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.

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.

Schedule-dependent antagonism of gemcitabine and cisplatin in human anaplastic thyroid cancer cell lines.

Anaplastic thyroid carcinoma (ATC) affects primarily elderly patients, with a median survival of 4-12 months after diagnosis. Presently, under clinical investigation the combination of cisplatin (CDDP) and gemcitabine (GEM) has promising activity in several of human tumor types. To develop new approaches for therapy of ATC, we evaluated the antineoplastic activity of GEM and CDDP alone (1-h and 24-h drug exposure) or in combination in the ATC cell lines SW1736, 8505C, C643, and HTh74. IC50 values were determined by the sulforhodamine B assay, activity was evaluated by the relative antitumor activity (RAA) and drug interaction assessed by isobologram analysis. GEM seemed to be active in ATC, with RAA ranging from 12-114 and CDDP only modestly active (RAA, 0.24-1.4). In four different drug schedules tested, the drug combination was additive when GEM preceded CDDP exposure (combination index, approximately 1), whereas when CDDP preceded GEM exposure the combination was significantly antagonistic (combination index, >1). In SW1736 and 8505C cells, we observed a strong S phase arrest and DNA synthesis inhibition 24 h after a 1-h exposure to an IC50 of CDDP. On the basis of molecular drug targets, cell cycle arrest points, and DNA synthesis inhibition, a model was developed to explain the interaction observed for the combination of GEM and CDDP. In conclusion, GEM shows promising cytostatic activity in ATC. Interaction of GEM and CDDP was schedule and dose dependent, favoring a regime in which GEM is followed by CDDP. Additionally, our model system suggests that DNA-synthesis inhibition and S phase arrest may be important determinants for the drug interaction between GEM and CDDP.