Abstract Purpose Radiation combined with chemotherapy has recently been proposed to treat patients with localised extranodal natural killer (NK)/T lymphoma (ENKTL), nasal type. However, the ...modalities of the chemoradiotherapy combination and drug choices remain a matter of debate. We conducted a concurrent chemoradiotherapy (CCRT) study with the ESHAP (Etoposide, Steroid, High-dose Ara-C and Platinum) regimen. Methods An induction phase with two upfront courses of CCRT delivering a 40 Gy dose of radiation concurrently with two cycles of the ESHAP chemotherapy regimen, followed by a consolidation phase with 2–3 cycles of ESHAP chemotherapy alone. Results Thirteen patients with localised ENKTL nasal type were enrolled between January 2005 and December 2014. The median age was 62 years. Ten and three patients had Ann Arbor stage IE and IIE disease, respectively. They all completed the induction CCRT phase. A median of two consolidation ESHAP cycles were delivered. During consolidation, 8/13 (62%) patients had a reduction in the number of chemotherapy cycles or reduced chemotherapy doses, due to haematologically adverse events. The other five patients (38%) received the full number of ESHAP cycles of chemotherapy scheduled without a dose reduction. All but one patient (92%) experienced grade 3–4 haematological toxicity. The main non-haematological grade 3–4 toxicity was mucositis in 6/13 (46%) patients. All but one patient (92%) achieved a complete remission. Two-year overall survival was 72%. Conclusions With optimal management of the specific toxicities induced by this treatment modality, CCRT with the ESHAP regimen yielded high efficacy against localised ENKTL, nasal type.
Abstract Angiogenesis has been a central theme of oncologic research for several years. Recently, improved understanding of its mechanisms has led to the development of several antiangiogenic agents. ...Some have demonstrated their effectiveness in large randomized studies; however, no antiangiogenic agent has yet been approved for treatment in combination with radiotherapy. Numerous preclinical studies and a few small clinical trials have recently reported encouraging results. The objective of this article is to review the concept of targeted antiangiogenic agents and the early clinical results of their use in combination with radiation therapy.
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.
Purpose
The phase III European Organization for Research and Treatment of Cancer 55874 study has shown that external beam radiotherapy (EBRT) given as adjuvant treatment decreased locoregional ...recurrences from 40% to 20% in patients (pts) with localized uterine sarcomas (US). No data exist, however, on the place of brachytherapy (BT).
Material and Methods
We conducted a single‐center retrospective analysis of pts receiving adjuvant BT of the vaginal vault based on the vaginal mold technique as part of their multimodal adjuvant treatment for a high‐grade US from 1985 to 2015. Treatment characteristics, patterns of relapse, and toxicity were examined.
Results
Median follow‐up time was 5.5 years. A total of 98 pts with high‐grade US were identified: 81 leiomyosarcomas and 17 undifferentiated sarcomas. Postoperative chemotherapy was delivered in 53 pts. Median dose of EBRT was 45 Gy in 25 fractions. High‐dose rate, low‐dose rate, and pulsed‐dose rate techniques were used in 66, 31, and 1 pts, respectively. At last follow‐up, six pts (6.1%) experienced a locoregional relapse as first event. The International Federation of Gynecology and Obstetrics stage and the tumor size were associated with a higher probability of local relapse. When focusing on pts with stage I‐III disease, 5‐year overall survival was 77% (95% confidence interval: 67%–87%) and 5‐year survival without locoregional failure was 91% (83%–98%). Toxicities were mild to moderate, with only four acute grade 3 toxicities and two grade 3 late effects.
Conclusion
Vaginal vault BT as part of a multimodal adjuvant treatment was associated with a high locoregional control rate and with acceptable side effects in localized high‐grade US.
Implications for Practice
This study suggests that an aggressive adjuvant treatment combining chemotherapy and pelvic external beam radiotherapy followed with a brachytherapy of the vaginal vault is associated with a high locoregional control rate and an acceptable toxicity rate in patients with high grade uterine sarcoma. Adding a brachytherapy boost could also allow deescalating the total dose of pelvic external beam radiotherapy, in order to decrease the side effects of adjuvant treatment in these patients without increasing the risk of local relapse. However, the prognosis remains determined by a high frequency of systemic relapses.
