Medical Oncology Treatment Research Articles

One more chemo or one too many? Defining the limits of treatment and innovation in medical oncology

During the past few years, debates have frequently erupted in oncology journals regarding the question of whether to prolong or end treatment. These debates have been informed by developments from both within and outside the field. Within Bioethics, some writers have put forward a number of principles for judging the legitimacy of medical interventions, notably that of patient autonomy. Broad social and political developments have also profoundly affected medical practices at the end of life. Though therapeutic options have evolved, whether to stop or to pursue treatment in the face of certain death has been a central issue in medical oncology since the early 1950s. A critical appraisal of the history of this issue can help us to better understand the tangled relationship(s) between innovation, “cure,” death, and the symptoms and subjective experiences of sufferers. This paper addresses an aspect of this complex problem, namely how limits are established regarding both treatment and therapeutic innovation near the end of life. Utilizing a grounded theory and situational analysis approach it traces how the issues at stake were defined and the ways in which the dilemma was progressively transformed as a result of the combined effects of a proliferating number of stakeholders, molecules, instruments, and techniques. It discusses three different moments, as they epitomize how the links between chemotherapy and palliation were construed through the evolving forms of clinical research and innovative therapies.

Is No News, Good News? Assessing the Nutritional Status of Cancer Patients Undergoing Treatment in Radiation Oncology, Medical Oncology, and Palliative Care Departments in Spain: Results of the Multicenter Nationwide Nutridis Study

Is No News, Good News? Assessing the Nutritional Status of Cancer Patients Undergoing Treatment in Radiation Oncology, Medical Oncology, and Palliative Care Departments in Spain: Results of the Multicenter Nationwide Nutridis Study

Targeted KRAS Mutation Assessment on Patient Tumor Histologic Material in Real Time Diagnostics

BackgroundTesting for tumor specific mutations on routine formalin-fixed paraffin-embedded (FFPE) tissues may predict response to treatment in Medical Oncology and has already entered diagnostics, with KRAS mutation assessment as a paradigm. The highly sensitive real time PCR (Q-PCR) methods developed for this purpose are usually standardized under optimal template conditions. In routine diagnostics, however, suboptimal templates pose the challenge. Herein, we addressed the applicability of sequencing and two Q-PCR methods on prospectively assessed diagnostic cases for KRAS mutations.Methodology/Principal FindingsTumor FFPE-DNA from 135 diagnostic and 75 low-quality control samples was obtained upon macrodissection, tested for fragmentation and assessed for KRAS mutations with dideoxy-sequencing and with two Q-PCR methods (Taqman-minor-groove-binder [TMGB] probes and DxS-KRAS-IVD). Samples with relatively well preserved DNA could be accurately analyzed with sequencing, while Q-PCR methods yielded informative results even in cases with very fragmented DNA (p<0.0001) with 100% sensitivity and specificity vs each other. However, Q-PCR efficiency (Ct values) also depended on DNA-fragmentation (p<0.0001). Q-PCR methods were sensitive to detect ≤1% mutant cells, provided that samples yielded cycle thresholds (Ct) <29, but this condition was met in only 38.5% of diagnostic samples. In comparison, FFPE samples (>99%) could accurately be analyzed at a sensitivity level of 10% (external validation of TMGB results). DNA quality and tumor cell content were the main reasons for discrepant sequencing/Q-PCR results (1.5%).Conclusions/SignificanceDiagnostic targeted mutation assessment on FFPE-DNA is very efficient with Q-PCR methods in comparison to dideoxy-sequencing. However, DNA fragmentation/amplification capacity and tumor DNA content must be considered for the interpretation of Q-PCR results in order to provide accurate information for clinical decision making.

P31 The impact of a Comprehensive Geriatric Assessment (CGA) on medical oncology treatment decisions for elderly patients with cancer

P31 The impact of a Comprehensive Geriatric Assessment (CGA) on medical oncology treatment decisions for elderly patients with cancer

Outcomes of medical and surgical inpatients newly diagnosed with advanced cancers

