Efficacy and safety of CT-guided 125I seed implantation as a salvage treatment for locally recurrent head and neck soft tissue sarcoma after surgery and external beam radiotherapy: A 12-year study at a single institution.

OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of CT-guided radioactive 125I seed implantation as a salvage treatment for locally recurrent head and neck soft tissue sarcoma (HNSTS) after surgery and external beam radiotherapy. METHODS AND MATERIALS: From December 2006 to February 2018, 25 patients with locally recurrent HNSTS after surgery and external beam radiotherapy were enrolled. All the patients successfully underwent CT-guided 125I seed implantation. The primary end points included the objective response rate (ORR) and local progression-free survival (LPFS). The secondary end points were survival (OS) and safety profiles. RESULTS: After 125I seed implantation, the ORR was 76.0%. The 1-, 3-, and 5-year LPFS rates were 65.6%, 34.4%, and 22.9%, respectively, with the median LPFS of 16.0 months. The 1-, 3-, and 5-year OS rates were 70.8%, 46.6%, and 34.0%, respectively, with the median OS of 28.0 months. Furthermore, univariate analyses showed that the recurrent T stage and histological grade were prognostic factors of LPFS, whereas only the histological grade was a predictor of OS. The major adverse events were skin/mucosal toxicities, which were generally of lower grade (≤Grade 2) and were well tolerated. CONCLUSIONS: Radioactive 125I seed implantation could be an effective and safe alternative treatment for locally recurrent HNSTS after failure of surgery and radiotherapy. Recurrent T stage and histological grade were the main factors influencing the efficacy.

Recent progress in pediatric soft tissue sarcoma therapy.

Soft tissue sarcomas of childhood are a heterogenous group of tumors with a wide spectrum of presentations and outcomes. Most patients require multimodal therapy with chemotherapy, surgery and/or radiation. Improved outcomes in recent decades have been achieved through improvements in the comprehensive care of these children through large cooperative group studies, even as little progress has been made in the standard chemotherapy backbone. A thorough understanding of the nuances of surgical therapy for these children is required to minimize both the risk of local failure and the possibility of loss of vital form or function.

Neoadjuvant chemotherapy plus radiation versus chemotherapy plus regional hyperthermia in high-grade soft tissue sarcomas: a retrospective comparison.

PURPOSE: Localized adult high-grade soft tissue sarcomas (STS) usually require multimodality treatment including surgery, radiotherapy, chemotherapy and hyperthermia. If maximal preoperative tumor-shrinkage is envisaged, neoadjuvant chemotherapy + radiation (CRT) is often applied, however at the expense of relatively high toxicities and increased postoperative complication rates. This study aims to compare preoperative CRT with neoadjuvant chemotherapy + regional hyperthermia (HCT) regarding histopathological response, toxicity and outcome. METHODS: In this retrospective analysis, 61 consecutive high-grade STS patients treated between 2009 and 2016 were included. All patients were treated within a prospective treatment protocol. 28 patients received neoadjuvant CRT 33 patients HCT. CRT consisted of four cycles doxorubicin/ifosfamide and two cycles ifosfamide concomitant to 50.4 Gray external beam radiotherapy. HCT consisted of 4-6 cycles doxorubicin/ifosfamide with deep regional hyperthermia administered bi-weekly during each cycle. Association of treatment modality with overall survival (OS), local control (LC) and freedom from distant metastases (FFDM) was evaluated by Kaplan-Meier and log-rank analyses. RESULTS: The overall patient characteristics were well balanced. Histopathological tumor response did not differ significantly between both groups (p = .67), neither did higher-grade toxicities during neoadjuvant treatment. Wound dehiscence (p = .018) and surgical hospital re-admissions (p < .001) were both significantly more frequent in the CRT group. Two-year OS, LC and FFDM rates of all patients were 93, 85 and 71% with no significant differences between CRT and HCT. CONCLUSION: Compared to CRT, HCT seems equally efficient and appears to bear less surgical complications. Interpretation should be cautious due to the low number of patients and the retrospective nature of this study.

Radiation Therapy as an Alternative Treatment for Desmoid Fibromatosis.

