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Purpose Data from the randomized Intergroup Trial 116 suggest effectiveness of adjuvant radiochemotherapy in patients with advanced gastric cancer. Late toxicity, however, especially with respect to the kidneys, may pose significant longtime problems. Intensity-modulated radiotherapy (IMRT) may reduce toxicity to organs at risk. To evaluate the relative merits of different IMRT approaches, we performed a plan comparison between a step-and-shoot class solution and an AP-PA setup, a conventional box technique and the Peacock tomotherapy approach. Methods and materials Computed tomographies and structure data from 15 patients who had been treated postoperatively for advanced (T3/T4/N+) gastric cancer at our department formed the basis of our plan comparison study. For each patient data set, 5 plans or plan combinations (conventional 3D plan, AP-PA plan, step-and-shoot IMRT, tomotherapy with 1-cm or 2-cm collimation) were chosen, and evaluation was performed for a total dose of 45 Gy delivered as the median dose to the target volume for each plan or plan combination. Results Median kidney dose generated from the IMRT plans is reduced individually by >50% for the kidney with the highest exposure (usually the left kidney) from 20 to 30 Gy with conventional 3D planning down to values between 8 and 10 Gy for IMRT. On average, median dose to the right kidney is the same for the conventional box technique and IMRT (between 8 and 10 Gy) but lower for the AP-PA technique. In 3 patients, kidney dose might have been ablative for both kidneys with both the AP-PA technique and the box technique, whereas it was acceptable with IMRT. Median dose to the liver was subcritical with all modalities but lowest with AP-PA fields. Differences between step-and-shoot IMRT and tomotherapy plans are small when compared to the differences between IMRT plans and conventional conformal 3D plans. For some patients, however, their body and target diameters obviate treatment with tomotherapy. Treatment time for the step-and-shoot approach and for tomotherapy with 2-cm collimation can be kept Conclusions For postoperative radiotherapy of advanced gastric cancer, step-and-shoot IMRT as well as tomotherapy can deliver efficient doses to target volumes while delivering dose to the kidneys in a fashion that is different from a conventional technique and is clearly advantageous in a small number of patients. An advantage for the majority of patients is likely with the normal tissue complication probability data presented in this series, but, given the uncertainty of the reaction of the kidney to inhomogeneous dose distributions, cannot be considered unequivocal at the moment. Different technical limitations apply to the different IMRT techniques. The choice of approach is therefore determined by departmental circumstances.

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. Semin. Surg. Oncol. 20:40–49, 2001. © 2001 Wiley-Liss, Inc.

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°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. Int. J. Cancer 82:84–91, 1999. © 1999 Wiley-Liss, Inc.

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.

A small number of patients exist with carcinoma of the pancreas with an inoperable but not metastasized tumor. Prospective randomized studies defined the standard of combined radiochemotherapy during the early 1980s for these patients. Since then, new drugs have shown considerable activity and in parallel improvements in radiotherapy treatment planning and delivery have been achieved. Therefore, it is time to ask whether patients with locally advanced, inoperable pancreatic cancer without metastases should still be irradiated or not. This review summarizes the current literature on combined radiochemotherapy for locally advanced carcinoma of the pancreas. Median survival times of 10–11 months and 1-year survival rates of about 40% can be achieved with modern radiochemotherapy regimens.

Background and Purpose: Locoregional relapse is a problem frequently encountered with advanced gastric cancer. Data from the randomized Intergroup trial 116 suggest effectiveness of adjuvant radiochemotherapy, albeit with significant toxicity. The potential of intensity-modulated radiotherapy (IMRT) to reduce toxicity by significantly reducing maximum and median doses to organs at risk while still applying sufficient dose to the target volume in the upper abdomen was studied. Patient and Methods: For a typical configuration of target volumes and organs, a step-and-shoot IMRT plan (eight beam orientations), developed as a class solution for treatment of tumors in the upper abdomen (Figures 1 to 3), a conventional plan, a combination of the conventional plan with a kidney-sparing boost plan, and a conventional plan with noncoplanar ap and pa fields for improved kidney sparing were compared with respect to coverage of target volume and dose to organs at risk with a dose of 45 Gy delivered as the median dose to the target volume. Results: When using the conventional three-dimensionally planned box techniques, the right kidney could be kept below tolerance, but median dose to the left kidney amounted to between 14.8 and 26.9 Gy, depending on the plan. IMRT reduced the median dose to the left kidney to 10.5 Gy, while still keeping the dose to the right kidney < 8 Gy. Liver was spared better with IMRT. Dose to the lungs was not significantly different, and dose to the spinal cord was higher (but well below tolerance) with IMRT. The dose distribution within the target volume was less homogeneous than for the conventional plans. With regard to target coverage, > 90% of prescription dose were delivered to > 90% of target volume with IMRT (Table 1). Conclusion: IMRT has the potential to deliver efficient doses to target volumes in the upper abdomen, while delivering dose to organs at risk in a more advantageous fashion than a conventional technique. For clinical implementation, the possibility of extensive organ motion in the upper abdomen has to be taken into account for treatment planning and patient positioning. The multitude of potential risks related to its application has to be the subject of thorough follow-up and further studies.

Background Radiation therapy is an essential modality in the treatment of breast cancer. Addition of radiotherapy to surgery has significantly increased local control and survival rates of the disease. However, radiotherapy is also associated with side effects, such as tissue fibrosis or enhanced vascular morbidity. Modern radiotherapy strategies, such as intensity modulated radiotherapy (IMRT), can shorten the overall treatment time by integration of the additional tumor bed boost significantly. To what extent this might be possible without impairing treatment outcome and cosmetic results remains to be clarified. Methods/Design The IMRT-MC2 study is a prospective, two armed, multicenter, randomized phase-III-trial comparing intensity modulated radiotherapy with integrated boost to conventional radiotherapy with consecutive boost in patients with breast cancer after breast conserving surgery. 502 patients will be recruited and randomized into two arms: patients in arm A will receive IMRT in 28 fractions delivering 50.4 Gy to the breast and 64.4 Gy to the tumor bed by integrated boost, while patients in arm B will receive conventional radiotherapy of the breast in 28 fractions to a dose of 50.4 Gy and consecutive boost in 8 fractions to a total dose of 66.4 Gy. Discussion Primary objectives of the study are the evaluation of the cosmetic results 6 weeks and 2 years post treatment and the 2- and 5-year local recurrence rates for the two different radiotherapy strategies. Secondary objectives are long term overall survival, disease free survival and quality of life. Trial Registration ClinicalTrials.gov Protocol ID: NCT01322854.

Normal thyroid function is vital for growth and nervous system myelinization. The number of myocardial β-adrenergic receptors and the rate of synthesis and use of myocardial high-energy phosphates are thyroid hormone dependent. Abnormal thyroid function may occur after cardiac surgery; we therefore assessed perioperative thyroid hormone secretion in children. 82 patients (age range 2 days to 16 years) with congenital heart disease were studied before and after surgery (day 1, 3, 5, 7). Plasma TSH, T3, T4, fT4, TG and urinary iodine excretion were measured. Results are expressed as mean ± SEM. Statistical analysis was performed by ANOVA (preoperative vs. postoperative) and a general linear models procedure (SAS).