What's Hot at ASCO Annual Meeting This Year

There's already a buzz about immunotherapy and, among the new data that will be presented this year, there are 2 big trials with bevacizumab.
Medscape Medical News

ASCO Plenary Session: Not Your Usual Suspects

Dr. Kathy Miller previews the exceptional studies to be presented at the ASCO plenary session, ranging from rare tumors of the brain and thyroid to a screening strategy that has global implications.
Medscape Oncology

Cervical Cancer Studies Take Center Stage

Dr. Maurie Markman predicts that ASCO 2013 will be a hotbed for gynecologic cancer research, including highly anticipated studies in ovarian cancer and plenary-featured studies in cervical cancer.
Medscape Oncology

NLST Reveals Details of First Round of Lung Cancer Screening

The National Lung Screening Trial unveils details on the results of its first round of screening and what they mean to clinicians and patients in terms of diagnostic procedures and treatments.
Medscape Medical News

Whole-Genome Sequencing: Clinical Guidelines for Europe

The European Society of Human Genetics has issued guidelines for diagnostic whole-genome sequencing.
Medscape Medical News

[Correspondence] Radiotherapy capacity in Europe

In their analysis of the radiotherapy capacity in 33 European countries based on the International Atomic Energy Agency's (IAEA) Directory of Radiotherapy Centres (DIRAC) database, Eduardo Rosenblatt and colleagues identified shortfalls in infrastructure in some European countries, and an apparent surplus in others.

[Comment] Patients would benefit from simplified ethical review and consent procedure

In a draft report about the upcoming European Union Data Protection Directive, the European Parliament Committee on Civil Liberties, Justice and Home Affairs suggests, by contrast with the position of the European Commission, that processing of data for scientific reasons should not be exempt from strict requirements of specific consent by research particpants. The committee's amendment is an example of how the regulatory framework for the protection of human research participants seems not to keep pace with developments in biomedical research.

[Comment] Targeted treatments for breast cancer: a step forward

Breast cancer was the first solid tumour for which targeted treatments were available. Endocrine therapy—targeting the oestrogen receptor—was described more than 100 years ago and, as biological knowledge has grown, major advances in treatment and prevention of breast cancer have been made. Classification of molecular subtypes of breast cancer highlighted the importance of the oestrogen receptor and the HER2 oncogenic pathway in some populations.

[Correspondence] Non-invasive ventilation for end-of-life oncology patients – Authors' reply

We thank Arun Azad and Michael Franco, and Elie Azoulay and colleagues, for their comments on our Article.

[Comment] ALK-targeted therapy for poor-prognosis childhood cancers

The development of drugs for poor-prognosis childhood cancers remains challenging despite many advances in the specialty. New drugs targeting specific molecular aberrations in the patients' tumours are becoming available for adult cancers and proving successful even in early stages of development. For many years, paediatric oncologists have hoped similar achievements could be seen in children and adolescents with cancer, but little success has been noted to date.

Recreational and household physical activity at different time points and DNA global methylation

Publication date: June 2013
Source:European Journal of Cancer, Volume 49, Issue 9
Author(s): Alexandra J. White , Dale P. Sandler , Sophia C.E. Bolick , Zongli Xu , Jack A. Taylor , Lisa A. DeRoo
Background DNA methylation patterns are heritable but can change over time and in response to exposures. Lower global DNA methylation, which may result in increased genomic and chromosomal instability, has been associated with increased cancer risk. Physical activity is a modifiable factor that has been inversely related to the risk of cancer. Changes in DNA methylation may be a mechanism by which lifestyle and environment factors influence disease. We investigated the relationship between DNA methylation and physical activity in a sample of women enroled in The Sister Study, a large United States (U.S.) cohort study of women aged 35–74years with a family history of breast cancer. Methods Global DNA methylation was measured using bisulphite-converted DNA and pyrosequencing of a LINE-1 repetitive sequence in the peripheral blood of 647 non-Hispanic white women. Physical activity (average hours per week) was retrospectively assessed for three time periods: childhood (ages 5–12), teenage years (ages 13–19) and the previous 12months. Findings Compared with women with physical activity levels below the median for all three time periods, those at or above the median physical activity for one (β =0.20, 95% confidence interval (CI): −0.10, 0.49), two (β =0.22, 95% CI: −0.08, 0.52) or all three (β =0.33, 95% CI: 0.01, 0.66) time periods had increased global methylation. Interpretation Maintaining higher levels of physical activity over these three time periods was associated with increased global DNA methylation, consistent with reported associations between exercise and decreased cancer risk.

