Critical Reviews in Oncology / Hematology - Articles in Press

The effect of under-treatment of breast cancer in women 80 years of age and older - Corrected Proof

2010-07-26

Abstract: Background: Several authors have demonstrated a trend toward the under-treatment of elderly and very elderly women with breast cancer. This study was undertaken to determine the impact of under-treatment of breast cancer in women age 80 and older.Methods: A retrospective chart review of all patients 80 years and older with a newly diagnosed breast cancer at the MD Anderson Cancer Center, Houston, TX, between September 1, 1989 and September 1, 2004 was performed. Data extracted from charts included patient demographics, comorbidity, treatments recommended, treatments received, complications of therapy, disease recurrence and disease related death. Treatments undertaken were analyzed in the context of accepted therapy at the time of diagnosis.Results: Two hundred twelve patients were identified. The median age was 83.5 years (range 80–97). Overall survival in the entire cohort was 7.28 years with a median follow up of 4 years for patients still alive at the end of the study period. Fifty seven percent of patients were under-treated according to institutional and national guidelines. Women who underwent hormonal therapy only demonstrated decreased disease specific survival (P<0.001 respectively) compared with patients who received multi-modality therapy. Women who underwent partial mastectomy without radiation treatment experienced a significant increase in local regional recurrence (P=0.045). There was an association of increased disease specific survival in patients who had surgical lymph node evaluation compared to those who did not (P=0.04).Conclusions: Outcomes are compromised in very elderly women with breast cancer in whom less than complete combined modality treatment is undertaken. With the previously demonstrated safety of radiation therapy, hormonal therapy and surgery in the very elderly population, multi-modality therapy should not be routinely withheld in patients in this age category.

Adjuvant chemotherapy in elderly patients with early breast cancer. Impact of age and comprehensive geriatric assessment on tumor board proposals - Corrected Proof

2010-07-26

Abstract: Purpose of the study: Elderly breast cancer (EBC) patients are often denied adjuvant chemotherapy because of age. Breast cancer is among the most frequent cancer in Western Countries and recent data suggest that adjuvant chemotherapy could be active in selected elderly patients. We investigated the impact of age and comprehensive geriatric assessment (CGA) among other variables taken into account in tumor boards to recommend adjuvant chemotherapy in EBC patients.Method(s): We retrospectively reviewed breast cancer tumor board records of all consecutive EBC patients (over 70 years old) discussed from July 2006 to July 2009 in our institution. The recorded variables included age, comorbidities, tumor stage, grade, ER/PR and HER2 status, treatment characteristics and CGA conclusions. Agreement with breast cancer treatment guidelines was verified. Reasons for deviations were recorded.Result(s): A total of 192 early EBC patients files (mean age 76.7 years, range 70–98) were analyzed. Elderly patients were less likely to receive adjuvant chemotherapy even when deemed appropriate by guidelines (p 80 years, but not CGA result, was an independent variable associated with a decreased likelihood to receiving adjuvant chemotherapy. Moreover, 93 patients (48.4%) underwent CGA, of whom no Balducci's class III patient received adjuvant chemotherapy. An appropriate treatment was administered in only 69% and 42% of Balducci's class I and II patients, respectively.Conclusion(s): Our results suggest that age remains an independent variable associated with a decreased use of adjuvant chemotherapy. However, in our series systemic adjuvant chemotherapy was probably underused in “fit” patients. Further efforts are needed to better integrate CGA into tumor boards proposals for early EBC patients.

Enteropathy-associated T-cell lymphoma - Corrected Proof

Andrés J.M. Ferreri, Pier Luigi Zinzani, Silvia Govi, Stefano A. Pileri — 2010-07-26

Abstract: Enteropathy-associated T-cell lymphoma (EATL) is an intestinal tumour of intraepithelial T lymphocytes, usually presenting as a neoplasm composed of large lymphoid cells and often associated with necrosis and an inflammatory background, including large numbers of histiocytes and eosinophils. Intestinal intraepithelial α–β T-cells have been postulated as the normal-cell counterpart for EATL. EATL is the most common neoplastic complication of coeliac disease. The disease is uncommon in most parts of the world, but is seen with greater frequency in those areas with a high prevalence of coeliac disease, in particular Northern Europe. Usually, EATL occurs in adults, and generally present with abdominal pain, often associated with jejunal perforation, weight loss, diarrhoea, or bowel obstruction. EATL is characterized by multifocal presentation in 10–25% of cases. Small-bowel lymphoma is more common than large-bowel or rectal lymphomas. The prognosis of EATL is very poor, with low chemosensitivity, rapid tumour growth and a tendency to dissemination. Moreover, the high incidence of severe postsurgical complications and the poor nutritional and immunological conditions lead to progressive deterioration of these patients, preventing the use of an adequate and effective treatment.

MUTYH-associated polyposis (MAP) - Corrected Proof

Maartje Nielsen, Hans Morreau, Hans F.A. Vasen, Frederik J. Hes — 2010-07-22

Abstract: The human mutY homologue (MUTYH) gene is responsible for inheritable polyposis and colorectal cancer. This review discusses the molecular genetic aspects of the MUTYH gene and protein, the clinical impact of mono- and biallelic MUTYH mutations and histological aspects of the MUTYH tumors. Furthermore, the relationship between MUTYH and the mismatch repair genes in colorectal cancer (CRC) families is examined. Finally, the role of other base excision repair genes in polyposis and CRC patients is discussed.

Management strategy of early-stage breast cancer patients with a positive sentinel lymph node: With or without axillary lymph node dissection - Corrected Proof

Jia-Jian Chen, Jiong Wu — 2010-07-22

Abstract: Sentinel lymph node biopsy (SLNB) has been generally adopted as an alternative procedure to axillary lymph node dissection (ALND) for node staging. ALND remains the standard management of the axilla when a tumor-positive sentinel lymph node (SLN) is identified. However, further analysis has demonstrated that in 40–70% of cases with metastasis to the axillary lymph nodes, the SLN is the only positive node. Therefore, the traditional recommendation that ALND is always necessary for management of early-stage breast cancer patients with a positive SLN should be re-evaluated. Several nomograms and scoring systems have been developed to calculate the probability of non-SLN involvement on the basis of several clinicopathological variables. However, the actual value of such nomograms or scoring systems in daily clinical practice should be evaluated. This review focuses on the above topics and pushes forward the current heated debate on the management of early-stage breast cancer patients with a positive SLN.

Comparison of two frailty screening tools in older women with early breast cancer - Corrected Proof

M.J. Molina-Garrido, C. Guillen-Ponce — 2010-07-21

Abstract: Introduction and objectives: We have tested two frailty screening tools (the Barber Questionnaire [BQ] and the Vulnerable Elderly Survey [VES-13]) to select patients who may benefit from Comprehensive Geriatric Assessment (CGA).Materials and methods: We included women ≥65 years old, diagnosed with early breast cancer at the University General Hospital in Elche. We compared impairment in the BQ score (score <0 vs. >0) and impairment in the VES-13 score (<3 vs. ≥3), with impaired CGA results (<2 scales with deficits vs. ≥2). We evaluated the diagnostic performance of both questionnaires by Area Under Curve [AUC] and analyzed their concordance with CGA scales (intraclass correlation coefficient [ICC]).Results: Forty-one women were included. The risk of frailty was 41.76%, 29.3%, and 55.7% when evaluated with BQ, VES-13 and CGA, respectively. The correlation between BQ and CGA was fair (ICC=0.672), but between VES-13 and CGA was very good (ICC=0.814). The predictive capacity of the BQ and the VES-13 for detecting frailty risk was intermediate (AUC=0.719) and high (AUC=0.876), respectively.Conclusions: We propose the use of the VES-13 in older women with early breast cancer and the implementation of CGA when VES-13<3.

