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All Oncology jobs for Mon Feb 6 2012

Oncology jobs in "Temecula" - CA

Southwest Riverside County - located about 90 minutes from the Los Angeles Metro, less than an hour from San Diego or Palm Springs and just 30 minutes to Riverside, Temecula, Hemet and Menifee

Oncology jobs in "Oncology Specialists For Brand New Cancer Center" - OK

Clinician, Educator, Scientist Clinical prestige, ahead-of-the-curve technology and an unrivaled team environment await you at The University of Oklahoma Medical Center. This summer, The Peggy

Oncology jobs in "Oncologist - Western North Carolina" - NC

120117-1864 Oncologist - Western North Carolina NC Seeking BC/BE Oncologist to join two other BC physicians at busy private medical oncology & hematology practice Staff also consists of 3 PA-Cs

Oncology jobs in "Medical Oncology - North Dakota" - ND

101216-1480 Medical Oncology - North Dakota ND Seeking BC/BE medical oncologist to join growing practice Group includes 3 medical oncologists supported by 2 mid-levels Competitive compensation

Oncology jobs in "Medical Oncologist - Minnesota" - MN

110120-1527 Medical Oncologist - Minnesota MN Seeking BC/BE medical oncologist for multi-specialty group J1/H1B sponsorship available New state-of-the-art outpatient cancer center recently opened

Oncology jobs in "Southern California Oncology" - CA

Southern California Oncology With an advantageous base salary, amazing Southern California location and a patient-oriented organization, we provide an ideal working environment for a prospective

Oncology jobs in "Oncologist - North Dakota" - ND

100104-874 Oncologist - North Dakota ND BC/BE medical oncologist for established practice of seven medical oncologists, three radiation oncologists and two pediatric oncologists Oncologists actively

Oncology jobs in "Oncologist - Minnesota" - MN

100104-873 Oncologist - Minnesota MN BC/BE medical oncologist to join 64-physician mutil-specialty group practice J1/H1B approved Clinic-based practice with procedure rooms available in the adjacent

Oncology jobs in "Huntsville/Birmingham" - AL

We cordially invite you to consider an outstanding Oncology opportunity where you can have both an extraordinary practice and an incredible lifestyle. Located in the lower Tennessee River

Oncology jobs in "Southern California" - CA

Oncology Physician Needed - Southern California Join a Well Established Comprehensive Cancer Center Hospital Operated Practice Turn-key practice with office staff and space awaiting your

Oncology jobs in "Northern Colorado" - CO

Colorado Oncology Physician Directorship Financials Employed Position: Health, Dental and Vision Insurance , Life, Disability, 401K and 457b Retirement; Paid Malpractice, Vacation

Oncology jobs in Pennsylvania

All Oncology jobs in Pennsylvania for Mon Feb 6 2012

Oncology jobs in "Metro St. Louis" - MO

Actively seeking BE/BC Medical Oncologist to join a very busy private practice that is associated with a state of the art hospital in west St. Louis county. This can also be an employed position with

Oncology jobs in "Cheraw" - VA

Medical Oncologist needed near Richmond, VA Southside Regional Medical Center (400 Beds) located just ten minutes south of the Richmond suburb of Colonial Heights is actively seeking a Medical Oncologist

Oncology jobs in "Fort Wayne" - IN

Our client in the Greater Fort Wayne area of Indiana is looking to bring on a Radiation Oncologist to complete their very well trained group. Full time permanent

Oncology jobs in "Ski Resort" - MT

Medical Oncology Mountain West Employed Position Turn-Key Practice You will be a valued employee of this practice with all the benefits and comforts that follow. There will be zero managerial responsibilities

Oncology jobs in "Kingsport" - TN

Wellmont Health System and Kingsport Hematology Oncology are seeking an Oncology Nurse Practitioner for immediate placement in Kingsport , TN. Oncology experience required.

Oncology jobs in "Charlotte" - NC

Hi Dr., We have an outstanding opportunity for a BC/BE Oncologist to join two other BC physicians at a busy private medical oncology & hematology practice in the Greater

Oncology jobs in "Southwest" - MO

Hematology / Oncology - Southwest Missouri Take a Good Luck at this opportunity! Seeking 2 Hematologists or Medical Oncologists to replace a physician leavig to reurn to area closer to family.

Oncology jobs in "Spokane" - WA

Spokane, Washington: Providence Health & Services is partnering with a well-respected private practice to bring an excellent BE/BC Medical Oncologist to serve the community. Group is affiliated with

Oncology jobs in "Riyadh" - SA

Head Medical: Consultant Oncologist required for the Gulf Region Ref Number: ANS0041 Excellent tax free remuneration packages including; Travel + Housing

Oncology jobs in "State College" - OK

Oklahoma Hospital-employed Oncology Opportunity St. Marys Regional Medical Center is recruiting a new Oncologist for an employed position. This is a great opportunity for an Oncologist to join

Heine H. Hansen, 1938-2011: a European oncologist

Screening mammography and socioeconomic inequalities in breast cancer survival

A meta-analysis on alcohol drinking and esophageal and gastric cardia adenocarcinoma risk

Background: In order to provide a precise quantification of the association between alcohol drinking and esophageal and gastric cardia adenocarcinoma risk, we conducted a meta-analysis of available data. Patients and methods: We identified 20 case–control and 4 cohort studies, including a total of 5500 cases. We derived meta-analytic estimates using random-effects models, taking into account correlation between estimates, and we carried out a dose–risk analysis using nonlinear random-effects meta-regression models. Results: The relative risk (RR) for drinkers versus nondrinkers was 0.96 [95% confidence interval (CI) 0.85–1.09] overall, 0.87 (95% CI 0.74–1.01) for esophageal adenocarcinoma and 0.89 (95% CI 0.76–1.03) for gastric cardia adenocarcinoma. Compared with nondrinkers, the pooled RRs were 0.86 for light (≤1 drink per day), 0.90 for moderate (1 to <4 drinks per day), and 1.16 for heavy (≥4 drinks per day) alcohol drinking. The dose–risk model found a minimum at 25 g/day, and the curve was <1 up to 70 g/day. Conclusions: This meta-analysis provides definite evidence of an absence of association between alcohol drinking and esophageal and gastric cardia adenocarcinoma risk, even at higher doses of consumption.

