer, adjuvant radiotherapy, intensity‐modulated radiation therapy (IMRT), radiation dermatitis, randomized clinical trials
Correspondence: Jean‐Philippe Pignol, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto ON, Canada M4N3M5. Tel: (1)‐416‐480‐5329; Fax: (1)‐416‐480‐6002; e‐mail: jean‐philippe.pignol@sunnybrook.ca

Importance of a Dental Approach in Head and Neck Cancer Therapy

Cankaya Hulya, Guneri P.  Importance of a Dental Approach in Head and Neck Cancer Therapy.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  107-114

Review Article

Importance of a Dental Approach in Head and Neck Cancer Therapy

Hulya Cankaya and Pelin Guneri

Affiliation: Ege University School of Dentistry, Department of Oral Diagnosis and Radiology, Bornova, Izmir, Turkey


ABSTRACT

Squamous cell carcinoma is the most common form of head and neck cancer, which is usually diagnosed at an advanced stage. These patients receive surgery, radiotherapy, and chemotherapy to improve their survival rates; however, these therapy protocols have significant side‐effects, which cause considerable morbidity that can affect the patients’ quality of life and even interfere with the patients’ therapy compliance. Inclusion of dental healthcare providers in the multidisciplinary team not only helps to prevent or decrease the severity of side‐effects of cancer therapy, but also influences its prognosis.

Keywords: Chemotherapy, radiotherapy, mucositis, radiation, xerostomia, saliva, osteoradionecrosis
Correspondence: Pelin Güneri, Ege University School of Dentistry, Department of Oral Diagnosis and Radiology, Bornova 35100, İzmir, Turkey. Tel: (90)‐232‐3881081; Fax: (90)‐232‐3880325; e‐mail: peleen_2000@yahoo.com

Recent Advances in Chemotherapy for Advanced Gastric Cancer

Kang YK, Yoon DH, Ryoo BY, Ryu MH.  Recent Advances in Chemotherapy for Advanced Gastric Cancer.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  67-74

Review Article

Recent Advances in Chemotherapy for Advanced Gastric Cancer

Yoon-Koo Kang, Dok Hyun Yoon, Baek-Yeol Ryoo and Min-Hee Ryu

Affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Submission date: 1 September 2009, Revision date: 15 September 2009, Acceptance date: 25 September 2009


ABSTRACT

Several important issues in the treatment of advanced gastric cancer remain controversial. These include the surgical extent of lymph node dissection, the method of administering adjuvant treatment to patients with resectable disease, and the optimal first‐line chemotherapy for unresectable disease. Doublet treatment with fluoropyrimidine plus platinum is the mainstream approach in Asia and the United States, whereas triplet therapy employing a combination of anthracycline, fluoropyrimidine, and platinum is popular in Europe. New agents, including capecitabine, S‐1, and oxaliplatin, are as efficacious as the prototype agents, but have more favorable toxicity profiles. The introduction of trastuzumab began the era of targeted therapy for advanced gastric cancer, and trials incorporating bevacizumab, cetuximab, panitumumab, and lapatinib are ongoing. Positive results from the INT‐0116, MAGIC, and ACTS‐GC trials, using adjuvant treatment, support the value of postoperative chemoradiation, perioperative and postoperative chemotherapy respectively. Various adjuvant treatments are used according to the regional standard of care, differing in terms of the extent of lymph node dissection. The positive results of the AMC 0101 trial highlight the utility of early adjuvant or intraperitoneal chemotherapy as effective adjuvant treatments. Diverse strategies to improve the efficacy of adjuvant therapy are currently under development.