AIM: To determine the outcome after radiation therapy for desmoid fibromatosis. MATERIALS AND METHODS: A retrospective review of 50 patients treated between 1988 and 2016 in a specialised bone and soft tissue tumour clinic. RESULTS: The median age at the time of radiation therapy was 36.8 years (range 15.1-69.0) and the median follow-up time was 51 months. Forty-three patients underwent radiation therapy as the definitive treatment with a median dose of 56 Gy (range 30-58.8 Gy). The median dose for the seven patients treated with postoperative radiation therapy was 50.4 Gy (range 48-56 Gy). Eleven patients (22%) developed progressive disease after radiation therapy at a median time of 41 months (range 12-113 months). The recurrences were within the radiation therapy field in four patients and outside the field in seven patients. One patient developed a radiation-induced malignancy 20 years after treatment. CONCLUSIONS: Radiation therapy is an alternative treatment in the management of desmoid fibromatosis. It should be considered in patients for whom surgical resection is not feasible, or as adjuvant therapy after surgery with involved margins where any further recurrences would cause significant morbidity.

[Insufficiency fractures after irradiation therapy - case series]. / Insuffizienzfrakturen nach Strahlentherapie : Eine Fallserie.

BACKGROUND: Radiation therapy plays an essential part in modern treatment regimes of musculoskeletal tumors. Nevertheless damage to the surrounding tissue does occur inevitably. Postradiogenic changes of bone are associated with decreased stability and an increased fracture rate. The orthopedic surgeon therefore faces a challenging situation with altered bone metabolism, changes in perfusion and soft tissue problems. PATIENTS/MATERIAL AND METHODS: We present 3 cases of radiation induced fractures during the treatment of soft tissue tumors, all of which received radiation doses of > 58 Gy. All fractures occurred over 1 year after the exposure to radiation in otherwise uneventful follow ups. RESULTS: Postoperative follow up showed fracture healing or in the case of the arthroplasty, osseous integration without further complications. CONCLUSIONS: Radiation doses of ≥ 58 Gy are a major risk factor for pathological fractures in long bones. Regardless of their low incidence, fracture rates between 1,2 and 6,4 % prove their importance. Local tumor control has therefore to be weighed against the resulting decrease in bone quality and stability. Treatment options should always take into consideration the increased risk for complications such as infection, pseudarthroses and wound healing disorders. Our results show that substitution of vitamin D and calcium as well as the the use of reamed intramedullary implants benefits the outcome.

Analgesic effects of microwave ablation of bone and soft tissue tumors under local anesthesia.

OBJECTIVE: To assess the feasibility and efficacy of microwave ablation (MWA) of painful refractory bone and soft tissue tumors performed under local anesthesia. STUDY DESIGN: A retrospective study between 2011 and 2013. SETTING: A single center, Academic Interventional Pain Management Unit. SUBJECTS: Fifteen patients with 25 refractory painful bone (N = 19) or soft tissue (N = 6) tumors treated with MWA were consecutively included. METHOD: Local Institutional Review Board approval was obtained, and written informed consent was waived. Lesions included spinal (N = 3), sacral (N = 4), and extraspinal (N = 18) locations. Pain was measured on a visual analog scale (VAS) from 0 to 10 before and immediately after procedure, at 1 week, and on a monthly basis following procedure. MWA procedures were always performed under computed tomography guidance and local anesthesia along with nitrous oxide inhalation. RESULTS: Mean ablation time was 4.09 minutes (range 1-11) with an average of 4.2 cycles with a mean ablation power of 60 W. Preprocedure mean VAS score was 7.2 ± 0.97 (range 6-9). Follow-up postprocedure VAS scores were as follows: day 0: 1.64 ± 1.86, day 7: 1.82 ± 1.79, month 1: 2.05 ± 2.03 (14/15 patients), month 3: 2.13 ± 1.81, month 6: 2.36 ± 2.17; and were statistically significant (P < 0.001). Mean pain relief was 5.5 months. CONCLUSION: MWA is feasible, safe, and effective in the management of painful refractory bone and soft tissue tumors. It may therefore be considered as a potential alternative to existing percutaneous ablation techniques in the management of bone and soft tissue tumors.

Aortic homograft reconstruction of partial laryngectomy defects: a new technique.

OBJECTIVES: Wide-field transcervical partial laryngectomy often precludes tracheotomy decannulation. It is done infrequently today, primarily because of the popularity of chemotherapy-radiotherapy treatment regimens and limited enthusiasm for using transcervical partial laryngectomy after failed radiotherapy. We sought to identify a new reconstructive technique that would provide an alternative to total laryngectomy in as many patients as possible. METHODS: We performed a retrospective examination of 15 patients who underwent single-stage wide-field transcervical partial laryngectomy with cryopreserved aortic homograft reconstruction. Eight of the 15 patients had previously undergone failed radiotherapy. At least 40% of the cricoid circumference was resected in 8 patients. RESULTS: All 15 patients had their tracheotomy tube removed and have laryngeal phonation, and 14 of the 15 resumed oral intake. There were no major surgical complications. CONCLUSIONS: Use of aortic homografts is a new, reliable, and versatile reconstructive option for performing conservation laryngeal cancer surgery that allows for airway, swallowing, and voice preservation.

