[Radiotherapy of soft tissue sarcoma--part of a multidisciplinary strategy]. / Radiotherapie der Weichteilsarkome--Teil einer multidisziplinären Strategie.

The management of soft tissue sarcoma has evolved from a solitary surgical treatment to an interdisciplinary multimodal approach including radiotherapy. These fundamental changes are the result of increased knowledge in tumor biology, radiation sensitivity and the improvement in modern radiation therapy techniques. A successful effective therapy regimen strongly depends on distinct preoperative diagnostics, preoperative conception of the surgical intervention and an experienced oncological team. Of significant importance for the prognosis is early diagnosis as well as tumor excision with a wide negative margin. However, even after complete wide resection in sano, the use of postoperative radiotherapy can further improve local control and should therefore be applied to the majority of patients. Consequently, radiotherapy should only be omitted in cases in which the tumor has been excised with a very wide negative margin; this implies, however, high quality of surgery and distinct histopathological analysis. Patients with non- or questionable resectable tumors, should be referred for pre-operative radiotherapy in order to improve the surgical results. Recent studies have underlined the efficiency of modern radiotherapy regimens. The different radiotherapy regimens will be highlighted against the background of tumor stage and tumor resectibility.

Concomitant Non-Small Cell Lung Cancer and Hairy Cell Leukemia in a Patient Harboring BRAF-V600E Mutation in Both Tissues: A Case Report.

The BRAF-V600E mutation has been established as a signature alteration occurring almost universally in hairy cell leukemia. Moreover, it can be detected in a small percentage of patients with non-small cell lung cancer. We report the case of a patient with a metastatic BRAF-V600E-mutated lung adenocarcinoma suffering from concomitant hairy cell leukemia. The identification of an identical BRAF mutation in both malignancies raises physiopathological considerations and might offer unique therapeutic strategies for this group of patients.

Isolated Splenic Metastasis from Non-Small-Cell Lung Cancer: A Case Report and Review of the Literature.

Metastases to the spleen are rare but have been reported for different tumor entities, including breast cancer, lung cancer, colorectal cancer, ovarian cancer, and melanoma. As an isolated event, splenic metastasis from non-small-cell lung cancer (NSCLC) is exceedingly rare. Until now, only 28 cases have been reported in the medical literature. We report the case of a 66-year-old woman with NSCLC (adenocarcinoma) who presented with a synchronous, isolated splenic metastasis. Operative removal of both primary tumor and metastasis was not possible due to multiple comorbidities. Therefore, treatment was limited to combined systemic chemotherapy and simultaneous radiation of the primary tumor, which led to partial remission of the disease. Isolated metastasis to the spleen in NSCLC has been reported only 28 times in the medical literature, most often in male patients with right-sided lung tumors, most of which were adenocarcinomas. The majority of patients were asymptomatic with respect to splenic metastasis. About half of the reported cases were isolated metachronous splenic metastases. Splenectomy seems to confer a survival advantage. We review the pertinent medical literature.

Gene expression profiling of advanced head and neck squamous cell carcinomas and two squamous cell carcinoma cell lines under radio/chemotherapy using cDNA arrays.

BACKGROUND AND PURPOSE: The response of squamous cell carcinomas of the head and neck (HNSCC) to radio/chemotherapy is accompanied by complex changes in patterns of gene expression. It is highly probable that a better understanding of molecular and genetic changes can help to optimize the treatment of HNSCC. cDNA arrays provide a powerful tool for high-throughput monitoring of gene expression in small clinical specimens. MATERIALS AND METHODS: We used tumour biopsies from four patients with HNSCC which have been taken prior to and during radio/chemotherapy. The patterns of gene expression obtained from clinical samples were compared with gene expression profiles of two squamous cell carcinoma cell lines (FaDU and UD-7A). RESULTS: The experimental data analysis revealed changes in expression levels of several genes during radio/chemotherapy. Despite treatment, independent samples taken from the same cell line or tumour in situ were more similar to each other than either was to other specimens. The data indicate a high gene heterogeneity of HNSCC that is preserved during treatment. CONCLUSIONS: From our preliminary results we conclude that the cDNA array experimental approach can detect differences in gene expression between treated and untreated small tumour biopsies, as well as inter-individual differences in expression profiles between HNSCC tumours. The examination of a greater sample size will be needed to make this preliminary evaluation useful to elucidate the functional significance of individual genes which exhibit altered levels of expression under radiation therapy.

[Role of radiation therapy on the use of primary ("neoadjuvant") systemic treatment of breast cancer]. / Radiotherapie im Konzept der primären ("neoadjuvanten") systemischen Behandlung des Mammakarzinoms.