WITHDRAWN: Falls in men on androgen deprivation therapy for prostate cancer - Corrected Proof

Shabbir Hussain, Henriette Breunis, Narhari Timilshina, Shabbir M.H. Alibhai — 2010-07-12

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Positron emission tomography and colorectal cancer - Corrected Proof

Michael Lin, Karen Wong, Weng Leong Ng, Ivan Ho Shon, Matthew Morgan — 2010-07-12

Abstract: Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality. Molecular imaging using positron emission tomography (PET) is now an integral part of multidisciplinary cancer care. In this review, we discuss the role of PET in CRC including well established indications in the assessment of recurrent disease and emerging applications such as initial staging, monitoring therapy efficacy and using PET for radiotherapy planning. With rapid advancement in imaging technology, we also discuss the future potential of combining PET and magnetic resonance imaging and the use of novel radiotracers.

Cetuximab plus irinotecan after irinotecan failure in elderly metastatic colorectal cancer patients: Clinical outcome according to KRAS and BRAF mutational status - Corrected Proof

2010-07-09

Abstract: Background: Scarce data are available about safety and efficacy of cetuximab in elderly metastatic colorectal cancer (mCRC) patients.Patients and methods: We retrospectively analysed 54 irinotecan-refractory mCRC patients aged≥70 years treated with cetuximab plus irinotecan and evaluated clinical outcome according to KRAS and BRAF mutational status.Results: Median age was 73 years (70–82). Main grade 3–4 toxicities were skin rash (15%), diarrhea (19%) and neutropenia (13%). Irinotecan dose reduction was necessary in 39% of patients. Fifty-two (96%) patients were analysed for KRAS and BRAF status. The 29 KRAS wild-type patients achieved better RR (31% vs 4%; p=0.030) and median PFS (4.21 months vs 3.95 months; p=0.034; HR: 0.50, 95% CI: 0.27–0.95) when compared with KRAS mutated ones. RR (41% vs 3%; p=0.001) and mPFS (4.57 months vs 3.78 months, p=0.001; HR: 0.35, 95% CI: 0.19–0.66) were significantly higher among the 22 KRAS and BRAF wild-type patients compared to the 30 KRAS or BRAF mutated ones.Conclusion: Cetuximab plus irinotecan has a favourable safety profile in elderly mCRC patients, but a reduced dose of irinotecan should be considered. Such a combination can be a useful option for elderly KRAS and BRAF wild-type patients.

Radiotherapy for invasive breast cancer: Guidelines for clinical practice from the French expert review board of Nice/Saint-Paul de Vence - Corrected Proof

2010-07-08

Abstract: Purpose: While new strategies for the treatment of invasive breast cancer (BC) are emerging, radiotherapy (RT) modalities are still under debate. The French expert review board of Nice-Saint-Paul de Vence was asked firstly to conduct a qualitative evidence-based systematic review and then to establish clinical practice guidelines for the use of post operative RT in invasive BC.Methods and materials: A search to identify eligible studies was undertaken using the Medline® database. All phase III randomized trials and systematic reviews evaluating the role and modalities of RT in invasive BC were included, together with some noncontrolled studies if no randomized trials were identified. The quality and clinical relevance of the studies were evaluated to determine the level of evidence.Results: The maximum delay between surgery and RT should ≤8 weeks when chemotherapy (CT) is not indicated. This should not exceed 24 weeks when adjuvant CT is administered. Whole breast RT delivering 50Gy in 25 fractions followed by a boost of 10–16Gy remains the standard of care after conservative surgery (CS). In the elderly population, for certain cases presenting comorbidities associated with a limited life expectancy, RT indication (even hypofractioned) and boost delivery may be unnecessary in the light of an unfavourable risk/benefit ratio. RT technique and indications should not vary in case of neoadjuvant CT followed by CS. After total mastectomy, RT should be indicated in N+ and in N− patients with high risk of local recurrence. The experts recommend to initiate tamoxifen at the end of RT, while aromatase inhibitors could be administered either concomitantly or sequentially with RT. There is no consistent data to delay (or suspend) trastuzumab administration during RT. As for all patients, in case of concurrent RT-trastuzumab administration, reduction of cardiac tissues exposure is highly recommended. After breast reconstruction, RT should be delivered as after standard CS without boost.Conclusion: Due to significant variations in practice in the treatment of patients with BC, our group aimed to provide guidelines for clinical practice. The systematic review of the literature formed the basis of our evidence-based recommendations; however expert agreements were necessary on those subjects that are still under debate. Our group will update these guidelines every 4 years, taking in consideration new advances in technology, new drugs administration, biologic tools and innovative therapeutic options.

Targeted anti-cancer therapy in the elderly - Corrected Proof

Wilson Gonsalves, Apar Kishor Ganti — 2010-07-05

Abstract: Cancer is a disease of the elderly with the majority of new diagnoses and deaths from cancer occurring in persons greater than 65 years of age. A major goal of cancer therapy, in the elderly is the preservation of functional independence and quality of life. The advent of targeted therapies has raised the hope that older patients with cancer could be treated as effectively as younger patients and without added toxicities. However, caution must be exercised while addressing the use of these therapies in the elderly population and only after taking into consideration the risks, benefits and prognosis of patients on an individual basis. This article reviews the current literature on the efficacy, cost-effectiveness and toxicity of the currently approved targeted agents in the elderly population.

Potential drug interactions in elderly cancer patients - Corrected Proof

2010-07-02

Abstract: Introduction: Drug interaction constitutes a major challenge in elderly cancer patients. This study investigated the number and types of medications patients and potential drug interactions in these patients.Methods: Treatments received by 105 cancer outpatients aged ≥70 years were analyzed using the French Thesaurus to identify drug–drug interactions according to four levels: contraindication, concomitant use not recommended, concomitant medications requiring precautions and concomitant medications to be taken into account.Results: The mean number of medications per patient was 4.7 (range: 0–14). Among 97 patients taking ≥2 drugs, 45 potential interactions were identified, occurring in 32 patients. No contraindication, 2 cases of concomitant use not recommended, 9 cases requiring precautions (20%) and 34 cases of concomitant medications to be taken into account were identified. Drug interactions caused respiratory distress and increased bleeding risk.Conclusion: Drug interactions are common in the elderly, but almost half of interactions were moderate.

