Scarce data exist on concurrent chemotherapy in locally advanced cervical cancer (LACC) patients (pts) treated with image-guided adaptive brachytherapy (IGABT). We examined the effect of a number of ...chemotherapy cycles and their interaction with brachytherapy dose/volume parameters. Clinical records of 209 consecutive pts treated for a LACC were reviewed. Pts received CRT concurrently with cisplatin 40 mg/m² or carboplatin AUC2. An additional cycle could have been delivered during the pulse-dose rate (PDR)-IGABT. The impact of a number of chemotherapy cycles on outcome was examined, as well as the interactions with dose volume parameters. The number of cycles was four in 55 (26.3%) pts, five in 154 (73.7%) including 101 receiving the fifth cycle during IGABT. Median follow-up was 5.5 years. Pts receiving five cycles had a better outcome on all survival endpoints, including three year local control rate (93.9% vs. 77.2%; p < 0.05). In the subgroup, only pts with tumor FIGO (Fédération Internationale de Gynécologie Obstétrique) stage ≤IIB or with CTVHR > 25 cm3 had a better outcome. Pts receiving four cycles with D90CTVHR > 80GyEQD2 had the same locoregional control–(LRC) as those receiving five cycles and achieving D90CTVHR ≤ 80 GyEQD2 (p = 0.75). An optimal propensity score matching the balance for the FIGO stage, CTVHR volume and D90CTVHR confirmed the effect, with the largest life expectancy benefit for locoregional failure-free survival (absolute gain: 1.5 years; p = 0.017). Long-term radiation-induced toxicity was not increased. Increasing the total number of cycles from 4 to 5 improved LFS, suggesting a place for systemic strategies aimed at in-field cooperation. Delivering an additional cycle at the time of brachytherapy did not increase morbidity and there permitted an increase in chemotherapy dose intensity.
The poor outcome of patients with recurrent ovarian cancer constitutes a continuous challenge for decision-making in clinical practice. In this setting, molecular targets have recently been ...identified, and novel compounds are now available. Bevacizumab has been introduced for the treatment of patients with ovarian cancer and is, to date, the most extensively investigated targeted therapy in this setting. However, potential toxicities are associated with the use of this monoclonal antibody. These toxicities have been reported in clinical trials, and can also be observed outside of trials. As limited data is currently available regarding the safety of bevacizumab treatment in daily clinical practice, the current retrospective study was designed to evaluate this. Data from 156 patients with recurrent ovarian cancer who had received bevacizumab treatment between January 2006 and June 2009 were retrospectively identified from the institutional records of five French centers. In contrast to clinical trials, the patients in the present study were not selected and had a heterogeneous profile according to their prior medical history, lines of treatment prior to bevacizumab introduction and number of relapses. The results first confirm the effect of heavy pretreatment on the occurrence of serious and fatal adverse events in clinical practice, as previously reported for clinical trials and for other retrospective cohort studies. Importantly, the data also demonstrates, for the first time, that medical history of hypertension is an independent predictive risk factor for the development of high-grade hypertension during bevacizumab treatment. These results thus suggest that treating physicians must consider all risk factors for managing bevacizumab toxicity prior to its introduction. Such risk factors include the time of bevacizumab introduction, a patient's history of hypertension and a low incidence of pre-existing obstructive disease.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Objective To examine the clinical results of a preoperative image-guided pulse-dose-rate brachytherapy (PDR-BT) in early stage cervical cancer. Materials/methods We examined the outcome of ...consecutive patients with early stage cervical cancer undergoing preoperative image-guided PDR-BT between 2004 and 2013 because of risk factors (lymphovascular embols and/or tumour > 2 cm). The objective was to deliver 60 Gy to 100% of the intermediate risk clinical target volume. Brachytherapy was followed, 6–8 weeks later, by a radical hysterectomy/bilateral salpingo-oophorectomy plus pelvic +/− para-aortic lymph node dissection. Patients with positive lymph nodes had postoperative chemoradiation. Results 77 patients met the above criteria of preoperative PDR-BT. On hysterectomy specimen, 54 (70.1%) presented a complete histological response. Four (5.2%) had a tumour residuum ⩾ 1 cm. Median follow-up was 46.8 months. 5-Year disease-free survival (DFS) rate was 84.4%. Only one local recurrence was observed. The presence of lymph nodal metastases, a tumour size > 3 cm and a brachytherapy/surgery time interval ⩾ 9 weeks correlated with a poorer DFS. Six postoperative complications were encountered (7.8%). Total reference air kerma correlated with late vaginal toxicity ( p = 0.02). Conclusions A preoperative image-guided PDR-BT was safe and effective. Predictive factors for survival and toxicity were evidenced.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Primary vaginal cancer is a rare disease for which treatment has been modeled based on cervical cancer. We report our experience in the use of image-guided adaptive brachytherapy (IGABT) in this ...indication.