17530 Background: The prognosis of patients (pts) with advanced cancers that are newly diagnosed during hospital admission is unclear. A better understanding of their outcomes can streamline management and facilitate referrals to specialists. Our aims were to evaluate the likelihood of hospital discharge and receipt of outpatient palliative systemic therapy (ST) in this group of pts and examine clinical factors associated with treatment. Methods: Pts who were admitted to a medical or surgical ward from 2004 to 2007 and assessed by the medical oncology inpatient consultation service for de novo stage IV lung or gastrointestinal (GI) cancers were reviewed. Logistic regression analyses were performed to determine pt demographics, disease characteristics and baseline admission laboratory investigations that predicted for subsequent assessment in an outpatient medical oncology clinic (OMOC) and treatment with ST. Results: Of the 139 eligible pts, 80 (58%) were male, 58 (42%) had lung cancer and 86 (62%) were admitted to a medical ward. The median age was 66.6 years (range 19 to 93). Dyspnea and abdominal discomfort were the most common hospital presenting complaints from lung and GI cancer pts, respectively. Median time from admission to first medical oncology consultation and median duration of hospital stay was 1.4 and 2.9 weeks, respectively. In 52 (37%) cases, pts successfully proceeded to hospital discharge. Within this cohort, median interval from discharge to OMOC assessment was 3.2 weeks. In multivariate analysis, pts with low hemoglobin and high AST levels were less likely to be seen in the OMOC for ST (OR 0.13 p=0.02 and OR 0.03 p=0.01, respectively). Other demographical features and disease parameters failed to predict for prognosis (all p>0.05). Conclusions: More than one-third of inpatients diagnosed with advanced cancers are discharged from hospital and given outpatient palliative ST, but time from discharge to first outpatient assessment is long. Conversely, close to two-thirds of inpatients never receive outpatient ST for their advanced diseases suggesting that admission to hospital at the time of initial diagnosis is a poor prognostic factor. In the subset of individuals with evidence of anemia and liver dysfunction on admission, early palliative care referral may be beneficial. No significant financial relationships to disclose.

Do clinical practice guidelines (CPGs) change clinical practice? An analysis of CPG impact on referral and treatment patterns for neoadjuvant chemotherapy in bladder cancer

5077 Background: Neoadjuvant chemotherapy (CT) for muscle invasive urothelial BC improves survival and is considered standard of care. In Alberta, Canada, CPGs recommending CT were developed with input from the wider urologic community and disseminated in May 2005. To evaluate the effect of CPG on practice patterns, a review of referral and treatment patterns before and after CPG implementation was undertaken. Methods: All patients in the Calgary Health Region who underwent radical cystectomy for BC from a 5 year period encompassing the CPG release date were identified. Two cohorts (A: 2.5 to 0.5 years prior to CPG, B: 0.5 to 2.5 years post CPG) were defined. Charts were reviewed to identify patients who were eligible for CT based upon the diagnosis of clinical stage 2 or 3 urothelial BC. Rates of referral to medical oncology and actual treatment with CT were ascertained for each cohort. Logistic regression analysis was undertaken to identify variables impacting referral and treatment decisions. Results: 141 patients were identified. Of these, 67 (Cohort A: 32; Cohort B: 35) were eligible for CT by CPG criteria. The referral rates for cohorts A and B were 2 (6.3%) and 11 (31%) respectively (OR 6.88, p=0.018, 95% CI 1.34, 34.04) In cohort A no referred patients were offered CT. In cohort B, 9 patients (25%) were offered treatment and 6 (17%) received CT. In subgroup analysis there was a significant correlation between referral rate, female sex and pathologic stage 3 or 4 disease. Conclusions: Referral and treatment rates for CT have improved significantly after release of CPGs in Alberta, but are still low. Of patients who are referred to medical oncology in this jurisdiction the majority (82%) are offered treatment, indicating that the most significant limitation to provision of standard of care treatment is at the level of referral. While CPGs have positively impacted referral rates, it remains clear that the majority of BC patients are ultimately not accessing comprehensive cancer care. Further work should focus on both improving methods of effectively disseminating CPGs and on novel tools for increasing the uptake of evidence based practice. No significant financial relationships to disclose.

Where Adolescents and Young Adults With Cancer Receive Their Care: Does It Matter?

