Review of current best practice and priorities for research in radiation oncology for elderly patients with cancer: the International Society of Geriatric Oncology (SIOG) task force.

Radiotherapy (RT) is a key component of the management of older cancer patients. Level I evidence in older patients is limited. The International Society of Geriatric Oncology (SIOG) established a task force to make recommendations for curative RT in older patients and to identify future research priorities. Evidence-based guidelines are provided for breast, lung, endometrial, prostate, rectal, pancreatic, oesophageal, head and neck, central nervous system malignancies and lymphomas. Patient selection should include comorbidity and geriatric evaluation. Advances in radiation planning and delivery improve target coverage, reduce toxicity and widen eligibility for treatment. Shorter courses of hypofractionated whole breast RT are safe and effective. Conformal RT and involved-field techniques without elective nodal irradiation have improved outcomes in non-small-cell lung cancer (NSCLC) without increasing toxicity. Where comorbidities preclude surgery, stereotactic body radiotherapy (SBRT) is an option for early-stage NSCLC and pancreatic cancer. Modern involved-field RT for lymphoma based on pre-treatment positron emission tomography data has reduced toxicity. Significant comorbidity is a relative contraindication to aggressive treatment in low-risk prostate cancer (PC). For intermediate-risk disease, 4-6 months of hormones are combined with external beam radiotherapy (EBRT). For high-risk PC, combined modality therapy (CMT) is advised. For high-intermediate risk, endometrial cancer vaginal brachytherapy is recommended. Short-course EBRT is an alternative to CMT in older patients with rectal cancer without significant comorbidities. Endorectal RT may be an option for early disease. For primary brain tumours, shorter courses of postoperative RT following maximal debulking provide equivalent survival to longer schedules. MGMT methylation status may help select older patients for temozolomide alone. Stereotactic RT provides an alternative to whole-brain RT in patients with limited brain metastases. Intensity-modulated radiation therapy provides an excellent technique to reduce dose to the carotids in head and neck cancer and improves locoregional control in oesophageal cancer. Best practice and research priorities are summarised.

Adjuvant radiotherapy for extremity and trunk wall atypical lipomatous tumor/well-differentiated LPS (ALT/WD-LPS): a French Sarcoma Group (GSF-GETO) study.

BACKGROUND: The role of adjuvant radiotherapy (RT) in the management of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WD-LPS) remains controversial. METHODS: Two hundred eighty-three patients with operable ALT/WD-LPS, no history of previous cancer, chemotherapy (CT) or RT, treated between 1984 and 2011 registered in the Conticabase database were included and described. Overall (OS), progression-free survival (PFS) and time to local relapse (TTLR) were evaluated from the time of first treatment. RESULTS: Three of 20 centers enrolled 58% of the patients. Median age at diagnosis was 61 (range 25-94) years, 147 patients (52%) were males, 222 (78%) patients had their primary tumor located in an extremity while 36 (13%) and 25 (9%) had tumors involving the girdle and the trunk wall, respectively. The median size of primary tumors was 17 cm (range 2-48 cm). Adjuvant RT was given to 132 patients (47%). Patients who received adjuvant RT had larger tumors (P = 0.005), involving more often the distal limbs (P < 0.001). Use of adjuvant RT varied across centers and along the study period. Other characteristics were balanced between the two groups. Median follow-up was 61.7 months. None of the patients developed metastasis during follow-up. The 5-year local relapse-free survival rates were 98.3% versus 80.3% with and without adjuvant RT, respectively (P < 0.001). Once stratified on time period (before/after 2003), adjuvant RT, tumor site and margin status (R0 versus other) were independently associated with TTLR. No OS difference was observed (P = 0.105). CONCLUSION: In this study, adjuvant RT following resection of ALT/WD-LPS was associated with a reduction of LR risk.

[Informed consent in radiotherapy care]. / Consentement aux soins en radiothérapie.

Obtaining consent to care requires the radiation oncologist to provide loyal information and to ensure that the patient understands it. Proof of such an approach rests with the practitioner. The French Society for Radiation Oncology (SFRO) does not recommend the signature of a consent form by the patient but recommends that the radiation oncologist be able to provide all the elements demonstrating the reality of a complete information circuit.