Patients treated for vaginal cancer with a combination of external beam radiation therapy and IGABT were identified through electronic search. The Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology recommendations for cervical cancer have been extrapolated with the definition of two clinical target volumes (CTVs) corresponding to the residual disease after external beam radiation therapy (CTV
), assessed from clinical and imaging findings, and the so-called CTV
, comprising the CTV
with directional margins and at least the initial disease at diagnosis.
Twenty-seven patients were identified. MRI was used for brachytherapy guidance in 82% of the cases. An interstitial component was used in 59% of the cases. The D
CTV
and D
CTV
were 73.1 ± 12.8 Gy and 66.6 ± 6.7 Gy, respectively. After a median followup of 40.1 months, nine recurrences in 8 patients were observed of which four were local. Local relapses occurred within the CTV
. Three-year local control and disease-free rates were 82% and 65%, respectively. At 2 years, the Grade 2-4 gastrointestinal or urinary morbidity accrual rate was 9%. Twelve patients experienced late sexual morbidity, including three patients with Grade 3 stenosis.
IGABT is feasible in vaginal cancer with promising outcomes. Harmonizing the definition of CTVs is required to allow comparisons between experiences and to perform multicenter studies.
To identify an imaging signature predicting local recurrence for locally advanced cervical cancer (LACC) treated by chemoradiation and brachytherapy from baseline 18F-FDG PET images, and to evaluate ...the possibility of gathering images from two different PET scanners in a radiomic study.
118 patients were included retrospectively. Two groups (G1, G2) were defined according to the PET scanner used for image acquisition. Eleven radiomic features were extracted from delineated cervical tumors to evaluate: (i) the predictive value of features for local recurrence of LACC, (ii) their reproducibility as a function of the scanner within a hepatic reference volume, (iii) the impact of voxel size on feature values.
Eight features were statistically significant predictors of local recurrence in G1 (p < 0.05). The multivariate signature trained in G2 was validated in G1 (AUC=0.76, p<0.001) and identified local recurrence more accurately than SUVmax (p=0.022). Four features were significantly different between G1 and G2 in the liver. Spatial resampling was not sufficient to explain the stratification effect.
This study showed that radiomic features could predict local recurrence of LACC better than SUVmax. Further investigation is needed before applying a model designed using data from one PET scanner to another.
This paper investigates the theory of robustness against adversarial attacks. It focuses on the family of randomization techniques that consist in injecting noise in the network at inference time. ...These techniques have proven effective in many contexts, but lack theoretical arguments. We close this gap by presenting a theoretical analysis of these approaches, hence explaining why they perform well in practice. More precisely, we make two new contributions. The first one relates the randomization rate to robustness to adversarial attacks. This result applies for the general family of exponential distributions, and thus extends and unifies the previous approaches. The second contribution consists in devising a new upper bound on the adversarial generalization gap of randomized neural networks. We support our theoretical claims with a set of experiments.
Gouy d'Arsy Louis Marthe, marquis de, Vernier Théodore, Démeunier Jean Nicolas, Bureaux de Pusy Jean Xavier, Talleyrand-Périgord Charles Maurice de, Harambure Louis François Alexandre, baron d'. ...Suite de la discussion sur la liquidation de la dette publique, lors de la séance du 18 septembre 1790. In: Tome XIX - Du 16 septembre au 23 octobre 1790. pp. 48-61.
Ambly Claude Jean, marquis d', Gouy-d'Arsy Louis Marthe, marquis de, Bouche Charles-François, Liancourt François Alexandre Frédéric, duc de La Rochefoucauld, Boisgelin de Cucé Jean-de-Dieu de, ...Boussay Jacques-François de Menou, baron de, Mirabeau Honoré-Gabriel Riquetti, comte de. Discussion suite à la lettre de M. de La Luzerne, lors de la séance du 2 décembre 1789. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome X - Du 12 novembre au 24 décembre 1789. Paris : Librairie Administrative P. Dupont, 1878. p. 357.
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