Modern surgical therapy: limb salvage and the role of amputation for extremity soft-tissue sarcomas.

Historically the surgical management of extremity soft-tissue sarcomas (ESTS) commonly involved amputation. Nowadays limb-sparing, function-preserving surgery is the standard of care for ESTS. Adjuvant therapies such as radiation therapy and chemotherapy are used selectively in an effort to minimize both local recurrence and distant spread. Less common modalities, such as isolated limb perfusion, isolated limb infusion, and hyperthermia are being evaluated to potentially expand the cohort of individuals who may be eligible for limb-sparing surgery and to improve outcomes. This article reviews the standard and evolving approaches to the management of ESTS.

[Current state of neoadjuvant therapy of soft tissue sarcoma]. / Aktueller Stand der neoadjuvanten Therapie bei Weichteilsarkomen.

The treatment of soft tissue sarcoma is clinically challenging. Referral to an experienced center with an interdisciplinary team is strongly recommended. Neoadjuvant therapy, including irradiation and chemotherapy, has been applied to improve local control rates, eradicate micrometastases and assess chemosensitivity. However, the role of neoadjuvant therapy remains controversial, especially for systemic therapy, as the only available randomized trial failed to prove a benefit for survival. Nevertheless, on the basis of the current body of literature, neoadjuvant therapy can be considered on an individual basis for patients with high-risk tumors. Whenever possible, patients should be included in a clinical trial.

Image-guided percutaneous (125)I seed implantation as a salvage treatment for recurrent soft tissue sarcomas after surgery and radiotherapy.

The purpose of this study was to evaluate the safety and efficacy of percutaneous iodine-125 ((125)I) seed implantation using computed tomography (CT) or ultrasound guidance in the treatment of recurrent soft tissue malignancies after surgery and radiotherapy. From February 2002 to September 2009, 18 patients with recurrent soft tissue sarcomas were treated under ultrasound or CT guidance. The actuarial median number of (125)I seeds implanted was 35 (range, 6-129), and the actuarial D90 of the implanted (125)I seeds ranged from 107.9 to 204.4 Gy (median, 147.1 Gy). The activity of the seeds ranged from 0.4 to 0.8 mCi (median, 0.7 mCi). Follow-up times ranged from 4 to 78 months (median, 20 months). The median local control was 41 months (95% CI, 15.9-66.1 months). The 1-, 2-, 3-, 4-, and 5-year local controls were 78.8%, 78.8%, 78.8%, 26.3%, and 0%, respectively. The median survival was 32 months (95% CI, 16-48 months). The actuarial 1-, 2-, 3-, 4-, and 5-year survivals were 76.6%, 61.3%, 39.4%, 39.4%, and 39.4%, respectively. Seven (7) patients (38.9%) experienced recurrence after seed implantation. Six (6) patients (33.3%) died of distant metastases and 1 died of stroke. Two (2) patients developed ulceration, 1 case caused by recurrence and another by a reaction of the skin to radiation. Percutaneous (125)I seed implantation for recurrent soft tissue malignancies under CT or ultrasound guidance is safe and is associated with high efficacy and low morbidity.

Infected giant lymphangioma circumscriptum treated with a combination therapy.

Lymphangioma circumscriptum is an uncommon benign disorder of skin and subcutaneous tissues characterized by dilated lymphatic channels. It is an uncommon vascular tumor and it rarely becomes infected. We report a 20-year-old man who had an infected giant tumor in his left thigh. After an extensive resection and radiofrequency energy therapy, he recovered well with an acceptable cosmetic result. We followed up the patient for 2 years without any recurrence.

Alveolar rhabdomyosarcoma of the extremity and nodal metastasis: Is the in-transit lymphatic system at risk?