Cancer of unknown primary: progress in the search for improved and rapid diagnosis leading toward superior patient outcomes

This paper explores the enigma of cancer of unknown primary (CUP) in relation to rapidly improving molecular diagnostic approaches. It is based on the first global collaboration meeting on improving research and clinical outcomes in CUP organized by the CUP Foundation. We review the difficulties of classifying this widely heterogeneous disease and the available diagnostic and pathological evaluative techniques, focusing on molecular profiling. Retrospective studies in CUP patients are shown to provide indirect validation of the accuracy of several platforms of gene expression profiling assays that may identify CUP subsets that respond favorably to active chemotherapy regimens. This review concludes that the recent major improvements in pathologic and molecular diagnostics, coupled with new improved therapies for several specific advanced solid tumors, need to be harmonized with more evidence from clinical–translational trials. All patients with CUP could thus be appropriately managed without the constant uncertainty that has previously severely hampered patient care and optimal outcomes. The longer-term objective is to understand the biology of highly metastatic disease, leading to the development of future global therapeutic programs. Current clinical studies, such as CUP-ONE, will address some of these issues.

CMF revisited in the 21st century

Over the last 35 years, classical CMF (combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil) has been a milestone in the adjuvant treatment of women with breast cancer. However, after an early burst of success lasted just over 10 years, classical CMF has been supplanted by ‘third-generation’ regimens containing taxanes and anthracyclines. Questions have been raised in the past years concerning the true effectiveness of adjuvant CMF for specific subgroups of patients and particularly, recent retrospective data support the fact that the CMF might have a role in the treatment of patients with triple-negative breast cancer. One possible justification for supporting this role of CMF may be sought in the mechanism of action of drugs used in the regimen, as triple-negative cells may be sensitive to alkylating agents that cause double-strand breaks in DNA. The lesson learned from the CMF could lead us to identify new combinations of drugs that could include the optimal chemotherapy backbone for triple-negative breast cancer such as platinum compounds or alkylating agents or Poly (ADP-ribose) polymerase inhibitors. In conclusion, although we have learned a lot from the use of CMF, many questions are still open and hopefully stimulate our thinking, as clinicians, leading us to find new and more effective ways to treat breast cancer.

A meta-analysis of coffee consumption and pancreatic cancer

Background: Since when in 1981 a case–control study showed a positive association between coffee and pancreatic cancer, several studies reported inconsistent results on this issue. Materials and methods: We conducted a systematic bibliography search updated March 2011 to identify observational studies providing quantitative estimates for pancreatic cancer risk in relation to coffee consumption. We used a meta-analytic approach to estimate overall relative risk (RR) and 95% confidence interval (CI) for the highest versus the lowest coffee consumption categories, using random-effects models. Results: Based on 37 case–control and 17 cohort studies (10 594 cases), the pooled RR for the highest versus lowest intake was 1.13 (95% CI 0.99–1.29). Considering only the smoking-adjusting studies, the pooled RRs were 1.10 (95% CI 0.92–1.31) for the 22 case–control, 1.04 (95% CI 0.80–1.36) for the 15 cohort, and 1.08 (95% CI 0.94–1.25) for all studies. The pooled RR for the increment of one cup of coffee per day was 1.03 (95% CI 0.99–1.06) for the 28 smoking-adjusting studies reporting three or more coffee consumption categories. No significant heterogeneity was observed across strata of study design, sex, geographic region, and other selected characteristics. Conclusions: This meta-analysis provides quantitative evidence that coffee consumption is not appreciably related to pancreatic cancer risk, even at high intakes.

Does an organised screening programme reduce the inequalities in breast cancer survival?

Background: The aim of the present study was to examine whether the implementation of an organised mammographic screening programme in Florence has been successful in reducing socioeconomic inequalities in breast cancer survival. Patients and methods: All invasive breast cancer cases diagnosed in women resident in the city of Florence in a prescreening period and in the first 10 years of the screening programme were selected. Their socioeconomic status (SES) was determined by using the national census 2001 data. All breast cancers were followed up to 10 years after the diagnosis. Results: In the prescreening period, the survival of deprived women was 12 percentage points lower than the reference class, both in the younger age class (<50 years old) and in the age class target of the screening programme (50–69 years old). This difference progressively decreases until disappearing completely during the first 10 years of the screening programme for the age class invited to screening, whereas it remains stable in the younger age class. Participation in breast cancer screening and diagnostic accuracy were similar by SES. Conclusion: The organised breast cancer screening implemented in the Florentine area achieved the goal of reducing inequalities in breast cancer survival.

Breast cancer subtypes and outcome after local and regional relapse

Background: To evaluate the outcome of breast cancer patients after locoregional recurrence (LRR) according to tumor biological features evaluated at first diagnosis and at the time of recurrence. Patients and methods: We collected information on all consecutive breast cancer patients operated at the European Institute of Oncology between 1994 and 2005. The tumor characteristics and subsequent outcome of patients who experienced LRR were analyzed. Results: Two hundred and seventy nine patients with LRR were identified, 197 and 82 patients with local and regional recurrence respectively. The overall discordance rate between primary cancer and LRR was 9% for estrogen receptor expression, 22% for progesterone receptor and 4% for human epidermal growth factor receptor 2. For patients with regional recurrence, the risk of distant metastasis was significantly higher compared with local relapse in case of late recurrence (hazard ratio [HR] = 2.76; 95% CI 1.31–5.85). Patients with triple-negative breast cancer at LRR experienced a higher risk of subsequent relapse (HR 2.87 [1.67–4.91]) and death (HR 2.00 [1.25–3.19]). Conclusion: LRR correlates with a high risk of subsequent events and death in particular in patients with triple-negative subtype.

