Search

Background: Palbociclib, a small-molecule inhibitor of cyclin-dependent kinases (CDK4 and CDK6), combined with letrozole increases progression-free survival among patients with previously untreated ER-positive, HER2 negative advanced breast cancer. However, the data on the safety of the concomitant association between Palbociclib and radiation therapy are scarce. The purpose of our study was to retrospectively evaluate the tolerance of the first patients treated with this concomitant combination at Institut Curie. Materials and methods: Between April 2017 and July 2019, 27 women with ER-positive, HER2 negative metastatic breast cancer received locoregional and/or symptomatic irradiation at a metastatic site concomitantly with Palbociclib at a daily dose of 125 mg, from d1 to d21 every 28 days. Palbociclib was always associated with an endocrine treatment: Letrozole (17 patients /27, with or without an LHRH analogue) or Fulvestrant (10 patients /27). Median age at the time of diagnosis of metastases was 60 years (range, 35-85 years). Thirty-two sites were irradiated: 9 patients received post-operative locoregional radiation therapy, including the chest wall or breast and lymph node areas, and 23 sites of metastases were irradiated: 15 at the spine (3 cervical, 6 thoracic, 4 lumbar, 2 sacral), 2 pelvic lesions, 4 peripheral skeletal lesions, 1 brain lesion and 1 choroidal lesion (two patients received locoregional treatment and irradiation in one metastatic site and two patients were treated in two different metastatic sites). The dose prescribed for locoregional mammary radiotherapy was 50 Gy in 25 fractions and varied for the treatment of metastatic sites: 20 Gy in 5 fractions (n=14), 30 Gy in 10 fractions (n=7) and 8 Gy in 1 fraction (n=1). The brain metastasis was stereotactically treated (1 fraction of 18 Gy). The primary endpoint was toxicity scored according to the common terminology criteria for NCI adverse events, version v4.0. Results: Median follow-up was 22 months (range, 4 to 54). Mean number of days of Palbociclib during radiation therapy was 8.7 days (range, 1 to 23 days). Most common acute toxicities were radiodermatitis (12/27, including 1 grade 3, 2 grade 2 and 9 grade 1) and neutropenia (13/27, including 1 grade 4, 7 grade 3, 5 grade 2). Palbociclib had to be stopped during the radiation therapy of three patients (3/27): one patient treated locoregionally (bilateral breast and lymph nodes irradiation) developed a grade 3 radiodermatitis and febrile neutropenia, another treated locoregionally developed grade 2 dysphagia (loss of 4 kg in 1 month) and one patient treated for sacral metastases (20 Gy in 4 fractions) developed grade 3 proctitis. Of the 19/27 patients with a follow-up of more than 6 months none developed late toxicities. Conclusion: Concomitant administration of Palbociclib with radiation therapy was reasonably well tolerated in our series of 27 patients. Caution should be exercised when a large volume is irradiated, and when the dose per fraction is high. It remains unsure whether the interruption-causing side effects of Palbociclib was based on synergistic toxicity with radiation therapy. We suggest that our findings are to be confirmed in prospective registration studies collecting larger number of patients. Citation Format: Arnaud Beddok, Alexandre Arsene-Henry, Baptiste Porte, Kim Cao, Louis Bazire, Nathaniel Scher, Alain Labib, Ilan Darmon, Joëlle Otz, Mathieu Minsat, Hamid Mammar, François Clément Bidar, Alain Fourquet, Paul Cottu, Phlip Poortmans, Youlia Kirova. A retrospective study of 27 patients with ER-positive, HER2 negative metastatic breast cancer treated with concomitant palbociclib and radiation therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-05.