[Ethical stakes of information in radiation oncology: Thinking the risk and building the therapeutic alliance]. / Enjeux éthiques de l'information en oncologie radiothérapie : penser le risque et construire l'alliance thérapeutique.

Informing patients before receiving radiation therapy is a fundamental ethical imperative. As a condition of the possibility of autonomy, information allows people to make health decisions concerning themselves, which is required by French law. This information includes in particular the potential risks due to radiation therapy. It is therefore necessary to think about what risk is, and how to define and assess it, in order to finally communicate it. The practice of informing people involves many ethical issues relating to the very content of the information, the form in which it is transmitted or even the intention that leads the health professional to say (or not to say) the risk. The transmission of information also questions the way to build a relationship of trust with the patients and how to integrate their own representations about these treatments. Between the risks of paternalism or even defensive medicine, this practice is at the heart of our professional practice.

[Understanding/acceptance of radiotherapy: An ethical dilemma resolved by an ethics of care]. / Compréhension/acceptation de la radiothérapie : un dilemme éthique résolu par une éthique de la considération et de la sollicitude.

PURPOSE: Ethical questions are poorly investigated specifically in radiation oncology. The objective of the study was to identify and understand the main ethical issue in radiation oncology. MATERIALS AND METHODS: A quantitative analysis was based on the answers to a questionnaire of 200 professionals from 22 radiation oncology departments. The questionnaire mainly aimed to characterize the main ethical issue. A monocentric qualitative analysis was based on semi-structured interviews focused on the main identified ethical issue, carried out with eight technologists, and 20 patients undergoing radiotherapy. RESULTS: The main ethical issue was the understanding and/or acceptance of the treatment by the patients (71 %), which frequently arises (more than once a month) (52 %), and corresponds to an ethical tension between the principles of respect for autonomy and beneficence (the good as viewed by the patient) as defined by Beauchamp and Childress. The technologists, wish the patient to be fully involved in his treatment, with the even possibility of refusing it. However, excluding paternalism and autonomic relentlessness, the technologists have the feeling of acting for the good of the patients by treating them with radiation, even if the patients are not always aware of it, because they are within a situation of vulnerability. If the hierarchy of principles is a compromise alternative, this problem is finally well resolved by the effective implementation of an ethic of consideration and solicitude, restoring the patient capabilities, i.e. the maximum development of his potentialities in his situation of vulnerability. Beyond the legal dimension, patient information is crucial and must consider the specific temporality of the patient. CONCLUSION: The main ethical issue in radiation oncology is the understanding and/or acceptance of the treatment involving the development of an ethic of consideration and solicitude.

Radiotherapy of bone metastases.

We present the update of the recommendations of the French society of oncological radiotherapy on bone metastases. This is a common treatment in the management of patients with cancer. It is a relatively simple treatment with proven efficacy in reducing pain or managing spinal cord compression. More complex treatments by stereotaxis can be proposed for oligometastatic patients or in case of reirradiation. In this context, increased vigilance should be given to the risks to the spinal cord.

[Crisis situations: Ethical reflection on prioritization of care access in radiation oncology]. / Situations de crise : réflexion éthique sur la priorisation de l'accès aux soins en oncologie radiothérapie.

Understood as a disruption of the conditions of care practice according to established protocols or procedures, crisis situations in radiation oncology departments can have multiple causes. Their seriousness can sometimes impose changes in the decision-making, organizational or technical paradigms. A possible consequence may be the need to make prioritization decisions in access to care, when there is a mismatch between the care needs of a population and the available health resources (whether technical or human). The specificities of care pathways and the wide variety of clinical situations in radiation oncology make these ethical decisions particularly difficult. Anticipation, collegial and multi-professional decision-making procedures or the integration of patient representatives in these prioritization processes are essential tools. Particular attention must be paid to the information to be provided to patients in a concern of transparency and respect. Prioritization situations are real tests for our departments. They go beyond the purely technical aspect of radiation oncology. They can lead to real ethical suffering for health professionals when their values come up against the limits imposed by crisis situations.