A phase II pilot trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node positive breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group

Background: E2104 was designed to evaluate the safety of two different strategies incorporating bevacizumab into anthracycline-containing adjuvant therapy as a precursor to a definitive randomized phase III trial. Patients and methods: Patients were sequentially assigned to one of two treatment arms. In addition to dose-dense doxorubicin and cyclophosphamide followed by paclitaxel (Taxol) (ddAC->T), all patients received bevacizumab (10 mg/kg every 2 weeks x 26) initiated either concurrently with AC (Arm A: ddBAC->BT->B) or with paclitaxel (Arm B: ddAC->BT->B). The primary end point was incidence of clinically apparent cardiac dysfunction (CHF). Results: Patients enrolled were 226 in number (Arm A 104, Arm B 122). Grade 3 hypertension, thrombosis, proteinuria and hemorrhage were reported for 12, 2, 2 and <1% of patients, respectively. Two patients developed grade 3 or more cerebrovascular ischemia. Three patients in each arm developed CHF. There was no significant difference between arms in the proportion of patients with an absolute decrease in left ventricular ejection fraction of >15% or >10% to below the lower limit of normal post AC or post bevacizumab. Conclusions: Incorporation of bevacizumab into anthracycline-containing adjuvant therapy does not result in prohibitive cardiac toxicity. The definitive phase III trial (E5103) was activated with systematic and extensive cardiac monitoring to define the true impact of bevacizumab on cardiac function.

Tumor markers in metastatic breast cancer subtypes: frequency of elevation and correlation with outcome

Background: Little is known about the correlations between tumor markers (TMs), breast cancer subtypes, site(s) of metastasis and prognosis. Methods: Women diagnosed with metastatic breast cancer were included. Breast cancer subtypes were defined as LuminalA, LuminalB, LuminalHer2, Her2, Basal and non-Basal triple negative (TN). Levels of elevation of TM values [cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA 125)] among the subtypes were analyzed. Site(s) of metastasis and outcomes were captured. Results: Eight hundred and ten patients were included. Luminal subtypes were associated with an elevation in at least one TM: 90.8% of LuminalHer2+, 90% of LuminalB and 88.6% of LuminalA. TMs were less frequently elevated in Basal (74.1%) and non-Basal TN (71.4%) cases (P < 0.001). CA 15-3 was the most frequently elevated TM. The incidence of TM elevation did not differ between patients with solitary versus multiple metastatic sites. Breast cancer-specific survival (BCSS) was significantly worse for patients with elevated TMs (P = 0.001). Conclusions: TM elevation of CA 15-3, CEA and/or CA 125 was documented in the majority of patients with metastatic breast cancer with CA 15-3 occurring most commonly. Luminal subtypes expressed elevated TMs significantly more frequently compared with the non-Luminal groups. TM elevation was not different between the different sites of metastasis. Overall, elevated TMs predicted a worse BCSS.

Weekly paclitaxel as a single agent or in combination with carboplatin or weekly topotecan in patients with resistant ovarian cancer: the CARTAXHY randomized phase II trial from Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO)

Background: Platinum rechallenge or weekly topotecan in combination have not been evaluated in randomized trials for resistant recurrent ovarian cancer (ROC). Methods: Patients with ROC after first- or second-line treatment including a platinum and taxane and progression within 6 months were randomized to weekly paclitaxel (wP, 80 mg/m2/week) alone or in combination with carboplatin (C, area under the curve of 5 mg/ml/min every 4 weeks) or weekly topotecan (wT, 3 mg/m2/week). Primary end point was progression-free survival (PFS) comparing wP and combination therapy. Results: Patients (n = 165) received a median three cycles in each arm. Nonhematologic toxicity was not different, except increased hypersensitivity reactions with wP + C. Grade 3–4 hematologic toxic effects with wP, wP + C, and wP + wT, respectively, were neutropenia in 13%, 54%, and 42%; febrile neutropenia in 0%, 4%, and 5%; and anemia in 6%, 19%, and 29%. Response rates were 35%, 37%, and 39%, and median PFS times were 3.7, 4.8, and 5.4 months, respectively. PFS was not significantly different among the treatment arms [hazard ratio (HR) 0.922; 95% confidence interval (CI) 0.765–1.111; P = 0.46] or between monotherapy and combination therapy (HR 0.951; 95% CI 0.686–1.318; P = 0.76). Conclusions: Combination chemotherapy in platinum-resistant ROC was more toxic than weekly paclitaxel and did not significantly prolong PFS.

Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience

Background: Majority of gastrointestinal stromal tumours (GISTs) are characterised by KIT-immunopositivity and the presence of KIT/platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. Patients and methods: Spectrum and frequency of KIT and PDGFRA mutations were investigated in 427 GISTs. Univariate and multivariate analysis of relapse-free survival (RFS) was conducted in relation to tumours' clinicopathologic features and genotype. Results: Mutations were found in 351 (82.2%) cases, including 296 (69.3%) KIT and 55 (12.9%) PDGFRA isoforms. Univariate analysis revealed higher 5-year RFS rate in women (37.9%; P = 0.028) and in patients with gastric tumours (46.3%; P < 0.001). In addition a better 5-year RFS correlated with smaller tumour size ≤5 cm (62.7%; P < 0.001), tumours with mitotic index ≤5/50 high-power fields (60%; P < 0.001), and characterised by (very) low/moderate risk (70.2%; P = 0.006). Patients with GISTs bearing deletions encompassing KIT codons 557/558 had worse 5-year RFS rate (23.8%) than those with any other KIT exon 11 mutations (41.8%; P < 0.001) or deletions not involving codons 557/558 (33.3%; P = 0.007). Better 5-year RFS characterised patients with KIT exon 11 point mutations (50.7%) or duplications (40%). By multivariate analysis, tumours with PDGFRA mutations and KIT exon 11 point mutations/other than 557/558 deletions had lower risk of progression than with KIT exon 11 557/558 deletions (both Ps = 0.001). Conclusions: KIT/PDGFRA mutational status has prognostic significance for patients' outcome and may help in management of patients with GISTs.

