[Current Trends in Radiotherapy Following Surgical Resection of Soft-tissue Sarcoma of the Extremities and Trunk]. / Aktuelle Trends bei der Strahlenbehandlung nach chirurgischer Entfernung von Weichgewebesarkomen der Extremitäten und des Rumpfes.

Besides surgery, radiotherapy plays its well-established part in the multimodality treatment of soft-tissue sarcomas. It can be delivered before or after surgery with similar control rates. Adjuvant radiotherapy increases the local control rates as well as the overall survival in intermediate or high-grade soft-tissue sarcomas. Due to the complex and sophisticated nature of the treatment, patients should be referred to specialised centres where modern radiotherapeutic options like intensity modulated radiotherapy and image-guided radiotherapy can be offered.

[Cervical, inguinal and abdominal lymphnode dissection]. / Zervikale, inguinale und abdominelle Lymphknotendissektion.

Diagnostic lymph node dissections can be defined as a form of oncological service surgery. These procedures aim at clarification of differential diagnoses of local or systemic lymph node pathologies or contribute to tumor staging. Procedure implementation can either involve incisional biopsy, selective lymph node extirpation or regional systematic lymph node dissection. Sentinel lymph node lymphadenectomy is a focused form of selective lymphadenectomy. Both surgeon and oncologist must have a preoperative consensus and mutual understanding about the detailed purpose of the procedure in the individual patient setting. Terminology conventions must be considered in communication. Potential reasons to extend surgery should be strategically reflected prior to surgery. Interventional techniques and minimally invasive forms of surgical lymph node dissection must be technically taken into account in order to reduce procedural morbidity. Clinically indicative scenarios, pathophysiological concepts and technical options of surgical lymph node dissection are described and discussed for various anatomical regions.

Do structural changes in the tumour bed after intraoperative radiotherapy (IORT) of breast cancer complicate the evaluation of mammograms in a long-term follow-up?

The purpose of the study was to assess whether postoperative changes in the tumour bed after intraoperative radiotherapy (IORT) with low-energy X-rays complicate the mammographic evaluation. 54 patients receiving breast-conserving surgery and IORT were compared to a control group of 48 patients with conventional breast-conserving treatment. All patients were included in routine follow-ups (≥3 years) with mammography accompanied by ultrasound. By retrospective consensus reading the mammographic changes in the tumour bed were classified as absent, low or distinct. Using the same grading it was classified whether mammographic evaluation was complicated due to postoperative changes. Focusing the yearly follow-ups within a period of four years, distinct changes were found significantly more often after IORT (52-62% vs. 7-30%). After IORT the evaluation was significantly more often distinctly complicated in each follow-up, except for year 1 (16-21% vs. 0-8%). In the IORT group the distribution of findings was nearly stable over time. In the control group it changed over time and a distinctly complicated evaluation was no longer seen in the follow-ups of years 3 and 4. Overall, further non-routine diagnostic procedures due to unclear findings in the tumour bed became necessary in 7% (IORT) vs. 8% (control group) of the patients (p=0.86). Evaluation of mammograms is complicated after IORT. In contrast to conventionally treated patients postoperative changes and difficulties of evaluation do not decrease over time. Overall, after IORT the diagnostic uncertainty does not seem to be increased in ultrasound supported mammographic follow-ups. The topic needs further evaluation with larger study samples.

Long-term follow-up-findings in mammography and ultrasound after intraoperative radiotherapy (IORT) for breast cancer.