This study reports on an experience with adjuvant treatments in localized high‐grade uterine sarcomas, rare tumors accounting for 1%‐2% of all uterine cancers. The local efficacy and toxicity of a multimodal adjuvant strategy including brachytherapy of the vaginal vault were examined.
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.
Objectifs : Etablir des corrélations dose-volume effet entre les paramètres dosimétriques proposés par le GEC-ESTRO et la probabilité de survenue d’événements tels que le contrôle tumoral ou une ...toxicité radio-induite.Matériel et méthodes : Les données cliniques et dosimétriques de cohortes de patientes traitées à Gustave Roussy et dans différents centres ont été confrontées. Dans un premier temps les paramètres dosimétriques de la curiethérapie 3D ont été comparés à ceux de la curiethérapie classique. Dans un second temps, la topographie des zones les plus exposées des organes à risque, ainsi que l’impact des mouvements de la vessie, du rectum, et du colon sigmoïde sur l’évaluation de la dose délivrée, ont été étudiés. Enfin, des analyses dose-volume effets ont été réalisées.Résultats : Les valeurs des paramètres dosimétriques volumétriques (D2cm3) de la vessie et du rectum se sont révélées faiblement corrélées et significativement supérieures aux doses évaluées aux points de l’ICRU ou à un point vésical alternatif. Les zones les plus exposées de la vessie et du rectum sont apparues situées au-dessus des points de l’ICRU. Les mouvements des organes autour de l’implant pendant la délivrance du traitement sont apparus marginaux pour la vessie et sigmoïde, en dehors de variations individuelles. En revanche, la dose délivrée au rectum étaient en moyenne plus élevée que le dose planifiée. Les analyses dose-volume effets ont montré des corrélations significatives entre D0.1cm3 et D2cm3 et la probabilité de survenue d’une morbidité tardive urinaire ou rectale. De la même manière, des corrélations significatives ont été établies entre la D90 des CTV à haut risque et à risque intermédiaire et la probabilité d’obtention du contrôle local. Divers caractéristiques tumorales (largeur au diagnostic, volume du CTV-HR, stade FIGO), impactent ces relations, de même que l’étalement total du traitement.Conclusion : Des corrélations dose-volume effets ont été établies entre les paramètres dosimétriques modernes et la probabilité d’obtenir le contrôle local ou d’entraîner une morbidité tardive. En ce qui concerne le contrôle tumoral, les objectifs de prescription doivent être personnalisés en fonction de critères carcinologiques. Pour les organes à risque, de contraintes de dose basées sur l’expérience de la curiethérapie 3D peuvent être établies, mais doivent être affinées dans de futures études en fonction de cofacteurs tels que les comorbidités. Les points gardent un intérêt en recherche clinique, pour l’étude de la morbidité vésicale ou vaginale.Ce travail a l'objet de 6 publications dans des revues internationales à comité de lecture. La septième est présentée sous forme de manuscrit.
Objectives: To establish dose-volume effects correlations between volumetric dosimetric parameters proposed by the GEC-ESTRO and the probability of occurrence of events such as tumor control or radiation-induced toxicity.Methods: Clinical and dosimetric data of patients treated at Gustave Roussy and in different centers have been reviewed. At first step, dosimetric parameters of image-guided brachytherapy were compared with those of conventional brachytherapy. Secondly, the topography of the most exposed areas of the organs at risk, and the impact of the movements of the bladder, rectum, and sigmoid colon on the assessment of the delivered dose, were studied. Finally, analyzes dose-volume effects were performed.Results: The values of volumetric dosimetric parameters (D2cm3) of the bladder and rectum appeared weakly correlated and significantly higher than the doses evaluated at ICRU points of bladder and rectum , an even in an alternative bladder point. The most exposed areas of the bladder and rectum appeared located above the points of the ICRU. The movements of the organs around the implant during the delivery of the treatment appeared marginal for the bladder and sigmoid, apart from individual variations. However, the mean delivered dose to the rectum was higher than the planned dose. Dose-volume effects correlations showed significant correlations between D0.1cm3 and D2cm3 and the probability of occurrence of urinary or rectal late morbidity. Similarly, significant correlations have been established between the D90 of the high risk, intermediate risk-CTV and the probability of achieving local control. Various tumor characteristics (width, HR-CTV volume, FIGO stage) impact these relationships, as well as the treatment time.Conclusion: Dose-volume effects correlations have been established between modern dosimetric parameters and the probability of achieving local control or cause late morbidity. Regarding tumor control, prescription aims must be customized according to oncologic criteria. For organs at risk, new dose constraints based on 3D brachytherapy experience can be established but should be refined in future studies based on cofactors such as comorbidities. The points retain an interest in clinical research for the study of bladder or vaginal morbidity.
