Clinical Outcomes of 130 Patients with Primary and Secondary Lung Tumors treated with Cyberknife Robotic Stereotactic Body Radiotherapy.

BACKGROUND: Authors report clinical outcomes of patients treated with robotic stereotactic body radiotherapy (SBRT) for primary, recurrent and metastatic lung lesions. PATIENTS AND METHODS: 130 patients with 160 lesions were treated with Cyberknife SBRT, including T1-3 primary lung cancers (54%), recurrent tumors (22%) and pulmonary metastases (24%). The mean biologically equivalent dose (BED10Gy) was 151 Gy (72-180 Gy). Median prescribed dose for peripheral and central lesions was 3×20 Gy and 3×15 Gy, respectively. Local control (LC), overall survival (OS), and cause-specific survival (CSS) rates, early and late toxicities are reported. Statistical analysis was performed to identify factors influencing local tumor control. RESULTS: Median follow-up time was 21 months. In univariate analysis, higher dose was associated with better LC and a cut-off value was detected at BED10Gy ≤ 112.5 Gy, resulting in 1-, 2-, and 3-year actuarial LC rates of 93%, vs 73%, 80% vs 61%, and 63% vs 54%, for the high and low dose groups, respectively (p = 0.0061, HR = 0.384). In multivariate analysis, metastatic origin, histological confirmation and larger Planning Target Volume (PTV) were associated with higher risk of local failure. Actuarial OS and CSS rates at 1, 2, and 3 years were 85%, 74% and 62%, and 93%, 89% and 80%, respectively. Acute and late toxicities ≥ Gr 3 were observed in 3 (2%) and 6 patients (5%), respectively. CONCLUSIONS: Our favorable LC and survival rates after robotic SBRT, with low rates of severe toxicities, are coherent with the literature data in this mixed, non-selected study population.

The timing of surgery after neoadjuvant radiotherapy influences tumor dissemination in a preclinical model.

Neoadjuvant radiotherapy (neoRT) used in cancer treatments aims at improving local tumor control and patient overall survival. The neoRT schedule and the timing of the surgical treatment (ST) are empirically based and influenced by the clinician's experience. The current study examines how the sequencing of neoRT and ST affects metastatic dissemination. In a breast carcinoma model, tumors were exposed to different neoRT schedules (2x5Gy or 5x2Gy) followed by surgery at day 4 or 11 post-RT. The impact on the tumor microenvironment and lung metastases was evaluated through immunohistochemical and flow cytometry analyses. After 2x5Gy, early ST (at day 4 post-RT) led to increased size and number of lung metastases as compared to ST performed at day 11. Inversely, after 5x2Gy neoRT, early ST protected the mice against lung metastases. This intriguing relationship between tumor aggressiveness and ST timing could not be explained by differences in classical parameters studied such as hypoxia, vessel density and matrix remodeling. The study of tumor-related inflammation and immunity reveals an increased circulating NK cell percentage following neoRT as compared to non irradiated mice. Then, radiation treatment and surgery were applied to tumor-bearing NOD/SCID mice. In the absence of NK cells, neoRT appears to increase lung metastatic dissemination as compared to non irradiated tumor-bearing mice. Altogether our data demonstrate that the neoRT schedule and the ST timing affect metastasis formation in a pre-clinical model and points out the potential role of NK cells. These findings highlight the importance to cautiously tailor the optimal window for ST following RT.

Dosimetric comparison of high-dose-rate brachytherapy and intensity-modulated radiation therapy as a boost to the prostate.