Serum CD44 levels predict survival in patients with low-risk myelodysplastic syndromes - Corrected Proof

2010-06-28

Abstract: Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders that are preferentially diagnosed in the elderly. Aberrant expression of the adhesion receptor CD44 correlates with poor prognosis in various neoplasms. To evaluate the prognostic impact of CD44 in MDS serum levels of soluble CD44 standard (solCD44s) were measured in 130 MDS patients (median age 68 years) using an enzyme-linked immunosorbent assay (ELISA). solCD44s levels were significantly elevated in MDS patients as compared to those of healthy donors (p<0.001) and were found to correlate with distinct FAB and WHO subtypes. The highest levels of solCD44s were found in patients with CMML, in RAEB and in patients with MDS transformed into secondary acute myeloid leukaemia (AML). In univariate analysis elevated levels of solCD44s (cut-off level>688.5ng/ml) correlated significantly with shorter overall survival in MDS patients (12 versus 39 months; p<0.001). In multivariate analysis solCD44s displayed prognostic significance independent of the International Prognosis Scoring System (IPSS). To test for refined prognostication, IPSS risk groups were split into two separate categories based on the solCD44s levels. Using this approach, MDS patients with a shorter survival were identified both in the IPSS low-risk (p=0.037) and in the IPSS intermediate-1-risk group (p=0.015). The CD44s-adjusted IPSS defines a cohort of MDS patients with unfavorable prognosis, which might be helpful in risk stratification and in therapeutic algorithms.

Comorbidity, not age, is prognostic in patients with advanced pancreatic cancer receiving gemcitabine-based chemotherapy - Corrected Proof

2010-06-25

Abstract: Objective: To evaluate the impact of age and comorbidity on clinical outcomes in advanced pancreatic cancer.Methods: Consecutive 237 patients with advanced pancreatic cancer were studied. Comorbidity was scored by Charlson comorbidity index (CCI). We compared the clinical outcomes by age or comorbidity.Results: Sixty-nine patients were elderly (≥75 years), and CCI was 0 in 69 patients, 1 in 98, and ≥2 in 70. Gemcitabine-based chemotherapy was administered in 183 patients and was well tolerated in both elderly group and in those with comorbidities. In a multivariate analysis, CCI, not age, was prognostic in addition to PS, distant metastasis, chemotherapy and CA19-9: the hazard ratios of CCI 1 and ≥2 were 1.25 and 1.55, compared with CCI 0 (p=0.027).Conclusions: Gemcitabine-based chemotherapy can be an effective treatment, without significant toxicity, in elderly patients. Comorbidity, not age, was prognostic in patients with advanced pancreatic cancer.

The role of hypoxia inducible factor-1alpha in gynecological cancer - Corrected Proof

2010-06-07

Abstract: Understanding the mechanisms of carcinogenesis and progression of gynecological tumors is important as these insights might lead to improved diagnostic tools for the pathologist, improved prediction of prognosis, response to therapy, and eventually better biology-based disease management, thereby improving prognosis and quality of life for the individual patient. Hypoxia is an important event in carcinogenesis because it renders a more aggressive phenotype with increased invasiveness and proliferation, formation of metastases and poorer survival. Although selecting patients with hypoxic tumors may therefore be clinically important, there is no consensus as to the method best suited for routine assessment of hypoxia. One of the potential tumor hypoxia markers is hypoxia inducible factor 1 (HIF-1). HIF-1 is the key cellular survival protein under hypoxia, and is associated with tumor progression and metastasis in various solid tumors. In this review, we show that in gynecological cancers, HIF-1A is emerging as an important factor in carcinogenesis, and that overexpression of HIF-1A and its target genes CA9 and SLC2A1 seems associated with shorter progression free- and overall survival. Since hypoxia and HIF-1A expression are associated with treatment failure, targeting HIF-1A could be an attractive therapeutic strategy with the potential for disrupting multiple pathways crucial for tumor growth. Currently, HIF-1A inhibitors are being studied in clinical trials in recurrent ovarian- and cervical cancer, and trials in other gynecological cancers are expected.

Suicide and cancer: Where do we go from here? - Corrected Proof

2010-06-02

Abstract: Although suicide in cancer patients is a burdening public health problem with ethical, medical and psychiatric implications, it still has to be clarified why cancer patients commit suicide and how cancer suicides differ from others. Therefore, a review of the literature on suicide and suicidal ideation in cancer patients was conducted, starting from an overview of these issues in the general population. Evidence suggests that suicidality in the general population can be explained according to a genetic and psychological vulnerability to stress. The psychological and physical stressors found to be associated with suicide in cancer patients corroborate this model. Nevertheless, based on the well-described immunological disturbances due to cancer, we propose that suicide is not just a secondary reaction to cancer but is linked to an intrinsic bio-psychological vulnerability to distress. Upcoming studies should better characterize the neurobiology of suicidality in cancer, opening new avenues for treatment and prevention.

Malignant melanoma of unknown primary site. To make the long story short. A systematic review of the literature - Corrected Proof

K. Kamposioras, G. Pentheroudakis, D. Pectasides, N. Pavlidis — 2010-05-31

Abstract: Introduction: Although more than 90% of melanomas have a cutaneous origin, occasionally it is discovered as a secondary deposit without evident primary site. The aim of this study was to systematically review published literature and analyse data on incidence, presentation, therapeutic interventions, survival and prognostic factors.Methods: We searched MEDLINE, (search terms Melanom*, unknown origin, unknown primary, indolent, occult) and the abstracts from major congresses of the last 4 years and perused the references of the retrieved relevant articles.Results: 4348 patients with MUP were reported along with 132,643 patients with Melanoma of Known Primary (MKP). The incidence of MUP was 3.2%. The male to female ratio was 2:1 while the age peak was in the 4th and 5th decades. MUP patients harbouring nodal disease had a median overall survival ranging between 24 and 127 months, 5-year survival rate between 28.6% and 75.6% and 10-year survival rate between 18.8% and 62.9%. MUP patients with visceral disease had median survival times between 3 and 16 months, and 5-year survival rates between 5.9% and 18%. Presence of tumour regression in metastatic sites and low nodal burden were associated with favourable outcome. Potentially curative surgical treatment offered survival advantage in comparison to patients with residual metastatic foci. MUP patients who received adjuvant chemotherapy or radiotherapy paradoxically seemed to fare worse compared to patients observed.Conclusions: This is the first review to bring together the information of 89 years and to analyze all the potential information accumulated. Although a well know entity no consensus is reached in order to describe MUP presentation, management or prognosis.

Disseminated and circulating tumor cells: Role in effective cancer management - Corrected Proof

Henry Lin, Marija Balic, Siyang Zheng, Ram Datar, Richard J. Cote — 2010-05-31

Abstract: Dissemination of tumor cells from primary tumors in the circulatory system is an early event in carcinogenesis. The presence of these single disseminated tumor cells (DTC) in peripheral blood, bone marrow and distant organs is the rationale for adjuvant systemic treatment. Detection of DTC in bone marrow aspirates from breast cancer patients and other solid tumors at the primary diagnosis impacts the prognosis of disease. In peripheral blood these cells are termed as circulating tumor cells (CTC). Due to technical difficulties the clinical significance of CTC detection at early stages is less established. This review focuses on available techniques for detection of DTC and CTC, recent technical advances in development of more sensitive microfluidic methods for capture of DTC and CTC and possibilities for further detection and their potential molecular characterization. Not only the clinical significance of DTC but also the presence of cancer stem cells in dissemination clearly demonstrates the need for development of sensitive technologies allowing for definition of biomarkers and molecular targets on cells in dissemination, thus eventually leading to optimization of systemic therapies.