The purpose of this study was to assess mammographic and sonographic findings in a long-term follow-up (>or=3 years) after breast-conserving surgery (BCS) and IORT, either applied as boost or exclusively. Follow-up-findings of 54 patients were retrospectively evaluated and compared to a control group of 48 patients, treated with BCS and whole-breast radiotherapy. After IORT patients had a higher incidence of fat necroses manifesting as oil cysts in the late follow-up mammograms (n = 31 vs n = 8); furthermore, oil cysts were larger in the IORT group (median 4.5 vs 1.4 cm(2)). In 25 IORT patients the oil cysts arose from partially organized hematomas/seromas, which in this group were generally more frequent (n = 38 vs n = 9) and larger (median 3.6 vs 1.8 cm(2)). After IORT a decreasing incidence of hematomas/seromas was reciprocal to an increasing incidence of oil cysts, and the size of both entities correlated with each other. Liquid lesions with polypoid inner wall thickening on ultrasound, attributed to organized hematomas/seromas or fat necroses, appear more frequently after IORT (n = 15 vs n = 1). In conclusion, IORT is associated with a high incidence of large oil cysts, which arise from likewise large partially organized wound cavities. On ultrasound pronounced partial organization with polypoid inner wall thickening is a frequent finding in those cavities.

A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer.

We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy (CapIri-RT) as neoadjuvant treatment in rectal cancer in a phase-II trial. Patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive irinotecan (50 mg m(-2) weekly) and capecitabine (500 mg m(-2) bid days 1-38) with a concurrent RT dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the completion of chemoradiation. A total of 36 patients (median age 62 years; m/f: 27:9) including three patients with local recurrence were enclosed onto the trial. The median distance of the tumour from the anal verge was 5 cm. The main toxicity observed was (NCI-CTC grades 1/2/3/4 (n)): Anaemia 23/9/-/-; leucocytopenia 12/7/7/2, diarrhoea 13/15/4/-, nausea/vomiting 9/10/2/-, and increased activity of transaminases 3/3/1/-. One patient had a reversible episode of ventricular fibrillation during chemoradiation, most probably caused by capecitabine. The relative dose intensity was (median/mean (%)): irinotecan 95/91, capecitabine 100/92). Thirty-four patients underwent surgery (anterior resection n=25; abdomino-perineal resection n=6; Hartmann's procedure n=3). R0-resection was accomplished in all patients. Two patients died in the postoperative course from septic complications. Pathological complete remission was observed in five out of 34 resected patients (15%), and nine patients showed microfoci of residual tumour (26%). After a median follow-up of 28 months one patient had developed a local recurrence, and five patients distant metastases. Three-year overall survival for all patients with surgery (excluding three patients treated for local relapse or with primary metastatic disease) was 80%. In summary, preoperative chemoradiation with CapIri-RT exhibits promising efficacy whereas showing managable toxicity. The local recurrence and distant failure rates observed after a median 28 months are low compared with standard 5-fluorouracil based therapy.

Early mammographic and sonographic findings after intraoperative radiotherapy (IORT) as a boost in patients with breast cancer.

The aim of this study was to evaluate mammographic and sonographic changes at the surgical site within the first 2 years after IORT as a boost followed by whole-breast radiotherapy (WBRT), compared with a control group treated with WBRT alone. All patients had breast-conserving surgery for early-stage breast cancer. Group A: n = 27, IORT (20 Gy) followed by WBRT (46 Gy). Group B (control group): n = 27, WBRT alone (56-66 Gy). Mammography: fat necrosis in 14 group A versus four group B patients (P < 0.001); parenchymal scarring classified as unorganized at the last follow-up in 16 vs seven cases, respectively (P = 0.03). Ultrasound: overall number of patients with circumscribed findings 27 vs 18 (P < 0.001); particular hematomas/seromas in 26 vs 13 patients (P < 0.001). Synopsis of mammography and ultrasound: overall postoperative changes were significantly higher classified in group A (P = 0.01), but not judged to have a significantly higher impact on interpretation. Additional diagnostic procedures, due to unclear findings at the surgical site, were performed on four patients of both groups. Within the first 2 years after IORT as a boost, therapy-induced changes at the original tumor site are significantly more pronounced compared with a control group. There is no evidence that the interpretation of findings is complicated after IORT.

Plasmocytoma of the urethra.