External validation of nomogram for the prediction of recurrence after curative resection in early gastric cancer

Background: Nomograms are statistics-based tools that provide the overall probability of a specific outcome. In our previous study, we developed a nomogram that predicts recurrence of early gastric cancer (EGC) after curative resection. We carried out this study to externally validate our EGC nomogram. Patients and methods: The EGC nomogram was established from a retrospective EGC database that included 2923 consecutive patients. This nomogram was independently externally validated for a cohort of 1058 consecutive patients. For the EGC nomogram validation, we assessed both discrimination and calibration. Results: Within the follow-up period (median 37 months), a total of 11 patients (1.1%) experienced recurrence. The concordance index (c-index) was 0.7 (P = 0.02) and the result of the overall C index was 0.82 [P = 0.006, 95% confidence interval (CI) 0.59–1.00]. The goodness of fit test showed that the EGC nomogram had significantly good fit for 1- and 2-year survival intervals (P = 0.998 and 0.879, respectively). The actual and predicted survival outcomes showed good agreement, suggesting that the survival predictions from the nomogram are well calibrated externally. Conclusions: A preexisting nomogram for predicting disease-free survival (DFS) of EGC after surgery was externally validated. The nomogram is useful for accurate and individual prediction of DFS, patient prognostication, counseling, and follow-up planning.

Small bowel adenocarcinoma copy number profiles are more closely related to colorectal than to gastric cancers

Background: Small bowel adenocarcinoma (SBA) is a rare cancer and consequently, the options for clinical trials are limited. As they are treated according to either a colorectal or a gastric cancer regimen and the molecular biology of a tumor is a pivotal determinant for therapy response, chromosomal copy number aberrations were compared with the colorectal and gastric adenocarcinomas. Materials and methods: A total of 85 microsatellite stable (MSS) adenocarcinomas from the stomach, colorectum and small bowel were selected from existing array comparative genomic hybridization (aCGH) datasets. We compared the aCGH profiles of the three tumor sites by supervised analysis and hierarchical clustering. Results: Hierarchical clustering revealed substantial overlap of 27 SBA copy number profiles with matched colorectal adenocarcinomas but less overlap with profiles of gastric adenocarcinomas. DNA copy number aberrations located at chromosomes 1p36.3-p34.3, 4p15.3-q35.2, 9p24.3-p11.1, 13q13.2-q31.3 and 17p13.3-p13.2 were the strongest features discriminating SBAs and colorectal adenocarcinomas from gastric adenocarcinomas. Conclusions: We show that MSS SBAs are more similar to colorectal than to gastric cancer, based on the 27 genome-wide DNA copy number profiles that are currently available. These molecular similarities provide added support for treatment of MSS small bowel cancers according to colorectal cancer regimens.

Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4)

Background: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. Methods: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case–control studies (5585 cases and 11 827 controls) participating in the International Pancreatic Cancer Case–Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. Results: Compared with abstainers and occasional drinkers (<1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2–2.2 for subjects drinking ≥9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. Conclusion: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.

Lung cancer physicians' referral practices for palliative care consultation

Background: Integration of palliative care with standard oncologic care improves quality of life and survival of lung cancer patients. We surveyed physicians to identify factors influencing their decisions for referral to palliative care. Methods: We provided a self-administered questionnaire to physicians caring for lung cancer patients at five medical centers. The questionnaire asked about practices and views with respect to palliative care referral. We used multiple regression analysis to identify predictors of low referral rates (<25%). Results: Of 155 physicians who returned survey responses, 75 (48%) reported referring <25% of patients for palliative care consultation. Multivariate analysis, controlling for provider characteristics, found that low referral rates were associated with physicians’ concerns that palliative care referral would alarm patients and families [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.21–0.98], while the belief that palliative care specialists have more time to discuss complex issues (OR 3.07, 95% CI 1.56–6.02) was associated with higher rates of referral. Conclusions: Although palliative care consultation is increasingly available and recommended throughout the trajectory of lung cancer, our data indicate it is underutilized. Understanding factors influencing decisions to refer can be used to improve integration of palliative care as part of lung cancer management.

Survival benefit with erlotinib maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC) according to response to first-line chemotherapy

Background: In the placebo-controlled phase III SATURN study, maintenance erlotinib after first-line chemotherapy demonstrated significantly prolonged progression-free survival (PFS) and overall survival (OS) in the overall study population of patients with advanced non-small-cell lung cancer (NSCLC). Methods: After four cycles of platinum-based doublet chemotherapy, patients without progressive disease (PD) were randomised to erlotinib (150 mg/day) or placebo until PD or unacceptable toxicity. In this pre-planned analysis, data are assessed according to response to first-line chemotherapy (complete/partial response [CR/PR] or stable disease [SD]). Results: Following first-line chemotherapy, 889 non-PD patients were included in the intention-to-treat population (55% SD; 44% CR/PR; <1% unknown response). Erlotinib maintenance therapy significantly prolonged PFS in both the SD (hazard ratio [HR] = 0.68; P < 0.0001) and CR/PR (HR = 0.74; P = 0.0059) groups, while OS was significantly prolonged in the SD group only (HR = 0.72; P = 0.0019). The erlotinib-related OS benefit in the SD group remained significant across subgroups, irrespective of tumour histology and/or EGFR mutation status. The incidence of adverse events was similar in the SD group and the overall population, and erlotinib treatment did not negatively impact quality of life. Conclusions: Patients with advanced NSCLC and SD following first-line platinum-based doublet chemotherapy derive a significant OS benefit from maintenance erlotinib therapy.