Keywords: gastric cancer, chemotherapy, oxaliplatin
Correspondence: Yoon‐Koo Kang, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon‐gil, Songpa‐gu, Seoul 138‐736, Korea. Tel: (82)‐2‐3010‐3230; Fax: (82)‐2‐3010‐6961; e‐mail: ykkang@amc.seoul.kr

Risk of Venous Thromboembolism in Patients receiving Systemic Therapy for Early Breast Cancer

Hoy J, Davis A.  Risk of Venous Thromboembolism in Patients receiving Systemic Therapy for Early Breast Cancer.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  49-56

Review Article

Risk of Venous Thromboembolism in Patients receiving Systemic Therapy for Early Breast Cancer

Julia Hoy¹ and Alison Davis^1,2

Affiliations: ¹The Australian National University Medical School, Acton, Australia and ²Medical Oncology Unit, The Canberra Hospital, Woden, Australia


ABSTRACT

The association between malignancy and the development of venous thromboembolism (VTE) is well recognized. The incidence of VTE in early breast cancer (EBC) is lower than in metastatic disease and a number of other common malignancies, but still presents a significant problem in terms of morbidity and mortality. The risk of VTE is further increased in patients receiving adjuvant chemotherapy for EBC, with the reported incidence ranging from 1.5% to 16.6%. It is unknown which chemotherapeutic agents or regimens are associated with the highest risk. Hormonal therapy also increases risk, most notably tamoxifen, but also, to a lesser extent, the aromatase inhibitors. Molecular targeting agents such as trastuzumab and bevacizumab are entering routine clinical practice for breast cancer and, although trastuzumab has not been shown to increase VTE, bevacizumab has been linked to the development of both venous and arterial thrombosis. At present, the use of thromboprophylaxis is not recommended for ambulatory patients being treated for EBC. However, risk analysis tools are emerging that may play some role in identifying high‐risk patients who would benefit from prophylactic anticoagulation in the future. More prospective research is required to establish the risk of VTE with different chemotherapy regimens as well as newer targeted therapies. For now, clinical vigilance is required to ensure early VTE detection and optimal management to reduce morbidity and mortality.

Keywords: early breast cancer, systemic therapy, venous thromboembolism, chemotherapy
Correspondence: Alison Davis, Medical Oncology Unit, The Canberra Hospital, Woden, ACT 2606, Australia. Tel: (+61-2)6244-2220; Fax:
(+61-2)6244-4266; e-mail: alison.davis@act.gov.au

Low Incidence of Venous Thromboembolism in Asian Myeloma Patients Treated with Thalidomide plus Dexamethasone

Shyu VB, Wang P-N, Chu P-H.  Low Incidence of Venous thromboembolism in asian Myeloma Patient Treated with Thalidomide plus Dexamethasone.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  41-47

Review Article

Low Incidence of Venous Thromboembolism in Asian Myeloma Patients Treated with Thalidomide plus Dexamethasone

Victor Bong-hang Shyu¹, Po-Nan Wang² and Pao-Hsien Chu, F.C.C.P., F.A.C.C, F.E.S.C.¹

Affiliations: ¹Division of Cardiology and ²Division of Hematology/Oncology, Department of Internal Medicine,
Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan


ABSTRACT

Multiple myeloma is associated with an increase in risk for venous thromboembolic (VTE) events. Treatment with immunomodulatory agents and their combinations in chemotherapy increases the risk for VTE. Specifically, the combination of thalidomide and dexamethasone seems to present the highest risk for VTE. This phenomenon has been examined extensively through various trials conducted in North American and Europe, with suggestions of prophylactic anticoagulation in various forms after evaluation of patient risk factors. However, as the literature has suggested that Asians are at less risk for VTE in general compared with white or black ethnic groups, Asian patients should be further evaluated before initiation of prophylactic anticoagulation. With the literature from several Asian nations suggesting a lower incidence of VTE with thalidomide monotherapy or combination therapy with dexamethasone in myeloma, this review intends to examine the existing literature for such observations, and provide information on risk factors, prophylaxis, and therapy if indicated. More research is needed to evaluate the risk deduction of Asian ethnicity and the specific risk factors that accompany this ethnic group.

