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Oncology Research and Treatment

Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy

Published online: 10/18/2017 12:00:00 AM
Oncol Res Treat (DOI:10.1159/000481353)

Liquid Biopsy: Approaches to Dynamic Genotyping in Cancer

Malignant tumors release tumor cells and fragments of nucleic acids into the bloodstream. Liquid biopsies are non-invasive blood tests that detect circulating tumor cells (CTC) and circulating nucleic acids such as mRNA, microRNA, and cell-free circulating tumor DNA, also known as ctDNA. The presence of ctDNA or CTCs in the plasma has prognostic impact. Since ctDNA contains tumor-specific mutations, its detection in the blood or other body fluids can predict response to treatment and relapse. Moreover, repeated analysis and quantitation of ctDNA can inform about changes in clonal composition over time and thus allow dynamic treatment stratification. Today, the routine clinical use of liquid biopsy diagnostic tests is limited; however, in the near future, they might become commonly used sensitive and specific biomarkers to guide cancer treatment. This review will summarize recent findings on the use of ctDNA for monitoring response to therapy and dynamic genetic treatment stratification.

Published online: 7/13/2017 12:00:00 AM
Oncol Res Treat 2017;40:409-416 (DOI:10.1159/000478864)

Human Papillomavirus-Related Head and Neck Cancer

Human papillomavirus(HPV)-related head and neck cancer is recognized as a distinct tumor entity with rising incidence reported for several countries. These tumors arise from squamous cells, typically in the oropharynx. In contrast to cancer associated with other risk factors, HPV-related cancer is driven by viral oncoprotein activity and has individual profiles regarding protein expression, and genetic and epigenetic alterations. Molecular characteristics are p16IN4A overexpression, absence of p53 inactivating mutations, and PI3K/AKT and Wnt pathway modulation. Patients with HPV-related head and neck cancer have improved survival compared to those with HPV-negative tumors, and p16INK4A staining has been introduced into tumor staging recently. However, no specific or toxicity-reduced treatment modalities have been established for this entity so far. Although the still incomplete and partially inconsistent data in this field needs further study, particular features of HPV-related cancers such as specific microRNA expression, immunology, or gene methylation patterns certainly have the potential to be implemented in future diagnostic and therapeutic concepts.

Published online: 5/19/2017 12:00:00 AM
Oncol Res Treat 2017;40:334-340 (DOI:10.1159/000477252)

Total Skin Electron Beam Therapy as Part of Multimodal Treatment Strategies for Primary Cutaneous T-Cell Lymphoma

Total-skin electron beam therapy (TSEBT) is one of most effective treatments that has been used for cutaneous T-cell lymphoma. Low-dose TSEBT regimens (10-12 Gy) appear to be an effective alternative to conventional-dose TSEBT (30-36 Gy), yielding short-term remission of cutaneous manifestations with minimal toxicity. TSEBT can be administered to patients any time after a diagnosis of mycosis fungoides (MF). Patients requiring rapid relief from cutaneous lesions or symptoms may particularly benefit from TSEBT as an initial therapy. Radiotherapy (RT) dose, boost radiation delivery, maintenance treatment, and radiation tolerability may enhance remission rates and improve relapse-free survival following TSEBT. In addition, salvage local RT or TSEBT may be safely applied with high effectiveness. In this review, we focus on the use of TSEBT in patients with several forms of primary cutaneous T-cell lymphoma, and highlight the potential of low-dose TSEBT as part of a promising therapeutic approach.

Published online: 4/25/2017 12:00:00 AM
Oncol Res Treat 2017;40:244-252 (DOI:10.1159/000475634)

PD-1/PD-L1 Pathway in Breast Cancer

The programmed cell death-1 receptor (PD-1) is an immune checkpoint inhibitor which is expressed on the surface of immune effector cells. It is activated mainly by PD-L1 which can be expressed by all human cells. The PD-1/PD-L1 pathway plays a subtle role in maintaining peripheral T-lymphocyte tolerance and regulating inflammation. In cancer, the expression of PD-L1 seems to be one of the major immune escape mechanisms. Many studies have shown efficacy of blocking PD-1 or PD-L1 with specific antibodies like pembrolizumab or atezulizumab. In breast cancer, potential response was demonstrated in metastatic triple-negative breast cancers.