αvβ3 Integrin and Fibroblast growth factor receptor 1 (FGFR1): Prognostic factors in a phase I–II clinical trial associating continuous administration of Tipifarnib with radiotherapy for patients with newly diagnosed glioblastoma

Publication date: June 2013
Source:European Journal of Cancer, Volume 49, Issue 9
Author(s): Anne Ducassou , Emmanuelle Uro-Coste , Pierre Verrelle , Thomas Filleron , Alexandra Benouaich-Amiel , Vincent Lubrano , Jean-Christophe Sol , Marie-Bernadette Delisle , Gilles Favre , Solea Ken , Anne Laprie , Peter De Porre , Christine Toulas , Muriel Poublanc , Elizabeth Cohen-Jonathan Moyal
Background Based on our previous results showing the involvement of the farnesylated form of RhoB in glioblastoma radioresistance, we designed a phase II trial associating the farnesyltransferase inhibitor Tipifarnib with radiotherapy in patients with glioblastoma and studied the prognostic values of the proteins which we have previously shown control this pathway. Patients and methods Patients were treated with 200mg Tipifarnib (recommended dose (RD)) given continuously during radiotherapy. Twenty-seven patients were included in the phase II whose primary end-point was time to progression (TTP). Overall survival (OS) and biomarker analysis were secondary end-points. Expressions of αvβ3, αvβ5 integrins, FAK, ILK, fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor 1 (FGFR1) were studied by immuno-histochemistry in the tumour of the nine patients treated at the RD during the previously performed phase I and on those of the phase II patients. We evaluated the correlation of the expressions of these proteins with the clinical outcome. Results For the phase II patients median TTP was 23.1weeks (95%CI=[15.4; 28.2]) while the median OS was 80.3weeks (95%CI=[57.8; 102.7]). In the pooled phase I and II population, median OS was 60.4w (95%CI=[47.3; 97.6]) while median TTP was 18.1w (95%CI=[16.9; 25.6]). FGFR1 over-expression (HR=4.65; 95%CI=[1.02; 21.21], p =0.047) was correlated with shorter TTP while FGFR1 (HR=4.1 (95% CI=[1.09–15.4]; p =0.036)) and αvβ3 (HR=10.38 (95%CI=[2.70; 39.87], p =0.001)) over-expressions were associated with reduced OS. Conclusion Association of 200mg Tipifarnib with radiotherapy shows promising OS but no increase in TTP compared to historical data. FGFR1 and αvβ3 integrin are independent bad prognostic factors of OS and TTP.

Oral adjuvant clodronate therapy could improve overall survival in early breast cancer: Results from an updated systematic review and meta-analysis

Publication date: June 2013
Source:European Journal of Cancer, Volume 49, Issue 9
Author(s): Jianhong Zhu , Yayuan Zheng , Zhikun Zhou
Object The aim of this study was to evaluate the effectiveness of clodronate in the adjuvant therapy of early breast cancer on patient survival. Methods We performed a literature search to identify studies that investigated the effects of clodronate treatment on early breast cancer. Random and fixed-effect meta-analytical models were used where indicated and between-study heterogeneity was assessed. The primary study end-points were overall survival. Secondary end-points were bone metastasis-free survival and non-skeletal metastasis (mainly visceral metastases) free survival. Results Four randomised controlled trials met the inclusion criteria. Risk ratio (95% confidence interval (CI)) of overall survival was 0.84 (0.56–1.26); risk ratio (95% CI) of bone metastasis-free survival was 0.77 (0.58–1.02); risk ratio (95% CI) of non-bone metastasis-free survival was 0.89 (0.61–1.30). Outcomes after sensitivity analysis were: risk ratio (95% CI) of overall survival was 0.71 (0.52–0.96); risk ratio (95% CI) of bone metastasis-free survival was 0.70 (0.56–0.86); risk ratio (95% CI) of non-bone metastasis-free survival was 0.76 (0.64–0.92). Conclusion Compared with the control arm, adjuvant treatment with clodronate may improve the overall survival, bone metastasis-free survival and non-bone metastasis-free (mainly visceral metastases) survival in patients with early breast cancer. However, further meta-analyses involving all known randomised trials with analysis of sub-groups by age or menopausal status, accessing original trial data, should be performed.

