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Despite recent advances in radiochemotherapy, treatment of locally advanced head and neck squamous cell carcinoma is still challenging, and survival rates have improved only slightly. This is due to the high frequency of metastases and local and/or regional tumor recurrences that have acquired radio- or chemoresistance. MiRNAs regulate diverse processes in tumorigenesis, metastasis, and therapy resistance in head and neck squamous cell carcinoma. Hence, miRNAs are highly valued in biomarker studies. Establishment of the miRNA profiles of oropharyngeal tumors enables personalized treatment selection, since expression of distinct miRNAs can predict the response to two different radiochemotherapy regimens. Development of novel miRNA therapeutics has a high clinical potential for further improving treatment of cancerous disease. The use of nanoparticles with distinct surface modifications as miRNA vectors permits prolonged bioavailability, high efficacy in tumor targeting, and low toxicity. Nevertheless, the efficacy of miRNA therapy has only been shown in animal models to date.

Purpose: Adenoid cystic carcinomas are rare tumours. Regional lymphatic spread is rather uncommon. Distant metastases occur in approximately half of all patients. High local failure rates of up to 50% after surgery have been reported. Even after adjuvant radiation, the results remain poor for locally advanced tumours after incomplete resection. We report on a safe and effective salvage option in the treatment of adenoid cystic carcinoma., Material and Methods: A 44 year old woman with the diagnosis of adenoid cystic carcinoma of the oropharynx and simultaneous pulmonary metastases received a mixed beam photon radiotherapy and a neutron boost. Three years later, the patient developed a dysphagia grade 2, dysarthria and pain. A local recurrence in the base of tongue and floor of mouth was histologically confirmed., Results: Because of the local symptoms, we offered the patient Ir-192-HDR brachytherapy with palliative intent. Under general anaesthesia, eight needles were implanted into the palpable tumour. On the basis of a pretreatment MRI, a single dose of 5 Gy encompassing the palpable tumour was given to a total dose of 15 Gy. The patient remains free from local symptoms at 8 month after brachytherapy., Conclusion: HDR-Ir brachytherapy is an effective method for the treatment of local recurrences of an adenoid cystic carcinoma, even after preradiotherapy. Excellent palliative effects can be achieved without increased toxicity after previous radiotherapy.

There is an increasing body of evidence showing that patients with resectable pancreatic cancer might benefit from adjuvant therapy. Based on phase III trials, potential options for adjuvant treatment are chemotherapy alone or a multimodal approach involving radiotherapy. Available data are heterogeneous and have been discussed controversially. Hitherto, a worldwide standard of care has not yet been established. Adequate patient selection might be the key element for a tailored adjuvant treatment. Clinical research currently focusses on gemcitabine alone or in combination, and some molecular biologic approaches with epidermal growth factor receptor monoclonal antibodies (EGFR-MoABs) and anti-angiogenic drugs. Recent advances in radiooncology offer better dose conformality and reduced morbidities. Currently, the co-operative Radiotherapy and Gastrointestinal Groups have launched a multicentric European Organization for Research and Treatment of Cancer (EORTC) trial investigating the impact of radiotherapy in combination with gemcitabine in R0-resected pancreatic head cancer.

Primary malignant bone neoplasms are relatively rare. The most common bone tumors are osteosarcoma,Ewing's sarcoma,chondrosarcoma, fibrosarcoma,malignant fibrous histiocytoma of bone, giant cell tumor, aneurysmal bone cyst and chordoma. These tumors are generally considered to be a radioresistant entities, but it has been suggested that radiotherapy may be effective in a palliative and in some curative situations, if a sufficient dose is given to an adequate volume. Only for the management of primary Ewing's sarcoma the radiation therapy is an essential part in the multimodal therapy concept. The most common bone neoplasms and the role of the radiotherapy are discussed in these chapter.

Forty-one patients with locally advanced hypopharyngeal carcinomas were followed for at least 3 years (median, 60 months) after simultaneous radiochemotherapy. Conventionally fractionated radiotherapy was administered as 5 x 2 Gy/week to a total dose of 30 Gy within 3 weeks. From the fourth week an accelerated hyperfractionated schedule was used as 2 x 1.4 Gy/day five days weekly given exclusively to the first order target volume of macroscopic tumor (adding up to a total dose of 72 Gy in six weeks). The second and third order target volumes received conventional fractionation only to 60 Gy and 50 Gy, respectively. The moderate acceleration of the concomitant boost scheme in the second half was counterbalanced during the first week by the introduction of a 5-fluorouracil bolus of 350 mg/M2 with 200 mg/M2 folinic acid and a subsequent continuous infusion using the same dose each 24 h for 5 days. Additionally, a Mitomycin-C bolus of 10 mg/M2 was infused at the fifth day and on the first day of the sixth week. Six weeks after treatment the patients were restaged. In cases with residual carcinoma salvage surgery was performed (11 patients). Late effects of therapy were analyzed according to the Lent-Soma index and life quality according to the European Organisation for Research and Treatment of Cancer-Module. Late effects of treatment were tolerable and were controlled locally. The 3-year-survival rate was 39%, with a local-regional recurrence-free control rate of 71%. Fifty-two percent of all cases of death were caused by distant metastases, secondary carcinomas or other diseases not related to tumor recurrence. The poor prognosis of hypopharyngeal carcinomas despite acceptable local tumor control may be due to specific biological factors present in affected patients.

