Desmoid Tumor Treated with Polychemotherapy Followed by Imatinib: A Case Report and Review of the Literature

Desmoid tumors, also known as aggressive fibromatosis, are tumors of intermediate dignity, which grow slowly but are locally aggressive. These tumors do not metastasize but can be potentially life threatening when infiltrating vital structures. The therapy strategy consists of surgery, radiation and systemic therapy with non-steroidal anti-inflammatory drugs, antiestrogen compounds and cytotoxic chemotherapy. We report on a 40-year-old male patient with advanced fibromatosis of the neck who has been treated with 7 cycles of polychemotherapy (adriablastin, ifosfamide and dacarbazine) followed by targeted therapy with imatinib. Tumor response was evaluated clinically and by magnetic resonance imaging. The tumor decreased significantly after the first cycle of chemotherapy and tumor-related symptoms declined. The response continued after switching to targeted therapy with imatinib, which is currently ongoing. The best treatment for this rare tumor remains under discussion. Doxorubicin and dacarbazine are frequently used agents. We included ifosfamide in our therapy, which is standard in the treatment of soft tissue tumors. The tyrosine kinase inhibitor imatinib seems to offer new possibilities and is currently investigated in randomized trials. We conclude that combination chemotherapy including doxorubicin, ifosfamide and dacarbazine in the treatment of aggressive fibromatosis should be considered for patients suffering from unresectable, advanced disease and clinical symptoms which require a rapid response to therapy

Risk stratification for venous thromboembolism in patients with testicular germ cell tumors

BACKGROUND:Patients with testicular germ cell tumors (TGCT) have an increased risk for venous thromboembolism (VTE). We identified risk factors for VTE in this patient cohort and developed a clinical risk model. METHODS:In this retrospective cohort study at the Medical University of Graz we included 657 consecutive TGCT patients across all clinical stages. A predictive model for VTE was developed and externally validated in 349 TGCT patients treated at the University Hospital Zurich. RESULTS:Venous thromboembolic events occurred in 34 (5.2%) patients in the Graz cohort. In univariable competing risk analysis, higher clinical stage (cS) and a retroperitoneal lymphadenopathy (RPLN) were the strongest predictors of VTE (p<0.0001). As the presence of a RPLN with more than 5cm in greatest dimension without coexisting visceral metastases is classified as cS IIC, we constructed an empirical VTE risk model with the following four categories (12-month-cumulative incidence): cS IA-B 8/463 patients (1.7%), cS IS-IIB 5/86 patients (5.9%), cS IIC 3/21 patients (14.3%) and cS IIIA-C 15/70 patients (21.4%). This risk model was externally validated in the Zurich cohort (12-month-cumulative incidence): cS IA-B (0.5%), cS IS-IIB (6.0%), cS IIC (11.1%) and cS IIIA-C (19.1%). Our model had a significantly higher discriminatory performance than a previously published classifier (RPLN-VTE-risk-classifier) which is based on the size of RPLN alone (AUC-ROC: 0.75 vs. 0.63, p = 0.007). CONCLUSIONS:According to our risk stratification, TGCT patients with cS IIC and cS III disease have a very high risk of VTE and may benefit from primary thromboprophylaxis for the duration of chemotherapy

Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing

Background Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively. Methods We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, that is, Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage. After intensive testing of our approach with samples from 25 individuals without cancer we analyzed 13 plasma samples derived from five patients with castration resistant (CRPC) and four patients with castration sensitive prostate cancer (CSPC). Results The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9-month period, which is consistent with the presence of one metastatic clone. Conclusions The genomic landscape of prostate cancer can be established by non-invasive means from plasma DNA. Our approach provides specific genomic signatures within 2 days which may therefore serve as 'liquid biopsy'

Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and

Five years of adjuvant tamoxifen has been the standard endocrine treatment for early-stage breast cancer for several decades. Adjuvant endocrine therapy following primary surgery for breast cancer reduces the risk of recurrence and increases overall survival beyond the period of treatment for women with estrogen receptor (ER) -positive disease ( 1 ). Mature meta-analysis data on 15-year recurrence and breast cancer mortality probabilities demonstrate substantial and persistent benefits of receiving adjuvant tamoxifen compared with no adjuvant treatment ( 1 ). Most of the effect of adjuvant tamoxifen on recurrence is seen during the first 5 years after surgery, when tamoxifen is generally still administered, with gains in recurrence-free survival of 11.4%. However, many women who are treated with 5 years of adjuvant tamoxifen still develop recurrent disease, and most of the effect of adjuvant tamoxifen on breast cancer mortality occurs after the fifth year after surgery

Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and

Five years of adjuvant tamoxifen has been the standard endocrine treatment for early-stage breast cancer for several decades. Adjuvant endocrine therapy following primary surgery for breast cancer reduces the risk of recurrence and increases overall survival beyond the period of treatment for women with estrogen receptor (ER) -positive disease ( 1 ). Mature meta-analysis data on 15-year recurrence and breast cancer mortality probabilities demonstrate substantial and persistent benefits of receiving adjuvant tamoxifen compared with no adjuvant treatment ( 1 ). Most of the effect of adjuvant tamoxifen on recurrence is seen during the first 5 years after surgery, when tamoxifen is generally still administered, with gains in recurrence-free survival of 11.4%. However, many women who are treated with 5 years of adjuvant tamoxifen still develop recurrent disease, and most of the effect of adjuvant tamoxifen on breast cancer mortality occurs after the fifth year after surgery

Plasmapheresis reverses all side-effects of a cisplatin overdose – a case report and treatment recommendation

BACKGROUND: Cisplatin is widely used as an antineoplastic agent since it is effective against a broad spectrum of different tumours. Nevertheless, it has several potential side effects affecting different organ systems and an overdose may lead to life-threatening complications and even death. CASE PRESENTATION: We report on a 46-year old woman with non-small cell lung cancer who accidentally received 225 mg/m(2 )of cisplatin, which was threefold the dose as scheduled, within a 3-day period. Two days later, the patient presented with hearing loss, severe nausea and vomiting, acute renal failure as well as elevated liver enzymes. In addition, she developed a severe myelodepression. After plasmapheresis on two consecutive days and vigorous supportive treatment, the toxicity-related symptoms improved and the patient recovered without any sequelae. CONCLUSION: To date, no general accepted guidelines for the treatment of cisplatin overdoses are available. Along with the experience from other published cases, our report shows that plasmapheresis is capable of lowering cisplatin plasma and serum levels efficiently. Therefore, plasma exchange performed as soon as possible can ameliorate all side effects of a cisplatin overdose and be a potential tool for clinicians for treatment. However, additional intensive supportive treatment-modalities are necessary to control all occurring side effects