Why Some Women Have an Optimistic or a Pessimistic Bias About Their Breast Cancer Risk: Experiences, Heuristics, and Knowledge of Risk Factors

Perceived risk to a health problem is formed by inferential rules called heuristics and by comparative judgments that assess how one's risk compares to the risk of others. The purpose of this cross-sectional, community-based survey was to examine how experiences with breast cancer, knowledge of risk factors, and specific heuristics inform risk judgments for oneself, for friends/peers, and comparative judgments for breast cancer (risk friends/peers - risk self). We recruited an English-speaking, multicultural (57% nonwhite) sample of 184 middle-aged (47 +/- 12 years old), well-educated women. Fifty percent of participants perceived that their breast cancer risk was the same as the risk of their friends/peers; 10% were pessimistic (risk friends/peers - risk self < 0), whereas 40% were optimistic (risk friends/peers - risk self > 0). Family history of breast cancer and worry informed risk judgments for oneself. The availability and cultural heuristics specific for black women informed risk judgments for friends/peers. Knowledge of risk factors and interactions of knowledge with the availability, representativeness, and simulation heuristics informed comparative judgments (risk friends/peers - risk self). We discuss cognitive mechanisms with which experiences, knowledge, and heuristics influence comparative breast cancer risk judgments. Risk communication interventions should assess knowledge deficits, contextual variables, and specific heuristics that activate differential information processing mechanisms. (C) 2010 Lippincott Williams & Wilkins, Inc.

Stereotactic Radiosurgery for Retreatment of Gross Perineural Invasion in Recurrent Cutaneous Squamous Cell Carcinoma of the Head and Neck

Objectives:To report outcomes, failure patterns, and toxicity after stereotactic radiosurgery (SRS) for recurrent head and neck cutaneous squamous cell carcinoma with gross perineural invasion (GPNI). Methods:Ten patients who received SRS as part of retreatment for recurrent head and neck cutaneous squamous cell carcinoma with GPNI were included. All patients exhibited clinical and radiologic evidence of GPNI before SRS. Previous treatments included surgery alone in 3 patients and surgery with adjuvant external beam radiotherapy (EBRT) in 7 patients. Retreatment included SRS alone in 2 and EBRT boosted with SRS in 8 patients. Magnetic resonance images were obtained every 3 to 6 months after SRS to track failure patterns. Results:At a median 22-month follow-up, the 2-year progression-free and overall survival rates were 20% and 50%, respectively. Seven patients exhibited local failures, all of which occurred outside both SRS and EBRT fields. Five local failures occurred in previously clinically uninvolved cranial nerves (CNs). CN disease spreads through 3 distinct patterns: among different branches of CN V; between CNs V and VII; and between V1 and CNs III, IV, and/or VI. Five patients experienced side effects potentially attributable to radiation. Conclusions:Although there is excellent in-field control with this approach, the rate of out-of-field failures remains unacceptably high. We found that the majority of failures occurred in previously clinically uninvolved CNs often just outside treatment fields. Novel treatment strategies targeting this mode of perineural spread are needed.

A New Method to Predict Values for Postoperative Lung Function and Surgical Risk of Lung Resection by Quantitative Breath Sound Measurements

Objectives:We evaluated quantitative acoustic measurements, as a simpler alternative to perfusion scintigraphy, for estimation of predicted postoperative (ppo) lung function after resection surgery in our patient population. Methods:Patients with lung cancer, considered as candidates for lung resection, were enrolled in the study. All patients underwent lung function testing and quantitative breath sound testing by vibration response imaging (VRI) on the same day. A subset of patients also had perfusion testing. Forced expiratory volume in 1 second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) predictions derived from VRI testing were compared with perfusion values and actual FEV1 values at 1 month postoperatively. Results:Fifty-three subjects (40 males; age 66±8 y) participated. There was high correlation between both methods for the calculation of ppoFEV1% (R=0.94; n=39) and ppoFEV (L) (R=0.90; n=39). PpoFEV1 were 58±18% versus 56±20% and 1.69±0.49 L versus 1.62±0.52 L, based on perfusion and VRI methods, respectively. In 92% (36/39) of calculations, the difference between the 2 methods was <10%. High correlations also existed between VRI and perfusion for the calculation of ppoDLCO% (R=0.95; n=37) and ppoDLCO mL/min/mm Hg (R=0.90; n=37). VRI predictions showed good correlation for the 34 patients with actual postoperative lung function (R=0.88 and R=0.80 for FEV1% and FEV1L, respectively). Accuracy of the VRI to predict surgical risk (<40% cutoff threshold for ppo values) compared with actual postoperative values was 85% (29/34). Conclusions:Predictions of postoperative lung function using VRI agree well with radionuclide techniques and actual measured postoperative values. VRI may provide a noninvasive, simpler alternative for estimation of ppo values, particularly when perfusion testing is not readily available.