CASE HISTORY AND FINDINGS: A 35-year-old male patient presented with a 1-year history of hesitancy in voiding. An urethrogram revealed urethral stricture, therefore an urethrotomy with biopsies was performed. Histologic results suggested the diagnosis of extramedullary mature plasmocytoma. TREATMENT AND OUTCOME: After external beam radiotherapy with a total dose of 45 Gy the patient is disease-free without any therapy-related late effects after a follow-up of 36 months. CONCLUSION: Primary localization of extramedullar plasmocytomas in the genitourinary tract is very rare. This case report discusses a case of a male patient suffering from plasmocytoma of the urethra, who could be treated successfully by primary external beam radiotherapy.

[Optimizing the use of radiotherapy with IMRT and image guided location of advanced prostate cancer]. / Optimierter Einsatz der Strahlentherapie durch IMRT und Präzisionslokalisationsverfahren bei der Behandlung des fortgeschrittenen Prostatakarzinoms.

Intensity modulated radiotherapy (IMRT) combined with recently developed noninvasive image-guided targeting techniques for tumor localization/repositioning provide a means to further improve on conformal radiotherapy of prostate cancer by optimally sparing the rectum. This refined approach may potentially improve treatment results for locally advanced prostate cancer while reducing side effects. This review summarizes the clinical requirements for effective prostate radiotherapy and describes the new technology that helps to better fulfil these requirements. These noninvasive developments, their potential benefit as well as their limitations, together with new data on fractionation sensitivity of prostate cancer that may lead to shortened overall treatment times may be of interest for all physicians treating patients with prostate cancer.

Radiochemotherapy for anal carcinoma - effectivity and late toxicity.

BACKGROUND: Radiochemotherapy of anal carcinoma is an organ-sparing approach with a high curative potential. The purpose was to evaluate the effectivity and late toxicity for patients treated with radiochemotherapy in our department. PATIENTS AND METHODS: During 1990-2000, 27 patients with anal carcinoma were treated at the Universitätsklinikum Mannheim. The median follow-up time was 23 months (max. 68 months). Before treatment, 23 patients were colostomy-free. Patients were treated according to 3 different protocols (Cummings n = 8, EORTC n = 5, RTOG n = 14). Acute toxicity was scored according to the RTOG/EORTC scale, and late toxicity according to the LENT/SOMA scale. RESULTS: 25 patients completed the therapy. One patient died due to leukopenic sepsis, and 1 patient interrupted therapy. 4 patients had a tumor relapse (2 patients immunosuppressed, 1 T4 tumor and 1 recurrence at the field-margin), one underwent abdomino- perineal resection. This resulted in a disease-free survival of about 80% and colostomy-free survival of 90% at 5 years. Total doses < 50 Gy and immunosuppression resulted in higher recurrence rates. Most patients suffered from acute toxicity grades 2 (n = 7) and 3 (n = 19) and late toxicity grades 1 (n = 7) and 2 (n = 4). CONCLUSIONS: Radiochemotherapy for anal carcinoma is an effective therapy with acceptable toxicity. Immunosuppressed patients have a higher risk for tumor recurrences and should be monitored more closely.

[The search for therapeutic gain in radiation oncology]. / Auf der Suche nach der Therapeutischen Breite in der Radioonkologie.

The Search for Therapeutic Gain in Radiation Oncology Novel strategies in radiation oncology aim at increasing the therapeutic gain, i.e., to decrease side effects while maintaining cure rates, or to increase cure rates at the same level of complications. Over the years, physical and biological strategies have been developed to achieve this goal. The physical development led to the possibility of precise, computer-controlled beam application by using modern imaging techniques and three-dimensional treatment planning. Improved patient immobilization methods allow minimal safety distances, resulting in steep dose gradients when used together with isocentric multi-field techniques. These predominantly stereotactic irradiation techniques yield therapeutic gain towards the tumor surrounding normal tissue. A critical issue that determines the tolerance of radiation therapy are structures at risk within the target volume. Fractionation is a reliable method to exploit the differential potential for recovery of radiation-induced DNA damage in normal tissues. Radiogenetic strategies aim at the sensibilization of tumor cells by targeting specific characteristics like mutations of p53. The reverse idea, gene-therapeutic radioprotection of normal tissue, is under investigation.

Intraoperative radiotherapy for gastrointestinal cancer.

