CBCT evaluation of inter- and intra-fraction motions during prostate stereotactic body radiotherapy: a technical note.

BACKGROUND: In most clinical trials, gold fiducial markers are implanted in the prostate to tune the table position before each radiation beam. Yet, it is unclear if a cone-beam computed tomography (CBCT) should be performed before each beam to monitor a possible variation of the organs at risk (OARs) fullness, especially in case of recto-prostatic spacer implantation. The present study aimed at assessing the inter- and intra-fraction movements of prostate, bladder and rectum in patients implanted with a hyaluronic acid spacer and undergoing prostate stereotactic body radiotherapy (SBRT). METHODS: Data about consecutive patients undergoing prostate SBRT were prospectively collected between 2015 and 2019. Inter-and intra-fraction prostate displacements and volume variation of organs at risk (OARs) were assessed with CBCTs. RESULTS: Eight patients were included. They underwent prostate SBRT (37.5Gy, 5 fractions of 7.5Gy) guided by prostate gold fiducial markers. Inter-fraction variation of the bladder volume was insignificant. Intra-fraction mean increase of the bladder volume was modest (29 cc) but significant (p < 0.001). Both inter- and intra-fraction variations of the rectum volume were insignificant but for one patient. He had no rectal toxicity. The magnitude of table displacement necessary to match the prostate gold fiducial marker frequently exceeded the CTV/PTV margins (0.4 cm) before the first (35%) and the second arc (15%). Inter- and intra-fraction bladder and rectum volume variations did not correlate with prostate displacement. CONCLUSION: Major prostate position variations were reported. In-room kV fiducial imaging before each arc seems mandatory. Intra-fraction imaging of the OARs appears unnecessary. We suggest that only one CBCT is needed before the first arc. TRIAL REGISTRATION: NCT02361515, February 11th, 2015.

Chemoradiation and granulocyte-colony or granulocyte macrophage-colony stimulating factors (G-CSF or GM-CSF): time to think out of the box?

Concerns have been raised about potential toxic interactions when colony-stimulating factors (CSFs) and chemoradiation are concurrently performed. In 2006, the ASCO guidelines advised against their concomitant use. Nevertheless, with the development of modern radiotherapy techniques and supportive care, the therapeutic index of combined chemotherapy, radiotherapy, and CSFs is worth reassessing. Recent clinical trials testing chemoradiation in lung cancer let investigators free to decide the use of concomitant CSFs or not. No abnormal infield event was reported after the use of modern radiotherapy techniques and concomitant chemotherapy regimens. These elements call for further investigation to set new recommendations in favour of the association of chemoradiation and CSFs. Moreover, radiotherapy could induce anticancer systemic effects mediated by the immune system in vitro and in vivo. With combined CSFs, this effect was reinforced in preclinical and clinical trials introducing innovative radioimmunotherapy models. So far, the association of radiation with CSFs has not been combined with immunotherapy. However, it might play a major role in triggering an immune response against cancer cells, leading to abscopal effects. The present article reassesses the therapeutic index of the combination CSFs-chemoradiation through an updated review on its safety and efficacy. It also provides a special focus on radioimmunotherapy.

[From bench to bedside for new treatment paradigms in chordomas: An update]. / Depuis la recherche translationnelle jusqu'aux nouveaux paradigmes thérapeutiques : mise à jour des données dans les chordomes.

Chordomas are rare malignant tumours, which typically occur in the axial skeleton and skull base. They arise from embryonic remnants of the notochord. They constitute less than 5 % of primary bone tumours. They are characterised by their locally aggressive potential with high frequency of recurrences and a median overall survival of 6 years. The initial therapeutic strategy must be discussed in an expert centre and may involve surgery, preoperative radiotherapy, exclusive radiotherapy or therapeutic abstention. Despite this, more than 50 % of patients will be facing recurrences with few therapeutic options available at this advanced stage. This review aims to outline current treatment options available in chordomas, as well as discussing potentiality of new therapeutic approaches through their molecular characterization and the comprehension of their immunological environment.