Tumor-infiltrating Lymphocytes, Tumor Characteristics, and Recurrence in Patients With Early Breast Cancer

Background:The balance in the immune system between immune surveillance against non–self-antigens and tolerance of self-antigens is known to be associated with the prognosis of breast cancer patients. However, immunologic signals in tumor microenvironment according to biological characteristics of cancer cells have not been clearly elucidated. CD4+ T cells, CD8+ T cells, and forkhead box P3-positive (Foxp3+) regulatory T cells (Tregs) are the main keys for immune surveillance and tolerance, respectively. We evaluated the correlations between the immunologic balance and tumor characteristics and their impact on recurrence. Patients and Methods:CD8+ T cells and Foxp3+ Tregs were detected by immunohistochemistry using the paraffin-embedded tumor samples from the 72 patients with early stage (I to III) breast cancer. Clinicopathologic data including tumor size and grade, lymph node metastasis, stage, patient’s age, expression status of estrogen receptor (ER), progesterone receptor, p53, Ki-67, and human epidermal growth factor receptor-2/neu, and recurrence were reviewed. Results:The decreased number of CD8+ T cells was significantly associated with tumors with lymph node metastasis (P=0.027), higher stage (stage III, P=0.013), and immunopositivity of Ki-67 (P=0.026). In contrast, the increased number of Foxp3+ Tregs was significantly correlated with tumors with lymph node metastasis (P=0.027), immunopositivity for p53 (P=0.026), and positive for Ki-67 (P<0.001). There were significant correlations between the increased Foxp3+ Treg/CD4+ T-cell ratio and lymph node metastasis (P=0.011), the expression of ER (P=0.023), and immunopositivity of p53 (P=0.031) and Ki-67 (P= 0.003). Of note, lower Foxp3+ Treg/CD4+ T-cell ratio was significantly associated with triple-negative breast cancer (P=0.004). Disease-free survival of analyzed patients was significantly associated with the number of Foxp3+ Tregs (dichotomized by a cutoff point of 17, P= 0.014) only. Univariate analysis indicated that tumor grade (P=0.017), the expression of ER (P=0.032), and non–triple-negative breast cancer (P=0.022) were independent prognostic factors for disease-free survival. Conclusions:Our data showed that lymph node metastases, immunopositivity of p53 and Ki67, and non–triple-negative tumors were associated with high regulatory T-cell infiltration. The role of immunologic balance as a prognostic marker for recurrence must be evaluated more clearly in the future study.

Predictive Role of Midtreatment Changes in Survivin, GSTP1, and Topoisomerase 2[alpha] Expressions for Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer

Introduction:The primary aim of this study is to investigate the effect of change in the expression levels of survivin, glutathione-S-transferase P1 (GSTP1), and topoisomerase 2α (TOP2A) on the response to antracyclin-based and taxane-based neoadjuvant chemotherapy. Methods:This study included 32 locally advanced breast cancer patients. Tumoral expressions of survivin, TOP2A, and GSTP1 in serial biopsy specimens obtained before treatment, after sequential 4 cycles of doxorubicin+cyclophosphomide, and 4 cycles of docetaxel were analyzed by real-time polymerase chain reaction. Survivin expressions were additionally analyzed in serial blood samples. Results:The pathologic complete response (pCR) rate and the overall response rate (clinical complete and partial) were 28% (n=9) and 91% (n=29), respectively. There were no statistically significant correlations between serial TOP2A expression levels and response. There was a nonsignificant trend toward an improved response rate with decreased survivin expression. A significant decrease in the GSTP1 expression level throughout treatment (P=0.014), which was also shown to be significantly correlated with a pCR (P=0.0001), was seen. Downregulation of GSTP1 after 4 cycles of anthracycline-based combination was independently associated with improved progression-free survival (P=0.01). Conclusions:Downregulation of GSTP1 is a significant predictor of pCR and improved progression-free survival during anthracycline-based and taxane-based neoadjuvant chemotherapy in patients with locally advanced breast cancer.