Local recurrence following potentially curative tumor resection is a major problem in patients with gastrointestinal cancer. To augment surgical excision and to avoid the disadvantages of external beam irradiation, intraoperative radiotherapy (IORT) has been applied to primary and recurrent gastrointestinal cancer, both with curative intent and for palliation. There is ample evidence that the combination of radical surgery and IORT can improve local control. Whether this eventually can translate into improved overall survival has not yet been studied in adequately powered randomized and controlled trials.

Synergistic interaction of ultrasonic shock waves and hyperthermia in the Dunning prostate tumor R3327-AT1.

Pulsed high-energy ultrasound shock waves (PHEUS), similar to those used for clinical lithotripsy, can deposit energy deep in tissue and thereby destroy the microvasculature of solid tumors. We investigated the potential of PHEUS, generated by an electromagnetic shockwave source (19 kV capacitor voltage, 1 Hz pulse frequency), as a local cancer-therapy modality alone and in combination with local tumor hyperthermia (43.5 +/- 0.1 degrees C, 30 min). Copenhagen rats transplanted with the anaplastic Dunning-prostate-tumor sub-line R3327-AT1 received 1000 PHEUS pulses, which delayed tumor growth by one tumor-doubling time (5 days). Histopathology revealed hemorrhage, disruption of tumor vasculature, and necrosis in the focus of the sound field. Bromodeoxyuridine (BUdR) incorporation was significantly lower in PHEUS-treated tumors than in controls. Dynamic magnetic resonance imaging (MRI) studies using gadolinium-DTPA as contrast agent showed a strong reduction of tumor perfusion after PHEUS treatment, although this effect was partly reversible within 3 days after PHEUS. While hyperthermia alone produced no significant delay in tumor growth, the combination of PHEUS and hyperthermia produced tumor-growth delay by 2 tumor-volume-doubling times. The maximum growth delay was achieved when PHEUS and hyperthermia were separated by 24 hr at the time of maximum perfusion reduction indicated by MRI. Thus, the cytotoxic effect of PHEUS was enhanced by hyperthermia in the anaplastic prostate tumor R3327-AT1 grown on Copenhagen rats in a synergistic manner, due to blood-flow reduction. In conjunction with other agents, such as hyperthermia, PHEUS might become a local cancer-therapy modality in solid tumors accessible to ultrasound.

Transient secondary hypothyroidism in children after cardiac surgery.

Thyroid hormone status was assessed in 132 children with congenital heart defects undergoing cardiac surgery (median age 3.1 y; range 2 d to 16.2 y). Plasma TSH, thyroxine (T4), free thyroxine (fT4), triiodothyronine (T3), reverse triiodothyronine (rT3), thyroglobulin (Tg), and urinary iodine excretion were measured before and every other day after cardiac surgery (d 1-21). After surgery we observed strikingly low plasma concentrations of TSH (0.4 mU/L; 0.2-1.3), T3 (0.6 nmol/L; 0.3-1.2), T4 (48.9 nmol/L; 12.9-82.4), IT4 (12.9 pmol/L; 5.1-19.3), and Tg (9.4 micrograms/L; 1.5-20.6), whereas rT3 plasma concentrations increased (0.13 pmol/L; 0.05-0.3; n = 40). The maximal post-operative changes of TSH and rT3 preceded changes of T3, T4, fT4, and Tg. Postoperative urinary iodine excretion increased significantly (n = 109). Thyroid hormone plasma concentrations were lowest after cardiopulmonary bypass operations and in patients treated with dopamine. In patients with postoperative T3 plasma concentrations less than 0.6 nmol/L (n =52) the period of mechanical ventilation and intensive care treatment was significantly prolonged. Furthermore, the cumulative doses of inotropic and vasoactive catecholamines and furosemide were significantly higher in this patient group. Our results demonstrate transient secondary hypothyroidism in children after cardiac surgery that may contribute to postoperative cardiac and respiratory dysfunction and may delay recovery. Possible benefits of thyroid hormone replacement therapy need to be thoroughly examined.