Is the current concept of recurrent ovarian carcinoma as a chronic disease also applicable in platinum resistant patients?

Purpose: The treatment of recurrent ovarian carcinoma (ROC) has become increasingly oriented according to the therapy principles of a chronic disease. We evaluated whether it is justifiable to also apply this concept to the treatment of platinum resistant patients with their known poor prognosis and short overall survival (OS). Methods: We analyzed the overall courses of 85 unselected ROC patients and defined the following groups: A, platinum resistant patients (n=39); subgroup A.1, those who received no or at maximum one line of palliative chemotherapy (n=15, 38.5%); subgroup A.2, those who received≥two therapy lines (n=24, 61.5%); B, platinum sensitive patients, n=46. Results: Group A had significantly lower OS than group B (median: 16 vs. 25months; p=0.019). Group A.1 had significantly worse outcome compared to group A.2 (median: 5 vs. 21.5months; p<0.001). The comparison between study group A.2 and group B showed comparable survival rates (p=0.738). Considering only the patients who had completed treatment courses, the median number of therapy lines administered was higher in group A.2 than in group B (4 vs. 3; p=0.008). Conclusions: There is not only the known dichotomy between platinum sensitive and resistant ROC patients, but rather also within the platinum resistant subgroup itself. There is a considerably large subgroup of platinum resistant patients who will subsequently enter a phase where multiple treatment programs will be considered and administered. These patients have similar survival rates compared to those from the platinum sensitive patient group and the therapy principles of a chronic disease are applicabl

Clinical outcomes and patterns of severe late toxicity in the era of chemo-radiation for cervical cancer

Background: We present a comprehensive analysis of both therapy-induced severe late toxicity and outcome in a cohort of cervical cancer patients following radiation who were treated according to current guidelines and discuss the methodologic problems of systematically reporting these cases. We introduce a revised concept of reporting treatment failure. Patients and methods: The records of 128 cervical cancer patients who received radiation from 2003 to 2008 were reviewed. Results: Thirteen patients (10.2%) developed severe late toxicity. The combination of heavy smoking and cardiovascular diseases was found to be a significant contributing factor (HR 6.55, 95% CI 0.99-43.49, p=0.048). Thirty patients (23.4%) experienced treatment failure. Of these, 12 (9.4%) were defined to have persistent disease, and 18 (14.0%) developed recurrent disease. Patients with recurrent disease had significantly better survival time (p<0.001). Compared with the persistence subgroup, they had significantly more often multiple sites of relapse (66.7 vs. 8.3%, p=0.002) and the sites were more often diagnosed outside the pelvis (70.7 vs. 7.7%, p<0.001). Early disease stages (OR 4.46, 95% CI 1.87-10.63, p<0.001) and severe late toxicity (p=0.037) were found to be significant factors for an improved disease-free survival. Conclusions: A comprehensive depiction of both late therapy-related toxicity and treatment failure requires precise clinical descriptions and analyses of the clinical courses. Our new concept to differentiate treatment failure following radiotherapy in cervical cancer into persistent and recurrent disease permits a clear differentiation between distinct subgroups of patients with regard to prognosis and clinical presentation and will lead to a more precise description of these cases in the futur

Strictly defined familial male breast cancer

The term "familial male breast cancer” is often misleading, because in the breast cancer families reported in the literature, the vast majority of the patients were women and only a few were men. In this report, we present the rare case of a strictly defined familial male breast cancer (MBC) in which exclusively men were diagnosed with breast cancer. Three of four brothers developed the disease between the age of 46 and 64years within a period of 21years whereas all female relatives remained unaffected. The three affected men did not show the typical known clinical and genetic risk factors for MBC. An X-linked recessive inheritance may be possible in these cases. One way to potentially improve the identification of the causes of MBC could be a through a strictly studying families in which the male members were exclusively diagnosed with this malignancy. This approach emphasizes familial MBC as a distinct entity and not only as a variant of female breast cance