Resistance to HER2 inhibitors: Is addition better than substitution? Rationale for the hypothetical concept of drug sedimentation - Corrected Proof

Mario Campone, Philippe Juin, Fabrice André, Thomas Bachelot — 2010-05-31

Abstract: Twenty years were passed between the discovery of oncogene HER2, the description of its implication in mammary carcinogenesis, and the development of specific targeted therapies. To date, trastuzumab and lapatinib are the two anti-HER2 targeted therapies commonly used, demonstrating therapeutic effects. Although their clinical efficacy seems to be exclusively related to the amplification of the HER2 gene or to the overexpression of the protein, these factors are not sufficient since tumors can develop resistance. Because of a better knowledge in those mechanisms of resistance, novel therapeutic agents could help to bypass them. How should these be used with respect to current anti-HER2 targeted therapies? Recent notions such as oncogene addiction, tumor cell dormancy and residual disease led us to propose a new entity that we named the “sedimentation strategy”, in which distinct targeted approaches are summed during the treatment of metastatic breast cancer patients.

Renal outcome and monoclonal immunoglobulin deposition disease in 289 old patients with blood cell dyscrasias: A single center experience - Corrected Proof

2010-05-31

Abstract: Monoclonal components (MC) formed by chains/fragments of intact/truncated globulin components produced in different lymphoproliferative diseases are responsible for monoclonal immunoglobulin deposition disease (MIDD) and consequent tissue damage by organized (amyloid fibrils) or non-organized (amorphous) deposits.The kidneys are the most commonly affected organs in MIDD, and renal failure represents an important adverse factor for prognosis.The renal outcome and the role of renal pathology in diagnosing MIDD was evaluated in 289 elderly patients with multiple myeloma (MM, n=115) and monoclonal gammopathy (MGUS, n=174). Renal impairment was the only significant risk factor for patient death, while significant risk factors for renal impairment were diabetes (HR 3.65, 95% CI: 2.08–6.41), light chain (LC) proteinuria (HR 2.18; 95% CI: 1.10–4.32) and type of MC (p=0.0019). Renal pathology documented MIDD in 12/30 cases (40%): six cases of AL-amyloidosis, two of LC disease, one of heavy chain disease and three of cast nephropathy, as well as four cases of glomerulonephritis, eight of arteriolosclerosis and six of normal picture.Main conclusions are that diabetes, sharing common glomerular damage with LC disease, is the strongest risk factor for progression of renal disease, and glomerular proteinuria or heavy LC proteinuria should raise a strong suspicion index of MIDD and prompt pathology assessment to reach the correct diagnosis.

Shooting the messenger: Targeting signal transduction pathways in leukemia and related disorders - Corrected Proof

Suzita M. Noor, Richard Bell, Alister C. Ward — 2010-05-31

Abstract: Traditional treatments for leukemia and myeloproliferative disorders have involved invasive clinical regimes, including chemotherapy, phlebotomy, and bone marrow transplantation, together with supportive care. These have been of variable effectiveness and have often elicited adverse, sometimes life-threatening side effects. Perturbation of key signal transduction pathways has become a consistent finding in the pathophysiology of leukemia and related diseases. This has allowed the development of specific pharmacological agents targeting deviant pathway component(s). Of this class of therapeutics those directed at the leukemic oncoproteins BCR-ABL and PML-RARα have provided proof-of-concept of the approach and are now established mainstream therapies. Specific inhibitors for the JAK2 tyrosine kinase are now in active development for myeloproliferative disorders and may become a new class of targeted therapeutics. However, an emerging motif in the field is the convergence of multiple mutant pathways on key downstream messengers, such as STAT5 or PI3-kinase, which therefore constitute potential new therapeutic targets.

The impact of anemia on quality of life and hospitalisation in elderly cancer patients undergoing chemotherapy - Corrected Proof

2010-05-19

Abstract: Aim of the study: At present, there is very little data available about the impact of anemia on elderly cancer patient's quality of life (QoL). Most of the acquired knowledge has been derived from small studies selected for primary site cancer. This observational study investigates the association between hemoglobin (Hb) level and comprehensive geriatric assessment variables: Cancer Linear Analog Scale (CLAS), Activities of Daily Living (ADL), Mini-Mental State Examination (MMSE) in elderly cancer patients undergoing chemotherapy (CT).Methods: We enrolled 586 elderly cancer patients undergoing CT who were evaluated at baseline and every 3–4 weeks for at least 12 weeks. The correlation between Hb level changes and the examined index changes were performed using Pearson correlation analysis and a multivariate analysis was performed using a logistic regression model.Results: Both univariate and multivariate analyses at baseline showed that Hb values are related to ECOG performance status (PS), stage of disease and self-reported QoL. Hb level variation significantly correlated with CLAS and ADL changes measured at baseline and after 12 weeks. This correlation is highly significant in patients with Hb<11g/dl.Multivariate analysis showed that Hb change of at least 1g/dl was the only independent predictor of a better quality of life, when assessed by using the CLAS and ADL questionnaire (p<0.05). Moreover the median time of hospitalisation was found to be significantly lower in patients showing higher Hb level (Hb≥11g/dl) (p=0.037).Conclusions: The findings of this study seem to provide adequate support for the correlation between anemia and elderly cancer patient's QoL. Interestingly, we reported an association between anemia and the length of hospitalisation in this setting of patients. However, the above results do need to be confirmed by further prospective trials.

Malignant pleural mesothelioma: The standard of care and challenges for future management - Corrected Proof

Jan P. van Meerbeeck, Arnaud Scherpereel, Veerle F. Surmont, Paul Baas — 2010-05-13

Abstract: This review addresses the management of MPM. In an introductory section, the etiology, epidemiology, presentation, diagnosis and staging of MPM will be reviewed. The evidence was collected by a systematic analysis of the literature (2000–2009) using the databases Medline (National Library of Medicine, USA), Embase (Elsevier, Netherlands), Cochrane Library (Great Britain), National Guideline Clearinghouse (USA), HTA Database (International Network of Agencies for Health Technology Assessment – INAHTA), NIH database (USA), International Pleural Mesothelioma Program – WHOLIS (WHO Database) with the following keywords and filters: pleura, cancer, mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, palliation, supportive care, pleurodesis, review.

Effects of azacitidine compared with conventional care regimens in elderly (≥75 years) patients with higher-risk myelodysplastic syndromes - Corrected Proof

2010-05-07

Abstract: This analysis compared azacitidine (AZA) to conventional care regimens (CCR) and their associated overall survival (OS) and tolerability in the subset of 87 elderly (≥75 years) patients with higher-risk MDS (FAB: RAEB, RAEB-t, CMML and IPSS: Int-2 or High) from the AZA-001 trial. Patients were randomized to AZA (75mg/m2/daysubcutaneously×7 days every 28 days) (n=38) or CCR (n=49) and had median ages of 78 and 77 years, respectively. AZA significantly improved OS vs CCR (HR: 0.48 [95%CI: 0.26, 0.89]; p=0.0193) and 2-year OS rates were 55% vs 15% (p<0.001), respectively. AZA was generally well tolerated compared with CCR, which was primarily best supportive care (67%). Grade 3–4 anemia, neutropenia, and thrombocytopenia with AZA vs CCR were 13% vs 4%, 61% vs 17%, and 50% vs 30%, respectively. Given this efficacy and tolerability, AZA should be considered the treatment of choice in patients aged ≥75 years with good performance status and higher-risk MDS.