Keywords: Asia, multiple myeloma, venous thromboembolic event, thalidomide with dexamethasone therapy
Correspondence: Pao‐Hsien Chu, The First Cardiovascular Division, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, 199 Tun‐Hwa North Road, Taipei 105, Taiwan. Tel: (886)‐3‐328‐1200, ext 8162; Fax: (886)‐3‐327‐1192; e‐mail: pchu@adm.cgmh.org.tw

Targeted Therapies for the Systemic Treatment of Advanced Hepatocellular Carcinoma

Chionh F, Azad A, Cebon J.  Targeted Therapies for the Systemic Treatment of Advanced Hepatocellular Carcinoma. Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  81-94

Review Article

Targeted Therapies for the Systemic Treatment of Advanced Hepatocellular Carcinoma

F Chionh  ¹, A Azad  1 and J Cebon  ²
Affiliations: Department of Medical Oncology and ¹ Ludwig Institute for Cancer Research ² , Austin Health, Melbourne, Victoria, Australia


ABSTRACT

Advanced hepatocellular carcinoma is the third most common cause of cancer‐related mortality worldwide. Systemic therapy has historically had limited efficacy; however, targeted therapies offer promise in improving patient outcomes. Recently, two pivotal phase III randomized double‐blind trials of the oral multi‐tyrosine kinase inhibitor sorafenib compared with placebo demonstrated a survival benefit in advanced hepatocellular carcinoma. Other targeted agents have also shown promising results in early‐phase trials. This review examines the current knowledge about targeted therapies in advanced hepatocellular carcinoma and addresses some of the key issues for future research in this disease.

Keywords: hepatocellular carcinoma, targeted therapies, sorafenib, angiogenesis, growth factor, growth factor receptor, signal transduction pathways
Correspondence: Fiona Chionh, Medical Oncology Unit, Ludwig Institute for Cancer Research, Level 6, Harold Stokes Building, Austin Hospital, 145–163 Studley Rd, Heidelberg, Victoria, Australia, 3084. Tel: (61)‐3‐9496‐5000, Fax: (61)‐3‐9457‐6698; e‐mail: fionac49@yahoo.com.au

The Laboratory Assessment of KRAS Mutation Status in Colorectal Cancer

Karapetis CS, Snell LE.  The Laboratory Assessment of KRAS Mutation Status in Colorectal Cancer.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  75-79

Christos S Karapetis and Lesley E Snell

Affiliations: Department of Medical Oncology, Flinders Medical Centre


ABSTRACT

Monoclonal antibodies that bind to the epidermal growth factor receptor (EGFR), particularly cetuximab and panitumumab, can improve overall survival and prolong progression‐free survival in patients with advanced colorectal cancer. However, approximately 40% of patients will have tumours that have KRAS mutations, and these patients do not obtain benefit from such therapy. Such patients can be excluded from receiving a treatment that may otherwise cause toxicity. The majority of mutations occur in exon 2, at the first and second nucleotide positions of codons 12 and 13 of the gene. Commercial KRAS test kits target all or the most common of these mutations. Formalin‐fixed, paraffin‐embedded tissue is usually supplied to the molecular biology laboratory for DNA extraction and subsequent examination by the polymerase chain reaction (PCR). An accurate, reliable, rapid, and cost‐effective method to determine the KRAS mutation status of tumors is of crucial importance as clinicians start to apply this information in optimal treatment selection. Laboratory standardization and quality control initiatives are required processes in the adoption of new KRAS detection procedures. At the present time, there is no universally accepted gold standard technique for KRAS mutation evaluation. Several KRAS mutation detection methodologies, including PCR‐single strand conformational polymorphism (SSCP), high‐resolution melting (HRM), Sanger sequencing, pyrosequencing, the DxS kit, and the TIB MolBiol kits, have been compared and show a high degree of concordance. There are advantages and disadvantages to each platform. This review article will examine the clinical importance of KRAS mutations in advanced colorectal cancer, and outline the various KRAS mutation detection methods.

Keywords: colorectal carcinoma, KRAS mutation, cetuximab, panitumumab, polymerase chain reaction (PCR)
Correspondence: Chris Karapetis, Department of Medical Oncology, Flinders Medical Centre, Adelaide, SA 5042, Australia. Tel: (61)‐882048997; Fax: (61)‐882044997; e‐mail: c.karapetis@flinders.edu.au

Lenalidomide in Patients with Multiple Myeloma who have received One Prior Therapy

Hartley M, Baz R.  Lenalidomide in Patients with Multiple Myeloma who have Received One Prior Therapy.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  23-28

Review Article

Lenalidomide in Patients with Multiple Myeloma who have received One Prior Therapy

