Malignization of a vestibular schwannoma 13 years after radiation therapy.

This article presents a case of malignant transformation of vestibular schwannoma 13 years after stereotactic radiation therapy, which lead to an acute life-threatening condition. Although the observation is currently only based on case reports, an increasing number of these support the hypothesis that there is a relevant risk of malignant transformation in the long-term course of previously irradiated vestibular schwannomas. Therefore, long-term MRI follow-up should be considered.

[Malignization of vestibular schwannoma 13 years after radiation therapy]. / Malignisierung eines Vestibularisschwannoms 13 Jahre nach Bestrahlung.

This article presents a case of malignant transformation of vestibular schwannoma 13 years after stereotactic radiation therapy, which lead to an acute life-threatening condition. Although the observation is currently only based on case reports, an increasing number of these support the hypothesis that there is a relevant risk of malignant transformation in the long-term course of previously irradiated vestibular schwannomas. Therefore, long-term MRI follow-up should be considered.

Treatment of adolescents and young adults (AYA) with cancer in a multidisciplinary setting: on the way to a highly specialized AYA unit.

Further survival improvements of adolescents and young adults (AYA) with cancer are clearly affected by biological characteristics of the malignancies and age-specific needs. Multidisciplinary teams drawing expertice from both pediatric and adult cancer teams as well as clinical trials are required to meet the age specific needs of AYA patients with cancer. In 2011, the first AYA unit was established at the University Hospital Halle (Saale), where patients with newly-diagnosed cancer aged 15-25 are treated interdisciplinary by pediatric and adult oncologists. The enrollment into pediatric or adult clinical trials is controlled by age 18. Over the last 2 years, 19 AYA with cancer have been treated at the unit; and, in turn patients and their relatives reflected a high satisfaction with the offered novel health care approach. In the scope of the future Comprehensive Cancer Center at the University Hospital Halle (Saale), a complete ward is planned for all admitted AYA up to 25 years with cancer. The patients will be treated by a tumor-specialized multidisciplinary team of adult or pediatric oncologists and oncological surgeons. Therefore, we intend to establish a special teaching curriculum for physicians, nurses and psychosocial health care staff. Rather than age, cancer biology of a malignancy, surveillance data of late side effects as well as the age-specific needs of AYA patients will be crucial for best treatment options.

The NK-1 receptor-antagonist aprepitant in high-dose chemotherapy (high-dose melphalan and high-dose T-ICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination.

Complete protection from nausea/vomiting is currently achieved in a minority of patients receiving high-dose chemotherapy (HDC). Currently the use of 5-HT3-antagonists and dexamethasone (DEX) represents the standard of care. The role of the NK-1-antagonist aprepitant in HDC remains to be better defined. A total of 64 patients undergoing multiple days of HDC received granisetron, DEX plus aprepitant during chemotherapy. After the end of chemotherapy aprepitant plus DEX was given for a further 2 days. Primary end point was CR defined as no vomiting and no use of rescue medication in the overall phase (day 1 until 5 days after end of chemotherapy). Acute/delayed and overall CR were achieved in 83%/70% and 63%, respectively. Acute and delayed nausea were observed in 20 and 38% of the patients. The tolerability of the aprepitant regimen over 4-5 days was comparable with the 3-day antiemetic regimen. In our study, aprepitant demonstrated good tolerability. Taking into account the methodological constraints of comparing our results with those from the available literature, the addition of aprepitant to the antiemetic treatment regimen may provide improved prevention of chemotherapy-induced nausea and vomiting during HDC.

Bevacizumab in combination with sequential high-dose chemotherapy in solid cancer, a feasibility study.

We evaluated the feasibility and toxicity of bevacizumab in combination with sequential high-dose (HD) ifosfamide, carboplatin and etoposide refractory to standard chemotherapy in patients with sarcoma and germ cell cancer (GCC). Sixteen patients (13 sarcomas, 3 GCC) received SD-ICE followed by 4 cycles of HD-ICE, qd22 with stem cell support in combination with bevacizumab. All 16 patients were evaluable for toxicity and efficacy, and received 51 cycles (median 3.3). There was no increase in toxicity except of a relatively high incidence of ifosfamide encephalopathy in 17 cycles when compared with previous HD-ICE protocols. One almost complete response in the patient with GCC, previously progressive with three preceding protocols, was observed. Six patients had a partial response (sarcoma 4/13 patients; GCC 2/3 patients), and five patients stable disease (sarcoma 5/13 patients). The median PFS/OS for sarcoma was 5 months (confidence interval (CI): 3.1-6.9) and 13 months (CI: 3.6-24.4), respectively. To our knowledge, this is the first report of the addition of bevacizumab to HD-ICE. This combination did not show new unexpected toxicities except for a relatively high rate of ifosfamide encephalopathy. The efficacy in these heavily pretreated patients including possible reversal of chemotherapy resistance by the addition of bevacizumab indicates a possible potential of bevacizumab in this combination.