A randomised trial of mastectomy only versus tamoxifen for treating elderly patients with operable primary breast cancer—Final results at 20-year follow-up - Corrected Proof

2010-05-06

Abstract: A recent Cochrane review of trials involving elderly women with operable primary breast cancer showed no significant difference in overall survival between surgery (±adjuvant tamoxifen) and primary endocrine therapy using tamoxifen. We report the final results of a randomised pilot trial comparing primary tamoxifen and wedge mastectomy as initial treatment in this population.One hundred and thirty-one women >70 years with early operable primary breast cancer (<5cm), unselected for oestrogen receptor (ER), entered the trial in 1982–1987. Sixty-eight patients were allocated to tamoxifen only and 67 to wedge mastectomy only, as primary treatment.At 20 years of follow-up, the median time to local failure was significantly shorter in the tamoxifen arm though approximately one-fifth of patients in this group did not develop local failure requiring mastectomy. There was no difference in regional recurrence, distant metastases or overall survival between the mastectomy and tamoxifen arms.In this small study, primary endocrine therapy achieved local control in 30% of those surviving at 5 years and 20% at 10 years, unselected for ER. The primary therapy used did not significantly affect regional recurrence, incidence of distant metastases or overall survival. Primary endocrine therapy should certainly be considered in those patients with ER positive tumours and who are unfit (based on life expectancy) for or refuse surgery.

Are frailty markers useful for predicting treatment toxicity and mortality in older newly diagnosed cancer patients? Results from a prospective pilot study - Corrected Proof

2010-05-05

Abstract: Introduction: The concept of frailty may be useful to characterize vulnerability. The aim of this pilot study was to explore the association between frailty/functional status and treatment toxicity at 3 months and mortality at 6 months.Methods: Patients aged ≥65 years referred to the Jewish General Hospital, Montreal, with a new cancer diagnosis. Seven frailty markers and 4 functional status measures were examined. Logistic regression was used to examine the association between frailty/functional status and toxicity, and Cox models for time to death.Results: 112 participated, median age 74.1, 31 had toxicity and 15 died. At baseline, 88% had ≥1 frailty marker. Low grip strength predicted toxicity (OR 8.47, 95%CI: 1.3–53.6), ECOG performance status and ADL disability predicted time to death.Conclusion: The majority had ≥1 frailty marker. Low grip strength predicted toxicity, none of the functional measures did. Further researcher investigating the usefulness of frailty markers is needed.

WITHDRAWN: Cognitive effects of androgen deprivation therapy in an older cohort of men with prostrate cancer - Corrected Proof

2010-04-30

This article has been withdrawn from Critical Reviews in Oncology/Hematology. With the permission of the authors, it has been published in Volume1, issue 1 of the Journal of Geriatric Oncology (www.geriatriconcology.net). The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Pazopanib: Clinical development of a potent anti-angiogenic drug - Corrected Proof

Fabio A.B. Schutz, Toni K. Choueiri, Cora N. Sternberg — 2010-04-26

Abstract: Pazopanib is an oral, multi-targeted, tyrosine kinase inhibitor (TKI) that binds to the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and several other key proteins responsible for angiogenesis, tumor growth and cell survival. Pazopanib exhibited in vivo and in vitro activity against tumor growth and, in early clinical trials, was well tolerated with the main side effects being hypertension, fatigue and gastrointestinal disorders. Pazopanib showed clinical activity in several tumors including renal cell cancer (RCC), breast cancer, soft tissue sarcoma, thyroid cancer, hepatocellular cancer and cervical cancer. A phase III clinical trial in metastatic RCC patients showed a significant improvement in progression-free survival, leading to its approval in the US. In metastatic breast cancer, the combination of pazopanib with lapatinib was more effective than lapatinib alone. At the time of the current publication, pazopanib is being evaluated in more than 35 phase II and III trials.

The evolving role of adjuvant therapy in endometrial cancer - Corrected Proof

Angiolo Gadducci, Carlo Greco — 2010-04-26

Abstract: Extra-fascial total hysterectomy and bilateral salpingo-oophorectomy with or without lymph node dissection is the initial treatment for endometrial cancer. Unresolved scientific controversy exists regarding the selection of patients who may benefit from lymphadenectomy, the magnitude of such benefit, and the role of adjuvant therapy. External pelvic irradiation has been shown to reduce loco-regional recurrences without improving survival. Meta-analyses of randomized trials indicate that external pelvic irradiation offers a significant benefit in terms of survival only in high-risk disease (i.e. stage Ic grade 3). Intermediate risk patients (i.e. stage Ib grade 3 disease), therefore, may be treated with adjuvant intravaginal brachytherapy alone to avoid the risk of side effects associated with pelvic irradiation. Overall, patients with clinically early endometrial cancer develop relapses in less than 20% of cases, mostly at distant sites. Randomized trials comparing adjuvant external pelvic irradiation versus adjuvant chemotherapy have shown conflicting clinical results. Chemotherapy seems to prevent or delay distant spread more than radiotherapy, while radiotherapy appears to prevent or delay local relapses more than chemotherapy, although these trends fail to achieve statistical significance. Recent evidence from a randomized trial indicates that sequential external pelvic irradiation with or without brachytherapy and platinum-based chemotherapy result in significantly better progression-free survival than radiotherapy alone in patients with high-risk endometrial cancer. Reliable surgical/pathological variables predictive of high risk of distant failure may be used to identify a subset of patients suitable for randomized trials of adjuvant chemotherapy with or without external irradiation.

A retrospective analysis of outcomes by age in a three-arm phase III trial of gemcitabine in combination with carboplatin or paclitaxel vs. paclitaxel plus carboplatin for advanced non-small cell lung cancer - Corrected Proof

2010-04-22

Abstract: Purpose: Sufficient data are currently unavailable to assist in defining suitable regimens for patients ≥70 years with advanced non-small cell lung cancer (NSCLC).Methods: Chemonaïve patients with a performance status (PS) of 0 or 1 and stage IIIB or IV NSCLC were randomized to gemcitabine 1000mg/m2 on days 1 and 8 plus carboplatin area under the curve (AUC) 5.5 on day 1; the same schedule of gemcitabine plus paclitaxel 200mg/m2 on day 1; or paclitaxel 225mg/m2 on day 1 plus carboplatin AUC 6.0 on day 1. Cycles were every 21 days up to 6. Efficacy and toxicity results were compared by age groups.Results: Overall survival (OS) between patients <70 years (8.6 months, 95% CI: 7.9, 9.5) and ≥70 years (7.9 months, 95% CI: 7.1, 9.5) was similar. OS was 8.8 months (95% CI: 7.5, 10.3) among patients 70–74 years, 6.5 months (95% CI: 5.6, 9.3) among patients 75–79 years, and 7.9 months (95% CI: 6.3, 10.3) among patients ≥80 years. OS was lower among patients 75–79 years compared with patients 70–74 years (P=0.04). Compared with patients <70 years, patients ≥70 years experienced similar rates of myelosuppresion, but younger patients experienced more vomiting and nausea. There was no clear pattern with respect to differences in efficacy by treatments across age groups.Conclusions: Based on the similarity of patient outcomes across age groups, doublet chemotherapy is feasible among carefully selected elderly patients with good PS.

Febrile neutropenia: A critical review of the initial management - Corrected Proof

Jean Klastersky, Ahmad Awada, Mariane Paesmans, Mickael Aoun — 2010-04-22

Abstract: The present state of the art for management of patients with febrile neutropenia has been reviewed as well as potential ways to improve it in the future. A major advance has been the possibility to predict, accurately and early, the risk of complications and death in those patients. While the algorithm for therapy in low-risk patients is presently straightforward, significant progresses are needed for patients who are at higher risk of presenting severe complications.