Alveolar rhabdomyosarcoma (RMS) of the extremity is not infrequently associated with regional node metastasis. Knowledge of lymphatic drainage of extremity RMSs is important to determine radiotherapy fields. In this report we describe two patients with alveolar RMS of the lower extremity with inguinal metastasis at presentation. Both the distal lower extremity and inguinal region received local therapy consisting of surgery and postoperative radiotherapy. Both patients later developed in-transit lymphatic metastasis outside of the irradiated field. The in-transit lymphatics can be a site of failure in children with alveolar RMS of the extremity and nodal involvement.

Intraoperative radiotherapy (IORT) combined with external beam radiotherapy (EBRT) for soft-tissue sarcomas--a retrospective evaluation of the Homburg experience in the years 1995-2007.

PURPOSE: To retrospectively evaluate the results after a regimen of surgery, IORT (intraoperative radiotherapy), and EBRT (external beam radiotherapy) for soft-tissue sarcomas METHODS: 38 consecutive patients underwent IORT for soft-tissue sarcoma; 29 were treated for primary tumours, 9 for recurrences. There were 14 cases with liposarcomas, 8 with leiomyosarcomas, 7 with malignant fibrous histiocytomas. 27/38 tumours were located in the extremities, the remaining ones in the retroperitoneum or the chest. Radical resection was attempted in all patients; a R0-resection was achieved in 15/38 patients, R1 in 12/38 pats and R2 in 4/38 pats. IORT was performed using a J-125 source and a HDR (high dose rate) afterloading machine after suturing silicone flaps to the tumour bed. The total dose applied ranged from 8-15 Gy/0.5 cm tissue depth measured from the flap surface. After wound healing external beam radiotherapy (EBRT) was applied in 31/38 patients with total doses of 23-56 Gy dependent on resection status and wound situation. The mean duration of follow-up was 2.3 years. RESULTS: A local recurrence was found in 10/36 patients, lymph node metastases in 2/35, and distant metastases in 6/35 patients. The actuarial local control rate was 63%/5 years. The overall survival rate was 57%/5 years. There was no statistically significant difference between the results after treatment for primaries or for recurrences. Late toxicity to the skin was found in 13/31 patients, wound healing problems in 5/31 patients. A neuropathy was never seen. CONCLUSION: The combination of surgery, IORT, and EBRT yields favourable local control and survival data which are well within the range of the results reported in the literature. The complication rates, however, are considerable although the complications are not severe, they should be taken into account when therapy decisions are made.

[Treatment of haemangiomas and vascular malformations with the neodymium-YAG laser--strategy and results in over 2000 cases]. / Neodym-YAG-Laserbehandlung von Hämangiomen und vaskulären Malformationen--unsere Behandlungsstrategie und Ergebnisse in über 2000 Fällen.

BACKGROUND: Haemangiomas represent the most common type of benign vascular tumours in childhood. A proliferative phase of unknown duration and extent is followed by an involutional period, which passes into regression in approximately 70 % of all cases. A multitude of different treatment options, such as corticosteroids, cryotherapy, laser, sclerotherapy, radiotherapy and surgical methods have been published. Due to the high rate of spontaneous regression, many authors advise not to undertake any treatment. The dilemma of this "wait and see" approach constitutes those cases in which sudden and pronounced growth is not followed by complete regression with possible severe aesthetic and functional impairment. To avoid this dilemma, a specific algorithm for the treatment of haemangiomas was instituted at our department, based essentially on early laser treatment when relevant growth is present. PATIENTS AND METHODS: More than 2000 patients with haemangiomas as well as vascular malformations have been treated at our department in the last 16 years. An algorithm for treatment of these disorders is presented. RESULTS: All therapeutic procedures, especially direct neodymium-YAG laser treatment with either contact cooling or intralesional, is described and postinterventional results are presented. CONCLUSION: Early laser treatment of fast growing haemangiomas prevents uncontrolled proliferation of these childhood tumours and, in our experience, represents a definite improvement of long-term results when compared to the "wait and see" method.

Combined surgery and chemoradiation as a treatment for the Buschke-Löwenstein tumour.