Published online: 3/27/2017 12:00:00 AM
Oncol Res Treat 2017;40:294-297 (DOI:10.1159/000464353)

Stratified Treatment in Lung Cancer

Even though great efforts have been made to improve chemotherapy-based treatment approaches for lung cancer, the prognosis of patients with advanced and metastasized disease remains particularly poor. In recent years, a growing number of genetic aberrations driving lung cancer have been identified. Targeted inhibition of some of these aberrations, most prominently mutated EGFR and ALK, by tyrosine kinase inhibitors has dramatically increased efficacy and tolerability of systemic lung cancer treatment in subsets of patients. However, the duration of response is limited due to the acquisition of molecular mechanisms of resistance to targeted treatment. Modern next-generation inhibitors aim to break resistance. A deep understanding of the mechanisms of treatment failure is imperative to the development of new approaches. In this review, we focus on the current status of stratified therapy in lung cancer and highlight new, potentially promising treatment approaches.

Published online: 11/24/2016 12:00:00 AM
Oncol Res Treat 2016;39:760-766 (DOI:10.1159/000453406)

Overcoming Cost Implications of Mutational Analysis in Patients with Gastrointestinal Stromal Tumors: A Pragmatic Approach

Background: Genetic analysis of tissue derived from patients with advanced gastrointestinal stromal tumors (GISTs) is not uniformly applied on a national and international level, even though mutational data can provide clinically relevant prognostic and predictive information, especially in patients qualifying for treatment with expensive targeted agents. Methods: The current article describes the rationale for genetic testing of GIST tissue, looks at financial implications associated with such analysis and speculates on potential cost savings introduced by routine mutational testing and tailored use of tyrosine kinase inhibitors based on genotyping. This work is based on a hypothetical analysis of epidemiological data, drug costs, reimbursement criteria and market research figures. Results: The cost burden for routine genotyping of important genes in GISTs, especially in patients at high risk for relapse after primary surgery and in advanced, inoperable metastatic disease, is relatively low. The early identification of GISTs with primary resistance mutations should be the basis for personalized GIST treatment and reimbursement of drugs. As illustrated by Belgian figures, the exclusive use of a drug such as imatinib in patients who are likely to benefit from the agent based on genetic information can lead to significant cost savings, which outweigh the costs for testing. Conclusions: Mutational analysis of GIST should be considered early in all patients at risk for relapse after curative surgery and in the case of advanced, inoperable, metastatic disease. The costs for the actual genotyping should not be used as an argument against profiling of the tumor. The adjuvant and palliative systemic treatment of GISTs should be personalized based on the genotype and other known prognostic and predictive factors. Reimbursement criteria for essential agents such as imatinib should be adapted accordingly.

Published online: 11/18/2016 12:00:00 AM
Oncol Res Treat 2016;39:811-816 (DOI:10.1159/000453057)

Consultation Program for Patients with Cancer-Related Fatigue: A Systematic Evaluation of the Experiences of the Bavarian Cancer Society

Published online: 8/31/2016 12:00:00 AM
Oncol Res Treat 2016;39:646-651 (DOI:10.1159/000448907)

Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer

Neoadjuvant chemotherapy is indicated in patients who can tolerate the side effects of a chemotherapy and with preoperative presentation of one of the following clinical risk situations: bulky disease with a maximal tumor diameter of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed tomography (CT) scan or endosonography, histopathologically confirmed lymph node metastasis, or histopathologically documented risk factors such as G3 and L1V1. A neoadjuvant chemotherapy followed by surgery should be performed with cisplatin at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The previously published data suggests an improved rate of complete resection and reduced incidences of positive lymph nodes and parametric infiltration. Accordingly, the percentage of patients in need for adjuvant radiochemotherapy after operation can be significantly reduced. Some studies demonstrated a prolongation of progression-free and overall survival. Following the previously published studies, adjuvant chemotherapy after operation or after radiochemotherapy has no significant effect on the overall survival and, following the current guidelines, should be avoided.