During the last 25 years, improvement in survival for young children with cancer has been striking. Survival has also increased for older adults; however, 5-year survival rates have fallen for older adolescent and young adult (AYA) cancer patients. 1 Reasons for this decline, termed the “AYA Cancer Survival Gap,” remain unknown. Bleyer et al 2 suggested that a lower participation rate on clinical trials in this age group may partially account for poorer survival, but the reasons why remain unclear. The type of practice where cancer care is delivered may also influence clinical trial participation and outcome. Two articles in this issue of the Journal of Clinical Oncology analyzed where older adolescents and young adults received their cancer care. 3,4 Both utilized statewide, population-based cancer registries to describe the referral patterns for older AYAs with cancer. Newly diagnosed AYAs with cancer were categorized by whether or not they received their care at institutions that participate in the Children’s Oncology Group (COG). Albritton et al 3 identified characteristics predictive of receiving care at a pediatric oncology versus medical oncology treatment program. Whether care was delivered at Utah’s only pediatric cancer treatment program, the Primary Children’s Medical Center (PCMC; Salt Lake City), was determined for all incident cancer cases aged 0 to 24 years from the Utah Cancer Registry. Overall, 34% of older adolescents aged 15 to 19 years were seen at PCMC, whereas 97% of children age 0 to 9 years and 82% of children 10 to 14 years were seen at PCMC. The rate at which older adolescents were cared for at a pediatric center varied by diagnosis: 29% for lymphoma, 34% for brain tumors, and 53% for leukemias. Howell et al 4 found that 87% of young patients 0 to 14 years in Georgia were seen at one of the five COG-affiliated institutions in the state. Compared with younger patients, only 36% of 15- to 19-year-olds were seen at COG institutions. In an earlier analysis of Surveillance, Epidemiology, and End Results (SEER) cases from

Gender Medizin in der Onkologie

The whole field of Oncology benefits from the huge amount of basic science "invested" and from the experience accumulated during several decades that enables more patients with malignant diseases to be cured or to survive for longer periods. Incidence and mortality rates from cancer have been decreasing by around 1 % per year since the mid-nineties of the past century in the European Union. However, the spectrum of malignant diseases and the outcome is not equally distributed between the two sexes. Startlingly, in advanced cancers, women receiving the same treatment schemes as men fare better. Until recently, however, the pharmacological knowledge of the pharmacokinetic and pharmacodynamic action of cytotoxic drugs was scarce for women, as like in other fields of medicine, studies recruited far more men than women and because results were often not reported separately for both sexes. These practices are slowly changing and gender specific outcome data are progressively accumulating. Such data on gender-specific differences or similarities are essential for building newer, more adequate tools for dosing drugs than the current form based on a "falsely accurate and individualzed" estimation of the body surface area. Nevertheless, the socioeconomical and sociocultural context of living remains genderspecifically different, influencing the coping of individuals with a life-threatening disease. On the other hand, as recently shown for chronic lymphocytic leukaemia, gender-specific analysis might open new insights in the biology of the disease and modify treatment strategies.

Developing the Medical Oncology Treatment Plan and Summary

Developing the Medical Oncology Treatment Plan and Summary

Developing the Medical Oncology Treatment Plan and Summary

Developing the Medical Oncology Treatment Plan and Summary

Colorectal cancer in Slovenia – differences in surgical treatment and patient survival

Background: Colorectal cancer (CRC) is one of the most frequent malignant diseases in Slovenia. Its incidence rises constantly in the last years while the outcome of treatment is poorer than in other developed countries. Methods: In a retrospective study we analysed 940 colorectal cancer patients diagnosed in Slovenia in 1997. Results: Differences in outcome between the Slovenian institutions are due to different stage-distributions and differences in surgical radicality. Differences in pathohistological staging and medical oncological treatment are probably less important. The same can be said regarding some of the examples from abroad. Conclusions: With constant and objective auditing, the improvement of all aspects of treatment can be achieved, resulting in better survival of all Slovenian colorectal cancer patients.

Onkologische Pharmakotherapie alter Patienten

Age is the major risk factor for the development of cancer. Difficulties in medical treatment of elderly patients with cancer may be due to age dependent changes in physiological organ function, which result in pharmacokinetical and pharmacodynamical changes. They also may be due to co-morbidities with the need of pharmacological therapy. The choice of adequate treatment protocols has to consider this age dependent changes in pharmacokinetics and the presence of co-morbidities. Most of the data reporting results of medical oncological treatment in patients with cancer are collected in younger patients. Therefore, the present knowledge concerning medical oncological treatment of elderly patients with cancer is still limited.

