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.

[Care of Merkel cell carcinoma and role of the radiotherapy]. / Principe de prise en charge du carcinome à cellules de Merkel et place de la radiothérapie.

Merkel cell carcinoma is a rare neuro-endocrine tumor of skin with a poor prognosis. Data available in literature are scarce. Current treatment for locoregional disease is based on combined treatment by surgery and radiotherapy. However these treatments are controversial. The aim of the present review is to sum up the different available studies and to compare national and international guidelines.

[Reappraisal role of locoregional radiation therapy in metastatic cancers]. / Place d'une radiothérapie locorégionale dans les cancers métastatiques.

Recent innovations in oncology area helped to improve the prognosis of certain cancers including metastatic ones with a decrease in mortality. Recommendations describe the treatment of metastatic cancer as systemic therapy or complementary care and the role of locoregional treatment in the treatment plan only occurs in a palliative context. Currently, in the clinical practice, out of "the evidence based medicine", an early locoregional therapy (surgery or radiation therapy) can be proposed in several cases of metastatic cancers. The aim of the present review is to describe the role of the primary tumor radiation therapy in metastatic disease. In metastatic breast, prostate, cervix, rectal or nasopharyngeal cancers, locoregional treatment including radiation therapy can, in some cases, be discussed and decided in MDT. Ongoing clinical trials in these locations should soon precise the benefit of this locoregional treatment. It will also be important to define the specific criteria in order to select patients who could benefit from this treatment.

The world of targeted therapies in kidney cancers: pitfalls, tips and tricks.

In the past few years, metastatic renal cell carcinoma prognosis was improved by the development of molecular targeted therapies (TTs). At the metastatic stage, the tolerance to treatment is a major concern, not only because of the challenge of the efficacy/toxicity ratio improvement but also because of the importance of an optimal adherence to oral treatments. The present case series relates the issues of dealing with uncommon and sometimes never described side effects of sunitinib and sorafenib. The first case report deals with grade 3 vomiting during hemodialysis with concurrent administration of sunitinib. The second case is an iterative gout attack induced by sunitinib. The third case presents a grade 3 scalp dysesthesia with sorafenib. The fourth case includes an astonishing efficacy of metronomic (ie, low doses during a long period of time) bevacizumab in monotherapy. Multidisciplinary management and systematic reporting of unexpected efficacies and toxicities are needed to better understand TTs real therapeutic index. Although TTs revolutionized metastatic renal cell cancer prognosis, they also brought about previously unknown side effects. Identification and management of these off-target effects may be tricky, and therefore, comedication must be wisely chosen. As the physiopathology of these side effects is still unclear, multidisciplinary management and systematic reporting of toxicities are essential.

Healing touch in radiation therapy: is the benefit tangible?

BACKGROUND: Cancer patients tend to use more and more complementary or alternative medicine concomitantly to radiotherapy. A large part of these patients have recourse to Mind and Body practice, mainly with biofield healers or magnetizers, without any level of evidence. The aim of the present study was to report epidemiologic data on biofield healers in radiation therapy patients, and to assess the possible objective and subjective benefits. MATERIALS AND METHODS: A retrospective study was conducted in a French cancer institute. All consecutive breast or prostate cancer patients undergoing a curative radiotherapy during 2015 were screened (n = 806). Healer consultation procedure, frequency, and remuneration were collected. Patient's self-evaluation of healer's impact on treatment tolerance was reported. Tolerance (fatigue, pain) was assessed through visual analogic scale (0 to 10). Analgesic consumption was evaluated. Toxicities were described according to NTCAEv4.0. RESULTS: 500 patients were included (350 women and 150 men). A total of 256 patients (51.2%) consulted a healer during their radiation treatment, with a majority of women (58%, p < 0.01). Most of patients had weekly (n = 209, 41.8%) or daily (n = 84, 16.8%) appointments with their healer. Regarding the self-reported tolerance, > 80% of the patients described a "good" or "very good" impact of the healer on their treatment. Healers were mainly voluntary (75.8%). Regarding the clinical efficacy, no difference was observed in prostate and in breast cancer patients (toxicity, antalgic consumption, pain). CONCLUSIONS: This study reveals that the majority of patients treated by radiotherapy consults a healer and reports a benefit on subjective tolerance, without objective tolerance amelioration.

Lysophosphatidic acid (LPA) as a pro-fibrotic and pro-oncogenic factor: a pivotal target to improve the radiotherapy therapeutic index.

Radiation-induced fibrosis is widely considered as a common but forsaken phenomenon that can lead to clinical sequela and possibly vital impairments. Lysophosphatidic acid is a bioactive lipid involved in fibrosis and probably in radiation-induced fibrosis as suggested in recent studies. Lysophosphatidic acid is also a well-described pro-oncogenic factor, involved in carcinogenesis processes (proliferation, survival, angiogenesis, invasion, migration). The present review highlights and summarizes the links between lysophosphatidic acid and radiation-induced fibrosis, lysophosphatidic acid and radioresistance, and proposes lysophosphatidic acid as a potential central actor of the radiotherapy therapeutic index. Besides, we hypothesize that following radiotherapy, the newly formed tumour micro-environment, with increased extracellular matrix and increased lysophosphatidic acid levels, is a favourable ground to metastasis development. Lysophosphatidic acid could therefore be an exciting therapeutic target, minimizing radio-toxicities and radio-resistance effects.

Immunotherapy in head and neck cancer: Harnessing profit on a system disruption.

Immune system deregulation and evasion play a key role in cancers' evolution and progression, including squamous cell carcinoma of the head and neck (SCCHN). Development of basic research proposed a whole new vision of cancer treatment, based on a strong biological rational, and targeting intrinsic deregulations. Immunotherapies provide an encouraging strategy for patients' improved outcomes. Immune-based therapies could act on cancer growth and/or development throughout many pathways. If cetuximab is for now the only monoclonal antibody approved for SCCHN management, other strategies, e.g. immune checkpoints openers, are arousing enthusiasm. Clinical trials are multiplying in patients with recurrent/metastatic SCCHN and primary results offer promising outcomes. Prospects of combining various immunotherapies with more established treatments, such as chemotherapy and radiotherapy, seem very encouraging and could provide synergistic benefits. Ongoing phase III clinical trials should soon enlighten us on the next "standard of care" for SCCHN. In the present review we summarized the different immunotherapy strategies that are currently under clinical investigation for SCCHN' medical care.

Targeting stem cells by radiation: From the biological angle to clinical aspects.

Radiotherapy is a cornerstone of anticancer treatment. However in spite of technical evolutions, important rates of failure and of toxicity are still reported. Although numerous pre-clinical data have been published, we address the subject of radiotherapy-stem cells interaction from the clinical efficacy and toxicity perspective. On one side, cancer stem cells (CSCs) have been recently evidenced in most of solid tumor primary locations and are thought to drive radio-resistance phenomena. It is particularly suggested in glioblastoma, where CSCs were showed to be housed in the subventricular zone (SVZ). In recent retrospective studies, the radiation dose to SVZ was identified as an independent factor significantly influencing overall survival. On the other side, healthy tissue stem cells radio-destruction has been recently suggested to cause two of the most quality of life-impacting side effects of radiotherapy, namely memory disorders after brain radiotherapy, and xerostomia after head and neck radiotherapy. Recent publications studying the impact of a radiation dose decrease on healthy brain and salivary stem cells niches suggested significantly reduced long term toxicities. Stem cells comprehension should be a high priority for radiation oncologists, as this particular cell population seems able to widely modulate the efficacy/toxicity ratio of radiotherapy in real life patients.