Published online: 8/23/2016 12:00:00 AM
Oncol Res Treat 2016;39:522-524 (DOI:10.1159/000449023)

Immunotherapy of Melanoma

Arising from melanocytes in skin, mucosal membranes, eye, and meninges, melanoma is a tumor that has been associated with poor prognosis in advanced disease stages. Given the poor response to chemotherapy and radiation therapy, new treatment approaches with targeted therapy, immunotherapy, and adoptive T-cell therapy have revolutionized the standard of care for patients with advanced melanoma. This review provides a short overview of past, present, and future immunotherapeutic approaches and their limitations, with a focus on new combination agents in early clinical trials.

Published online: 5/25/2016 12:00:00 AM
Oncol Res Treat 2016;39:369-376 (DOI:10.1159/000446716)

Intrinsic Subtypes of Primary Breast Cancer - Gene Expression Analysis

Intrinsic subtypes based on gene expression have substantially improved the understanding of the biological diversity and heterogeneity of breast cancer. The efficacy of adjuvant therapies depends on the level of risk for an individual patient. Because of this, careful estimation of the level of risk is mandatory. In addition to well-established clinicopathological factors, validated gene expression signatures are useful especially in estrogen receptor-positive and HER2-negative patients. Commercially available gene expression signatures like Prosigna, MammaPrint, Oncotype DX, and EndoPredict are recommended by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) for use in selected patients.

Published online: 2/24/2016 12:00:00 AM
Oncol Res Treat 2016;39:102-110 (DOI:10.1159/000444409)

State-of-the-Art Treatment and Novel Agents in Chronic Lymphocytic Leukemia

Chemoimmunotherapy is the established first-line treatment of patients with chronic lymphocytic leukemia (CLL) who do not display the high-risk genetic features del(17p) and/or TP53 mutation: Physically fit patients without or with only mild comorbidities should receive fludarabine, cyclophosphamide and rituximab, while bendamustine and rituximab can be considered in fit elderly patients of over 65 years and in patients with a higher risk of infections. Patients with relevant coexisting conditions should receive chlorambucil with a CD20 antibody, preferably obinutuzumab. Patients with a del(17p) and/or TP53 mutation respond poorly to conventional chemo(immuno)therapies. However, the recently approved BTK and PI3K inhibitors ibrutinib and idelalisib have the best efficacy ever documented in patients with these high-risk genomic alterations and/or refractory CLL. The choice between ibrutinib and idelalisib should be based on the patients' comorbidities and concomitant medications since both agents have a distinct toxicity profile, although they are generally well tolerated in the majority of patients. For treatment of patients with a late relapse, chemoimmunotherapy instead of kinase inhibitors is still a reasonable approach, but has to be determined for every patient individually. Further targeted drugs and their combinations are currently being evaluated in clinical trials and have the potential to eradicate all residual CLL cells and thus lead to a cure of CLL.

Published online: 1/22/2016 12:00:00 AM
Oncol Res Treat 2016;39:25-32 (DOI:10.1159/000443903)

CD19-Targeted CAR T Cells: A New Tool in the Fight against B Cell Malignancies

Adoptive cell immunotherapy is a novel tool in the fight against cancer. Serving both effector and memory functions for the immune system, T cells make an obvious candidate for adoptive cell immunotherapy. By modifying native T cells with a chimeric antigen receptor (CAR), these cells can theoretically be targeted against any extracellular antigen. To date, the best-studied and clinically validated CAR T cells recognize CD19, a cell surface molecule on B cells and B cell malignancies. These CD19-directed T cells have shown clinical utility in chronic lymphocytic leukemia, acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphomas, with some patients achieving long-term disease remissions after treatment. This review will briefly summarize the current data supporting the use of adoptively transferred CAR T cells for the treatment of CD19-positive malignancies. Given these exciting results, the Food and Drug Administration has granted a ‘breakthrough' designation for several variations of CD19-directed CAR T cells for treatment of adult and pediatric relapsed/refractory ALL.

Published online: 11/18/2015 12:00:00 AM
Oncol Res Treat 2015;38:683-690 (DOI:10.1159/000442170)

High-Risk Prostate Cancer: Role of Radical Prostatectomy and Radiation Therapy

Up to 12% of European men aged 55-69 years diagnosed with prostate cancer have high-risk disease and thus are at increased risk of mortality. There remains a lack of consensus on definitive treatment for prostate cancer, although both radiation therapy and radical prostatectomy are frequently utilized. Furthermore, the different types of radiation and surgical options also increase the complexity of deciding on a single treatment, as does the use of multimodal treatment plans. Here, we provide an overview of radiation therapy and radical prostatectomy in treating high-risk prostate cancer.