Sunitinib followed by sorafenib or vice versa for metastatic renal cell carcinoma--data from the Czech registry

Background: Sequential therapy with tyrosine kinase inhibitors (TKIs), sunitinib and sorafenib, is a common treatment choice for patients with advanced/metastatic renal cell carcinoma (mRCC) despite lack of randomised trials. The aim of this retrospective registry-based study was to analyse the outcomes of RCC patients treated with sunitinib–sorafenib or sorafenib–sunitinib sequence. Patients and methods: The Czech database containing information on patients treated for mRCC using targeted agents was used as a source of data for retrospective analysis. There were 138 patients treated with sunitinib–sorafenib sequence and 122 patients treated with sorafenib–sunitinib sequence. Results: Progression-free survival (PFS) was 17.7 months for patients treated with sunitinib–sorafenib sequence and 18.8 months for those receiving sorafenib followed by sunitinib (P = 0.47). Overall survival (OS) at 1 year was 83% [95% confidence interval (CI) 77% to 90%] for patients treated with sunitinib–sorafenib and 84% (95% CI 77% to 91%) for sorafenib–sunitinib patients (P = 0.99). Treatment toxic effects were predictable but a significant proportion of patients (up to 14%–25% for different lines of therapy and used TKI) switched between TKIs or discontinued TKI therapy because of toxicity. Conclusions: In contrast to most of the previously published reports, we have not observed improved PFS or OS for mRCC patients treated with the sorafenib–sunitinib sequence as compared to the sunitinib-sorafenib sequence.

The hOGG1 mutant genotype is associated with prostate cancer susceptibility and aggressive clinicopathological characteristics in the Korean population

Background: The gene encoding human 8-oxoguanine glycosylase 1 (hOGG1) is involved in DNA base excision repair from oxidatively damaged DNA. A case–control study was conducted to evaluate the correlation between the susceptibility and clinicopathological outcomes of prostate cancer (CaP) and hOGG1 genotype. Patients and methods: Subjects were recruited from 266 CaP patients and 266 age-matched benign prostatic hyperplasia patients. The hOGG1 codon 326 genotype was determined by peptide nucleic acid-mediated PCR clamping and compared with Gleason score and tumor stage. Results: The Cys allele at codon 326 of hOGG1 was associated with an increased risk of CaP in comparison with the Ser allele (P = 0.005). Gleason scores of 8 or higher were observed more often in patients with the mutant genotypes Ser/Cys and Cys/Cys than in those with a wild-type genotype (P = 0.045), and the Cys/Cys homozygous genotype was associated with a significantly higher risk of metastatic disease in comparison with the Ser/Ser genotype (P = 0.017). Conclusions: These results suggest that hOGG1 is associated with the susceptibility to CaP and its aggressive clinicopathological characteristics.

Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma

Background: Cisplatin-based chemotherapy is a standard treatment of metastatic urothelial carcinoma (UC), though carboplatin-based chemotherapy is frequently substituted due to improved tolerability. Because comparative effectiveness in clinical outcomes of cisplatin- versus carboplatin-based chemotherapy is lacking, a meta-analysis was carried out. Methods: PubMed was searched for articles published from 1966 to 2010. Eligible studies included prospective randomized trials evaluating cisplatin- versus carboplatin-based regimens in patients with metastatic UC. Individual patient data were not available and survival data were inconsistently reported. Therefore, the analysis focused on overall response (OR) and complete response (CR) rates. The Mantel–Haenszel method was used for combining trials and calculating pooled risk ratios (RRs). Results: A total of 286 patients with metastatic UC from four randomized trials were included. Cisplatin-based chemotherapy was associated with a significantly higher likelihood of achieving a CR [RR = 3.54; 95% confidence interval (CI) 1.48–8.49; P = 0.005] and OR (RR = 1.34; 95% CI 1.04–1.71; P = 0.02). Survival end points could not be adequately assessed due to inconsistent reporting among trials. Conclusions: Cisplatin-based, as compared with carboplatin-based, chemotherapy significantly increases the likelihood of both OR and CR in patients with metastatic UC. The impact of improved response proportions on survival end points could not be assessed.

Risk of second cancers in Waldenstrom macroglobulinemia

Background: An increased incidence of second cancers has been reported in lymphoproliferative disorders. Patients and methods: We assessed the frequency, characteristics and predictive factors of second cancers in 230 patients with Waldenström macroglobulinemia (WM) and compared the incidence of second cancers in WM with that of an age- and sex-matched control population. Results: Twenty-two patients (10%) developed solid cancers and 10 (4%) second hematologic malignancies. In a competing risk model, the cumulative incidence of solid cancers was 12% at 10 years and 17% at 15 years while the incidence of hematologic malignancies was 6% and 8%, respectively. The overall risk of second cancer in WM was 1.69 times higher than expected (P = 0.002). WM patients were at increased risk for diffuse large B-cell lymphoma [standardized incidence ratio (SIR) 9.24, P < 0.0001], myelodisplastic syndrome/acute myeloid leukemia (SIR 8.4, P < 0.0001), brain cancer (SIR 8.05, P = 0.0004). The risk of a second hematologic malignancy was fourfold higher in patients previously treated, though not reaching statistical significance (P = 0.19). Conclusions: WM patients are at higher risk of second cancers as compared with the general population. The sample size does not allow firm conclusions about the effect of therapy on the development of second cancers.

