Critical Reviews in Oncology / Hematology

Editorial Board

2010-03-01

Pdcd4, a colon cancer prognostic that is regulated by a microRNA

Heike Allgayer — 2009-10-19

Abstract: The novel tumor suppressor Pdcd4 inhibits neoplastic transformation, tumor progression and translation. Furthermore, we and others have recently shown that Pdcd4 suppresses invasion and intravasation, at least in part by suppressing expression of the invasion-related urokinase receptor (u-PAR) gene via the transcription factors Sp1/Sp3. Nevertheless, relatively little is known about mechanisms that regulate Pdcd4 expression in cancer. MicroRNAs (miRNAs) have been recently discovered and shown to be naturally occurring non-coding RNAs that control gene expression via specific sites within the 3′UTR of target miRNAs. This short review will focus on our recent finding that the microRNA miR-21 posttranscriptionally regulates Pdcd4, as well as invasion, intravasation, and metastasis. Furthermore, we will review the first translational and clinical results concerning the prognostic value of Pdcd4, in particular our own data that show Pdcd4 to be a novel and independent prognostic factor in colorectal cancer, and a potential supportive diagnostic tool for discriminating normal colonic tissues from benign adenomas and colorectal carcinomas.

The beneficial role of vitamin D and its analogs in cancer treatment and prevention

Khanh vinh quoc Luong, Lan Thi Hoang Nguyen — 2009-05-15

Abstract: Background: Cancer is the leading cause of death in the United States, and the probability of developing cancer increases dramatically with age. Interestingly, vitamin D deficiency is also recognized more often in people of advanced ages. A potential relationship between vitamin D deficiency and cancer has been reported in the literature.Method: Review Medline database literature and discuss the relationship between vitamin D status and cancer.Results: Environmental (including seasonal and geographic) and genetic factors contribute to the development of both vitamin D deficiency and cancer. The vitamin D receptor is present in many tissues, especially in malignant cells, and may contribute to the successful use of vitamin D and its analogs in the treatment of some cancer patients.Conclusion: Further investigation of the role of vitamin D in the treatment of cancer is warranted.

Clinical relevance of contrast-enhanced ultrasound in monitoring anti-angiogenic therapy of cancer: Current status and perspectives

2009-06-22

Abstract: Angiogenesis regulation is one of the newest fronts in the fight against cancer. Anti-angiogenic therapy is based on inhibiting factors required to solicit vessel formation thus cutting-off the tumor's supply of nutriments and oxygen. Initial vascular response is followed by formation of necrosis. Volumetric regression occurs more tardively. Effective monitoring of this new therapeutic approach thus requires imaging techniques that can detect early microvascular changes. A number of clinical studies provide evidence that contrast-enhanced ultrasound (CEUS) can provide early indication of tumor response to anti-angiogenic therapy. More sophisticated imaging and analysis techniques for CEUS and contrast agents targeted for adhesion to anti-angiogenic markers have also demonstrated promise in animal model studies. This review underlines the relevance of CEUS for anti-angiogenic therapy monitoring by summarizing the current clinical results, emerging CEUS techniques and preclinical data.

Electrolyte disorders related to EGFR-targeting drugs

2009-04-29

Abstract: It is now clearly established that anti-vascular endothelial growth factor (VEGF) drug class induces hypertension and proteinuria sometimes related to thrombotic microangiopathy and/or various glomerulopathies, according to capillary and glomerular VEGF and VEGF-receptor expressions. As reported in the literature, anti-epidermal growth factor receptor (EGFR) therapies seem to be less nephrotoxic. Indeed, many reports of anti-EGFR nephrotoxicity are tubular dependent such as acute tubular necrosis, electrolyte disorders (hypophosphatemia, hypomagnesemia, etc.) or both. This is explained by elective tubular expression of renal EGF/EGFR. In this paper, we focus on electrolyte disorders related to anti-EGFR treatment and discuss the tubular involvement of these drugs based on their renal expression.

Fulvestrant in the treatment of advanced breast cancer: A systematic review and meta-analysis of randomized controlled trials

2009-04-15

Abstract: Purpose: To compare efficacy and tolerability of fulvestrant with aromatase inhibitors and tamoxifen that actually represent the standard of care in hormone-sensitive breast cancer.Methods: Systematic review and meta-analysis of available trials. Primary outcomes were overall survival, time to progression, clinical outcome and objective response. Secondary outcome was the tolerability profile of the drugs.Results: Four trials were identified with 2125 eligible patients. There was no statistically significant difference between fulvestrant and other hormonal agents in terms of overall survival (pooled HR: 1.047, 95% CI: 0.688–1.592), time to progression (pooled HR: 0.994, 95% CI: 0.691–1.431), clinical benefit (pooled OR: 1.044, 95% CI: 0.828–1.315) or objective response rate (pooled OR: 0.949, 95% CI: 0.736–1.224). A higher incidence of joint disorders (pooled OR: 0.621, 95% CI: 0.424–0.909; P=0.014) was noted in patients receiving hormonal agents other than fulvestrant.Conclusion: Fulvestrant was similar to other hormonal agents with respect to efficacy measures, with good tolerability profile.