Misrepresentation of Facts by the Expert Witness

THE EXPERT WITNESS is fully protected under most state statutes and federal law from incorrect opinions expressed under oath. Statements of fact that are intentional lies are subject to punishment under the laws for perjury. The medical expert has a vast amount of leeway as to what may be said under oath, as long as it is expressed as his or her opinion. It is sometimes difficult to differentiate between a lie and what a misinformed physician believes is the truth. A case will often turn on the opinion of an expert who is believable because of his or her demeanor and not necessarily what is scientifically true or actually the standard of practice. The truth can best be shown to a jury by actual statements from peer-reviewed medical papers in journals or a reliable text. But what text is completely reliable? For instance, there are texts edited by experts in a particular field, but lesser “authorities” or even doctors in another field of practice write the actual chapters. One prime example is when a radiation oncologist, professor of medicine, and professor of surgery, but no professor of hematology–oncology, write a chapter on breast cancer in a major oncology text and the chapter covers the medical oncology treatment of breast cancer.(1) The expert witness may provide incorrect opinions through failure to obtain the correct facts or information, failure to study the literature, failure to find out if there are reliable minority opinions, or by receiving misinformation. There may be improper exuberance to win the case for the side on which he or she is testifying, rather than being impartial. Sometimes, although not often, it is a matter of financial gain by helping to win the case so as to receive further referrals or be hired again.

Current concepts of treatment in medical oncology: new anticancer drugs.

General principles for anticancer drug development include traditional drug-screening methods in biological test systems. Today, testing of a drug in a panel of selected human tumor xenografts in mice is assumed to have the best predictive value for clinical efficacy. Chemical modification of well-known antitumor drugs from compound groups such as purine analogs, vinca alkaloids, antifolates and platinum analogs are carried out to increase anticancer activity, to reduce toxic side-effects and to improve pharmacokinetic properties of the drugs. In the last decade the enormous development in molecular techniques has led to the discovery of key proteins that are intimately involved in the regulation of cancer growth control. Cell growth inhibitors could be developed by structure-based design, creating small organic molecules ("peptide mimetics") to target crucial enzymes, oncogenes or oncogene products, tumor-suppressor genes and their products as well as growth factors and their corresponding receptors. Drugs representing new leading structures, like alkylphosphocholines, topoisomerase I inhibitors, taxoids and suramin, have already entered the clinic. Novel therapeutic approaches may provide substantial progress in cancer treatment in the very near future. Examples are the concept of high-dose chemotherapy with hematopoietic stem cell support, the various strategies of gene therapy, the modulation of multi-drug resistance of cancer cells, and strategies to inhibit tumor angiogenesis.

The Out-Patient Clinic for Medical Oncology Treatment. Experience at the Istituto Nazionale Tumori of Milan

The possibility to administer chemo-hormone- and immunotherapy on an out-patient basis has greatly increased because of the progress reached in the management of the out-patient departments. The improved knowledges on tossicological, pharmacodynamic and therapeutic data as well as the advent of the cyclic schedules determined the feasibility of medical treatments even when they are combined with surgical and/or radio-therapeutic modalities. To the patient, the possibility to be carefully and effectively treated on out-patient clinic, renders more acceptable, both from a psychologic and economic point of view, even a prolonged combined treatment. On the same time, also the Institutions have some advantages both on their organization (a shorter median stay in hospital and consequently a reduced waiting list) and for their scientific program (increased number of patients who can be treated according to a therapeutic program, possibilities to obtain statistically valuable information on the treatment program of a given disease and on the knowledge of its natural history). The last five year increasing activity of the Out-Patient Clinic for Medical Oncology Treatment of the Istituto Nazionale Tumori of Milan is illustrated in Text-figure 1, while Text-figure 2 represents its actual organization; this is obviously of a multidisciplinary type, both on its diagnostic and therapeutic phase. Table 1 shows the activity carried out in 1975; it is notewhorthy that 2,570 patients have been followed, thus accounting for a total of 20,164 medical examinations and/or intravenous drug administrations. Table 2 presents the incidence of the different types of neoplasia followed in the out-patient department: the large majority was represented by breast cancer (40%); followed by malignant lymphomas (31.5%) and pediatric tumors (7.5%). During 1975, 22 therapeutic protocols have been applied, 10 of which (table 4) required an initial hospitalization and 12 (table 5) could be entirely carried out in the out-patient department. As shown in Table 6 chest x-rays accounted for 52 % and skeletal survey for 18 % of the 11.906 radiological examinations. Table 7 shows the number of off-hand required radiological reports carried out for patients not geographically accessible who, in one single day, could have their radiological, and medical examinations as well as their hemogram and treatment performed. A total 467 scintiscans have been required, 86 % of which of the liver (table 8). The hemato-pathology unit counted out about 16,000 hemograms with platelets (table 9). The hemograms were always performed within 1–2 hours with immediate communication of the counts to the out-patient department. In order to modify clinical situations which were deteriorated because either of the disease or of the treatment 358 blood units were transfused.