Surgery is the initial treatment of choice for most patients with rectal neoplasms. The objectives are to remove of tumor and drain the primary nodes. In stage I disease the surgical approach is though to be sufficiently effective. However, at least in the case of abdominoperineal resection, this causes considerable morbidity. Therefore, at the present time, there are efforts to reduce the extent of the resection by applying other treatment modalities in stage I disease. After curative resection in stage II/III disease a considerable number of patients suffer from local recurrence or distant metastases. In these patients adjuvant therapy is currently recommended. In locally advanced disease, primary resection is not feasible. Different treatment settings which apply combinations of all treatment modalities are possible. The article reviews the literature and shows future directions.

From March 1991 to June 1993 50 patients with local advanced NSCLC (mediastinoscopy obligatory) have been entered into an ongoing trial with preoperative chemotherapy and simultaneous chemo-/radiotherapy, followed by re-mediastinoscopy and surgery. Clinical response rates after chemotherapy amounted to 66.8% after chemo/radiotherapy 77.5%, no severe toxicity was observed. 36 patients ultimately underwent operation, 29 with a curative, 5 with a palliative resection and 2 with an explorative thoracotomy. Pathological complete remission rates of the primary tumor were found in 11 (32.3%), R0-resection in 18 (52.9%) and R1-resection in 5 (14.7%) cases. Sterilisation rates of mediastinal nodes were found in 86.3% of N2 tumors and 66.6% of N3 tumors. Median survival time ranged between 21 months for stage III a and 16 months for III b disease. This intensive preoperative neoadjuvant treatment is tolerable and effective, the requirements for a randomised comparative trial was met.

The in vivo development of radiation- and doxorubicin-induced resistance was studied in a chemosensitive and radiosensitive human neurogenic sarcoma (Essen neuroectodermal tumor line 2) xenografted in nude mice. Dose-response curves were generated for the parent tumor line, and growth delay (GD) and specific growth delay (SGD) were the study end points. An intravenous injection of doxorubicin at 10 mg/kg, the lethal dose for 10% of the study population (LD10) in nude mice, and a single dose of 12 Gy radiation were determined to be isoeffective and were thus maintained for all subsequent treatments. For the induction of resistance to both treatment modalities, regrowing tumors were transplanted into successive generations of nude mice and retreated. This procedure was repeated 13 and 9 times, respectively, for the doxorubicin and radiation treatments. The response was monitored in all passages. As compared with the parent tumor line, a 50% decrease in SGD was observed following 3.9 and 8.5 treatments with doxorubicin and radiation, respectively. Following four treatments with doxorubicin, SGD in tumors crossed over to radiation therapy declined by 50%. Radiation therapy, on the other hand, caused significant reductions in GD and SGD in tumors that were subsequently exposed to doxorubicin, but it did not induce a 50% decline in response. Overexpression of P-170-glycoprotein was not observed for either treatment modality. The data suggest that treatment with doxorubicin or radiation can potentially induce resistance to subsequent continued or crossover treatment and that this resistance develops gradually. The lack of P-170-glycoprotein over-expression in the resistant cell lines indicates the existence of alternative pathways that may lead to resistance.

Soft tissue sarcomas account for under 1% of all cancers in adults. Most soft tissue tumours are benign, only about 1% being characterized clinically and histomorphologically as malignant neoplasms. Since these tumours are often treated by excisional biopsies without any further diagnostic imaging, precise planning of postoperative irradiation therapy is often difficult to achieve. Therefore, all soft tissue tumours with a short history should be regarded as malignant until the contrary has been proven. In general, the mode of tumour resection should be postponed until CT or MR diagnosis is complete and a biopsy of the tumour has been carried out. Whereas benign lesions need only marginal tumour resection, malignant lesions require considerable safety margins. In soft tissue sarcomas of the extremities, which account for 50-60% of all sarcomas, a wide local resection followed by postoperative irradiation with about 66 Gy can guarantee local control rates above 80% and preserve the function of the limb. Radical surgery alone can achieve the same local control, but without the high level of functional integrity. In the case of marginally resectable tumours, preoperative irradiation can induce partial tumour remission and thus allow definitive limb-sparing tumour resection. Recently, multimodal and neoadjuvant therapeutic strategies have been developed. The efficacy of these experimental strategies is not yet proven.

To study the potential benefit of sequential chemotherapy in inoperable small cell lung cancer (SCLC), from 1982 to 1986 ninety-one patients with histologically proven and previously untreated SCLC (median age: 53 years; median Karnofsky status: 80%) were randomly assigned to an initial therapy with adriamycin (since 1984 epirubicin), cyclophosphamide, vincristine (ACO resp. EPICO) or etoposide/cisplatin (VP16/DDP). Treatment courses were repeated every 3 weeks for a total of less than or equal to 6 courses with a crossover after a maximum of 3 cycles of either regimen. Limited disease (LD) patients with bronchoscopical, computertomographical and (re-) mediastinoscopical complete remission (CR) randomly received either a thoracic irradiation with 40 Gy or observation only. Overall, 60 out of 85 evaluable patients achieved an objective remission. A CR was observed in 24/51 patients (47%) with limited disease, and in 8/34 patients (24%) with extensive disease. Both, ACO (EPICO) and VP16/DDP were equally effective as initial and second-line therapy. Moreover, after failure to the initial therapy an objective remission could be achieved in 13% of the patients following the alternative second line combination. In 28% of LD patients with an otherwise complete remission residual tumor was detected by (re-) mediastinoscopy. Median survival times were 14 (CR: 16) months in LD patients and 10 (CR: 15) months in ED patients. At present, median survival is significantly improved in irradiated versus non-irradiated LD patients (25 vs. 13 months, p less than 0.04). The remission rates and median survival times observed in this study are comparable to those of a historical control group treated with ACO plus radiotherapy alone.