Monique Hartley ^{1 2} and Rachid Baz ²
Affiliations: ¹ Department of Internal Medicine, University of South Florida and ² Department of Malignant Hematology, H Lee Moffitt Cancer Center and Research Institute


ABSTRACT

Lenalidomide, an IMiD® immunomodulatory drug, has been shown to enhance NK and T‐cell function as well as to result in direct tumoricidal effects on multiple myeloma (MM) cell lines. Lenalidomide is more potent yet has differential toxicities than the parent compound thalidomide. Two pivotal studies by Weber, et al, and Dimopoulos, et al, have demonstrated clinically significant long‐term benefits in patients with relapsed/refractory MM, including overall response rate, progression‐free survival, and survival of the combination of lenalidomide and dexamethasone compared with dexamethasone alone. In addition, lenalidomide has been extensively evaluated in combination with other agents and in the newly diagnosed setting for MM with demonstrable activity. In this paper, we review the preclinical and clinical data underlying its use in patients with MM.

Keywords: multiple myeloma, novel therapies, lenalidomide
Correspondence: Rachid Baz, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, FOB‐3, Tampa, FL 33646, USA. Tel: (1)‐813‐745‐8212; Fax: (1)‐813‐745‐3071; e‐mail: Rachid.baz@moffitt.org

Intensity‐Modulated Radiation Therapy with or without Chemotherapy for Nasopharyngeal Carcinoma: A Clinical Review

Approaching Locally Advanced, Metastatic, or Recurrent Endometrial Cancer: Exploring Ixabepilone as a Therapeutic Option

Response to Bortezomib in Refractory/Relapsed Multiple Myeloma Patients: A Single Center Experience with Discussion on Specific Issues

Kyrtsonis M-C, Maltezas D, Koulieris E, Zaroulis C, Tzenou T, Sachanas S, Bartzis V, Georgiou G, M Dimou, Siakavellas S, TP Vassilakopoulos, Angelopoulou MK, Koutra E, Mouzaki A, Pangalis GA, Panayiotidis P.  Response to Bortezomib in Refractory/Relapsed Multiple Myeloma Patients:  A Single Center Experience with Discussion on specific Issues.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  29-39

Review Article

Response to Bortezomib in Refractory/Relapsed Multiple Myeloma Patients: A Single Center Experience with Discussion on Specific Issues

M-C Kyrtsonis^1,2, D Maltezas¹, E Koulieris^1,2, C Zaroulis3, T Tzenou^1,2, S Sachanas², V Bartzis^1,2, G Georgiou², M Dimou², S Siakavellas¹, TP Vassilakopoulos², MK Angelopoulou², E Koutra³, A Mouzaki4, GA Pangalis² and P Panayiotidis²

Affiliations: ¹First Department of Propedeutic Internal Medicine, ²Department of Hematology, National and Kapodistrian University of Athens, Laikon Hospital, Athens, Greece; ³Neurology Department, Evangelismos Hospital, Athens, Greece and ⁴Division of Hematology, Medical School, University of Patras, Patras, Greece


ABSTRACT

Prognostic factors of response to bortezomib, event‐free (EFS) and overall survival (OS), and patients' course, were evaluated in a series of relapsed/refractory multiple myeloma (MM) patients with long follow‐up. Eighty relapsed and five refractory patients were treated with bortezomib at standard doses and schedule, while intermediate‐dose dexamethasone was added if at least MR was not observed. The median time from diagnosis to bortezomib administration was 25.3 months. Seventy‐one patients responded (including 42% complete remission (CR) and near CR (nCR)). Median time to response was 1.4 months. The 1‐year EFS was 34% and the 2‐year OS was 61%. Median survival after bortezomib was 26.4 months. In multivariate analysis, elevated lactate dehydrogenase (LDH) and anemia were independent factors for EFS, and increased LDH, thrombocytopenia, and performance status (PS) for OS (P = 0.0001, 0.0006, and 0.043 respectively). The depth of response affected both EFS and OS. Patients' 1‐year EFS and 2‐year OS was 11 months and not reached for CR/nCR, respectively, vs 9.5 and 27 months for partial remission (PR), vs 3.5 and 18 months for minimal response (MR)/progressive disease (PD) (P = 0.0006 and 0.002 respectively). The main side‐effect was peripheral neuropathy that was mainly of axonal type and affected sensory nerves of distal extremities, had peak manifestations after three or four cycles, and usually regressed after 3 months. In conclusion, bortezomib produced impressive response rates in this observational study. The depth of response influenced both EFS and OS, the main other prognostic factors were LDH, PS, and thrombocytopenia, while the significance of staging and serum‐free light chains was overcome.