Effects of pain, fatigue, insomnia, and mood disturbance on functional status and quality of life of elderly patients with cancer - Corrected Proof

Karis K.F. Cheng, Diana T.F. Lee — 2010-04-20

Abstract: Background: Most elderly patients with cancer suffer from a multitude of intense physical and psychological symptoms regardless of the stage of disease. The current paper describes the prevalence of pain, fatigue, insomnia, and mood disturbance, alone and in combination in elderly cancer patients, as well as the inter-correlations among these four symptoms, and the relationship of the symptom cluster to functional status and quality of life (QoL) during cancer therapy.Patients and methods: This cross-sectional study used secondary data from a convenience sample of 120 patients, 65 years of age and older, with colorectal, lung, head/neck, breast, gynecological, prostate or esophageal cancer receiving chemotherapy or radiotherapy. Measuring instruments included the Karnofsky Performance Scale (KPS), the respective items from the Chinese version of the Symptom Distress Scale (SDS-C), and the Functional Assessment of Cancer Therapy-General (FACT-G [C]). The influence of the symptom cluster on patients’ functional status and QoL was determined by hierarchical multiple regression.Results: Twenty percent and 29.2% of patients reported co-occurrence of any two and any three symptoms of pain, fatigue, insomnia, and mood disturbance, respectively. About one-third of patients (31.2%) reported co-occurrence of all of the four symptoms. The inter-correlations among pain, fatigue, insomnia, and mood disturbance were mild to moderate (r=0.29–0.43, p<0.01). In terms of functional status, the KPS showed a moderate negative correlation with the four symptoms (r=−0.29 to −0.55, p<0.01). Correlations between the FACT-G (C) subscale/total scores and symptom cluster showed moderate negative correlations (r=−0.23 to −0.55, p<0.01). About 8.7–52.9% of variance in functional status and QoL is explained by the symptom cluster of pain, fatigue, insomnia, and mood disturbance in elderly cancer patients receiving cancer therapy after adjustment for gender, age, co-morbidity, stage of disease, and treatment modality.Conclusions: Our results suggest that pain, fatigue, insomnia, and mood disturbance are highly prevalent in elderly patients who undergone cancer therapy. These four symptoms may occur in a cluster and may negatively influence elderly patients’ functional status and QoL during cancer therapy.

Experience with sorafenib and adverse event management - Corrected Proof

Joaquim Bellmunt, Timothy Eisen, Mayer Fishman, David Quinn — 2010-04-20

Abstract: Sorafenib was the first multikinase inhibitor to be approved for use in renal cell cancer (RCC) in the US (2005) and in Europe (2006). In the Treatment Approaches in Renal Cell Cancer Global Evaluation Trial (TARGET), sorafenib showed a significant progression-free survival advantage over placebo in patients with advanced RCC. Incidence rates of adverse events were significantly higher with sorafenib than with placebo. Management of adverse events is an essential component of care to prevent negative impact on patient quality of life and dose modification of sorafenib therapy. This report, based on an expert panel discussion held in February 2009, presents recommendations for the management of skin rash, hand-foot skin reaction, diarrhea, and hypertension, and strategies to help lessen the frequency and severity of these events. In addition, general recommendations for dose modifications are discussed. The goal of these management recommendations is to optimize sorafenib therapy for advanced RCC.

Guidelines, minimal requirements and standard of cancer care around the Mediterranean Area: Report from the Collaborative AROME (Association of Radiotherapy and Oncology of the Mediterranean Area) working parties - Corrected Proof

AROME — 2010-04-20

Abstract: Guidelines are produced in oncology to facilitate clinical decision making and improve clinical practice. However, existing guidelines are mainly developed for countries with a certain availability of means and cultural aspects are rarely taken into account. Around the Mediterranean Area, countries share common cultural backgrounds but also great disparities with respect to availability of means; current guidelines by most societies are not applicable to all of those countries. Association of Radiotherapy and Oncology of the Mediterranean Area (AROME) is a scientific organization for the promotion and overcoming of inequalities in oncology clinical practice around the Mediterranean Area. In an effort to accomplish this goal, members of the AROME society have developed clinical recommendations for most common cancer sites in countries around the Mediterranean Area. The structure of these recommendations lies in the concept of minimal requirements vs. standard of care; they are being presented and discussed in the main text.

Thrombopoietic growth factors in the treatment of immune thrombocytopenic purpura - Corrected Proof

Tingting Wang, Zhao Wang, Renchi Yang — 2010-04-08

Abstract: Immune thrombocytopenic purpura (ITP) is a relatively common blood disorder related to the production of anti-platelet antibodies. It is now clear that platelet production is also substantially impaired in most patients. After the cloning of TPO and analogs, there were reported therapeutic successes in a few refractory ITP patients, but neutralizing antibodies led to the withdrawal of first-generation thrombopoietic growth factor from development. Second-generation thrombopoietic growth factors are now available that stimulate c-mpl but share no homology with the native hormone. Second-generation thrombopoietic growth factors have shown responses in 50–80% of ITP patients with only modest toxicity, and thus they offer another therapeutic option. The first of these agents to enter clinical trials and to be approved by the FDA is romiplostim, a once weekly subcutaneous peptibody. Eltrombopag is the second FDA-approved thrombopoietic growth factor and has the advantage of oral formulation. Some concerns persist on the potential of these agents to cause increased thrombosis risk, rebound thrombocytopenia on drug withdrawal, reticulin fibrosis of the marrow, and induction of malignancy, but these have not emerged as major problems in clinical trials.

Impact of an all-oral capecitabine and vinorelbine combination regimen on functional status of elderly patients with advanced solid tumours: A multicentre pilot study of the French geriatric oncology group (GERICO) - Corrected Proof

2010-03-31

Abstract: Background: Elderly metastatic cancer patients typically have short life expectancy and frequently suboptimal treatment. Goals of therapy should include preservation of functional status as well as clinical response. For elderly patients, oral chemotherapy could be a valuable strategy, avoiding the constraints and risks of intravenous drugs.Methods: This study assessed effect of an all-oral combination of capecitabine and vinorelbine on functional status (measured by basic Activities of Daily Living [ADL]), toxicity, efficacy and compliance in patients ≥70 years with advanced breast, prostate or lung cancer.Results: Eighty patients were enrolled. After three cycles, 81.8% of patients had stabilised or improved ADL, and 8.6% and 42.9% had a response or stabilised disease. Compliance was excellent (68.8%). The most common grade 3–4 toxicities were haematological (17.9%) and gastrointestinal (7.7%).Conclusion: In elderly cancer patients, an all-oral combination of capecitabine and vinorelbine maintains functional status, is well tolerated, and provides good disease control.

