Gemcitabine and carboplatin in intensively pretreated patients with metastatic breast cancer

Background: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. Patients and Methods: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. Results: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombo-cytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. Conclusion: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2). Copyright (c) 2008 S. Karger AG, Basel

Simultaneous integrated boost therapy of carcinoma of the hypopharynx/larynx with and without flattening filter - a treatment planning and dosimetry study

Background: The aim of this study was to investigate if the flattening filter free (FFF) irradiation mode of a linear accelerator (linac) is advantageous as compared to the flat beam (FF) irradiation mode in intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for carcinoma of the hypopharynx/larynx. Methods: Four treatment plans were created for each of 10 patients for an Elekta Synergy linac with Agility collimating device, a dual arc VMAT and a nine field step and shoot IMRT each with and without flattening filter. Plan quality was compared considering target coverage and dose to the organs at risk. All plans were verified by a 2D-ionization-chamber-array and delivery times were compared. Peripheral point doses were determined as a measure of second cancer risk. The Wilcoxon test was used for statistical analysis with a significance level of 0.05. Results: Plan quality was similar for all four treatment plans without statistically significant differences of clinical relevance. The clinical goals were met in all plans for the PTV-SIB (V-95% > 95%), the spinal cord (D1ccm < 45 Gy) and the brain stem (D-1ccm < 48 Gy). For the parotids, the goal of D-50% < 30 Gy was met in 70% and 60% of the plans for the left and right parotid respectively, and the V-95% of the SIB reached an average of 94%. Delivery times were similar for FF and FFF and significantly decreased by around 70% for VMAT as compared to IMRT. Peripheral doses were significantly reduced by 18% in FFF mode as compared to FF and by 26% for VMAT as compared to IMRT. Lowest peripheral doses were found for VMAT FFF, followed by VMAT FF. Conclusions: The FFF mode of a linear accelerator is advantageous for the treatment of hypopharynx/ larynx carcinoma only with respect to reduction of second cancer induction in peripheral organs for the combination of Elekta Synergy linacs and Oncentra (R) External Beam v4.5 treatment planning system. This might be of interest in a therapy with curative intent

Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer—comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial

Background: Defining risk categories in breast cancer is of considerable clinical significance. We have developed a novel risk classification algorithm and compared its prognostic utility to the Web-based tool Adjuvant! and to the St Gallen risk classification. Patients and methods: After a median follow-up of 10 years, we retrospectively analyzed 410 consecutive node-negative breast cancer patients who had not received adjuvant systemic therapy. High risk was defined by any of the following criteria: (i) age 2 cm. All patients were also characterized using Adjuvant! and the St Gallen 2007 risk categories. We analyzed disease-free survival (DFS) and overall survival (OS). Results: The Node-Negative-Breast Cancer-3 (NNBC-3) algorithm enlarged the low-risk group to 37% as compared with Adjuvant! (17%) and St Gallen (18%), respectively. In multivariate analysis, both Adjuvant! [P = 0.027, hazard ratio (HR) 3.81, 96% confidence interval (CI) 1.16-12.47] and the NNBC-3 risk classification (P = 0.049, HR 1.95, 95% CI 1.00-3.81) significantly predicted OS, but only the NNBC-3 algorithm retained its prognostic significance in multivariate analysis for DFS (P < 0.0005). Conclusion: The novel NNBC-3 risk algorithm is the only clinicopathological risk classification algorithm significantly predicting DFS as well as O