Keywords: multiple myeloma, bortezomib treatment, observational study, quality of response, survival, neurotoxicity
Correspondence: Marie‐Christine Kyrtsonis, First Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens School of Medicine, Laikon University Hospital, Agiou Thoma 17, Athens 11727, Greece

Predictive Value of D‐Dimer Test, Persistent Residual Venous Thrombosis, and Thrombophilia for Venous Thromboembolism Recurrence

Spieza L, Prandoni P.  Predictive Value of D-Dimer Test, Persistent Residual Venous Thrombosis, and Thrombophilia for Venous Thromboembolism Recurrence.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  57-62

Review Article

Predictive Value of D‐Dimer Test, Persistent Residual Venous Thrombosis, and Thrombophilia for Venous Thromboembolism Recurrence

Luca Spiezia and Paolo Prandoni

Affiliation: Department of Cardiothoracic and Vascular Sciences, 2nd Chair of Internal Medicine, University of Padua Medical School, Padua, Italy


ABSTRACT

The optimal duration of anticoagulation aimed at preventing recurrence of venous thromboembolism (VTE) in patients presenting with deep venous thrombosis (DVT) of the lower extremities is unknown. In recent years, a number of studies have been conducted in an attempt to identify predictors of recurrent VTE in order to tailor the duration of oral anticoagulant therapy (OAT). Several baseline characteristics of the index event (type of presentation, location of VTE, age, gender, inherited thrombophilia, cancer, antiphospholipid syndrome, etc.) have been extensively evaluated as predictive of recurrence. More recently, post‐basal conditions have been considered as possible risk factors for recurrent VTE. In particular, the positivity of D‐dimer after OAT withdrawal and the persistence of thrombus burden, as shown by repeated ultrasonography over time, have been found to be predictors of recurrent VTE in patients with DVT. In carriers of thrombophilia, who develop an episode of proximal DVT, the thrombus mass persists for a longer time than in non‐carriers. This finding supports the view that persistent residual thrombosis is to be regarded as a possible marker of hypercoagulability. Further studies are needed to clarify the pathophysiology of this feature and to evaluate its clinical implications.

Keywords: residual vein thrombosis, thrombophilia, venous thromboembolism, deep vein thrombosis, recurrence, risk factor, D dimer
Correspondence: Luca Spiezia, Department of Cardiothoracic and Vascular Sciences, Clinica Medica II of the University of Padua, Via Giustiniani 2, 35128 Padua, Italy. Tel: (39)‐049‐8212653; Fax: (39)‐049‐8218731; e‐mail: luca.spiezia@unipd.it

Immunoglobulin Heavy Chain Variable Region Mutational Status: Principle and Applications of a Clinically Available Assay

Czuchlewski DR, Gale JM, Vasef MA.  Immunoglobulin Heavy Chain Variable Region Mutational Status:  Principle and Applications of a Clinically Available Assay.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  63-66

Review Article

Immunoglobulin Heavy Chain Variable Region Mutational Status: Principle and Applications of a Clinically Available Assay

R. David Czuchlewski ^{1 2}, M. James Gale 2 and A. Mohammad Vasef ^{1 2}
Affiliations: ¹Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA and ²TriCore Reference Laboratories, Albuquerque, New Mexico, USA

ABSTRACT

The presence or absence of somatic hypermutation in the immunoglobulin heavy chain gene variable region (IGHV) holds prognostic significance in cases of chronic lymphocytic leukemia (CLL). As somatic hypermutation, by its nature, affects nucleotides in this region at random, molecular testing to determine mutational status has been limited to direct sequencing of the entire region, followed by comparison with the known germline sequence – a procedure well‐suited to the research laboratory but, until recently, unavailable for clinical purposes. As molecular genetic technology has advanced, a number of laboratories, including large commercial reference laboratories, have begun to offer clinical assays to determine IGHV mutational status directly. Herein, we describe the technical aspects of this test and present a strategy for integrating IGHV mutation status with other prognostic data in CLL.