A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by 90Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma

Background: A prospective, single-arm, open-label, multicenter, nonrandomised phase II trial to evaluate efficacy and safety of short fludarabine, mitoxantrone, and rituximab (FMR) induction followed by radioimmunotherapy, in untreated, intermediate/high-risk follicular non-Hodgkin’s lymphoma (NHL) patients. Patients and methods: Fifty-five patients were treated using a sequential treatment schedule of four induction cycles of FMR chemoimmunotherapy, and a subsequent consolidating single administration of 90Y-ibritumomab tiuxetan (90Y-IT), 8–14 weeks later. Patients were eligible for radioimmunotherapy if at least in partial response (PR) after induction, with normal platelet and granulocyte counts and a bone marrow infiltration ≤25%. Primary study end points were response rate and hematologic toxic effects; secondary end points were overall survival (OS) and progression-free survival (PFS). Results: All the 55 patients received four induction cycles with an overall response rate of 96% (38 complete responses [CR] and 15 PR). Fifty-one patients (38 in CR and 13 in PR) received 90Y-IT. By the end of the treatment, 49/55 patients achieved a CR. With a median follow-up of 21 months, the estimated 3-year PFS was 81% and the 3-year OS 100%. Conclusions: This study has established feasibility, tolerability, and efficacy of a regimen composed by short FMR induction with 90Y-IT consolidation in untreated intermediate/high-risk follicular NHL patients.

Risk of hepatitis B reactivation and the role of novel agents and stem-cell transplantation in multiple myeloma patients with hepatitis B virus (HBV) infection

Background: The purpose of the study is to analyse the prevalence of hepatitis B virus (HBV) infection and its incidence of reactivation among multiple myeloma (MM) patients treated in the era of novel therapy in an endemic Asian setting. Patients and methods: From 2000 to 2008, 273 patients with newly diagnosed MM were screened for the presence of hepatitis B virus surface antigen and HBV core antibody. HBV-infected patients were prospectively followed for reactivation with serial monitoring of serum alanine transferase and HBV DNA load. The patterns of HBV reactivation in relation to treatment received, exposure to high-dose therapy with autologous stem-cell transplantation (HDT/ASCT) and novel agents were studied. Results: The prevalence of HBV infection was 5.5%. Three cases of HBV reactivation despite lamivudine prophylaxis were reported. Two patients reactivated 3–5 months after HDT/ASCT while receiving thalidomide maintenance and one reactivated 3 years after HDT/ASCT and shortly after bortezomib salvage therapy. Emergence of a mutant HBV strain was documented in one patient. Conclusions: Use of prophylaxis may reduce but will not preclude HBV reactivation. Highest risk occurs during immune reconstitution phase of HDT/ASCT. The role of immunomodulatory agents in HBV reactivation needs to be further elucidated. Separate HBV prophylaxis and surveillance guidelines ought to be developed for patients with MM.

Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation

Background: Concomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial. Patients and methods: Totally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m2, epirubicin 75 mg/m2 and paclitaxel (Taxol) 175 mg/m2 (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m2 (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients). Results: Sixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT. Conclusion: IC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone.

T-cell therapy for EBV-associated nasopharyngeal carcinoma: preparative lymphodepleting chemotherapy does not improve clinical results

Background: We and others have demonstrated that adoptive cell therapy with Epstein–Barr virus (EBV)-specific autologous cytotoxic T lymphocytes (CTLs) may control disease progression in patients with EBV-associated nasopharyngeal carcinoma (NPC). With the aim of favoring in vivo T-cell expansion, we optimized our cell therapy approach by administering higher doses of EBV-specific CTLs, following lymphodepleting chemotherapy. Patients and methods: Eleven patients with EBV-related NPC in whom conventional treatment failed have been enrolled. Patients received nonmyeloablative lymphodepleting chemotherapy consisting of cyclophosphamide and fludarabine. Two doses of autologous EBV-specific CTLs were subsequently infused, 2 weeks apart. Study end points were feasibility and clinical outcome. Results: All patients enrolled completed the treatment and were assessable for analysis. The median dose of CTLs per infusion was 3.7 x 108. Therapy was well tolerated, with no severe adverse events ascribable to either chemotherapy or cell therapy. Disease control (defined as either tumor regression or disease stabilization lasting >4 months) was obtained in 6 of 11 patients, in keeping with previously published results. Conclusions: Our data confirm that EBV-specific CTL therapy is safe and associated with antitumor activity in patients with advanced NPC. The use of lymphodepleting chemotherapy before high-dose CTL infusion did not enhance the clinical benefit observed in our previous series.

Clinical outcome of patients with various advanced cancer types vaccinated with an optimized cryptic human telomerase reverse transcriptase (TERT) peptide: results of an expanded phase II study

Background: TERT (telomerase reverse transcriptase) plays a critical role in tumor cell growth and survival. In an expanded phase II study, we evaluated the immunological and clinical responses to the TERT-targeting Vx-001 vaccine in patients with advanced solid tumors. Methods: HLA-A*0201-positive patients received two subcutaneous injections of the optimized TERT572Y peptide followed by four injections of the native TERT572 peptide, every 3 weeks. Peptide-specific immune responses were evaluated by enzyme-linked immunosorbent spot at baseline, and after the second and the sixth vaccinations. Results: Fifty-five patients were enrolled and 34 (62%) completed the six vaccinations. A TERT-specific T-cell immune response was observed in 55% and 70% of patients after the second and the sixth vaccinations, respectively. The disease control rate (DCR) was 36% [95% confidence interval (CI) 24% to 49%], including one complete and one partial response. Immunologically responding patients had a better clinical outcome than nonresponders [DCR: 44% versus 14% (P = 0.047); progression-free survival (PFS): 5.2 versus 2.2 months (P = 0.0001) and overall survival: 20 versus 10 months (P = 0.041)]. Multivariate analysis revealed that the immunological response was an independent variable associated with increased PFS (hazard ratio = 3.35; 95% CI 1.7–6.7). Conclusion: Vx-001 vaccine was well tolerated and induced a TERT-specific immunological response, which was significantly correlated with improved clinical outcome.