BACKGROUND: The Buschke-Löwenstein tumour (BLT) or giant condyloma acuminata is a rare disease which affects the anogenital region. Although histologically benign, it behaves in a malignant fashion, infiltrating the surrounding tissues. The morbidity and mortality from this tumour is high, as is the risk of recurrence following treatment. It lies on the continuum between the benign condylomata acuminata and squamous cell carcinoma. The human papillomavirus is implicated in its aetiology. Treatment is controversial, with topical chemotherapy, radiotherapy, immunotherapy and radical surgery all having been employed. Chemoradiation remains the mainstay of treatment for anal cancers but has not been routinely employed in the management of the BLT without squamous cell carcinoma transformation. METHODS: Two cases of extensive perineal BLT treated with chemoradiation and subsequent surgical excision are presented. RESULTS: The first patient had a good symptomatic response to the chemoradiation but unfortunately died of recurrent disease following surgery. The second patient had a macroscopically complete response to chemoradiation and remains well following abdominoperineal excision. CONCLUSION: Pre-operative chemoradiation has proved to be useful in management for histologically proven benign BLT

[Clinical practice guidelines: 2006 update of recommendations for the radiotherapeutic management of patients with soft tissue sarcoma (sarcoma of the extremity, uterine sarcoma and retroperitoneal sarcoma]. / Recommandations pour la pratique clinique: mise à jour 2006 des standards, options et recommandations pour l'irradiaton des patients adultes atteints de sarcome de tissus mous (sarcomes des membres, sarcomes rétropéritonéaux et sarcomes utérins.

CONTEXT: The National French Federation of Comprehensive Cancer Centres (FNCLCC) initiated the update of clinical practice guideline for the management of patients with soft tissue sarcoma in collaboration with the French Sarcoma Group (GSF-GETO), specialists from French public universities, general hospitals and private clinics and with the French National Cancer Institute. This work is based on the methodology developed in the "Standards, Options and Recommendations" (SOR) project. OBJECTIVES: To update SOR guidelines for the management of patients with soft tissue sarcoma previously validated in 1995. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGsaccording to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers. RESULTS: This article presents the updated recommendations for radiotherapeutic management. The main recommendations are: 1) irradiation before or after surgical treatment is the standard for soft tissue sarcoma of the extremity and uterine sarcoma; 2) no systematic irradiation should be done in case of retroperitoneal sarcoma.

Isolated limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma: the value of adjuvant radiotherapy.

BACKGROUND: The aim was to investigate the value of adjuvant radiotherapy for locally advanced soft tissue sarcoma after hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan followed by limb-saving surgery. METHODS: From 1991 to 2003, 73 patients (median age, 54 years; range, 14-80 years) underwent 77 ILPs, followed by resection in 68 patients (93%). Radiotherapy was administered in case of marginally or microscopically positive resection margins. Local recurrences were scored and calculated according to the Kaplan-Meier method and log-rank test. RESULTS: After residual tumor mass resection, 58% received radiotherapy (external beam radiotherapy [EBRT]+ group), and 42% did not (EBRT- group). The median follow-up was 28 months (range, 2-159 months). A significantly better local control rate was observed in the EBRT+ compared with the EBRT- group (P<.0001). When only R0 resections in patients without metastasis were considered, the significance remained between groups (P=.0003). In the EBRT- group, an R1 or R2 resection resulted in earlier relapse of local disease compared with R0 resections (P=.0475). CONCLUSIONS: Adjuvant EBRT reduces the risk for local recurrence after delayed resection in soft tissue sarcoma patients treated with ILP and tumor necrosis factor and is indicated when resection margins are close or microscopically positive. It also seems beneficial after an R0 resection.

Optimizing radiation therapy and post-treatment function in the management of extremity soft tissue sarcoma.

When treating soft tissue sarcomas (STS) of the extremities, the major therapeutic goals are survival, local tumor control, optimal function, and minimal morbidity. Surgical resection of the primary tumor is the essential component of treatment for virtually all patients. However, local control by surgery alone is poor for the majority of patients with extremity lesions unless the procedure removes large volumes of grossly normal tissue (ie, widely negative margins are attained, because sarcomas tend to infiltrate normal tissue adjacent to the evident lesion). Thus, removal of the gross lesion by a simple excision alone is followed by local recurrence in 60% to 90% of patients. Radical resections reduce the local recurrence rate to 10% to 30%, but may compromise limb function. The combination of function-sparing surgery and radiation achieves better outcomes than either treatment alone for nearly all patients with STS. Because both surgical and radiation technique are critically important for optimizing local control of tumor and functional outcome, it is important to manage these patients in dedicated multispecialty clinics comprised of physicians with expertise in sarcomas, including orthopedic and general oncologic surgeons, radiation oncologists, medical oncologists, sarcoma pathologists, and bone and soft tissue diagnostic radiologists. Radiation therapy can be given by external beam radiation therapy (EBRT) or brachytherapy (BRT) or combination thereof. External beam radiation can be given either preoperatively or postoperatively. The clinical considerations and the outcome data that must be considered in choosing the most appropriate treatment technique for the individual patient are discussed.