Chemoradiation phase II trials: re-exploring a world of missed opportunities.

Background: Phase II trials are designed to assess the efficacy/toxicity ratio of experimental treatments and select those worth being tested in phase III trials. Although crucial limitations were identified when concurrent chemoradiation (cCRT) phase III trials characteristics were assessed, features of cCRT phase II trials have never been reported. The objective was to describe features of all cCRT phase II trials. Methods and material: Requests were performed in the Medline database (via PubMed). The latest update was performed in April 2016, using the following MESH terms: 'clinical trials: phase II as topic', 'chemoradiotherapy'. Results: Four hundred and fifty-eight cCRT phase II trials were identified. They were mainly multicenter (51.5%), single arm studies (77.7%) published after 2011 (55.0%). The median number of included patients was 52. Primary endpoints were mainly response rate (20.5%), pathological complete response (14.4%) and overall survival (12.6%). The primary endpoint was not defined in 22% of studies. Tumors were mostly lung (23.1%), head and neck (20.3%), colorectal (16.6%) and esophagogastric cancer (14.6%) treated at a locally advanced setting (81.7%). 55.2% of trials used 3D-conformal radiotherapy and 9.1% intensity-modulated radiotherapy, mainly with normo-fractionation (82.0% of the 573 arms with radiotherapy). Radiation technique was not reported in 19.9% of studies. Associated anticancer drugs (563 arms) were mainly conventional chemotherapies (559 arms): cisplatin (46.2%) and 5-fluorouracil (28.3%). Non cytotoxic agents (targeted therapies, immunotherapies) were tested in 97 arms (17%). With a median follow-up of 31 months, acute grades 3-5 were reported in 98.5% of studies and late toxicities in 44.5%. Follow-up was not reported in 17% of studies. Conclusions: cCRT phase II trials featured severe limitations, with outdated radiation techniques, insufficient reporting of crucial data and a small number of included patients. This certainly limited the impact of conclusions and hindered the development of successful phase III trials.

Quality insurance in head and neck cancer multidisciplinary team meetings: A watchful eye on real-life experience.

INTRODUCTION: Although Multidisciplinary Team Management (MDT) is integrated in most international head and neck cancer treatment guidelines, its applications and proceedings were rarely described. The present study explores a 6-year real-life experience in a French Comprehensive Cancer Care Center. METHODS: Patients, tumor and meeting characteristics of all consecutive cases discussed in head and neck MDT meetings between 2010 and 2015 were retrospectively reviewed. RESULTS: From 2010 to 2015, 1849 cases (accounting for 1786 patients) were discussed in 138 MDT meetings. Median age was 62 (range: 15-96). When reported (n = 310, 16.8%), performance status was ≥2 in 36.1% of patients. Tumors were mainly squamous cell carcinomas (n = 1664, 91.5%) of the larynx/hypo-pharynx (n = 630, 34.4%), oropharynx (n = 518; 28.3%) and oral cavity (n = 339; 18.5%). Tumors were diagnosed at a locally (n = 358, 25%), locally advanced (n = 946, 66%) or metastatic setting (n = 53, 3.7%). Mean number of discussed patients per MDT meeting was 16 (range: 3-32). Most patients were discussed once (n = 1663, 97%). Most patients (n = 969, 52%) underwent treatment before MDT meetings: mainly surgery (n = 709, 73.2%). The mean time between MDT meeting and first radiation course was 21 days (range: 1-116). DISCUSSION: Optimal multimodal treatment management is based on MDT meetings and results from the interaction and coordination of surgeons, medical and radiation oncologists. In the present series, most patients were discussed once despite the number of expected recurrences, suggesting that the management of tumor progression was not discussed in head and neck MDT meetings. Furthermore, most patients had surgery before MDT meeting, pointing out that MDT role and place still needs to be improved. Finally, the present population significantly differed from patients included in phase III clinical trials, with more advanced age and poorer condition. It calls for the necessity of a high-quality head and neck MDT meeting since evidence-based recommendations should be adapted to patient's frailties.