Immunogenicity and safety of the influenza A H1N1v 2009 vaccine in cancer patients treated with cytotoxic chemotherapy and/or targeted therapy: the VACANCE study

Background: Influenza vaccination is recommended to cancer patients undergoing chemotherapy, but vaccine coverage remains low. During the 2009 influenza pandemic, French recommendations were to vaccinate immunocompromised patients with two doses of adjuvanted vaccine. This study aimed to evaluate vaccine immunogenicity in cancer patients receiving chemotherapy. Patients and methods: VACANCE is a prospective open-label study that evaluated the immunogenicity and safety of two doses of AS03A-adjuvanted H1N1v vaccine in cancer patients receiving cytotoxic and/or targeted therapies. Serum haemagglutination-inhibited antibody titres against influenza A H1N1v were measured at days 1, 21, and 42, to estimate the proportion of participants with antibody titres ≥1 : 40 [seroprotection rate (SPR)], the efficacy of seroconversion, and factors that increased the geometric mean titre. Results: Sixty-five patients were included. At baseline, 5% of patients had vaccine strain titres of specific haemagglutination inhibition antibodies that were ≥1 : 40. After one and two doses of vaccine, SPRs were48% and 73%, respectively, and seroconversion rates were 44% and 73%, respectively. Vaccine-related adverse events were mild to moderate. Conclusions: A single dose of AS03-adjuvanted A/H1N1 vaccine triggered a low immune response in cancer patients on chemotherapy depending on their treatment type and frequency. Two doses are needed for these cancer patients.

Intracranial hemorrhage in patients with cancer treated with bevacizumab: the Memorial Sloan-Kettering experience

Background: Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor approved for recurrent glioblastoma (GBM), metastatic breast, colorectal and non-small-cell lung cancers (NSCLC). There has been a potentially increased risk of intracranial hemorrhage (ICH) in patients receiving bevacizumab. Methods: We retrospectively identified patients with ICH who received bevacizumab between 1 January 2001 and 10 January 2009. Results: We identified 1024 patients with ICH, 4191 patients who received bevacizumab and 12 (0.3%) who met both our criteria. There were eight women and four men with a median age of 66 years. Primary cancers were ovarian (n = 3), NSCLC (n = 3), colon (n = 1), angiosarcoma (n = 1) and GBM (n = 4). Intracranial tumors were present in 9 of the 12 patients; the remaining three (25%) had no evidence of intracranial pathology. Two hundred and fifty-seven patients with these same primary pathologies and brain tumors were treated with bevacizumab; ICH was seen in nine (3.7%), which was comparable to the 3.6% frequency seen in comparable patients not receiving bevacizumab. Conclusions: ICH with bevacizumab treatment in this population is rare and does not appear to increase its frequency over the baseline rate of ICH in a comparable population. Most bevacizumab-related ICH occurs into central nervous system tumors but spontaneous hemorrhages were seen.

Phase I safety, pharmacokinetic and pharmacodynamic trial of BMS-599626 (AC480), an oral pan-HER receptor tyrosine kinase inhibitor, in patients with advanced solid tumors

Purpose: We studied the safety, tolerability, and recommended dose of BMS-599626, an orally bioavailable inhibitor of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. Patients and methods: Patients with advanced solid tumors that expressed epidermal growth factor receptor (EGFR) and/or HER-2 were recruited and enrolled in a phase I, open-label, dose escalation trial of oral BMS-599626 starting at 100 mg/day given once daily for at least 28 days. Results: Forty-five patients received BMS-599626 (100–660 mg/day). Dose-limiting toxic effects were reported at 660 mg/day (grade 3 elevation of hepatic transaminases [two patients] and QTc interval prolongation [one patient]), therefore the recommended maximum tolerated dose was 600 mg/day. The most frequent drug-related toxic effects were diarrhea (30% of patients), anorexia (13%), asthenia (30%), and cutaneous toxic effects, including skin rash (30%). Pharmacokinetic analysis demonstrated Cmax and exposure to BMS-599626 in patients increased with dose. Eleven patients had stable disease and received BMS-599626 for ≥4 months. Serial skin and tumor biopsies taken before and after treatment revealed expected changes in pharmacodynamic biomarkers, indicating that the EGFR and HER-2 pathways were affected. Positron emission tomography imaging showed a metabolic response in 2 of 10 patients evaluated. Conclusion: BMS-599626 was generally well tolerated, with disease stabilization across a range of tumor types and doses.

Survival from common and rare cancers in Germany in the early 21st century

Background: Until recently, population-based data of cancer survival in Germany mostly relied on one registry covering ~1 million people (1.3% of the German population). Here, we provide up-to-date cancer survival estimates for Germany based on data from 11 population-based cancer registries, covering 33 million people and compare them to survival estimates from the United States. Patients and methods: Cancer patients diagnosed in 1997–2006 were included. Period analysis was employed to calculate 5-year relative survival for 38 cancers for 2002–2006. German and USA survival rates were compared utilizing the Surveillance, Epidemiology and End Results 13 database. Results: Five-year relative survival >80% was observed for testicular cancer (93.5%), skin melanoma (89.4%), cancers of the prostate (89.1%) and thyroid (87.8%), Hodgkin’s lymphoma (84.5%) and cancers of the breast (83.7%) and endometrium (81.0%), which together account for almost 40% of cases. For the majority of cancers, German survival estimates were close to or below those in the United States. Exceptions with higher survival in Germany were cancers of the stomach, pancreas and kidney and Hodgkin’s lymphoma. Conclusions: German cancer survival estimates are mostly higher than the 2000–2002 pan-European estimates. Further research is needed to investigate causes responsible for differences between German and USA cancer survival rates.