Development of a cancer-specific Comprehensive Geriatric Assessment in a University Hospital in Spain - Corrected Proof

M.J. Molina-Garrido, C. Guillén-Ponce — 2010-03-30

Abstract: Introduction: The Comprehensive Geriatric Assessment (CGA) is a key component of the treatment approach for older cancer patients. The goals of the current study were to develop a brief but non-self-administered cancer-specific geriatric assessment and to determine its feasibility, as measured by (1) the length of time to completion and (2) patient satisfaction.Methods: The literature was reviewed to select validated scales for geriatric assessment across the following domains: functional status, co-morbidity, cognition, social support and risk of malnutrition. Oncologic patients older than 70 years were included in the study.Results: The instrument was completed by 99 patients (mean age, 78.65 yrs). The mean time to completion of that was 12.9min (range, 9.5–20.5min). Most patients were satisfied with its length (63.6%), and most considered it fairly easy to complete (69.7%).Conclusions: The designed CGA was accepted by most patients and was not perceived to be overly time-consuming.

Quality of life in geriatric oncology—An evaluation of standard questionnaires in elderly men with urological malignancies - Corrected Proof

Catherine Terret, David Pérol, Gilles Albrand, Jean Pierre Droz — 2010-03-25

Abstract: Quality of life (QOL) is a critical issue in elderly patients with cancer. In the geriatric population, cancer is often associated with other chronic conditions possibly affecting QOL. This prospective study aimed to evaluate the validity of two QOL questionnaires, EORTC QLQ-C30 and SF-36, in older cancer patients. Seventy-two of 87 male patients with genitourinary cancer (median age, 76 years) completed the questionnaires (83% response rate). Internal consistency reliability was high (α≥0.7), except for SF-36 cognitive function (α=0.62) and QLQ-C30 general health status (α=0.57). QLQ-C30 and SF-36 appear similarly reliable for QOL assessment in this population. However, cognitive function and functional status, two factors likely to influence the value of QOL self-assessment, are poorly taken into account whereas they are correctly explored by the comprehensive geriatric assessment (CGA) procedure. QOL assessment in elderly cancer patients should therefore be associated with CGA to better meet the expectations of clinicians.

Difficulties in decision making regarding chemotherapy for older cancer patients: A census of cancer physicians - Corrected Proof

2010-03-24

Abstract: Introduction: The management of older cancer patients is often suboptimal. This study aims to understand the management of older cancer patients who may receive chemotherapy.Methods: A questionnaire was mailed in 2006–2007 to 181 medical oncologists and hematologists practicing in the Province of Quebec, Canada. Physicians, involved in treatment decisions regarding chemotherapy in cancer patients aged 70 years and older, were eligible.Results: The response rate was 45.7%. Treatment toxicity (24.4%), comorbidities (20.5%), and lack of social support (10.9%) were reported as challenges when caring for older cancer patients. Comorbidities and functional status were reported as principal factors when making treatment decisions regarding chemotherapy; 77.5% of respondents expressed interest in collaborating with geriatricians.Conclusions: The concerns of respondents about comorbidities, functional status, and social support, along with their interest to collaborate with geriatricians, support the need for a partnership between these two disciplines.

Targeting immune suppressing myeloid-derived suppressor cells in oncology - Corrected Proof

2010-03-22

Abstract: Emerging data suggests that host immune cells with a suppressive phenotype represent a significant hurdle to successful therapy for metastatic cancer. Among the suppressor cells, T regulatory cells (Treg) and myeloid-derived suppressor cells (MDSC) are significantly increased in hosts with advanced malignancies. MDSC mediate the suppression of the tumor antigen-specific T cell response through the induction of T cell anergy and the development of Treg in tumor-bearing mice. These results provide robust evidence of an in vivo immunoregulatory function of MDSC in the establishment of tumor antigen-specific tolerance and the development of Treg in tumor-bearing hosts. To achieve effective anti-tumor immunity, tumor-induced immunosuppression must be reversed. Our preliminary results indicate that c-kit ligand (stem cell factor) expressed by tumor cells may be required for MDSC accumulation in tumor-bearing mice, and that blocking the c-kit ligand/c-kit receptor interaction can prevent the development of Treg and reverse immune tolerance induced by MDSC. Since c-kit can be readily inhibited by several small molecule inhibitors including imatinib, sunitinib and dasatinib, targeting immune suppressing cells can be readily accomplished in the clinic.

Diffuse large B-cell lymphoma in the older - Corrected Proof

A. Gutiérrez, F. Mestre, G. Pérez-Manga, J. Rodríguez — 2010-03-22

Abstract: The incidence of diffuse large B-cell lymphoma (DLCL) in the older is growing to the point of becoming a health priority in the next decades. Prognostic factors and the biology of the tumor are not very different between younger and older populations. Furthermore, it seems that the response rate is basically similar in both populations, provided an appropriate dose of chemotherapy is administered. However, there seem to be differences with regard to a lower tolerance to treatment and a higher relapse rate in responsive older patients. To analyze these problems we review the most important differences between young and older DLCL patients in terms of immunologic status, treatment toxicity and the presence of other concomitant diseases or organ dysfunctions. We also consider the most relevant clinical studies that may allow us to make the appropriate decisions regarding DLCL therapy in this older population.

Nutritional processes of care for older adults admitted to an oncology-acute care for elders unit - Corrected Proof

Kellie L. Flood, Cynthia J. Brown, Maria B. Carroll, Julie L. Locher — 2010-03-18

Abstract: Background: Acute care for elders (ACE) units have been established in the United States to prevent functional decline in older hospitalized patients.Purpose: We sought to examine whether an ace unit that focused specifically on care of older oncology patients (OACE) compared with a usual care cancer ward (UCCW) demonstrated improved nutritional processes of care in patients who had documentation of nutritional deficits.Methods: We conducted a retrospective chart review to examine whether orders had been placed for a nutritional consult or use of nutritional supplements. Logistic regression analyses, controlling for confounding variables, were conducted to evaluate differences between the wards.Results: OACE unit patients were 2.1 times more likely than UCCW patients to have a nutrition consult placed and 2.5 times more likely to have nutritional supplements ordered.Conclusions: An OACE unit model of care resulted in increased nutritional interventions. Future work is warranted to evaluate outcomes of care.

Optimizing the use of anthracyclines in older patients with breast cancer - Corrected Proof

Patrick G. Morris, Monica N. Fornier — 2010-03-15

Abstract: Recently, a greater understanding of tumor biology, including the use of genetic signatures, has led to a more precise classification of breast cancer. This has translated into a more granular assessment of risk-benefit calculations for the selection of patients for adjuvant therapies. For unselected patients, anthracyclines offer a survival benefit over non-anthracycline-based regimens, but are associated with long-term risks including congestive heart failure. Until recently, the benefit of anthracyclines in older patients with early breast cancer was largely extrapolated from studies involving younger cohorts. Emerging data now suggest that for appropriately selected older patients anthracyclines offer distinct benefits and are associated with a manageable toxicity profile. This review will focus on the benefits and risks of anthracyclines in older patients with various subtypes of breast cancer.

Relative dose intensity of chemotherapy and its impact on outcomes in patients with early breast cancer or aggressive lymphoma - Corrected Proof

Hans Wildiers, Marcel Reiser — 2010-03-15

Abstract: Early studies suggested a link between chemotherapy dosing and outcomes in breast cancer and aggressive non-Hodgkin's lymphoma. To help define the impact of relative dose intensity (RDI) and the role of growth factor support, we conducted a systematic literature review. Many breast cancer patients do not achieve planned RDI. Older age, obesity and febrile neutropenia are associated with reduced RDI, which leads to worse survival in several studies, particularly those including anthracyclines. G-CSF prophylaxis improved RDI in most, but not all, studies. There may be a threshold above which increasing RDI does not further improve outcomes (∼85% for CMF and anthracycline-based regimens). For lymphoma, there is strong evidence that patients benefit from full-dose chemotherapy, with RDI reductions associated with reduced survival. The definition of “full dose” is, however, unclear. Older age and higher disease stage may be associated with reduced RDI, and G-CSF improved the chances of higher RDI in most studies.