Cannabinoid hyperemesis syndrome: an underreported entity causing nausea and vomiting of pregnancy

Introduction: In the western world, cannabis is the most widely used drug of abuse. Cannabinoid hyperemesis syndrome, which seems to be a rare paradoxical reaction in individuals with a particular predisposition, is characterized by cyclic severe nausea and vomiting in long-term cannabis users. While the symptoms are unresponsive to antiemetic drugs, compulsive hot baths result in a considerable symptom relief. Methods: We report the first case of cannabinoid hyperemesis syndrome in pregnancy. A 26-year-old patient was admitted to our clinic in the 10th week of gestation. Conclusion: Before undertaking time-consuming and expensive medical examinations to rule out other medical reasons for therapy-resistant hyperemesis in pregnancy, obstetricians should determine whether compulsive bathing or showering provides symptomatic relief and ask specific questions regarding possible/suspected cannabis consumptio

Competition in Innovation and Imitation - A Theoretical and Experimental Study -

For given product specifications by two competing firms the demand levels are determined by a randomly generated ideal composition of aspects. Firms can vary some or all aspects of these products, based on information about own (and other's) previous demand. Although the product space is much too large to be explored systematically, we expect (and test for) rather reasonable innovative success and welfare levels due to own innovative attempts and imitation of a successful other. Parameter variations concern the pioneer advantage and search costs.Innovation, Imitation, Patent Tournament, Trial and Error Process

Drug switch because of treatment-related adverse side effects in endocrine adjuvant breast cancer therapy: how often and how often does it work?

Therapy-related adverse side effects are a main reason for non-persistence to adjuvant endocrine breast cancer therapy. This study reports frequency of drug-related adverse side effects that were so severe that a modification of the therapy was necessary. We evaluated how many patients discontinued adjuvant endocrine therapy because of these side effects (non-persistence). Last, we analyzed how often a drug switch was undertaken for this reason and how often this measure led to the patient successfully continuing their endocrine therapy. Data concerning all postmenopausal breast cancer patients (≤80years), who initiated endocrine adjuvant therapy between 1998 and 2008 in a Swiss breast center (n=400), were analyzed. Out of these 400 women, 37 (9.3%) were defined as being non-persistent to the therapy; out of these, 24 (64.9%) because of therapy-related side effects. About 78 patients (19.5%) suffered from severe therapy-related side effects that made a modification of therapy necessary. Out of these 78 cases, 14 patients (17.9%) stopped the therapy without attempting a drug switch (non-persistence). In 64 patients (82.1%; 16% of all women who started endocrine therapy), a drug switch was undertaken. Out of these 64 cases, in 52 cases (81.3%) endocrine therapy was completed after therapy modification. Patients who reported one major adverse effect were more likely to continue the endocrine therapy after a drug switch (P=0.048) compared with those who suffered from at least two different side effects. In 10 of the 64 cases (15.6%), modification of the therapy was not successful and the patients stopped the treatment prematurely (non-persistence) because of ongoing side effects. In cases when therapy-related side effects occur, a drug switch is a promising step to further improve persistence and, by doing so, the outcome of breast cancer patient

Metastatic Breast Cancer as a Chronic Disease: Evidence-Based Data on a Theoretical Concept

Background: We challenge the concept of metastatic breast cancer (MBC) as a chronic disease. Methods: We analyzed an unselected cohort of 367 patients who were diagnosed with MBC over a 22-year period (1990–2011). Results: In order to create a “chronic disease subgroup”, we separated those patients from the entire cohort in whom systemic therapy was not applied after the diagnosis of MBC (n = 53; 14.4%). Three hundred fourteen patients (85.6%) comprised the “chronic disease subgroup”. The vast majority of those patients (89.8%) died of progressive disease after a median metastatic disease survival (MDS) of 25 months. Twenty patients (6.4%) died of non-MBC-related causes (MDS 38.5 months). Approximately 1 in 4 patients (26.8%) died within the first year after the MBC diagnosis. The 3- and 5-year MDS rates were 35.4 and 16.2%, respectively. Only 12 patients (3.8%) were exceptional survivors (MDS >10 years). Conclusion: The term “chronic disease” might be appropriate in selected MBC cases, bringing MBC into alignment with “classical” chronic diseases such as diabetes and hypertension. However, most cases display fundamental differences with regard to temporal progression and above all the case fatality rate. More than 90% of patients in the “chronic disease subgroup” died of the disease with a MDS of 2–3 years (even those who underwent systemic palliative therapies). Doctors and patients might understand the term “chronic disease” differently. The term must be used sparingly and explained carefully in order to create a common level of communication based on a shared understanding which avoids awakening false hopes and fostering misleading expectations