Association between body mass index and the colorectal cancer risk in Japan: pooled analysis of population-based cohort studies in Japan

Background: Obesity has been recognized as important risk factors for colorectal cancer. However, limited evidence is available on colorectal cancer and body mass index (BMI) in Asian population. Methods: We conducted a pooled analysis of eight population-based prospective cohorts studies in Japan with more than 300 000 subjects to evaluate an impact of obesity in terms of BMI on colorectal cancer risk with unified categories. We estimated summary hazard ratio (HR) by pooling of study-specific HR for BMI categories with random effect model. Results: We found a significant positive association between BMI and colorectal cancer risk in male and female. Adjusted HRs for 1 kg/m2 increase were 1.03 [95% confidence interval (CI) 1.02–1.04] for males and 1.02 (95% CI 1.00–1.03) for females. The association was stronger in colon, especially in proximal colon, relative to rectum. Males showed a stronger association than females. Population attributable fraction for colorectal cancer by BMI ≥25 kg/m2 was 3.62% (95% CI 1.91–5.30) for males and 2.62% (95% CI 0.74–4.47) for females. Conclusions: We found significant association between BMI and colorectal cancer risk by pooling of data from cohort studies with considerable number of subjects among Japanese population. This information is important in cancer control planning, especially in Asian population.

Dietary cholesterol intake and cancer

Background: This study assesses the association between dietary cholesterol intake and the risk of various cancers. Patients and methods: Mailed questionnaires were completed between 1994 and 1997 in eight Canadian provinces by 1182 incident histologically confirmed cases of the stomach, 1727 of the colon, 1447 of the rectum, 628 of the pancreas, 3341 of the lung, 2362 of the breast, 442 of the ovary, 1799 of the prostate, 686 of the testis, 1345 of the kidney, 1029 of the bladder, 1009 of the brain, 1666 non-Hodgkin's lymphomas (NHL), 1069 leukemia and 5039 population controls. Information on dietary habits and nutrition intake were obtained using a food frequency questionnaire, which provided data on eating habits 2 years before the study. Odds ratios (ORs) were derived by unconditional logistic regression to adjust for total energy intake and other potential confounding factors. Results: Dietary cholesterol was positively associated with the risk of cancers of the stomach, colon, rectum, pancreas, lung, breast (mainly postmenopausal), kidney, bladder and NHL: the ORs for the highest versus the lowest quartile ranged from 1.4 to 1.7. In contrast, cholesterol intake was inversely associated with prostate cancer. Conclusions: Our findings add to the evidence that high cholesterol intake is linked to increased risk of various cancers. A diet low in cholesterol may play a role in the prevention of several cancers.

Gemcitabine in advanced angiosarcoma: a retrospective case series analysis from the Italian Rare Cancer Network

Background: Angiosarcoma is a highly aggressive soft tissue sarcoma. Responses to anthracyclines plus/minus ifosfamide, and taxanes alone or in combination with gemcitabine are well documented. Very few data are available on gemcitabine as a single agent. Patients and methods: We retrospectively reviewed all cases of advanced progressive angiosarcoma treated with gemcitabine as a single agent (1000 mg/m2 i.v. every week for 3 weeks every 4 weeks), at Istituto Nazionale Tumori and within the Italian Rare Cancers Network from January 2008 to November 2010. Results: Twenty-five patients [mean age: 52 years; radiation therapy (RT)-related: 8] received gemcitabine. Best tumor response by RECIST was as follows: complete response = 2, partial response = 14, stable disease = 2, progressive disease = 7 cases, for an overall response rate (PR + CR) of 68%. Six of eight post-RT angiosarcomas responded to treatment. Median overall survival (OS) was 17 months. Median progression-free survival (PFS) was 7 months (range 1–40 months). One patient with a locally advanced thyroid angiosarcoma became resectable after 5 months of gemcitabine, with <10% residual viable tumor cells seen on surgical specimen. Overall, gemcitabine was well tolerated. Conclusions: Gemcitabine is active in both RT- and non-RT-related angiosarcoma, with dimensional and possibly long-lasting responses. A formal phase II study on gemcitabine as a single agent is warranted.

A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study

Purpose: After standard multimodal therapy, the prognosis of relapsed and unresectable high-grade osteosarcoma is dismal and unchanged over the last decades. Recently, mitogen-activated protein kinases were shown to be activated in osteosarcoma specimens, suggesting, therefore, they are suitable targets for the multikinase inhibitor sorafenib. Thus, we explored sorafenib activity in patients with relapsed and unresectable osteosarcoma. Experimental design: Patients >14 years, progressing after standard treatment, were eligible to receive 400 mg of sorafenib twice daily until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) at 4 months. Secondary objectives were PFS, overall survival (OS), clinical benefit rate (CBR), defined as no progression at 6 months and safety. This nonrandomized phase II study used a Simon two-stage design. PFS and OS at 95% confidence intervals (95% CIs) were calculated by the Kaplan–Meier method. All tests were two sided. Results: Thirty-five patients were enrolled. PFS at 4 months was 46% (95% CI 28% to 63%). Median PFS and OS were 4 (95% CI 2–5) and 7 (95% CI 7–8) months, respectively. The CBR was 29% (95% CI 13% to 44%). We observed 3 (8%) partial responses (PRs), 2 (6%) minor responses (<30% tumor shrinkage) and 12 (34%) stable diseases (SDs). For six patients (17%), PR/SD lasted ≥6 months. Noteworthy, tumor density reduction and [18F]2-fluoro-2-deoxy-d-glucose–positron emission tomography responses were observed among SD patients. Sorafenib was reduced or briefly interrupted in 16 (46%) patients and permanently discontinued in one (3%) case due to toxicity. Conclusions: Sorafenib demonstrated activity as a second- or third-line treatment in terms of PFS at 4 months with some unprecedented long-lasting responses. Sorafenib, the first targeted therapy showing activity in osteosarcoma patients, deserves further investigations.