Total Body Irradiation - an Attachment Free Sweeping Beam Technique

Introduction: A sweeping beam technique for total body irradiation in standard treatment rooms and for standard linear accelerators (linacs) is introduced, which does not require any accessory attached to the linac. Lung shielding is facilitated to reduce the risk of pulmonary toxicity. Additionally, the applicability of a commercial radiotherapy planning system (RTPS) is examined. Material and Methods: The patient is positioned on a low couch on the floor, the longitudinal axis of the body in the rotational plane of the linac. Eight arc fields and five additional fixed beams are applied to the patient in supine and prone position respectively. The dose distributions were measured in a solid water phantom and in an Alderson phantom. Diode detectors were calibrated for in-vivo dosimetry. The RTPS Oncentra was employed for calculations of the dose distribution. Results: For the cranial 120 cm the longitudinal dose profile in a slab phantom measured with ionization chamber varies between 94 and 107 % of the prescription dose. These values were confirmed by film measurements and RTPS calculations. The transmittance of the lung shields has been determined as a function of the thickness of the absorber material. Measurements in an Alderson phantom and in-vivo dosimetry of the first patients match the calculated dose. Discussion and conclusion: A treatment technique with clinically good dose distributions has been introduced, which can be applied with each standard linac and in standard treatment rooms. Dose calculations were performed with a commercial RTPS and should enable individual dose optimization

Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer--comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial.

Defining risk categories in breast cancer is of considerable clinical significance. We have developed a novel risk classification algorithm and compared its prognostic utility to the Web-based tool Adjuvant! and to the St Gallen risk classification. After a median follow-up of 10 years, we retrospectively analyzed 410 consecutive node-negative breast cancer patients who had not received adjuvant systemic therapy. High risk was defined by any of the following criteria: (i) age &lt;35 years, (ii) grade 3, (iii) human epithelial growth factor receptor-2 positivity, (iv) vascular invasion, (v) progesterone receptor negativity, (vi) grade 2 tumors &gt;2 cm. All patients were also characterized using Adjuvant! and the St Gallen 2007 risk categories. We analyzed disease-free survival (DFS) and overall survival (OS). The Node-Negative-Breast Cancer-3 (NNBC-3) algorithm enlarged the low-risk group to 37% as compared with Adjuvant! (17%) and St Gallen (18%), respectively. In multivariate analysis, both Adjuvant! [P = 0.027, hazard ratio (HR) 3.81, 96% confidence interval (CI) 1.16-12.47] and the NNBC-3 risk classification (P = 0.049, HR 1.95, 95% CI 1.00-3.81) significantly predicted OS, but only the NNBC-3 algorithm retained its prognostic significance in multivariate analysis for DFS (P &lt; 0.0005). The novel NNBC-3 risk algorithm is the only clinicopathological risk classification algorithm significantly predicting DFS as well as OS

Measurement of the neutron capture cross section of the s-only isotope 204Pb from 1 eV to 440 keV

The neutron capture cross section of 204Pb has been measured at the CERN n_TOF installation with high resolution in the energy range from 1 eV to 440 keV. An R-matrix analysis of the resolved resonance region, between 1 eV and 100 keV, was carried out using the SAMMY code. In the interval between 100 keV and 440 keV we report the average capture cross section. The background in the entire neutron energy range could be reliably determined from the measurement of a 208Pb sample. Other systematic effects in this measurement could be investigated and precisely corrected by means of detailed Monte Carlo simulations. We obtain a Maxwellian average capture cross section for 204Pb at kT=30 keV of 79(3) mb, in agreement with previous experiments. However our cross section at kT=5 keV is about 35% larger than the values reported so far. The implications of the new cross section for the s-process abundance contributions in the Pb/Bi region are discussed.Comment: 8 pages, 3 figures, article submitted to Phys. Rev.

New measurement of neutron capture resonances of 209Bi

The neutron capture cross section of Bi209 has been measured at the CERN n TOF facility by employing the pulse-height-weighting technique. Improvements over previous measurements are mainly because of an optimized detection system, which led to a practically negligible neutron sensitivity. Additional experimental sources of systematic error, such as the electronic threshold in the detectors, summing of gamma-rays, internal electron conversion, and the isomeric state in bismuth, have been taken into account. Gamma-ray absorption effects inside the sample have been corrected by employing a nonpolynomial weighting function. Because Bi209 is the last stable isotope in the reaction path of the stellar s-process, the Maxwellian averaged capture cross section is important for the recycling of the reaction flow by alpha-decays. In the relevant stellar range of thermal energies between kT=5 and 8 keV our new capture rate is about 16% higher than the presently accepted value used for nucleosynthesis calculations. At this low temperature an important part of the heavy Pb-Bi isotopes are supposed to be synthesized by the s-process in the He shells of low mass, thermally pulsing asymptotic giant branch stars. With the improved set of cross sections we obtain an s-process fraction of 19(3)% of the solar bismuth abundance, resulting in an r-process residual of 81(3)%. The present (n,gamma) cross-section measurement is also of relevance for the design of accelerator driven systems based on a liquid metal Pb/Bi spallation target.Comment: 10 pages, 5figures, recently published in Phys. Rev.