Published online: 11/16/2015 12:00:00 AM
Oncol Res Treat 2015;38:639-644 (DOI:10.1159/000441736)

Updated Evidence on the Mechanisms of Resistance to ALK Inhibitors and Strategies to Overcome Such Resistance: Clinical and Preclinical Data

Anaplastic lymphoma kinase(ALK) rearrangement is one of the oncogenes in non-small cell lung cancer (NSCLC) identified in 2007. The PROFILE trials demonstrated that patients with ALK-rearranged NSCLC can be successfully treated with crizotinib, and that crizotinib is superior to chemotherapy in both first- and second-line settings. Furthermore, next-generation ALK inhibitors, such as alectinib and ceritinib, have been shown to harbor excellent efficacy for NSCLC patients with ALK rearrangement. However, it is known that many cases ultimately acquire resistance to ALK inhibitors. Some potential mechanisms of resistance to ALK inhibitors are as follows: ALK dominant resistance, such as secondary mutations and copy number gain in the ALK gene; activation of the bypass tracks, including EGFR, KRAS, KIT, MET, and IGF-1R. Furthermore, treatment strategies to overcome these resistance mechanisms have been proposed, and next-generation ALK inhibitors, agents which inhibit the bypass tracks, and heat shock protein 90 inhibitors are thought to be promising. Thus, clinical and pre-clinical evidence on the resistance mechanisms to ALK inhibitors and treatment strategies to overcome the resistance have been gradually obtained. Herein, we concisely review the current clinical and pre-clinical data regarding the mechanisms of resistance to ALK inhibitors and treatments to overcome such resistance.

Published online: 5/13/2015 12:00:00 AM
Oncol Res Treat 2015;38:291-298 (DOI:10.1159/000430852)

Systemic Treatment Approaches for Sporadic Desmoid-Type Fibromatosis: Scarce Evidence and Recommendations

Desmoid-type fibromatosis (DF) is a rare disease characterized by a monoclonal, fibroblastic proliferation and a variable and often unpredictable clinical course. Although histologically benign, DF is locally invasive and associated with a high local recurrence rate, but lacks any metastatic potential. As there is no established or evidence-based treatment approach available as of today, an individualized treatment strategy is fundamental in the light of highly variable clinical presentations, anatomic locations, and biological behaviors. Surgery with negative margins has been the cornerstone of DF treatment; however, an overall reassessment of the management of DF patients has taken place in the last few years, and preservation of function and quality of life has become a priority in these patients. Evidence is scarce for systemic treatment; different pharmacological options can be proposed and will be reviewed here. To better define possible therapeutic strategies, a consensus approach has been initiated, bringing together sarcoma experts from the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) with patient advocates from Sarcoma Patients EuroNet (SPAEN). As a prerequisite, patients should be discussed in a multidisciplinary setting in centers/networks with specific expertise and experience in this disease.

Published online: 4/16/2015 12:00:00 AM
Oncol Res Treat 2015;38:244-248 (DOI:10.1159/000381909)

Activation of Innate Immunity in Graft-versus-Host Disease: Implications for Novel Targets?

Acute graft-versus-host disease (GvHD) is mediated by alloreactive donor-derived T cells with a suitable T cell receptor recognizing recipient major histocompatibility complex or minor histocompatibility antigens. However, the process of T cell activation and tissue injury sensing is also dependent on innate immune cells and non-hematopoietic cells. Different cell types of the innate immune system have the ability to sense danger-associated and pathogen-associated molecular patterns via pattern recognition receptors which can be transmembrane Toll-like receptors or cytoplasmic nucleotide-binding oligomerization domain-like receptors. Infectious stimuli include bacterial, viral, and fungal components, while non-infectious stimuli can be components derived from damaged cells or extracellular matrix. A better understanding of the complex sensing and effector mechanisms of innate immune cells in GvHD may help to improve preventive and therapeutic strategies in GvHD.