Purpose In literature, there are no guidelines on how to prescribe dose in the case of radiosurgery (SRS) or stereotactic irradiation of multiple and adjacent BM. Aim of this work is to furnish practical proposals of dosimetric methods for multiple neighboring BM, and to make a literature review about the SRS treatment of multiple BM, comparing radiotherapy techniques on the basis of different dosimetric parameters. Materials and methods A theoretical proposal of dosimetric approaches to prescribe dose in case of multiple contiguous BM is done. A literature review between 2010 and 2020 was performed on MEDLINE and Cochrane databases according to the PRISMA methodology, with the following keywords dose prescription, radiosurgery, multiple BM. Papers not reporting dosimetric solutions to irradiate multiple BM were excluded. Results Only one article in the literature reports a practical modality of dose prescription for multiple adjacent BM. Thus, we proposed other five practical solutions to prescribe radiation dose in case of two or more neighboring BM, describing advantages and drawbacks of each method in terms of different dosimetric parameters. The literature review about dosimetric solutions to irradiate multiple BM led to 56 titles; 14 articles met the chosen criteria and we reported their results in terms of dosimetric indexes and low doses to the normal brain tissue. Conclusions The six dosimetric approaches here described can be used by physicians for multiple contiguous BM, depending on the clinical situation. These methods may be applied in clinical studies to better evaluate their usefulness in practice.

Purpose The purpose of this study was to assess the feasibility, efficacy and toxicity of fiducial marker implantation and tracking in CyberKnife® stereotactic radiation therapy (SBRT) applied to extracranial locations. Materials and method This is a retrospective, single-centre, observational study to collect the data of all patients treated by stereotactic radiation therapy with fiducial marker tracking at extracranial locations, conducted between June 2014 and November 2017. Information regarding the implantation procedure, the types of toxicity related to marker implantation and the number of markers implanted/tracked during treatment were collected. Complication rates were evaluated using the CTCAE v4 [Common Terminology Criteria for Adverse Events] scale. The technical success rate was based on the ability to optimally track the tumor throughout all treatment fractions. Results Out of 2505 patients treated by stereotactic radiation therapy, 25% received treatment with fiducial marker tracking. The total number of implantation procedures was 616 and 1543 fiducial markers were implanted. The implantation-related complication rate was 3%, with 16 Grade 1 events and 4 Grade 2 events. The number of treated patients and the number of implanted markers has gradually increased since the technique was first implemented. The median treatment time was 27 min (range 10–76). 1295 fiducials were effectively tracked throughout all treatment fractions, corresponding to a technical success rate of 84%. The difference between the number of fiducials implanted and those tracked during treatment decreased significantly as the site’s experience increased. Conclusion Fiducial marker implantation and tracking is feasible, well-tolerated, and technically effective technique in SBRT for extracranial tumors.

Resume Le traitement de reference des carcinomes epidermoides du canal anal localement evolues (stades II et III) est la chimioradiotherapie exclusive. Celle-ci delivre une dose de 45 Gy a raison de cinq fractions de 1,8 Gy par semaine dans un volume pelvien, puis un complement de dose de 14 a 20 Gy dans la tumeur. La chimiotherapie concomitante la plus souvent utilisee comprend une association de 5-fluoro-uracile et de mitomycine-C delivree lors de la premiere et cinquieme semaine d’irradiation. Une couverture optimale des volumes cibles est parfois difficile a obtenir avec une irradiation conformationnelle (jonctions des faisceaux, combinaison d’electrons et photons parfois complexes dans les aires ganglionnaires). La toxicite cutaneomuqueuse et digestive induite par le traitement peut necessiter un intervalle libre avant la realisation du complement d’irradiation. Celui-ci peut avoir un effet deletere sur les resultats s’il est prolonge (plus de 38 jours). Les differentes techniques de radiotherapie conformationnelle avec modulation d’intensite (statique segmentee, dynamique, arctherapie volumique modulee et tomotherapie helicoidale) ont leur interet dans cette localisation. Elles permettent d’obtenir une sterilisation tumorale et ganglionnaire avec une baisse des doses intermediaires et elevees aux organes a risque (intestin grele, perinee/organes genitaux, vessie, moelle osseuse) entrainant une reduction de la toxicite aigue de grade 3 ou plus ainsi qu’une meilleure conservation fonctionnelle du sphincter anorectal. Une description de la realisation de l’arctherapie volumique modulee est presentee dans cet article. Les avantages et inconvenients de cette technique par rapport aux autres y sont discutes.