The spiritual dimension of cancer care

Antonella Surbone, Lea Baider — 2009-04-30

Abstract: Spirituality is more about constant questioning than about providing fixed or final answers. Cancer patients do not expect spiritual solutions from oncology team members, but they wish to feel comfortable enough to raise spiritual issues and not be met with fear, judgmental attitudes, or dismissive comments. Spiritual needs may not be explicit in all illness phases, yet spirituality is not only confined to the areas of palliative or end-of-life care. Sensitive and effective methods to assess and address spiritual needs of cancer patients are being developed and qualitative research on the topic is underway. In addition, formal education and training in communication about cancer patients’ spiritual issues and in how to assess and address them in the clinical context is being increasingly provided. Spirituality can be a major resource for both patients and physicians, yet it can never be imposed but only shared. Those oncology professionals who are familiar with their own spirituality will be better at recognizing, understanding and attending to their patients’ spiritual needs and concerns.

Comorbidity, disability and geriatric syndromes in elderly breast cancer survivors. Results of a single-center experience

Regina Gironés, Dolores Torregrosa, Roberto Díaz-Beveridge — 2009-09-14

Abstract: Advancing age is a major risk factor for breast cancer. Long-term follow-up is recommended after diagnosis and treatment of early breast cancer. With older age, the risk of comorbid conditions and functional impairment increases. A useful tool in the management and follow-up of these elderly patients could be a comprehensive geriatric assessment (CGA).Purpose: A descriptive, transversal study was carried out of the prevalence of other comorbidities and of the functional impairment in elderly patients on follow-up after curative treatment of early breast cancer.Patients: Women aged≥70 at diagnosis; early breast cancer treated surgically. No disease recurrence allowed.Methods: CGA was conducted in an oncology unit using screening instruments (activities of daily living [ADL]; instrumental activities of daily living [IADL]; body mass index [BMI]; geriatric depression scale [GDS]). Cognitive status was reported by the patient. Comorbidity was classified using the Charlson score.Results: From January 2005 to June 2006 91 patients were seen. Mean age at surgery: 76 (70–92). Mean age at CGA: 80 (71–95). Aged population (almost 25% were more than 84 at the time of CGA). Median follow-up: 5 years (range 1–12). Good performance status (PS) in most (only 9% PS 2). Eighty-three percent were fully independent for ADL and 71% for IADL. IADL most affected was the ability to drive/use public transport. Twenty-eight percent had geriatric syndromes and 23% were classified as “frail”. Increased age was associated with worsening PS (p=0.0001) and worsening function (ADL p<0.0001 and IADL p<0.0001).The study is remarkable for the high comorbidity index found in the elderly survivors. Median Charlson score was 2 (1–6). More than 75% of the series had a score ≥4. Cardiovascular disease (hypertension) was the most prevalent comorbid condition. As an effect of this, the majority of patients were polymedicated (75% took more than six drugs). Comorbidity was independent of functionality and age.Conclusions: Older patients with early breast cancer on follow-up have a high prevalence of comorbidity. In our series, function and independence were maintained. A selection bias cannot be excluded, as the fitter patients are those who usually continue with the follow-up, while those frail patients who do not continue because of their functional impairment are usually lost.

Male breast cancer. Evolution of treatment and prognostic factors. Analysis of 489 cases

2009-05-13

Abstract: Background: Infiltrating MBC represents less than 1% of all male cancers. Our study details clinico-pathological features, treatments and prognostic factors in a large French cohort.Material and methods: Four hundred and eighty-nine patients were collected from 1990 to 2005. Median age was 66 years (34% over 70 years) and median follow-up 58 months.Results: According to TN classification, we found T1: 39%, T2: 41%, T3T4: 9%, Tx: 11% and N1N2: 27%. Lumpectomy (L) and mastectomy (M) were performed in 8.6% and 91.4% of the cases. Axillary dissection (AD), sentinel node biopsy or both were performed in 90%, 2% and 5% of the cases, respectively. Ninety-five percent of tumours were ductal carcinomas; 47% were pT1, 20% pT2 and 33% pT3–T4. Axillary nodal involvement was present in 52.8% cases. ER and PgR were positive in 92% and 89% cases. Radiotherapy (RT) was performed in 85% of the patients. Hormonal treatment (HT) was delivered in 72% of the cases. Tamoxifen and aromatase inhibitors were used in 85% and 12% of the cases; 34% of the patients received chemotherapy (CT).Local recurrence (LR), nodal recurrences (NR) and metastases occurred in 2%, 5% and 22% of the cases; 2% and 10% developed contralateral BC and second cancer. The 5- and 10-year overall survival (OS) rates were 81% and 59%; disease-specific survivals (DSS) were 89% and 72%. Death causes were BC 56%, second cancer 8%, complications 3%, intercurrent disease 15% and unknown 18%. In a univariate analysis, metastatic risk factors were T stage (T1: 19%, T2: 26%, T3T4: 40%; p=0.013), pN status (pN0: 12% pN1–3: 26% pN>3: 44%; p<0.0001) and presence of locoregional recurrence (62% versus 18% p<0.0001). In a multivariate analysis, axillary nodal involvement and high SBR remain prognostic factors.Conclusion: Earlier diagnosis and wide use of adjuvant treatments (RT/HT/CT) widely decreased LR and increased survival rates in MBC, reaching female ones. Prognostic factors were also very similar to female ones.