Chemotherapy with paclitaxel and gemcitabine in progressive medullary and thyroid carcinoma of the follicular epithelium.

Nine patients (mean age 53) with metastasizing, progressive, medullary (MTC), thyroid carcinoma and progressive, nonradioiodine accumulating thyroid carcinoma of the follicular epithelium (follicular carcinoma, FTC and papillary carcinoma, PTC) were treated with a combination of paclitaxel and gemcitabine between 2004 and 2006. Tumors were histologically classified as follicular in 5 patients (56%), as papillary in 2 patients (22%), and medullary in 2 patients (22%). Paclitaxel (90-100 mg/m (2)) and gemcitabine (1,000 mg/m (2)) were applied for two, three, or 6 cycles every three weeks, depending on response and side effects. The effect of therapy was evaluated by radiographic imaging (CT images) and [(18)F]FDG-PET. All patients with papillary, follicular, or medullary thyroid carcinoma had continuous progression during restaging 14.8+/-8.8 weeks after initiation of chemotherapy, including one patient with stable disease after 3 cycles, but continuous progression after 6 cycles of chemotherapy. Paclitaxel and gemcitabine are not a valid chemotherapy option, in particular in patients with progressive, nonradioiodine-accumulating follicular thyroid carcinoma, who were already treated by other chemotherapeutic agents.

The hand-foot syndrome--a frequent secondary manifestation in antineoplastic chemotherapy.

The hand-foot syndrome (HFS) (palmoplantar erythrodysesthesia) designates acute, painful erythemas of the palms and soles of the feet caused by antineoplastic chemotherapies. The most frequent trigger substances are 5-fluoruracil and its derivates. At maximum severity, the HFS is bullous to erosive or ulcerous in character. The pathogenesis has not yet been clarified. Histologically, the HFS is characterized by a toxic keratinocyte reaction. Furthermore, there is sub-basal edema with a tendency to bullae, dilated blood and lymph capillaries and usually only mild perivascular lymphocytic infiltration. Early recognition and delineation from other differential diagnoses is prerequisite to targeted management of the disease. Depending on the severity, HFS requires dose reduction, interruption or switch in the antineoplastic chemotherapy.

Potential activity of paclitaxel, vinorelbine and gemcitabine in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) has a rapidly fatal course in the mostly elderly patients with a median survival after diagnosis of 4-12 months. Activity of commonly used chemotherapy (doxorubicin) is low, thus more active compounds need to be introduced into the therapeutic concept of ATC. Recently, based on preclinical data Ain et al. conducted a clinical phase II study with paclitaxel 96 h infusion in ATC achieving a promising response rate of 53%. To further improve therapeutic options in ATC, we evaluated the activity of topotecan, oxaliplatin, vinorelbine, gemcitabine and paclitaxel in comparision to cisplatin and doxorubicin (1 and 96 h drug exposure) alone or in combination in the ATC cell lines SW1736 and 8505C. IC50 values were determined by the sulforhodamine B assay, potential clinical activity was estimated by relative antitumor activity (RAA) and drug interaction was analyzed using a parametric response surface approach (Greco model) of the Loewe additivity. Duration of drug effect was estimated by regrowth kinetics. We found paclitaxel, vinorelbine and gemcitabine active in ATC with RAA (1 h drug exposure) ranging from 86 to 454, 15 to 17 and 31 to 140, respectively. The activity of doxorubicin and cisplatin was moderate with RAA ranging from 1.4 to 2.2 and 0.2 to 0.3, respectively. Combined drug exposure of gemcitabine/paclitaxel and gemcitabine/vinorelbine was synergistic with a Loewe index > 0. However, these results did not reach statistical significance with p > 0.05. At clinically relevant drug concentrations paclitaxel, gemcitabine and vinorelbine but not oxaliplatin exerted a sustained growth inhibition after cessation of drug exposure for the complete assay time of 15 days. In conclusion, paclitaxel, gemcitabine and vinorelbine but not topotecan or oxaliplatin appeared to be active in anaplastic thyroid carcinoma based on RAA or growth delay at clinically relevant drug concentrations. Combinations of vinorelbine/gemcitabine and paclitaxel/gemcitabine exerted a trend to synergy. Thus, further evaluation of paclitaxel, vinorelbine and gemcitabine alone or in combination with ATC seems warranted.