Preoperative Radiation Therapy Significantly Increases Patient Eligibility for Accelerated Partial Breast Irradiation Using 3D-conformal Radiotherapy

Introduction:Three-dimensional-conformal radiation (3D-CRT) is the most common approach used in National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 for accelerated partial breast irradiation (APBI). Administration of APBI-3D-CRT in the preoperative (preop) setting has been shown to decrease the planning target volume. The impact of this decrease on patient eligibility for APBI has not been evaluated in a comparative manner. Materials and Methods:Forty patients with 41 previously treated breast cancers (≤4 cm) were analyzed. A spherical preop tumor volume was created using the largest reported radiographic dimension and centered within the contoured lumpectomy cavity. Plans were created and optimized using the preop tumor volume and postoperative lumpectomy cavity using NSABP B-39 guidelines. The primary end point was to evaluate for differences in patient eligibility and normal tissue exposure. Results:Thirty-five tumors (85%) in the preop versus 19 tumors (46%) in the postoperative setting were eligible for 3D-CRT-APBI using NSABP B-39 criteria (P=0.0002). The most common reason for ineligibility was due to >60% of the ipsilateral breast volume receiving 50% of the dose. Other reasons included dose to the contralateral breast, heart, and ipsilateral lung. Preop 3D-CRT-APBI was associated with statistically significant improvements in dose sparing to the heart, ipsilateral normal breast tissue, contralateral breast, chest wall, ipsilateral lung, and skin. Conclusions:Dosimetrically, the use of preop radiation would increase patient eligibility for 3D-CRT-APBI and decrease dose to normal tissues, which will potentially decrease toxicity and improve cosmesis. These results provide the basis for a recently activated prospective study of preop 3D-CRT-APBI.

Building a Personalized Medicine Infrastructure at a Major Cancer Center [REVIEW ARTICLES]

Our understanding of cancer biology is rapidly increasing, as is the availability and affordability of high throughput technologies for comprehensive molecular characterization of tumors and the individual's own genetic makeup. Thus, the time is right to implement personalized molecular medicine for all patients with cancer. Personalized approaches span the full cancer care spectrum from risk stratification to prevention, screening, therapy, and survivorship programs. Several molecular therapeutics have entered clinical trials creating a huge opportunity to couple genomic markers with this emerging drug tool kit. The number of patients managed in major cancer centers creates a challenge to the implementation of genomic technologies required to successfully deliver on the promise of personalized cancer care. This requires a major investment in infrastructure to facilitate rapid deployment of multiplex, cost-effective, and tissue-sparing assays relevant across multiple tumor lineages in the Clinical Laboratory Improvement Amendments (CLIA) environment. Efforts must be made to ensure that assays are accessible to patients most likely to be enrolled onto molecular-marker–driven trials and that the tests are billable and payable, which will make them accessible to a wide range of patients. As the number of patients and aberrations increase, it will become critical to provide decision support for genomic medicine. Institutional commitment is needed to optimize accessibility and quality of research biopsies and to facilitate novel personalized cancer therapy trials. This article will focus on the challenges and opportunities that accompany the building of infrastructure for personalized cancer therapy.

Leveraging Cancer Genome Information in Hematologic Malignancies [REVIEW ARTICLES]

The use of candidate gene and genome-wide discovery studies in the last several years has led to an expansion of our knowledge of the spectrum of recurrent, somatic disease alleles, which contribute to the pathogenesis of hematologic malignancies. Notably, these studies have also begun to fundamentally change our ability to develop informative prognostic schema that inform outcome and therapeutic response, yielding substantive insights into mechanisms of hematopoietic transformation in different tissue compartments. Although these studies have already had important biologic and translational impact, significant challenges remain in systematically applying these findings to clinical decision making and in implementing new technologies for genetic analysis into clinical practice to inform real-time decision making. Here, we review recent major genetic advances in myeloid and lymphoid malignancies, the impact of these findings on prognostic models, our understanding of disease initiation and evolution, and the implication of genomic discoveries on clinical decision making. Finally, we discuss general concepts in genetic modeling and the current state-of-the-art technology used in genetic investigation.