Published online: 3/17/2015 12:00:00 AM
Oncol Res Treat 2015;38:239-243 (DOI:10.1159/000381296)

Changes in Prognostic and Therapeutic Parameters in Prostate Cancer from an Epidemiological View over 20 Years

Background: The study objective was to examine changes in prognosis and treatment of prostate cancer patients over 20 years and to evaluate their impact on survival. Patients and Methods: 38,861 prostate cancer patients diagnosed between 1990 and 2010 and living in the catchment area of the Munich Cancer Registry were analysed. Results: Pre-therapeutic prostate-specific antigen (PSA) testing increased substantially in the early 1990s. A shift from capsule-exceeding tumours to capsule-limited tumours also took place especially in the 1990s. The proportion of radical prostatectomy increased continuously over the last 20 years from 20% to almost 50% whereas hormone therapy decreased from 55% to 18%. Radiation therapy and transurethral resection of the prostate increased slightly from about 5% to 10%. The 5- and 10-year relative survival rates increased from 92% to 97% and from 86% to 92%, respectively. Conclusions: 2 reasons may account for the rise in survival rates over 20 years: First, the establishment of widely used PSA testing resulted in a shift towards more favourable T categories due to the detection of many additional small tumours as well as the noticeable change in initial treatment strategy towards more radical prostatectomies. The second factor that likely increased survival was improvements in the therapies themselves.

Published online: 1/26/2015 12:00:00 AM
Oncol Res Treat 2015;38:8-14 (DOI:10.1159/000371717)

Management of von Hippel-Lindau Disease: An Interdisciplinary Review

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumour predisposition syndrome with an incidence of 1:36,000 newborns, the estimated prevalence in Europe is about 1-9/100,000. It is associated with an increased risk of developing various benign and malignant tumours, thus affecting multiple organs at different time points in the life of a patient. Disease severity and diversity as well as age at first symptoms vary considerably, and diagnostic delay due to failure of recognition is a relevant issue. The identification of a disease-causing VHL germline mutation subsequently allows family members at risk to undergo predictive genetic testing after genetic counselling. Clinical management of patients and families should optimally be offered as an interdisciplinary approach. Prophylactic screening programs are a cornerstone of care, and have markedly improved median overall survival of affected patients. The aim of this review is to give an overview of the heterogeneous manifestations of the VHL syndrome and to highlight the diagnostic and therapeutic challenges characteristic for this orphan disease. A comprehensive update of the underlying genetic and molecular principles is additionally provided. We also describe how the St. Gallen VHL multidisciplinary group is organised as an example of interdisciplinary cooperation in a tertiary hospital in Switzerland.

Published online: 11/17/2014 12:00:00 AM
Oncol Res Treat 2014;37:761-771 (DOI:10.1159/000369362)

Predictive Factors for Response to Neoadjuvant Therapy in Breast Cancer

SummaryWithin 2 decades, neoadjuvant therapy (NAT) has become a standard treatment option in breast cancer. The advantage of NAT is the ability to monitor the treatment effect. Pathological complete response (pCR) after NAT is a very good predictor for long-term outcome. Clinical factors, such as age and body mass index, as well as recently identified biomarkers can predict the chance of achieving a pCR. Hormone-receptor status, proliferation markers, immune infiltrates and genetic alterations, such as germline BRCA and PIK3CA, can now be measured almost on a routine basis due to the decreased analysis costs.

Published online: 9/3/2014 12:00:00 AM
Oncol Res Treat 2014;37:563-568 (DOI:10.1159/000367643)

Significance of Lymph Node Dissection in Gynecological Oncology

Lymph node dissection has been an integral part of the surgical treatment of gynecological malignancies for over a century. The significance of lymph node dissection in gynecological oncology is reviewed in the light of our current knowledge of tumor biology. The original ‘centrifugal theory' of metastasis formation leading to the concept of ‘radical' surgery has its limitations. Lymph node dissection will still be necessary in gynecological oncology until molecular diagnostics have developed sufficiently and efficacious systemic therapies are available.