Abstract Background and purpose Online delineation workshops (ODW) permit training of geographically dispersed participants. The purpose is to evaluate the methodology of an ODW using FALCON to ...harmonize delineation within a European multicentre trial on locally advanced cervical cancer (LACC). Material and methods Two ODW included 46 clinicians (14 centres). Clinicians completed baseline (C1), guideline (C2) and final contours (C3) for external beam radiotherapy (EBRT) and brachytherapy (BT) for LACC. Interobserver and intraobserver variability was evaluated quantitatively (using the DICE index) and qualitatively compared to expert contours. Results Nine clinicians submitted for EBRT and BT for C1–C3. Thirty-two sent any contour. Interobserver quantitative comparisons for EBRT showed significant improvement for C2 vs. C1 for bowel, CTV node, CTV-p and GTV node with significant detriment for GTV node (C3 vs. C1; C2), CTV-p (C3 vs. C2) and bowel (C3 vs. C2), showing in general an improvement in C2 vs. C1, with a detriment in C3 vs. C2 for two target volumes and an organ at risk. For BT there was significant improvement for C2 vs. C1 for bladder, GTV, HR-CTV and IR-CTV, with significant detriment for bladder (C3 vs. C2), thus overall improvement in C2 vs. C1, with only a detriment in C3 vs. C2 for bladder. Centres using MRI imaging for BT contouring did significantly better in the BT case for HR-CTV than those which used other techniques (C2 vs. C1: p < 0.005; C3 vs. C1: p = 0.02). Intraobserver quantitative comparisons showed significant improvement contouring a region of interest between C2 vs. C1, C3 vs. C1 and C3 vs. C2 for EBRT and between C2 and C1 for BT. Conclusions ODW offer training, initial contouring harmonization and allow assessment of centres.
Introduction:Low-dose radiation therapy (LD-RT) is a therapeutic option in indolent non Hodgkin B-cell lymphomas (iNHL), usually in the palliative setting. If most iNHL are highly sensitive to ...radiation therapy, with good local control obtained with a dose of 4 Gy in 2 fractions, little is known about the efficacy and outcome of repetitive courses of LD-RT. We report here the results of a study cohort of repetitive LD-RT in iNHL.
Methods: We retrospectively reviewed the records of all iNHL patients treated by two or more courses of LD-RT at Gustave Roussy, between January 1990 and December 2015. Patients received LD-RT as palliative treatment for low-bulky disease, patient's comfort or painful adenopathy. Clinical data, histological types, outcome and treatment lines were collected. Overall survival was the time between lymphoma diagnosis and death from any cause. Last LD-RT follow-up period was the time between the last LD-RT session and latest news.
Results: Thirty-five pts were analyzed. Among them, 24 pts (69%) had Follicular Lymphoma (FL), 6 pts (17%) Marginal Zone Lymphoma (MZL), 3 pts (9%) had B-cell primitive Cutaneous Lymphoma Follicular Type (CL-FL) and 2 pts (6%) Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL). At lymphoma diagnosis, median age was 57 years range 20-80. Ann Arbor stage was I-II in 18 pts (51%), and III-IV in 17 pts (49%). Patients received a median of 4 therapeutics lines (range 2-11), and 2 LD-RT courses (range 2-6). Median overall survival was 146 months 29-298 months. Four patients had died: 2 of disease progression and 2 others from concomitant illness (1 cardiac disease and 1 hepatocellular carcinoma). No patient had experienced transformation to diffuse large B cell lymphoma after RT-LD treatments. In the vast majority of cases (31/35; 89%), the LD-RT were successively performed to lymphoma relapse outside irradiation fields. Exclusive repetitive courses of LD-RT without chemotherapy were received by 8/35 (23%) of patients; while 24/35 (69%) patients received repetitive LD-RT alternately with immunotherapies or chemotherapies; and 3/35 (9%) others repetitive LD-RT alternately with standard dose RT.