Genomics-Driven Oncology: Framework for an Emerging Paradigm [REVIEW ARTICLES]

A majority of cancers are driven by genomic alterations that dysregulate key oncogenic pathways influencing cell growth and survival. However, the ability to harness tumor genetic information for its full clinical potential has only recently become manifest. Over the past several years, the convergence of discovery, technology, and therapeutic development has created an unparalleled opportunity to test the hypothesis that systematic knowledge of genomic information from individual tumors can improve clinical outcomes for many patients with cancer. Rigorous evaluation of this genomics-driven cancer medicine hypothesis will require many logistic innovations that are guided by overarching conceptual advances in tumor genomic profiling, data interpretation, clinical trial design, and the ethical return of genetic results to oncologists and their patients. The results of these efforts and the rigor with which they are implemented will determine whether and how comprehensive tumor genomic information may become incorporated into the routine care of patients with cancer.

Advancing Precision Medicine for Prostate Cancer Through Genomics [REVIEW ARTICLES]

Prostate cancer is the most common type of cancer in men and the second leading cause of cancer death in men in the United States. The recent surge of high-throughput sequencing of cancer genomes has supported an expanding molecular classification of prostate cancer. Translation of these basic science studies into clinically valuable biomarkers for diagnosis and prognosis and biomarkers that are predictive for therapy is critical to the development of precision medicine in prostate cancer. We review potential applications aimed at improving screening specificity in prostate cancer and differentiating aggressive versus indolent prostate cancers. Furthermore, we review predictive biomarker candidates involving ETS gene rearrangements, PTEN inactivation, and androgen receptor signaling. These and other putative biomarkers may signify aberrant oncogene pathway activation and provide a rationale for matching patients with molecularly targeted therapies in clinical trials. Lastly, we advocate innovations for clinical trial design to incorporate tumor biopsy and molecular characterization to develop biomarkers and understand mechanisms of resistance.

Existing and Emerging Technologies for Tumor Genomic Profiling [REVIEW ARTICLES]

Ongoing global genome characterization efforts are revolutionizing our knowledge of cancer genomics and tumor biology. In parallel, information gleaned from these studies on driver cancer gene alterations—mutations, copy number alterations, translocations, and/or chromosomal rearrangements—can be leveraged, in principle, to develop a cohesive framework for individualized cancer treatment. These possibilities have been enabled, to a large degree, by revolutionary advances in genomic technologies that facilitate systematic profiling for hallmark cancer genetic alterations at increasingly fine resolutions. Ongoing innovations in existing genomics technologies, as well as the many emerging technologies, will likely continue to advance translational cancer genomics and precision cancer medicine.

Phase II Trial of Alternating mFOLFOX6 and FOLFIRI Regimens in the First-Line Treatment for Unresectable or Metastatic Colorectal Cancer (KSCC0701)

Oncology 2013;84:233–239 (DOI:10.1159/000346690)

BRCA1 and BRCA2 Mutations in the Ovarian Cancer Population across Race and Ethnicity: Special Reference to Asia

Oncology 2013;84:226–232 (DOI:10.1159/000346593)

Front & Back Matter

Oncology 2013;84:X (DOI:10.1159/000348341)

Correlation between Ki67 and Breast Cancer Prognosis

Oncology 2013;84:219–225 (DOI:10.1159/000346475)

Effect of the BCL2 Gene Polymorphism on Survival in Advanced-Stage Non-Small Cell Lung Cancer Patients Who Received Chemotherapy

Oncology 2013;84:214–218 (DOI:10.1159/000342854)

Dystonia in a Patient with Melanoma Metastatic to the Brain Treated with High-Dose Interleukin-2, Radiation Therapy, and Levetiracetam

Case Rep Oncol 2013;6:78–83 (DOI:10.1159/000346932)

Clinically Meaningful Responses to Sequential Gemcitabine-Based Chemotherapy Regimens in a Patient with Metastatic Pancreatic Cancer

Case Rep Oncol 2013;6:72–77 (DOI:10.1159/000346836)

Solitary Schwannoma of the Cecum: Case Report and Review of the Literature

Case Rep Oncol 2013;6:62–65 (DOI:10.1159/000346785)

Proton Beam Therapy and Continuous Intra-Arterial Chemotherapy for Polymorphous Low-Grade Adenocarcinoma in the Hard Palate