Published online: 8/11/2014 12:00:00 AM
Oncol Res Treat 2014;37:500-504 (DOI:10.1159/000366248)

Metastasis-Related Processes Show Various Degrees of Activation in Different Stages of Pancreatic Cancer Rat Liver Metastasis

Background: Most pancreatic ductal adenocarcinoma (PDAC) patients who undergo tumor resection will develop postoperative liver metastasis within the first 2 years. Our hypothesis was that, during liver colonization, the temporal modulation of processes related to metastasis will change in a specific manner and that information on these changes might be used for new therapeutic approaches. Material and Methods: PDAC rat ASML cells were inoculated into the liver of BDX rats and re-isolated after different time periods of liver colonization (early, intermediate, advanced, and terminal). The total RNA of these samples was used to evaluate the expression profiles of more than 23,000 genes by chip array analysis. Results: Depending on the time span following re-isolation, 7-15% of all known genes were deregulated. These genes were assigned to metastasis-related processes during the 4 stages of colonization. Except for apoptosis, all other processes were not activated in the early and middle colonization stages. In the terminal phase of liver colonization, cell proliferation, cell homing, cell movement, and vasculogenesis were significantly activated. Conclusion: We hypothesize that targeting the relatively few deregulated genes in the early stage of liver colonization could ultimately improve the survival of PDAC patients.

Published online: 7/11/2014 12:00:00 AM
Oncol Res Treat 2014;37:464-470 (DOI:10.1159/000365496)

Sequential Treatment with Taxanes and Novel Anti-Androgenic Compounds in Castration-Resistant Prostate Cancer

Several novel therapeutic agents have demonstrated ability to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC) in recent years. With as many as 5 new agents approved within the last 5 years and an ongoing lack of comparative and prospective data, strategies for patient selection and sequencing of drug treatments are urgently needed. This review will summarize current clinical evidence and relevant molecular mechanisms in mCRPC. The understanding of these mechanisms may provide valuable assistance in making therapeutic decisions, especially while robust clinical data remain sparse.

Published online: 7/11/2014 12:00:00 AM
Oncol Res Treat 2014;37:492-498 (DOI:10.1159/000365530)

Distress in Cancer Patients and Their Caregivers and Association with the Caregivers' Perception of Dyadic Communication

Background: Discrepancies within cancer-affected couples can disrupt security within the dyadic relationship during cancer treatment. This study investigated the patients' and caregivers' distress and associations between the caregivers' perception of the patients' degree of open communication and their distress. Participants and Methods: In a cross-sectional survey, 189 pairs of cancer patients (31% gastrointestinal, 34% lung, 35% urological cancers) and their partners were assessed for distress (QSC-R10), depression and anxiety (PHQ-2/GAD-2). The caregivers also reported their perception of the patients' degree of disclosure regarding cancer-relevant topics (CCAT-F Disclosure subscale), caregiver strain (CSI), and unmet needs (SCNS-P&C). Prevalences of clinically significant distress were calculated. Associations were calculated between the caregivers' and the patients' ratings and between the caregivers' distress and their perception of the patients' degree of disclosure. Results: 33% of the caregivers and 25% of the patients exhibited significant anxiety, with a tendency towards a higher frequency in the caregivers (p = 0.10). The prevalence of depression was lower but equally high in caregivers and patients. The caregivers' perceived non-disclosure by the patients was primarily associated with their anxiety (r = 0.31), disease-specific distress (r = 0.32), and psychological/emotional needs (r = 0.35). Conclusion: The identification of caregivers reporting problems in communicating with patients should be pursued in clinical practice as this might indicate that caregivers are particularly burdened.

Published online: 6/17/2014 12:00:00 AM
Oncol Res Treat 2014;37:384-388 (DOI:10.1159/000364885)

Soft Tissue Sarcoma: An Update on Systemic Treatment Options for Patients with Advanced Disease

Sarcomas are a group of rare solid tumours arising from mesenchymal or connective tissue. This review focuses on soft tissue sarcoma and covers general topics such as the epidemiology, age distribution, site of disease, histogenesis, histological subtypes, prognosis and outcome of treatment. In more detail, the article reviews current systemic treatment standards and selected adverse events of agents such as doxorubicin, ifosfamide, trabectedin and pazopanib, and briefly highlights some drugs that are used off-label in specific subtypes of sarcoma.