Keywords: chronic lymphocytic leukemia, immunoglobulin heavy chain, somatic hypermutation, DNA sequencing, CD38, ZAP‐70, molecular testing, clinical decision making
Correspondence: David R. Czuchlewski , MD, University of New Mexico, Department of Pathology, TriCore Reference Laboratories, 1001 Woodward Place NE, Albuquerque, NM 87102, USA

Autoimmune Thrombocytopenic Purpura in Acute Hepatitis A-A Report and Review of Literature

Jose W, Kumar K, Unnikrishnan A, Palaniappan M, Narir A, Pavithran K.  Autoimmune Thrombocytopenic Purpura in Acute Hepatitis A - A Report and Review of Literature.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  137-139

Review Article

Autoimmune Thrombocytopenic Purpura in Acute Hepatitis A—A Report and Review of Literature

Wesley Jose, Kishore Kumar, Athira Unnikrishnan, M Palaniappan, Anoop Nair and K Pavithran
Affiliation: Department of Medical Oncology and Hematology, Cancer Institute, Amrita Institute of Medical Sciences, Kochi 682041, Kerala, India

ABSTRACT

Hepatitis A is a common endemic infection in a country such as India where a large majority of population is unimmunized and is exposed to unhygienic food, water, and living conditions. Most of these patients develop a classic form of hepatitis A with jaundice, abdominal pain, fever, and diarrhea. However, a few patients develop rare extrahepatic and hematological complications. A case of autoimmune thrombocytopenic purpura with acute hepatitis A is presented here.

Keywords: hepatitis A, autoimmune thrombocytopenic purpura, corticosteroid
Correspondence: Dr.Wesley M Jose , MD, Department of Medical Oncology, Cancer Institute, Amrita Institute of Medical Sciences, Ponekkara P.O. – 41, Kochi, Kerala, India. e‐mail: wesleymjose@aims.amrita.edu

Coagulation Disorders in Women with Idiopathic Menorrhagia

Karimi M, Afrasiabi A, Amoeri S, Zolghadri J, Nairabadai S, Bordbar M, Peyundi F.  Coagulation Disorders in Women with Idiopathic Menorrhagia.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  19-22

ORIGINAL ARTICLE

Coagulation Disorders in Women with Idiopathic Menorrhagia

Mehran Karimi ¹, Abdolreza Afrasiabi ¹, Sedighe Amoei ², Jale Zolghadri ², Shiva Nasirabadi ¹, Mohammadreza Bordbar ¹ and Flora Peyvndi ³

Affiliations: ¹Hematology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran; ²Gynecology and Obstetric Department, Shiraz University of Medical Sciences, Shiraz, Iran and ³Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, University of Milan, and Luigi Villa Foundation, Milan, Italy


ABSTRACT

Hemostasis of the endometrium is directly related to platelet and fibrin function. Deficiencies in either of these components result in menorrhagia in women with coagulation disorders. We studied coagulation parameters in women with idiopathic menorrhagia in southern Iran to determine the relationship between menorrhagia and coagulation disorders. The study group included 121 women seen between July 2006 and August 2008. All patients were referred by two expert gynecologists during complete workup that included filling out a pictorial chart and diagnosing idiopathic menorrhagia based on blood loss of more than 80 mL per menstrual cycle or more than 7 days of continuous bleeding. Mean age of the women was 23 years (range 15–46 years). Laboratory diagnostic tests in all women included prothrombin time, partial thromboplastin time (PTT), complete blood count, bleeding time, factor assays (factors V, VII, VIII, X, XI), von Willebrand factor (vWF) antigen, ristocetin cofactor activity, and platelet function tests. Some 19.8% (24/121) of the patients had decreased vWF activity and antigen levels, 6.6% were diagnosed with type 2 von Willebrand disease (vWD), and 13.2% with type 1 vWD. In 12 patients (9.9%), PTT was prolonged with decreased FVIII level (8.3–47.8%). Three patients (2.5%) had mild FV, FVII, or FIX deficiency. Five patients (4%) had mild FX deficiency. Two women (1.6%) had Glanzman’s thrombasthenia, and one (0.8%) had Bernard–Soulier syndrome. This study confirms that menorrhagia may be the initial symptom of rare bleeding disorders as well as vWD and platelet disorders. These coagulation disorders should be investigated in women with idiopathic menorrhagia.