Case Rep Oncol 2013;6:66–71 (DOI:10.1159/000346840)

Table of contents

Editorial Board

Key factors influencing lung cancer survival in northern Italy

Abstract: Aim: Lung cancer is a major cause of cancer death worldwide. The aims of this study were to analyze presentation, treatment and survival for lung cancer in northern Italy, and identify factors influencing survival. Methods: A total of 1180 lung cancer cases diagnosed in four north Italian cancer registries (Biella, Modena, Reggio Emilia, Romagna) in 2003–2005 were analyzed. Information on morphology, stage, diagnostic examinations, chemotherapy, radiotherapy, and surgical treatment was collected from clinical records. Three-year relative survival and relative excess risks of death were estimated. Results: Overall, 10% of cases were stage I, 50% stage IV, and 12% stage unknown. Romagna – where sophisticated diagnostic examinations were performed more often – had proportionately more microscopically verified cases and resected cases than Biella. Romagna had also high proportions of cases given chemotherapy and radiotherapy. Three-year survival was 14%, range 10% (Biella) to 19% (Romagna); 69% for stage I, 3% for stage IV. Stage I survival was higher in Romagna (82%) than Reggio Emilia and Biella (60–61%) but for operated stage I cases, survival was similar (88%) in Romagna and Biella. The fully adjusted model showed a higher risk of death in Biella (1.23, 95%CI 1.02–1.48) than Modena (reference). Conclusions: Stage and surgery are key factors influencing survival. Centralizing lung cancer treatment to improve diagnostic work-up may improve outcomes.

Patterns and trends in cancer mortality in Colombia 1984–2008

Abstract: Background: Cancer has become increasingly acknowledged as a public health issue in Colombia. Rates of the most common malignancies have been generally increasing. We update an evaluation of mortality trends in the major cancers in Colombia one decade ago, discussing the trends in the context of cancer control.Methods: We calculated the annual age-standardized mortality rates for the major cancer sites by sex between 1984 and 2008; we also present the estimated annual percentage change (EAPC) for the entire period and for the last decade.Results: There was an average of 32,000 cancer deaths annually in Colombia in the period studied. Overall cancer mortality rates decreased slightly in both men and women. The four most common sites of cancer death among men were stomach (17.6%), prostate (15.0%), lung (14.8%) and colorectum (6.5%). In women, the most common cancer sites were breast (12.3%), cervix (12.1%), stomach (11.5%) and lung (9.2%). Colorectal and CNS cancers exhibited the greatest increases (EAPC of 2.0% and 3.4% respectively) while the largest declines were seen for cancers of the larynx, stomach and oesophagus (EAPC between −3% and −4%). In the last decade, the greatest declines were seen in cervical cancer mortality rates (EAPC=−3.2).Conclusions: The slight decrease in mortality trends from all cancers combined is partially driven by the strong declines in mortality of stomach and cervical cancer. It may be still too early to properly evaluate trends in mortality due to other cancers and the relative impact of changing access to health care in Colombia.

Editorial Board

First immunochemotherapy outcomes in elderly patients with CLL: A retrospective analysis

Abstract: Background: To date, the majority of trials on chronic lymphocytic leukemia (CLL) focused on patients considerably younger than the median age of onset for CLL. As a result, no definitive treatment exists for elderly patients, especially less medically fit patients.Objectives: The objectives of this study are to examine the impact of comorbidities on outcome as well as to compare three different therapeutic regimens in outcome efficacy.Materials and Methods: We retrospectively identified 143 patients aged >65 years, who received fludarabine, cyclophosphamide, and rituximab (FCR) (n=49), fludarabine and rituximab (FR) (n=74), or rituximab with chlorambucil (R–CLB) (n=20) as first initial immunochemotherapy.Results: At current follow-up (median: 24 months), the proportion of patients with a clinical response was higher with FCR (75%) than FR (57%) and R–CLB (28%). For FCR, FR, and R–CLB patients, 2-year overall survival (OS) was 94%, 76%, and 73%, respectively, (p=0.14), while 2-year progression-free survival (PFS) was 90%, 58%, and 30% (p<0.001). In the fludarabine based regimen (FR and FCR) population, higher rituximab doses (500mg/m2 vs. 375mg/m2) correlated with prolonged PFS.Conclusion: Despite the retrospective nature of this study, we demonstrate that elderly patients with CLL benefit from frontline immunochemotherapy, and emphasize the importance of maintaining rituximab dose intensity.