BACKGROUND: The indications for primary ("neoadjuvant") systemic treatment (PST) for breast cancer have evolved over the last few years. PST is not only used in patients with locally advanced breast cancer (LABC) and inoperable tumors but also plays a role for operable tumors aiming at breast conservation and higher complete remission rates (ypCR). The contribution of radiotherapy and the optimal sequencing of chemotherapy, surgery and radiotherapy still have to be defined. MATERIAL AND METHODS: Objectives and results of PST for inflammatory, locally advanced and operable breast cancer were analyzed according to tumor stage. RESULTS: Radiotherapy following PST and surgery is the standard of care for inflammatory breast cancer, LABC and nonresectable lesions. Comparable results are achieved for good responders after PST receiving radiotherapy or surgery. The evaluation of a preoperative radiotherapeutic approach is complicated by different chemo- and radiotherapy regimens, continuation of chemotherapy after surgery and heterogeneous patient groups. CONCLUSION: For LABC and inflammatory breast cancer the role of PST is well defined. For operable lesions, however, the value of preoperative radiotherapy still has to be established. This should be assessed within the framework of a clinical trial using standardized parameters for applying chemotherapy as well as radiation therapy.

Remission rates in breast cancer treated with preoperative chemotherapy and radiotherapy.

PURPOSE: Evaluation of remission rates after neoadjuvant chemotherapy alone or followed by preoperative radiotherapy. PATIENTS AND METHODS: 194 women with 198 biopsy-proven breast tumors were evaluated in this retrospective study. Of the 198 cases evaluated, 64 received neoadjuvant chemotherapy followed by surgery and adjuvant irradiation (CT group). In 134 cases, sequential preoperative chemo-/radiotherapy (CT-RT group) was given. In both groups, endocrine treatment was initiated in case of positive hormone receptor status after chemotherapy. The whole breast was homogeneously irradiated using 2-Gy fractions up to a total dose of 50 Gy, followed by a boost of 6-11 Gy to the tumor. RESULTS: A histologically proven complete remission (pCR) was achieved in 3% (2/64) in the CT and in 42% (56/134) in the CTRT group. The logistic regression analysis, including clinical tumor category (cT), lymph node (cN) and metastasis status (cM), grading (G), hormone receptor status (HRS), number of preoperative chemotherapy cycles, preoperative tumor volume, and preoperative radiotherapy, revealed that HRS (p = 0.0232) and radiotherapy (p < 0.0001) were significant factors for achieving pCR. CONCLUSION: Combination of neoadjuvant chemo-/radiotherapy results in significantly higher rates of complete remission than neoadjuvant chemotherapy alone. The significance for tumor-free and overall survival has to be evaluated.

Radiosensitivity and TP 53, EGFR amplification and LOH10 analysis of primary glioma cell cultures.

AIM: Determination of in-vitro radiosensitivity and genetic alterations of cell cultures derived from human glioma biopsy tissue and established glioma cell lines. MATERIAL AND METHODS: Fresh brain tumor specimens of six patients were processed to early passage cell cultures. In addition the cell lines D 384 and Gli 6 were used. Cell cultures were irradiated with doses from 2 to 10 Gy. Following irradiation, cell survival was determined by clonogenic assay and survival curves were generated. The surviving fractions after 2 Gy (SF2) and 4 Gy (SF4) were used as radiosensitivity parameters. Genetic analysis included determination of the mutational and loss of heterozygosity (LOH) status of TP 53 (exons 5-8), the LOH 10- and epidermal growth factor receptor gene (EGFR) amplification status. RESULTS: The SF2 and SF4 values ranged from 0.54 to 0.88 (mean: 0.70) and from 0.13 to 0.52 (mean: 0.32), respectively. Genetic alterations were found in the Gli 6 cell line and in two primary cell cultures. The genetic profile of Gli 6 showed LOH but no TP 53 mutation, complete LOH 10 and no EGFR amplification. The VU 15 cell culture showed TP 53 mutation but no LOH 10 or EGFR amplification, while VU 24 showed incomplete LOH 10, EGFR amplification and no TP 53 mutation. In the other four cell cultures and D 384 cell line no genetic alterations were diagnosed. Histopathological classification of glioblastoma multiforme and/or genetic alterations resulted in lower radiosensitivity. CONCLUSION: In this small series of early passage glioma cell cultures low radiosensitivity and alterations in cell regulatory genes were seen. Further testing of biological behavior in larger series of patient-derived material is ongoing.