Citation Details: Karimi M, Afrasiabi A, Amoei S, Zolghadri J, Nasirabadi S, Bordbar M, Peyvndi F. Coagulation Disorders in Women with Idiopathic Menorrhagia.  The Asia-Pacific Journal of Oncology & Hematology, February 2010; (2)1:111-114.

Comprehensive Meta‐Analysis of Survival Outcomes from Two Randomized Multicenter Trials in First‐Line Advanced Non‐Small Cell Lung Cancer in Patients Treated with the Novel Investigational Antitumor‐enhancing and Chemoprotective Agent Tavocept

Merminod T, Zulian GB.  Venous thromboembolism in Cancer Patients under Palliative Care:  Retrospective Study and Lessons for the Future.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  15-17

ORIGINAL ARTICLE

Comprehensive Meta‐Analysis of Survival Outcomes from Two Randomized Multicenter Trials in First‐Line Advanced Non‐Small Cell Lung Cancer in Patients Treated with the Novel Investigational Antitumor‐enhancing and Chemoprotective Agent Tavocept

Frederick Hausheer ¹, Stacey Bain ¹, Michael Perry ², Lingu Du ¹, Yasuo Ohashi ³, Yutaka Ariyoshi ⁴ and Masahiro Fukuoka ⁵

Affiliations: ¹BioNumerik Pharmaceuticals, Inc., San Antonio, TX, USA; ²University of Missouri/Ellis Fischel Cancer Center, Columbia, MO, USA; ³University of Tokyo School of Health Sciences and Nursing, Bunkyo-ku, Tokyo, Japan; ⁴Prefectural Aichi Hospital, Nagoya, Japan and ⁵Kinki University School of Medicine, Ohnohigashi, Osakasayama, Japan


ABSTRACT

We performed a comprehensive meta‐analysis of two recent, multicenter, randomized, and controlled trials of the investigational new drug Tavocept (vs. placebo or no Tavocept) in chemotherapy‐naïve patients with advanced non‐small cell lung cancer (NSCLC) who were treated with taxane plus cisplatin therapy. Significant improvements in overall and 1‐year survival were observed, which were most apparent in patients with the adenocarcinoma subtype. The results of this meta‐analysis support the view that Tavocept combined with taxane plus cisplatin first‐line therapy may result in significant increases in overall and 1‐year survival in patients with primary adenocarcinoma of the lung. The results of this systematic meta‐analysis were used for the design and scientific justification of an international, double‐blind, and placebo‐controlled phase III confirmatory trial of Tavocept in patients with advanced (stage IIIB/IV) primary adenocarcinoma of the lung treated with taxane plus cisplatin using a primary endpoint of overall survival.

Keywords: BNP7787, Tavocept, lung cancer, adenocarcinoma, antitumor enhancement, chemoprotection, survival, meta‐analysis
Correspondence: Frederick H Hausheer, BioNumerik Pharmaceuticals, Inc., Suite 1250, 8122 Datapoint Drive, San Antonio, TX 78229, USA

Prognostic Effect of Pathologic Fracture in Localized Osteosarcoma

Triapine in Clinical Practice

Miah AB, Harrington KJ, Nutting CM, Triapine in Clinical Practice. European Journal of Clinical & Medical Oncology., June 2010; 2 (2): 83-88

Review Article


AB Miah, KJ Harrington and CM Nutting

Affiliations: Head and Neck Unit, The Royal Marsden Hospital and The Institute of Cancer Research


ABSTRACT

Triapine is a ribonucleotide reductase inhibitor, which has been investigated in a variety of tumor cell lines in the preclinical setting. Phase I trials have reported encouraging results in the treatment of hematological malignancies, whereas the results have been disappointing for solid tumors. This article offers a review of preclinical data and clinical outcomes with future directions.