Compliance and persistence of endocrine adjuvant breast cancer therapy

This study evaluates compliance and persistence in adjuvant endocrine breast cancer (BC) therapy by clearly analyzing reasons of therapy cessation by differentiating clinical meaningful situations. In order to illuminate the complex field of personal motivation to therapy, a single institution study with a more individual-based approach might better be suited to provide a detailed case documentation than the more epidemiologic approach of large database studies. An unselected cohort of 698 patients (≤80years) diagnosed with hormonal receptor-positive BC from 1997 to 2008 at the University Hospital Basel, Switzerland, was analyzed. The term "non-persistence” was exclusively used for patients where the discontinuation of endocrine therapy (ET) could have been modified by more intensive care and improved counseling (e.g., in women who lost faith/motivation to therapy or those who suffered from therapy-related side effects). These cases must be differentiated from cases where therapy cessation was inevitable (e.g., due to recurrent disease or severe intercurrent illness). Out of the 685 patients to whom ET was recommended, 42 patients (6.1%) refused and never began treatment (non-compliance). Women younger than 50 were more likely to be non-compliant (P<0.001). 12.9% of the patients who started therapy were non-persistent to therapy. Patients who were treated by general practitioners tended to be non-persistent more often compared to those treated by oncologists (17.7% vs. 11.3%; P=0.07). The aim of a non-persistence rate between 10 and 15% is realistic when patients are treated by specialized oncologists. Interventions are needed to support patients, particularly the younger ones, to comply with therapy. Efforts should be made to make sure that all physicians, above all general practitioners, who are involved in BC treatment, are provided with current knowledge as to guarantee an optimal patient managemen

Systemic therapy developments and their effects regarding the current concept of recurrent ovarian carcinoma as a chronic disease

Purpose: To demonstrate how the current concept of recurrent ovarian carcinoma (ROC) as a chronic disease resulted in developments in the systemic treatment strategies and outcome over time. Methods: We compared therapy type and course of a population-based cohort whose recurrent disease was diagnosed from 1990 to 2006. We divided the patients into two subgroups depending on the year of diagnosis of ROC (group A 1990-1997, n=70; group B 1998-2006, n=63). Results: Both study groups showed similar results in survival (median recurrent disease-specific survival—A 18 months vs. B 19 months; P=0.549). In group B, the patients had significantly fewer combination therapies administered [12.0% vs. 24.1%; odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.81; P=0.0057], received more therapy lines (≥3 lines 56.1% vs. 31.1%; OR 3.10; 95% CI 1.37-7.17; P=0.005) and had significantly longer times of treatment (TT) in relation to the survival time (ST; mean TT/ST-ratio 57.5% vs. 47.5%; difference of the mean values B-A=−10.02; 95%CI −17.99 to −2.05; P=0.014). Conclusions: The finding that survival of ROC patients could not be improved over time should not necessarily be viewed with undue pessimism regarding the general therapy situation. In the more recent study period, a similar outcome could be achieved with less aggressive treatment regimens, i.e., with fewer combination therapies and with longer treatment periods using less toxic agents. When a disease which requires periodic chemotherapy to control progressive course is increasingly treated with a strategy that permits stabilization with limited cumulative toxicity, then the requirements of a chronic disease management have been fulfille