Deep inspiration breath-hold (DIBH) radiotherapy in left-sided breast cancer: Dosimetrical comparison and clinical feasibility in 20 patients.

BACKGROUND: Adjuvant radiotherapy after breast-conserving surgery (BCS) for breast cancer (BC) is a well-established indication. The risk of ischaemic heart disease after radiotherapy for BC increases linearly with the heart mean dose with no apparent threshold. Radiotherapy to the left breast in deep inspiration breath-hold (DIBH) reduces the dose to the heart. A new linac system with an integrated surface scanner (SS) for DIBH treatments was recently installed in our department. We tested it for potential benefits, safety, patients' acceptance/compliance and associated additional workload. MATERIALS AND METHODS: Twenty consecutive patients following BCS for breast carcinoma of the left side were enrolled in our institutional DIBH protocol. We compared dose to the heart and ipsilateral lung (IL) between plans in DIBH and free breathing (FB) using standard defined parameters: mean dose, maximal dose to a volume of 2 cm(3) (D2 cm (3)), volume receiving ≥ 5 Gy (V5), 10 Gy (V10), 15 Gy (V15) and 20 Gy (V20). Comparison of median calculated dose values was performed using a two-tailed Wilcoxon signed rank test. RESULTS: DIBH was associated with a statistically significant reduction (p < 0.001) in all studied parameters for the heart and the IL. In 16 of 20 patients the heart D2 cm (3) was less than 42 Gy in DIBH. In FB the heart D2 cm (3) was ≥ 42 Gy in 17 of 20 patients. The median daily treatment time was 9 min. CONCLUSION: Radiotherapy of the left breast in DIBH using a SS could easily be incorporated into daily routine and is associated with significant dose reduction to the heart and IL.

Long-term in vivo effects of cisplatin on gamma-H2AX foci signaling in peripheral lymphocytes of tumor patients after irradiation.

PURPOSE: This study determined the effects of cis-diamminedichloroplatinum(II) on radiation-induced foci formation of gamma-H2AX and Rad51 in lymphocytes. EXPERIMENTAL DESIGN: Twenty-eight cancer patients were irradiated for intrathoracic, pelvic, or head and neck tumors and received simultaneous cisplatin containing chemotherapy. The effect of cisplatin on radiation-induced gamma-H2AX and Rad51 foci as a response to ionizing radiation-induced DNA double-strand breaks was measured in lymphocytes after in vivo and in vitro radiochemotherapy. The role of DNA-dependent protein kinase and ataxia-telangiectasia mutated kinase in gamma-H2AX signaling, the consequences of altered gamma-H2AX foci formation on double-strand break end joining, was studied. RESULTS: Cisplatin decreased the number of induced gamma-H2AX foci in lymphocytes after in vivo or in vitro irradiation by 34% +/- 6% at days 0 to 3 after cisplatin (P < 0.0001) and remained significant until day 6. The variation in this cisplatin effect from patient to patient was larger than the retest error within the same patient (P = 0.01). The cisplatin effect was not accompanied by an inhibition of end joining of double-strand break as analyzed using gel electrophoresis of DNA under neutral conditions. Cisplatin also decreased radiation induced Rad51 foci formation in lymphocytes after stimulation of proliferation with phytohemagglutinin by 47% +/- 6% (P < 0.0001). CONCLUSION: Cisplatin has long-term effects on the early double-strand break response of gamma-H2AX and Rad51 foci formation after ionizing radiation. Inhibition of sensing and processing of double-strand break by gamma-H2AX and Rad51 foci formation are important mechanisms by which cisplatin can alter the radiation response.

gamma-H2AX foci formation in peripheral blood lymphocytes of tumor patients after local radiotherapy to different sites of the body: dependence on the dose-distribution, irradiated site and time from start of treatment.

PURPOSE: To evaluate the relationship between an estimated integral total body radiation dose delivered and phosphorylated histone H2AX protein (gamma-H2AX) foci formation in peripheral blood lymphocytes of cancer patients. MATERIAL AND METHODS: gamma-H2AX formation was quantified as the mean number of foci per lymphocyte (N(meanH2AX)) and the percentage of lymphocytes with > or =n foci. The integrated total body radiation dose was estimated from the dose volume histogram of patient's body corrected for the proportion of the body scanned by computed tomography for 3D treatment planning. RESULTS: There was a strong linear correlation between the mean number of gamma-H2AX foci per lymphocyte in the peripheral blood sample and integrated total body radiation dose (r = 0.83, p < 0.0001). The slope of the relationship was dependent on the site of body irradiated. In comparison to chest irradiation with a slope of 8.7 +/- 0.8 foci Gy(-1), the slopes for brain, upper leg and pelvic sites were significantly shallower by -4.7, -4.3, and -3.8 Gy(-1), respectively (p < 0.0001), while the slope for upper abdomen irradiation was significantly larger by 9.1 +/- 2.6 Gy(-1) (p = 0.0007). There was a slight time effect since the start of radiotherapy on the slopes of the in vivo dose responses leading to shallower slopes (-1.5 +/- 0.7 Gy(-1), p = 0.03) later (> or =10 day) during radiotherapy. After in vitro irradiation, lymphocytes showed 10.41 +/- 0.12 foci per Gy with no evidence of inter-individual heterogeneity. CONCLUSIONS: gamma-H2AX measurements in peripheral lymphocytes after local radiotherapy allow the estimation of the applied integral body dose. The site and time dependence have to be considered.