Factors affecting survival in patients aged 60 and over with diffuse large B cell lymphoma failing first-line therapy

Abstract: Objectives: Elderly patients with diffuse large B cell lymphoma (DLBCL) without prohibitive co-morbidities may be cured with standard immuno-chemotherapeutic regimens, as used in younger patients. Less is known about the survival prospects in older people, if first-line therapy fails. This study aimed to provide additional information regarding prognosis in this group.Materials and Methods: Databases were collated from three randomized trials of first-line therapy in those aged 60 and over, deemed fit enough for standard therapy. Overall survival from the point of treatment failure was calculated and comparisons were made between age groups and types of treatment failure.Results: Overall survival (OS) at 2years in 862 patients was 46%, 38%, 37% and 23%, respectively, for those aged 60–64, 65–69, 70–74 and >74. Type of treatment failure impacted on 2year OS as follows: initial partial remission (PR): 48%; complete response (CR) with late relapse: 37%; CR with early relapse: 17%; and less than PR to initial therapy: 12%.Conclusion: Older patients failing first-line therapy for DLBCL should be counseled differently regarding prognosis depending upon age and type of treatment failure. The chance of survival was greater in those achieving PR or CR with relapse more than 12months from diagnosis. This data may support the consideration of aggressive salvage therapy in fit patients in these categories, regardless of biological age per se. Palliative management may be more appropriate for those achieving less than PR to initial therapy or who enter CR but relapse within one year of diagnosis.

Biweekly XELOX (capecitabine and oxaliplatin) as first-line treatment in elderly patients with metastatic colorectal cancer

Abstract: Objective: The combination of oxaliplatin and oral capecitabine (XELOX) has shown to be an active regimen in metastatic colorectal cancer (MCRC). However, the experience with XELOX in elderly patients is limited. This study aimed to evaluate the efficacy and safety of XELOX as first-line treatment in elderly patients with MCRC.Patients and Methods: Patients aged ≥70years with previously untreated MCRC received oxaliplatin 85mg/m2 on day 1, every 2weeks plus capecitabine 1000mg/m2 (or capecitabine 750mg/m2 if creatinine clearance was 30–50mL/min) twice daily on days 1–7, every 2weeks. Treatment was continued until progression, intolerable toxicity, or for a maximum of 12cycles.Results: Thirty-five patients were enrolled. Median age was 78years (range, 70–83). Patients received a median of 11cycles of treatment. The objective response rate (ORR) was 49% and the tumor control rate was 86%. Median time to progression and overall survival were 8.6 (95% CI: 5.5–11.7) and 15.5 (95% CI: 9.6–21.3) months, respectively. Toxicities were generally mild to moderate. Major grade 1–2 toxicities were asthenia (40%), nausea (43%), and diarrhea (40%). No grade 4 toxicity was detected and grade 3 toxicities were reported in 17% of patients. There was no treatment-related death.Conclusion: Our findings show that the biweekly XELOX regimen represents an effective and tolerable first-line treatment option for elderly patients with MCRC.

Fine-Tuning Immunotherapy to Treat Prostate Cancer

Immunotherapy has become a well-accepted treatment for advanced prostate cancer, and researchers are now seeking to fine-tune our knowledge of how to use it most effectively. Dr. John Corman, medical ...

Author: patientpower
Added: 05/23/2013

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http://cancerGRACE.org/...

Dr. Phil Bonomi, from Rush University, offers his insights on how to approach a patient with gradual progression in a single site, especially in the brain, or more multifoca...

Author: cancergrace
Added: 05/23/2013

GRACEcastUC115_Lung_Dr. Kelly on Repeat Biopsy with Acquired Resistance Targeted Therapy

http://cancerGRACE.org/...

Dr. Karen Kelly, of the University of California, Davis, reviews her thought process in recommending a repeat biopsy after progression for patients with advanced lung cancer...

Author: cancergrace
Added: 05/22/2013

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http://cancerGRACE.org/...

Dr. Johannes Kratz, surgeon at Massachusetts General Hospital, reviews data supporting a method to define prognosis in early stage non-small cell lung cancer (NSCLC) based o...

Author: cancergrace
Added: 05/22/2013