Extracranial stereotactic radiotherapy has developed considerably in recent years and is now an important part of the therapeutic alternatives to be offered to patients with cancer. It offers opportunities that have progressively led physicians to reconsider the therapeutic strategy, for example in the case of local recurrence in irradiated territory or oligometastatic disease. The literature on the subject is rich but, yet, there is no real consensus on therapeutic indications. This is largely due to the lack of prospective, randomized studies that have evaluated this technique with sufficient recoil. We propose a review of the literature on the technical aspects and indications of extracranial stereotactic radiotherapy.

Objectifs La radiotherapie hypofractionnee a montre son equivalence en termes d’efficacite dans plusieurs essais randomises avec des profils de toxicite differents. Elle n’est pas encore un standard en France. L’objectif de l’etude est d’evaluer la tolerance en cours de radiotherapie et a 4–6 mois sur une serie de patients traites pour un adenocarcinome prostatique en radiotherapie moderement hypofractionnee avec escalade de dose. Methodes Au total, 212 patients ont ete traites consecutivement entre fevrier 2016 et mars 2018. La dose delivree etait de 75 gy en 30 fractions au niveau de la prostate et des vs proximales (eqd2 = 82,5 a 85,7 gy en fractions de 2 gy pour un α/β de 1,5 a 3). Cent quatre-vingt-quinze patients (92 %) ont recu une irradiation ganglionnaire pelvienne (46 gy en 23 fractions). La technique d’irradiation a ete une rcmi rotationnelle (Rapidarc®) guidee par l’image apres implantation de 3 grains d’or intraprostatiques. Les toxicites urinaires et digestives ont ete recueillies en cours de radiotherapie et a 4–6 mois. Des facteurs predictifs de toxicite ont ete recherches. Resultats Les caracteristiques des patients etaient : âge median = 71 ans [46–86], psa initial median = 9,46 ng/mL [1,97–652], stade t1, t2, t3, t4 : 32 %, 23 %, 43 % et 2 %. Stade n1 et m1 : 19 et 1 patients. Score de Gleason 6, 7 (3 + 4), 7 (4 + 3) et ≥ 8 dans 19 %, 44 %, 22 % et 15 % des cas. Les toxicites urinaires et digestives de grade 1 ont ete de 50 % et 61 %, celles de grade 2 de 44 % et 2 %. Avec un recul de 4–6 mois apres la fin de la radiotherapie, les toxicites urinaires et digestives de grade 1 ont ete de 52 % et 23 %, de grade 2 de 15 % et 0 %. Une toxicite urinaire grade 3 ( Fig. 1 , Fig. 2 , Fig. 3 ). Conclusion La radiotherapie prostatique moderement hypofractionnee avec escalade de dose est bien toleree. Elle permet de reduire sensiblement le temps de traitement. Ces donnees encourageantes doivent etre confirmees sur le long terme.

Resume La radiotherapie stereotaxique extracrânienne s’est considerablement developpee ces dernieres annees et tient desormais une part importante dans les alternatives therapeutiques a proposer aux patients atteints de cancer. Elle offre des possibilites qui ont progressivement amene les praticiens a reconsiderer la strategie therapeutique, par exemple en cas de recidive locale en territoire irradie ou de maladie oligometastatique. La litterature sur le sujet est riche mais il n’existe pas encore a ce jour de veritables consensus sur les indications therapeutiques. Cela est en grande partie lie au fait qu’il n’existe que peu d’etude prospective randomisee ayant evalue cette technique avec un recul suffisant. Nous proposons ainsi une revue de la litterature sur l’aspect technique et sur les indications de la radiotherapie stereotaxique extracrânienne.