A new chemoembolization protocol in refractory liver metastasis of colorectal cancer--a feasibility study.

INTRODUCTION: In patients with advanced colorectal cancer (CRC) refractory to systemic chemotherapy including 5-fluorouracil (5-FU) / folinic acid (FA), oxaliplatin and irinotecan we assessed the feasibility, toxicity and response to hepatic transcatheter arterial chemoembolization (TACE). At the time of treatment, patients had exclusively or dominantly liver metastasis of CRC. PATIENTS AND METHODS: The following protocol was applied via a selective transfemoral hepatic arterial approach: mitomycin C 5 mg/m(2), interferon-alpha2b 4.5 Mio IU, dexamethasone 20 mg mixed with Amilomer DSM 45/25 (Spherex((R))) days 1 and 2 i.a. (bolus), oxaliplatin 50 mg/m(2) (2 h) day 1 i.a., FA 500 mg/m(2) (2 h) day 1 i.v., and 5-FU 1.500 mg/m(2) (24 h) day 1 i.a. Cycles have been repeated at days 15-22. The dose was adjusted according to the pretreatment performance status and elevation of alkaline phosphatase, bilirubin and serum albumin. Treatment was continued until progression or emergence of intolerable toxicity. RESULTS: 11 patients received a total number of 43 TACE, with a range of 2-6 per patient. There was no TACE-related mortality. 4 patients died 5, 8, 10 and 11 months after initiation of treatment due to progression of disease. 7 patients are alive at 4+ (n = 2), 5+ (n = 1), 6+ (n = 1), 7+ (n = 1) and 11+ (n = 2) months after start of treatment. Toxicity (CTC) was mild with grade I-II asthenia (n = 10), grade I-II neurotoxicity (n = 5), grade II nausea and/or vomiting (n = 2) and grade II diarrhea (n = 1). Treatment had to be postponed due to grade I thrombocytopenia in 2 patients. No bleeding episodes or obvious infectious complications occurred during treatment intervals. 1 patient experienced an allergic reaction to oxaliplatin which led to exclusion from further therapy. Arterial catheter dislocation occurred in 3 patients. In 10 patients evaluable for response we observed 3 partial responses, 2 minor responses, and 4 times stable disease. Only 1 patient had further progression of disease under treatment. CONCLUSION: TACE, using a combination of mitomycin C, dexamethasone and interferon-alpha2b mixed with Spherex((R)), followed by oxaliplatin, FA and 5-FU, appears to be an effective and feasible treatment option in the case of liver metastasis of CRC refractory to standard systemic chemotherapy. This treatment is associated with tolerable toxicity, which becomes apparent mainly as asthenia, neurotoxicity or thrombocytopenia. These preliminary data warrant further evaluation for patients with refractory disease and would probably also be of interest for first-line treatment in this patient population.

CT of primary retroperitoneal soft tissue masses.

CT scans of 54 patients with primary peritoneal soft tissue masses were studied retrospectively. All lesions were untreated at the time of the CT examinations and the nature of the lesions was subsequently proven histologically. Each scan was evaluated initially without knowledge of clinical and pathological information in respect of several criteria including size and number of lesions, delineation of the lesions, border definition, and internal structure of the lesions. The lesions were demonstrated in all patients and displayed with great anatomical detail. The presence of gas and attenuation values below -30 HU were the only singular signs specifically indicative of abscesses or lipomatous tumors, respectively. All other applied criteria were found both in sarcomas and benign masses, and no malignant neoplasm had CT characteristics specific enough to differentiate it from any other one. Considering all criteria, the benign or malignant nature of the lesions could be predicted in 43% of the patients studied based solely on CT morphology. In context with the clinical information provided on the study request form, 54% of the lesions were correctly classified into aetiological sub-groups (i.e. soft tissue sarcoma, abscess).