Prevention of febrile neutropenia in chemotherapy-treated cancer patients: Pegylated versus standard myeloid colony stimulating factors. Do we have a choice? - Corrected Proof

Jean Klastersky, Ahmad Awada — 2010-03-15

Abstract: The pertinent literature on clinical studies comparing the respective value of myeloid colony stimulating factors to pegfilgrastim as a prevention of febrile neutropenia in chemotherapy-treated cancer patients has been reviewed.Pegfilgrastim is definitely not inferior to filgrastim or other myeloid colony stimulating agents with respect to duration of grade IV neutropenia and delivery of full chemotherapy dose on time; several comparative studies indicate a trend to less frequent febrile neutropenia with pegfilgrastim.

The combined effect of age and socio-economic status on breast cancer survival - Corrected Proof

2010-03-15

Abstract: The study aims to investigate the effect of age and socio-economic status (SES) on breast cancer relative survival at 5 years from diagnosis (RS-5%). The Liguria Region Cancer Registry collected clinico-pathological information for 1081 patients resident in Genoa city diagnosed in 1996 and 2000. Patients were divided into three age groups (0–49, 50–69 and ≥70 years) and into quintiles of SES, measured according to a synthetic regional deprivation index built by Census tract variables and validated by comparison with the national deprivation index. The association of prognostic factors and RS-5% was evaluated by bivariate and multivariate analyses. RS-5% was very high for the first two age groups (91%) and decreased in patients aged 70 or older (82%) (unadjusted HR=2.7, P=0.001). The first four SES quintiles had homogeneous RS-5% (89–92%) and only the last very deprived group had lower rates (77%) (unadjusted HR=2.3, P=0.011). Very deprived elderly patients showed a much lower RS-5% (58%). Elderly and very deprived women were more likely to have large tumours, positive lymph nodes and less likely to receive conserving surgery, axillary dissection and adjuvant therapies. After adjusting for tumour characteristics and treatment modalities the increased risk of dying in the elderly disappeared completely, while the higher risk of very deprived women was eliminated only after correction for all the covariates simultaneously. The survival observed for breast cancer patients resident in Genoa was very high, however elderly and very low SES women have to be monitored. These variations are probably due to inequity in healthcare access and to a difficult taken in charge.

Global graying, colorectal cancer and liver metastasis: New implications for surgical management - Corrected Proof

Daniel A. Anaya, Natasha S. Becker, Neena S. Abraham — 2010-03-08

Abstract: Aging of the population – global graying – is occurring rapidly, with significant effects on epidemiology, treatment and outcomes for cancer patients. In colorectal cancer, outcomes for the elderly are worse than those for younger patients, partially driven by treatment disparities between the two groups. Nonetheless, standard-of-care treatment for the elderly results in equivalent long-term outcomes to those observed in the younger population; and available data support the use of aggressive surgery and adjuvant therapies in well-selected patients. Data evaluating epidemiology, treatment patterns and outcomes in elderly patients with colorectal cancer liver metastasis are lacking. Liver resection offers the only curative approach, but it is rarely offered to older adults. Current data support the use of hepatectomy for well-selected elderly colorectal cancer patients with liver metastasis; however, this and other evolving therapies need to be assessed in the elderly to better define their role, indications, safety and outcomes.

Background and methodology of MONITOR-GCSF, a pharmaco-epidemiological study of the multi-level determinants, predictors, and clinical outcomes of febrile neutropenia prophylaxis with biosimilar granulocyte-colony stimulating factor filgrastim - Corrected Proof

2010-03-02

Abstract: The MONITOR-GCSF study is an international, prospective, observational, pharmaco-epidemiological study to evaluate the multi-level factors and outcomes associated with the use of Zarzio® in the prophylaxis of febrile neutropenia in chemotherapy-treated cancer patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates statistical methodologies from the social and behavioral sciences; assesses factors predictive of poor treatment response; and evaluates the congruence of treatment with EORTC guidelines and the approved label. This pan-European study will recruit at least 1000 patients from a minimum of 75 centers and follow them for maximum 6 cycles of chemotherapy. Apart from descriptive and associative procedures, statistical analysis will include variance attribution methods; hierarchical linear, logistic, and Poisson modeling; Kaplan–Meier time-to-event analysis, Mantel–Cox log-rank or generalized Wilcoxon–Breslow tests, and Cox proportional hazards modeling; and clustering and related data mining techniques.

Neoplastic stem cells: Current concepts and clinical perspectives - Corrected Proof

2010-02-26

Abstract: Neoplastic stem cells have initially been characterized in myeloid leukemias where NOD/SCID mouse-repopulating progenitors supposedly reside within a CD34+/Lin− subset of the malignant clone. These progenitors are considered to be self-renewing cells responsible for the in vivo long-term growth of neoplastic cells in leukemic patients. Therefore, these cells represent an attractive target of therapy. In some lymphoid leukemias, NOD/SCID mouse-repopulating cells were also reported to reside within the CD34+/Lin− subfraction of the clone. More recently, several attempts have been made to transfer the cancer stem cell concept to solid tumors and other non-hematopoietic neoplasms. In several of these tumors, the cell surface antigens AC133 (CD133) and CD44 are considered to indicate the potential of a cell to initiate permanent tumor formation in vivo. However, several questions concerning the phenotype, self-renewal capacity, stroma-dependence, and other properties of cancer- or leukemia-initiating cells remain to be solved. The current article provides a summary of our current knowledge on neoplastic (cancer) stem cells, with special emphasis on clinical implications and therapeutic options as well as a discussion about conceptual and technical limitations.

Ovarian function, reproduction and strategies for fertility preservation after breast cancer - Corrected Proof

2010-02-25

Abstract: There is strong evidence that infertility is a dramatic and frequent side effect in men and women of childbearing age who are undergoing chemotherapy for their cancer treatment. This, severe and often underestimated complication heavily deteriorates the quality of life of affected patients and risks to reduce the therapeutic efforts and the compliance towards the suggested treatments. Moreover, cancer related infertility is still considered a marginal aspect of the quality of life in cancer patients. Reproduction's preservation plays today an emerging role in the culture of industrialized countries and moves extraordinary interests from the scientific and economic points, of view. Unfortunately medical oncologists, surgeons and gynaecologists have little consideration, for this complication and often possess a limited knowledge about the clinical aspects of cancer, related infertility and the possibilities of prevention and treatment of cancer related gonadic failure.Since more young people are offered adjuvant treatments at earlier stages of cancer, the problem of, chemotherapy related gonadic toxicity has considerably increased in the last years. It is also important to consider the new opportunity derived from the assisted reproductive techniques available. From this point of view the treating physicians need to be able to make accurate assessments of risks and benefits of antineoplastic treatments in order to schedule the best approach to and to preserve the possibility of reproduction in their young patients. These aspects are more relevant in breast cancer patients, mainly in the early phase of the disease, due to the high probability to retain reproductive possibilities also after aggressive and integrated therapies.