Measurement of the radiative neutron capture cross section of 206Pb and its astrophysical implications

The (n, gamma) cross section of 206Pb has been measured at the CERN n_TOF facility with high resolution in the energy range from 1 eV to 600 keV by using two optimized C6D6 detectors. In the investigated energy interval about 130 resonances could be observed, from which 61 had enough statistics to be reliably analyzed via the R-matrix analysis code SAMMY. Experimental uncertainties were minimized, in particular with respect to (i) angular distribution effects of the prompt capture gamma-rays, and to (ii) the TOF-dependent background due to sample-scattered neutrons. Other background components were addressed by background measurements with an enriched 208Pb sample. The effect of the lower energy cutoff in the pulse height spectra of the C6D6 detectors was carefully corrected via Monte Carlo simulations. Compared to previous 206Pb values, the Maxwellian averaged capture cross sections derived from these data are about 20% and 9% lower at thermal energies of 5 keV and 30 keV, respectively. These new results have a direct impact on the s-process abundance of 206Pb, which represents an important test for the interpretation of the cosmic clock based on the decay of 238U.Comment: 11 pages, 8 figures, paper to be submitted to Phys. Rev.

Resonance capture cross section of 207Pb

The radiative neutron capture cross section of 207Pb has been measured at the CERN neutron time of flight installation n_TOF using the pulse height weighting technique in the resolved energy region. The measurement has been performed with an optimized setup of two C6D6 scintillation detectors, which allowed us to reduce scattered neutron backgrounds down to a negligible level. Resonance parameters and radiative kernels have been determined for 16 resonances by means of an R-matrix analysis in the neutron energy range from 3 keV to 320 keV. Good agreement with previous measurements was found at low neutron energies, whereas substantial discrepancies appear beyond 45 keV. With the present results, we obtain an s-process contribution of 77(8)% to the solar abundance of 207Pb. This corresponds to an r-process component of 23(8)%, which is important for deriving the U/Th ages of metal poor halo stars.Comment: 7 pages, 3 figures, to be published in Phys. Rev.

Sentinel node procedure in Ib cervical cancer: a preliminary series

The aim of this study was to determine the diagnostic accuracy and feasibility of sentinel lymph node (SLN) detection using a gamma probe in patients with Figo IB cervical cancer. Between January 1999 and September 2000, 14 patients with cervical cancer, planned for radical hysterectomy were eligible for the study. The day before radical hysterectomy we injected technetium99m-labelled nanocolloid in each quadrant of the cervix. Dynamic and static images were recorded using a gamma camera. SLNs were identified intraoperatively using a handheld gamma-detection probe. After resection of SLNs a standard radical hysterectomy with pelvic lymph node dissection was performed. Patients and tumour characteristics were compared with sentinel node detection and with final histopathological and immunohistochemical results. Scintigraphy showed focal uptake in 13 of the 14 patients. Intraoperatively we detected 26 sentinel nodes by gamma probe. In 8 of 13 patients, one or more sentinel nodes were identified unilaterally, in 5 women bilaterally. Histologically positive SLNs were found in only 1 patient. We did not find any false-negative SLN in our series. In conclusion identification of sentinel nodes in cervical cancer is feasible with preoperatively administered technetium99m-labelled nanocolloid. A larger series will be required to establish sentinel node detection in cervical cancer for further therapy concepts and planning. © 2001 Cancer Research Campaignhttp://www.bjcancer.co