Published online: 4/17/2014 12:00:00 AM
Oncol Res Treat 2014;37:355-362 (DOI:10.1159/000362631)

Nab-Paclitaxel for Metastatic Pancreatic Cancer: Clinical Outcomes and Potential Mechanisms of Action

For almost 15 years there has been stagnation in the systemic treatment of patients with pancreatic ductal adenocarcinoma (PDAC). Recently, several developments seem to indicate clinically relevant improvements in the treatment of patients with metastatic disease. One of these developments is the introduction of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) into the firstline treatment of metastatic disease. In this review, underlying preclinical and clinical data are discussed, with a special focus on mechanisms of action, the potential interaction with albumin and calcium-binding matricellular glycoproteins, such as the secreted protein acidic and rich in cysteine (SPARC), as well as the clinical outcome associated with the use of nab-paclitaxel.

Published online: 2/7/2014 12:00:00 AM
Oncol Res Treat 2014;37:128-134 (DOI:10.1159/000358890)

Clinical Benefit Response in Pancreatic Cancer Trials Revisited

Objectives: Clinical benefit response (CBR), based on changes in pain, Karnofsky performance status, and weight, is an established palliative endpoint in trials for advanced gastrointestinal cancer. We investigated whether CBR is associated with survival, and whether CBR reflects a wide-enough range of domains to adequately capture patients' perception. Methods: CBR was prospectively evaluated in an international phase III chemotherapy trial in patients with advanced pancreatic cancer (n = 311) in parallel with patient-reported outcomes (PROs). Results: The median time to treatment failure was 3.4 months (range: 0-6). The majority of the CBRs (n = 39) were noted in patients who received chemotherapy for at least 5 months. Patients with CBR (n = 62) had longer survival than non-responders (n = 182) (hazard ratio = 0.69; 95% confidence interval: 0.51-0.94; p = 0.013). CBR was predicted with a sensitivity and specificity of 77-80% by various combinations of 3 mainly physical PROs. A comparison between the duration of CBR (n = 62, median = 8 months, range = 4-31) and clinically meaningful improvements in the PROs (n = 100-116; medians = 9-11 months, range = 4-24) showed similar intervals. Conclusion: CBR is associated with survival and mainly reflects physical domains. Within phase III chemotherapy trials for advanced gastrointestinal cancer, CBR can be replaced by a PRO evaluation, without losing substantial information but gaining complementary information.

Published online: 1/21/2014 12:00:00 AM
Oncol Res Treat 2014;37:42-48 (DOI:10.1159/000357965)

Characteristics, Treatment and Prognostic Factors of Patients with Gynaecological Malignancies Treated in a Palliative Care Unit at a University Hospital

Background: Limited clinical data have been published on patients suffering from advanced gynaecological malignancies treated in palliative care units, and little is known about prognostic factors. Methods: In a retrospective study, the data of 225 patients with breast, ovarian and cervical cancer treated in the palliative care unit of a university hospital between 1998 and 2009 were assembled. Clinical aspects and baseline symptoms, laboratory parameters, the clinical course, and outcome were evaluated. Results: 225 patients (497 cases; cancer diagnoses: breast 79%, ovarian 13%, and cervix 8%) were included in the analysis. The main symptoms were weakness/fatigue (71%), pain (65%), anorexia/nausea (62%), and dyspnea (46%). Pain control was achieved in 85% of all cases, satisfying control of other symptoms in 80%. The median overall survival (OS) was 59 days. 53% of the patients died at the palliative care unit. In the Cox proportional hazards model, 8 parameters indicated an unfavourable outcome: anorexia/nausea, disordered mental status, elevated lactate dehydrogenase, γ-glutamyltransferase, leukocyte count, hypoalbuminaemia, anaemia and hypercalcaemia. Based on these parameters 3 risk groups were defined: low risk (0-2 factors), intermediate risk (3-5 factors), and high risk (6-8 factors). Median survival for high-risk group was 13 days, for intermediate group 61 days, and for low-risk patients 554 days (p < 0.0001). Conclusion: Weakness/fatigue, pain and anorexia were the main symptoms leading to the hospitalisation of patients with gynaecological malignancies. Symptom and pain control was accomplished in 80% of cases. 8 parameters were identified as indicating a poor outcome, and patients showing at least 6 or more of these factors had a very limited prognosis. Although studied retrospectively, these results may be helpful for individual treatment decisions in patients with advanced gynaecological malignancies. Prospective data and the introduction of documentation systems could help to gain more powerful knowledge about the quality of palliative care.