Effect of calcitonin gene related peptide vs sodium nitroprusside to increase temperature in spontaneous canine tumours during local hyperthermia.

The objectives of this study were to compare the effects of two vasodilators, sodium nitroprusside (SNP) and calcitonin gene-related peptide (CGRP) on mean arterial pressure (MAP), heart rate (HR) and temperatures in tumour and surrounding normal tissue during local hyperthermia treatment. Eleven tumour-bearing pet dogs with spontaneous soft tissue sarcomas were given SNP intravenously during local hyperthermia. The drug infusion rate was adjusted to maintain a 20% decrease in MAP. The median (95% CI) increase in the temperature distribution descriptors T(90) and T(50) was 0.2 degrees C (0.0-0.4 degrees C, p = 0.02) and 0.4 degrees C (0.1-0.7 degrees C, p = 0.02), respectively, in tumour. Normal subcutaneous tissue temperatures were mildly increased but remained below the threshold for thermal injury. The effects of CGRP were investigated in six tumour-bearing dogs following a protocol similar to that used for SNP. The median (interquartile (IQ) range) decrease in mean arterial pressure was 19% (15-26%) after CGRP administration and a significant increase was seen in tumour but not normal subcutaneous tissue temperatures. The median (95% CI) increase in the temperature distribution descriptors T(90) and T(50) was 0.5 degrees C (0.1-1.6 degrees C, p = 0.03) and 0.8 degrees C (0.1-1.6 degrees C, p = 0.13), respectively. Administration of SNP or CGRP did not result in local or systemic toxicity in tumour-bearing dogs. However, the magnitude of increase in tumour temperatures was not sufficient to improve the likelihood of increased response rates. Therefore, there is little justification for translation of this approach to human trials using conventional local hyperthermia.

An approach for cure: PEI-chemotherapy and regional deep hyperthermia in children and adolescents with unresectable malignant tumors.

BACKGROUND: Elevated temperatures of 40 - 44 degrees C increase the actions of various anticancer drugs including N-lost derivatives, cytotoxic antibiotics and platinum analoga. In clinical usage thermochemotherapy (TCH) should facilitate surgical resection and ameliorate local tumor control. PATIENTS AND METHODS: From 07/1993 to 12/2002 a total of 39 patients have been enrolled onto a phase-II study (female = 24, male = 15, age 1 - 37.5 years, median 5.2). Among these, 24 patients had extracranial non-testicular germ cell tumors and 15 patients soft tissue or chondrosarcomas. INDICATION: locoregional relapse (n = 29) or unresectable tumor after neoadjuvant chemotherapy (n = 10). Among these two groups, there were ten patients with poor response or progressive disease under primary or relapse chemotherapy. Ten out of the 29 relapse patients had more than one relapse. Tumor site: pelvis (30), abdomen (4), head and neck (2), proximal leg (2) and lumbar spine (1). Thermochemotherapy (TCH): 1800 - 2000 mg ifosfamide/m (2) and 100 mg etoposide/m (2) on days 1 - 4 and 40 mg cisplatin/m (2) on days 1 + 4 combined with regional deep hyperthermia (42 - 44 degrees C, 1 h) on days 1 + 4. RESULTS: In 39 protocol patients a total of 166 TCH courses (332 heat sessions) were applied. 20 patients achieved complete response, and 10 patients achieved partial response. TCH was followed by surgical tumor resection in 28/39 patients and/or radiotherapy in 13/39 patients. At a median follow-up of 27 months, outcome in this high-risk patient population was 22 NED, 3 AWD, 12 DOD, 2 DOC. Five year event free (EFS) and overall survival (OS) for the whole study cohort was 0.39 +/- 0.11 (20/39 patients) and 0.52 +/- 0.11 (25/39 patients), respectively. CONCLUSION: TCH shows substantial therapeutic efficacy and facilitates complete tumor resection in 14 out of 28 operated patients. Multimodal treatment including TCH, surgical resection and/or radiotherapy leads to sustained remission in the majority of patients with locoregional tumor recurrence. The therapeutic effect is most pronounced, if TCH is administered at first relapse. Due to the clinical and histologic heterogeneity the number of patients eligible for TCH is limited. Therefore, a more valid assessment of treatment efficacy can only be made by a matched-pair comparison in cooperation with the clinical registers.