International audience; Background. New approaches are needed for patients newly diagnosed with bulky glioblastoma (GB) and/or with severe neurological impairment that cannot benefit from first line temozolomide (TMZ)-based chemoradiotherapy. Bevacizumab (BEV), an antiangiogenic anti-VEGF-R monoclonal antibody, has a rapid impact on tumor-related brain edema in recurrent GB. The present study reports the feasibility and efficacy of an induction treatment with TMZ and BEV to alleviate the initial neurological impairment and/or to reduce the tumor volume before a delayed chemoradiotherapy. Methods. We retrospectively analyzed tumor and target volumes and clinical neurological status in 39 patients with bulky GB and/or with severe neurological impairment after an induction treatment combining TMZ and BEV. Neurological and radiological responses were assessed according to RANO criteria. Calculating gross tumor and clinical target volumes (GTV and CTV) was done at diagnosis and before radiotherapy. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan Meier methods. Safety was reported according to NCTCAE. Results. A cohort of 39 patients was analyzed between December 2010 and April 2014. Upfront standard TMZ-based chemoradiotherapy was recused due either to tumor volume or impairment of neurological status and/or performance status. After TMZ/BEV induction (median time of 3 months), 6 (15%) patients achieved a partial response (PR), and 17 (44%) had a stable disease. 24 patients (62%) received a radical-intent chemoradiotherapy. TMZ-BEV induced median reduction of the clinical target volume (CTV) was 25.9% [-84.4%; - 4.8%]. The median PFS and OS were 8.4 months [95% CI: (6.6 - 9.9)] and 11.0 months [95% CI: (9.3 - 13.7)], respectively in the whole cohort and 10.8 [95% CI: (9.3 - 12.9)] and 15.0 [95% CI: (13.2 - 17.8)] for irradiated patients. Induction treatment led to corticosteroid dose reduction or cessation in 21 patients (54%). KPS improvement was observed in 38% of patients. Toxicity was mild with only 7/39 (18%) grade III-IV toxicity, including 1 digestive bleeding and 1 epistaxis. Conclusion. TMZ-BEV induction led to CTV reduction allowing for optimal chemoradiotherapy in a majority (62%) of patients for which radiotherapy was initially recused. A clinical benefit was obtained with improved KPS and a decrease in steroid dose.

Objectif de l’etude L’objectif etait l’evaluation de la tolerance urinaire et digestive en cours de radiotherapie et a 4 mois. Materiel et methode Cent dix-huit patients ont ete pris en charge consecutivement entre fevrier 2016 et janvier 2017. La dose totale d’irradiation a ete de 75 Gy en 30 fractions dans la prostate. Cent sept patients (91 %) ont recu une irradiation ganglionnaire pelvienne de 46 Gy en 23 fractions. La technique d’irradiation a ete une radiotherapie conformationnelle avec modulation d’intensite (RCMI) rotationnelle (RapidArc®) guidee par l’image apres implantation de trois grains d’or dans la prostate. Quatre patients ont recu un boost integre dans des adenopathies et quatre une irradiation osseuse (oligometastases). Quatre-vingt-dix-neuf patients ont recu une privation androgenique. Les caracteristiques des patients etaient : l’âge median de 71 ans [51–85 ans], concentration mediane initiale d’antigene specifique de la prostate de 9,23 ng/mL [1,97–304 ng/mL] ; stade : T1, T2, T3, T4 dans respectivement 29 %, 23 %, 45 % et 3 % des cas ; stade N1 : chez dix patients et M1 chez quatre. Score de Gleason 6, 7(3 + 4), 7(4 + 3) et superieur ou egal a 8 dans respectivement 19 %, 48 %, 19 % et 13 % des cas. La toxicite urinaire et digestive a ete recueillie retrospectivement. Des facteurs predictifs de toxicite ont ete recherches. Resultats L’etalement median a ete de 49 jours [42–85 j], sans interruption en rapport avec la toxicite. Une toxicite urinaire de grade 1 ete observee chez 50 % des patients et une toxicite digestive chez 79 %, une de grade 2 chez 42 % et 3 %. Chez 80 patients avec un recul de 4 mois apres la fin de la radiotherapie, une toxicite urinaire de grade 1 a ete observee chez 44 % et une toxicite digestive de 33 %, une de grade 2 de 11 % et 0 %. Aucune toxicite de grade 3 n’a ete observee. Aucune correlation n’a ete retrouvee entre la survenue de cette toxicite et les differents parametres analyses. Conclusion Une radiotherapie prostatique moderement hypofractionnee avec escalade de dose a ete bien toleree. Elle a permis de reduire sensiblement la duree du traitement. Ces donnees encourageantes doivent etre confirmees sur le long terme.