After the second course of LD-RT, 12/35 (34%) patients were managed in watch and wait approach, 6/35 (17%) received another LD-RT and 17/35 (49%) patients had experienced a progressive disease and were treated with immunotherapy or chemotherapy or standard dose radiotherapy.
The LD-RT was the last treatment modality in 18/35 (51%) patients with histological types distributed in FL (n=10), MZL (n=5) and CT-FL (n=3). With a median last LD-RT follow up of 32 months 7-177 months, 23/35 (66%) patients remained in complete remission, 9/35 patients (26%) had experienced progressive disease and 3/35 (9%) patients had obtained stable disease.
Conclusion: As palliative treatment modality, the repetitive low dose radiation therapy 4 Gy in two fractions could provide alternative option treatment in iNHL. This study support further investigations of this simple, well tolerated and not costly therapy in iNHL, especially in the context of new immunotherapeutic agent's area.
Michot:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Ribrag:ArgenX: Research Funding; Esai: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; NanoString: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees.
With the increasing use of simultaneous integrated boost in the treatment of cervical cancer, there is a need to anticipate the brachytherapy (BT) contribution at the level of the pathologic pelvic ...lymph nodes. This study aimed to report the dose delivered at their level during BT.
Patients with pelvic nodal involvement and treated with a combination of chemoradiation followed by image-guided adaptive pulsed-dose-rate BT were selected. On per BT three-dimensional images, pelvic lymphadenopathies were delineated, without planning aim. For the purposes of the study, D
, D
, D
, and D
were reviewed and converted in 2-Gy equivalent doses, using the linear quadratic model with an α/β of 10 Gy.
Ninety-one patients were identified, allowing evaluation at the level of 226 lymphadenopathies. The majority of them were external iliac (48%), followed by common iliac (25%), and internal iliac (16%) regions. The 2-Gy equivalent doses D
were 4.4 ± 1.9 Gy, 5.4 ± 3.1 Gy, and 4.3 ± 2.1 Gy for the obturator, internal iliac, and external iliac, respectively, and 2.8 ± 2.5 Gy for the common iliac. The contribution to the common iliac nodes was significantly lower than the one of external and internal iliac (p < 0.001).
BT significantly contributes to the treatment of pelvic nodes at the level of approximately 5 Gy in the internal, external, and obturator areas and 2.5 Gy in the common iliac, allowing the anticipation of nodal boost with the simultaneous integrated boost technique. However, important individual variations have been observed, and evaluation of the genuine BT contribution should be recommended.
To investigate the impact of a primary para-aortic lymphadenectomy (PAL) in locally advanced cervical cancer patients receiving definitive chemoradiation, we reviewed the clinical records of ...consecutive patients treated in our Institution and receiving an external beam irradiation followed with an image-guided adaptive brachytherapy for a locally advanced cervical cancer. We examined the impact of performing a primary PAL as part of primary staging for guiding irradiation fields in patients without extra-pelvic PET uptake. The outcome of patients presenting para-aortic lymph node uptake (PALNU) was also examined. 186 patients were identified. Median follow-up was 44.4 months. Patients receiving a primary PAL (PAL group) and those who received upfront pelvic chemoradiation (no-PAL group) did not significantly differ for loco-regional failures. Survival without distant failure (DFFS), including para-aortic relapses, was at 3 years 87 % (95 % CI 84–90 %) in PAL group, 67 % (95 % CI 59–85 %) in the no-PAL group and 44 % (95 % CI 32–66 %) in the PALNU group (p = 0.04 for comparison between PAL and no-PAL groups). In a multivariate model including para-aortic lymphadenectomy, pelvic nodal uptake and high-risk clinical target volume as adjustment variables, a para-aortic lymphadenectomy was significant for DFS (HR = 0.47, 95 % CI 0.26–0.84, p = 0.01). Although confounding factors could account for these retrospective results, a primary PAL with tailored irradiation fields based on para-aortic histological findings seems to be associated with a better control for distant metastases. A randomized trial is testing the benefit of this strategy.
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