Keywords: 3‐aminopyridine‐2‐carboxaldehyde thiosemicarbazone, 3‐AP, triapine, ribonucleotide reductase inhibitors
Correspondence: C M Nutting, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK

Predictive Models of Survival in Patients with Advanced Cancer

Duhaiby EA, Pang J, Kwok S, Chow E.  Predictive Models of Survival in Patients with Advanced Cancer.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  121-130

Review Article

Predictive Models of Survival in Patients with Advanced Cancer

Eman Al Duhaiby, Jocelyn Pang, Sheldon Kwok and Edward Chow

Affiliation: Rapid Response Radiotherapy Program, Department of Radiation Oncology, Odette Cancer Center, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario, Canada


ABSTRACT

Accurate prognosis is necessary for terminally ill patients and their families to plan remaining time realistically and use available end‐of‐life resources effectively. Physicians also value this information in determining appropriate treatment plans. Nonetheless, predicting life expectancy is a difficult task. Clinical prediction of survival (CPS) has been extensively studied in recent decades and is found to be inaccurately optimistic. The actuarial estimation of survival employs prognostic factors of survival probability. These prognostic variables, which may sometimes include CPS, can be evaluated to develop prediction models for different populations and settings. This article gives an overview of the current issues of CPS as well as what the literature recognizes as important prognostic factors in cancer patients: symptoms, performance status, quality of life, and laboratory measures. It also provides details regarding the possible concerns and useful applications of several well‐validated prediction models, both cancer specific and non‐cancer specific. As prognostic models of survival have proven themselves in the literature to successfully aid in prognosis formulation, we suggest that health care providers familiarize themselves with existing models that may be specific to certain patient groups and clinical environments.

Keywords: prognostic models, prediction models, prognostic factors, survival probability
Correspondence: Edward Chow, Department of Radiation Oncology, Odette Cancer Center, Sunnybrook Health Sciences Center, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5. Tel: +1-416-480-4998; fax: +1-416-480-6002; e-mail: Edward.Chow@sunnybrook.ca

Venous Thromboembolism in Cancer Patients under Palliative Care: Retrospective Study and Lessons for the Future

Merminod T, Zulian GB.  Venous thromboembolism in Cancer Patients under Palliative Care:  Retrospective Study and Lessons for the Future.  Asia-Pacific Journal of Oncology and Hematology, February 2010; 2(1):  15-17

ORIGINAL ARTICLE

Venous Thromboembolism in Cancer Patients under Palliative Care: Retrospective Study and Lessons for the Future

Thierry Merminod and B Gilbert Zulian

Affiliation: Centre of Continuous Care (Cesco), Department of Rehabilitation and Geriatrics, University Hospitals of Geneva, Collonge-Bellerive, Switzerland


ABSTRACT
The exact incidence of venous thromboembolic events in advanced cancer patients under palliative care is unknown. In this context, prophylactic anticoagulation with the aim of improving symptom control is a matter of debate. The clinical notes of 1000 consecutive cancer patients who died in palliative care over a period of 6 years were thus retrospectively analyzed. Thirty deep vein thrombosis, 35 pulmonary embolisms, and 20 concomitant events were found. Four patients (4.7%) were under prophylactic anticoagulant therapy prior to the event. Thirty‐eight patients with deep vein thrombosis (57%) and 14 patients with pulmonary embolisms (43%) received curative anticoagulant therapy. Cancer patients under palliative care frequently developed venous thromboembolic events. Although a minority of the patients were on anticoagulant prophylaxis, half were treated with curative intent despite being considered in palliative care. Systematic prophylactic anticoagulation of cancer patients under palliative care should thus be considered to minimize both the risk of thromboembolic events and the risk of bleeding episodes related to anticoagulant therapy.

Keywords: Cancer, palliative care, thromboembolism
Correspondence: Gilbert B Zulian, Centre of Continuous Care (Cesco), Department of Rehabilitation and Geriatrics, University Hospitals of Geneva, 11, ch. de la Savonnière, CH‐1245 Collonge‐Bellerive, Switzerland