Introduction L’objectif etait de comparer les resultats de l’embolisation et de la chirurgie dans le cadre de l’ulcere duodenal hemorragique (UDH) resistant au traitement endoscopique. Methodes De janvier 2006 a decembre 2016, les patients pris en charge dans le cadre d’un UDH resistant au traitement endoscopique ont ete inclus. Le critere de jugement principal etait la reussite globale du traitement. Les criteres secondaires etaient les donnees pre-interventionnelles, les taux de recidive, la morbi-mortalite et la duree d’hospitalisation. Resultats Cinquante-neuf patients sur 396 (14,9 %) presentant un UDH ont necessite un geste complementaire, 15 patients ayant une chirurgie, (7 apres echec d’embolisation), et 44 une embolisation. Âge, choc preoperatoire, nombre de transfusions, delai entre FOGD et geste complementaire, nombre de FOGD etaient identiques. La reussite globale du traitement (80 % vs 79,5 %), les recidives hemorragiques (20 % vs 15,9 %) etaient identiques. L’hospitalisation en reanimation (14 jours vs 8), les complications Clavien ≥ 3 (53,3 % vs 27 %), la mortalite (26,3 % vs 11,4 %) etaient en faveur de l’embolisation (non-significatif). Soixante-quinze pour cent des deces apres chirurgie survenaient apres tentative d’embolisation. Conclusion Le succes global du traitement chirurgical et radiologique est similaire, avec plus de morbidite apres chirurgie. L’echec d’embolisation est associe a une pejoration du pronostic apres chirurgie.

The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45 Gy in 1.8 Gy per fraction in the prophylactic planning target volume and additional 14 to 20 Gy in the boost planning target volume (5 days per week) with a possibility of 15 days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment break that increases risk of local failure. These techniques also allow a reduction in late gastrointestinal and skin toxicities of grade 3 or above, as well as better functional conservation of anorectal sphincter. The technical achievements (simulation, contouring, prescription dose, treatment planning, control quality) of volumetric modulated arctherapy are discussed.