Published online: 10/18/2013 12:00:00 AM
Onkologie 2013;36:642-648 (DOI:10.1159/000355642)

Anxiety, Posttraumatic Stress, and Fear of Cancer Progression in Patients with Melanoma in Cancer Aftercare

Background: Several studies have described mental distress and anxiety in patients with melanoma. The findings of these studies varied from patients with a quality of life similar to the general population and those with increased mental distress. In the present study, we investigated anxiety, posttraumatic stress, and fear of cancer progression to gain a detailed picture of the burdens of these patients. Patients and Methods: 70 patients with malignant melanoma who attended cancer aftercare were surveyed using the psychometric instruments Hospital Anxiety and Depression Scale (HADS), Posttraumatic Symptom Scale (PTSS-10), and Fear of Progression Questionnaire (FoP-Q). The questionnaires were evaluated and an analysis of the single items carried out. Results: The scores for the three anxiety parameters were low, but 7% of the patients presented an increased HADS score, and 17% an increased PTSS-10 value. An analysis of the items showed that patients feared physical disabilities more than mental distress or lack of social support. Conclusion: Most of the patients perceived themselves as stable, and relied on the assistance of their families. However, a small group of patients suffered from clinically relevant anxiety; these patients should be given the support indicated for their specific distress.

Published online: 9/17/2013 12:00:00 AM
Onkologie 2013;36:540–544 (DOI:10.1159/000355137)

Afatinib, Erlotinib and Gefitinib in the First-Line Therapy of EGFR Mutation-Positive Lung Adenocarcinoma: A Review

Non-small cell lung cancer (NSCLC) consists of several histomorphologically defined phenotypes that display an enormous genetic variability. In recent years, epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma has emerged as a unique subset of NSCLC in terms of etiopathogenesis and tumor biology. Since the introduction of the reversible EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib, patients with metastatic EGFR mutation-positive lung cancer can be offered a therapeutic alternative that has proven its superiority over standard platinum-based chemotherapy. However, primary or acquired resistance limits the therapeutic success of these targeted agents. Irreversible inhibitors targeting all ErbB family receptor tyrosine kinases, such as afatinib and dacomitinib, have been developed to confer sustained disease control in ErbB-dependent cancers. The large LUX-Lung 3 phase III trial recently reported afatinib to be clearly superior over the most effective platinum doublet in patients with EGFR mutation-positive lung cancer. To fully exploit the clinical activity of afatinib, proactive management of its gastrointestinal and dermatologic toxicities is advised.

Published online: 8/19/2013 12:00:00 AM
Onkologie 2013;36:510–518 (DOI:10.1159/000354627)

Interval Debulking Surgery in Patients with Federation of Gynecology and Obstetrics (FIGO) Stage IIIC and IV Ovarian Cancer

Background: The feasibility of neoadjuvant chemotherapy (NAC) and the outcome in patients with Federation of Gynecology and Obstetrics (FIGO) IIIC and IV ovarian cancer were assessed. Patients and Methods: 67 patients undergoing interval debulking surgery (IDS) and ≥ 4 courses of platinum-based NAC were analyzed for survival, perioperative morbidity and mortality. Results: The median follow-up was 30 months. The median progression-free survival (PFS) was 17 months, the overall survival (OS) 34 months. The PFS of patients without residual disease (n = 23; 34.3%) was 31 months (p = 0.003), the OS 65 months (p = 0.001). PFS and OS were significantly longer in patients with no residual disease than in patients with 1-10 mm (n = 34; 47.9%) (p = 0.005 and p = 0.0001, respectively) residual disease. No survival benefit was seen for patients with 1-10 mm compared to > 1 cm (n = 12; 16.9%) residual disease (PFS p = 0.518; OS p = 0.077). 1 patient (1.4%) died; 12 patients needed interventional treatment or operation (16.9%) within the first 30 days postoperatively. Out of these, 5 patients (7.0%) had residual or lasting disability. Conclusions: NAC and IDS are safe and feasible in this series of patients with unfavorable prognosis. IDS does not change the goal of complete cytoreduction and therefore does not compensate for a less radical surgical approach.

Published online: 5/21/2013 12:00:00 AM
Onkologie 2013;36:324-332 (DOI:10.1159/000351256)