PURPOSE: We compared the dose conformity of two radiation modalities: high-dose-rate brachytherapy (HDR BT) and intensity-modulated radiation therapy (IMRT) to deliver a boost to the prostate after external beam radiotherapy (EBRT). METHODS AND MATERIALS: Ten successive patients with prostate adenocarcinoma treated with a single 10-Gy HDR BT boost after EBRT were investigated. Four theoretical IMRT plans were computed: (a) 32.85 Gy IMRT and (b) 26 Gy IMRT with CTV-PTV expansions, doses corresponding to the equivalent dose in 2-Gy fractions (EQD2) of one 10-Gy fraction calculated with a prostate alpha/beta ratio of respectively 1.5 and 3 Gy; and (c) 32.85 Gy IMRT and (d) 26 Gy IMRT without CTV-PTV expansions. The dose-volume histogram values converted in EQD2 with an alpha/beta ratio of 3 Gy for the organs at risk were compared. RESULTS: The HDR BT plan delivered higher mean doses to the PTV compared with IMRT plans. In all, 33% of the rectal volume received a mean dose of 5.32 +/- 0.65 Gy and 20% of bladder volume received 4.61 +/- 1.24 Gy with HDR BT. In comparison, doses delivered with IMRT were respectively 13.4 +/- 1.49 Gy and 10.81 +/- 4 Gy, even if only 26 Gy was prescribed to the PTV with no CTV-PTV expansion (p < 0.0001). The hot spots inside the urethra were greater with HDR BT but acceptable. CONCLUSIONS: Use of HDR BT produced a more conformal plan for the boost to the prostate than IMRT even without CTV-PTV expansions.

A dosimetric selectivity intercomparison of HDR brachytherapy, IMRT and helical tomotherapy in prostate cancer radiotherapy.

BACKGROUND AND PURPOSE: Dose escalation in order to improve the biochemical control in prostate cancer requires the application of irradiation techniques with high conformality. The dosimetric selectivity of three radiation modalities is compared: high-dose-rate brachytherapy (HDR-BT), intensity-modulated radiation radiotherapy (IMRT), and helical tomotherapy (HT). PATIENTS AND METHODS: Ten patients with prostate adenocarcinoma treated by a 10-Gy HDR-BT boost after external-beam radiotherapy were investigated. For each patient, HDR-BT, IMRT and HT theoretical treatment plans were realized using common contour sets. A 10-Gy dose was prescribed to the planning target volume (PTV). The PTVs and critical organs' dose-volume histograms obtained were compared using Student's t-test. RESULTS: HDR-BT delivers spontaneously higher mean doses to the PTV with smaller cold spots compared to IMRT and HT. 33% of the rectal volume received a mean HDR-BT dose of 3.86 + or - 0.3 Gy in comparison with a mean IMRT dose of 6.57 + or - 0.68 Gy and a mean HT dose of 5.58 + or - 0.71 Gy (p < 0.0001). HDR-BT also enables to better spare the bladder. The hot spots inside the urethra are greater with HDR-BT. The volume of healthy tissue receiving 10% of the prescribed dose is reduced at least by a factor of 8 with HDR-BT (p < 0.0001). CONCLUSION: HDR-BT offers better conformality in comparison with HT and IMRT and reduces the volume of healthy tissue receiving a low dose.

Does inverse planning applied to Iridium192 high dose rate prostate brachytherapy improve the optimization of the dose afforded by the Paris system?

BACKGROUND AND PURPOSE: The purpose of the work is to analyse for 192Ir prostate brachytherapy (BT) some of the different steps in optimizing the dose delivered to the CTV, urethra and rectum. MATERIALS AND METHODS: Between 07/1998 and 12/2001, 166 patients were treated with 192Ir wires providing a low dose rate, according to the Paris system philosophy and with the 2D version of the treatment planning IsisR. 40-45 Gy were delivered after an external beam radiotherapy of 40 Gy. The maximum tolerable doses for BT were 25 Gy to the anterior third of the rectum on the whole length of the implant (R dose) and 52 Gy to the urethra on a 1cm length (Umax). A Umax/CTV dose ratio >1.3 represented a pejorative value as the planned dose of 40-45 Gy could not be achieved. On the other side a ratio 1.25 decreased significantly with optimization required on CTV contours and additional constraints on urethra while the R/CTV ratio was maintained under 0.55. For initial Umax/CTV >1.3 or >1.25 but