Objectif Le traitement des patients atteints d’un glioblastome volumineux, non accessible a la chirurgie ou a la radiotherapie d’emblee, est mal etabli. Il repose essentiellement sur le temozolomide seul ou les soins de supports. L’objectif principal de notre etude etait d’evaluer la reduction du volume tumoral par une association de temozolomide et bevacizumab afin de permettre ensuite la realisation d’une radiotherapie complete (de 60 Gy). Les objectifs secondaires sont d’analyser la survie globale, la survie sans progression, les reponses clinique (indice de Karnofski) et radiologique (criteres RANO, Response Assessment in Neuro-Oncology) ainsi que la consommation de corticoides. Patients et methodes Il s’agit d’une etude retrospective, monocentrique, entre decembre 2010 et mai 2014, chez 14 patients atteints d’un glioblastome volumineux, recuse pour la chirurgie. Le volume evalue sur l’IRM ou les contraintes dosimetrique, contre-indiquaient la realisation d’une chimioradiotherapie d’emblee. Les patients ont recu un traitement par temozolomide (150 a 200 mg/m2/j pendant 5 j, j1–j28) associe a du bevacizumab (10 mg/kg/14 j). La reponse au traitement et la possibilite d’effectuer la radiotherapie ont ete evaluees selon les donnees de l’examen clinique et de l’IRM. Resultats A l’issue de la phase neoadjuvante, pour les 11 patients sur 14 (78,5 %) ayant pu beneficier d’une irradiation, nous avons observe une reduction mediane du volume cible anatomoclinique (CTV) de 38 % [24–58 %]. Ce traitement a permis de reduire ou arreter la corticotherapie chez cinq patients (36 %) et de stabiliser la dose chez six (43 %). Une amelioration l’indice de Karnofski a ete observee chez six patients (43 %) et une stabilite chez 7 sur 14 (50 %). Les durees mediane de survie sans progression et de survie globale etaient de 50 semaines [3–113] et de 62 semaines [16–151]. Conclusion L’association de temozolomide et de bevacizumab neoadjuvante a permis de delivrer une radiotherapie concomitante chez 78,5 % des patients dont la tumeur etait initialement consideree comme trop volumineuse avec un effet benefique potentiel sur la survie globale et la survie sans progression. L’analyse de ces resultats suggere que l’association de temozolomide et de bevacizumab neoadjuvante serait utile dans le traitement des glioblastomes volumineux et devrait etre confirmee par l’etude prospective de phase II « TEMOBEVA » en preparation.

The thermal angular motion of a classical linear rotator in an octahedral field with eight wells is studied both analytically and numerically. The strength of the coupling with the thermal bath is introduced. It is shown that in the deep-well case, for a coupling of intermediate strength, the ‘nex-twell-jump’ hypothesis is fulfilled and an absolute value can be calculated for the long-time exponential decay of the angular time correlation functions. The short-time behaviour of these functions reflects damped librations in the wells. The numerical simulation employs random torque impulses to represent the coupling with the thermal bath. For different values of the two parameters of the model (depth of the wells V and mean interval τ i between torque impulses), the complete correlation functions and the corresponding spectra are computed. The results are compared with experimental data bearing on matrix-isolated molecules, ‘plastic crystals’ and liquids.

Far infra-red spectra of chloroform, chlorobenzene and fluorobenzene are reported for the whole range of the liquid state along the orthobaric curve and in the coexisting dense gas. The spectra, and also those of OCS previously published, are interpreted in terms of the correlation function for the rotational velocities . Internal field corrections have been included and an estimate of the contribution due to non-permanent dipole absorption has been subtracted. In the lower density phases (including the liquid a few tens of degrees below the critical point) the rotational motion is a collision-perturbed free rotation. In the dense (cold) liquids the rotational motion at short times is better described as damped librational.

The far infrared (15–200 cm −1 ) spectra of OCS and CS 2 up to the critical point are reported. The experimental integrated intensities are calculated and, for OCS, compared to the theoretical one. One is led to the conclusion that induced-dipole absorption exists in the polar OCS as well as in non-polar CS 2 .

Absorption bands in the region 30–60 cm−1 have been observed at room and low temperature for crystalline samples of the chloro-methylbenzenes. These have been assigned to librational modes and their widths have been compared with those of the absorption bands below 100 cm−1 exhibited by plastic crystals. The lowest lying fundamental of hexachloro-benzene has been observed at 80 cm−1.

The far infrared (15–200 cm −1 ) spectra of liquid and gaseous OCS along their coexistence curve are reported. The cold liquid exhibits a broad absorption attributed to perturbed librational motion in the local structure. In less dense phases (gas and hot liquid) a free rotation envelope spectrum appears, together with smaller absorption at higher frequencies, whose origin is discussed.