[Ethical stakes in palliative care in radiation oncology]. / Enjeux éthiques de la pratique des soins à visée palliative en oncologie radiothérapique.

In 2021, the Ethics Commission of the SFRO has chosen the issue of the practice of palliative care in radiotherapy oncology. Radiation oncology plays a central role in the care of patients with cancer in palliative phase. But behind the broad name of palliative radiotherapy, we actually find a large variety of situations involving diverse ethical issues. Radiation oncologists have the delicate task to take into account multiple factors throughout a complex decision-making process. While the question of the therapeutic indication and the technical choice allowing it to be implemented remains central, reflection cannot be limited to these decision-making and technical aspects alone. It is also a question of being able to create the conditions for a singularity focused care and to build an authentic care relationship, beyond technicity. It is through this daily ethical work, in close collaboration with patients, and under essential conditions of multidisciplinarity and multiprofessionalism, that our fundamental role as caregiver can be deployed.

[Health democracy: Patient partnership]. / Démocratie sanitaire : le patient partenaire de sa prise en charge.

In 2019, the scientific committee of the French society of radiation oncology (SFRO) created an ethics committee. Its mission is to provide our professional community with food for thought on ethical issues, and to identify its specificities within the radiation oncology departments. For the 2020 annual conference, the commission looked into the evolution of the patient-carer relationship, and more particularly to the strong idea of patient partnership. Indeed, the writing of the White Book of Cancer gave voice to sick people and stressed the need for new devices, such as the Caregiving Time. Patients can no longer be considered as objects of care but as people whose dignity and autonomy must be imperatively respected. The acquisition of knowledge allows a bilateral exchange, prerequisite of a dynamic collaboration. Patients can be partners in their own care, partners in training and research (expert patient), but also partners in health institutions and policies. It is this notion of partnership and involvement of the person in their path of care in radiation oncology that we will analyse here. It will be about defining it, by developing the concept of autonomy, and bringing out its complexity and ambivalence through two examples from our clinical practice: the shared decision-making process for patients with localized prostate cancer and the patient's involvement in the success of his radiotherapy.

[State of the art and advances in radiotherapy for bladder cancer]. / Techniques et innovations en radiothérapie pour le traitement conservateur des cancers infiltrants localisés de vessie.

Radical cystectomy is the treatment of choice for nonmetastatic, muscle-infiltrating bladder cancer. However, bladder-sparing approaches can be discussed in carefully selected patients. Bladder-preservation protocols aim to guaranty local control and survival with a functional bladder and a good quality of life. Such strategies include combinations of transurethral resection and radiochemotherapy, partial cystectomy and brachytherapy, radiotherapy-cystotomy and electrontherapy. Strict selection criteria and close follow-up are mandatory. New irradiation techniques hold the promise to improve local control by selectively boosting the dose to the tumor while better sparing the organs at risk. Such advances include the use of multimodal imaging, image-guided radiotherapy, concomitant boost with conformal irradiation+/-intensity modulated radiation therapy. Brachytherapy, either high-dose or pulsed-rate, is a promising technique for selected cases. Highly-conformal irradiation with tumor tracking using the Cyberknifetrade mark technology may also provide opportunities to boost the tumor while reducing toxicities. Specific innovative irradiation techniques are discussed.

RILA blood biomarker as a predictor of radiation-induced sarcoma in a matched cohort study.

PURPOSE: Radiation-induced sarcoma (RIS) is a rare but serious event. Its occurrence has been discussed during the implementation of new radiation techniques and justified appropriate radioprotection requirements. New approaches targeting intrinsic radio-sensitivity have been described, such as radiation-induced CD8 T-lymphocyte apoptosis (RILA) able to predict late radio-induced toxicities. We studied the role of RILA as a predisposing factor for RIS as a late adverse event following radiation therapy (RT). PATIENTS AND METHODS: In this prospective biological study, a total of 120 patients diagnosed with RIS were matched with 240 control patients with cancer other than sarcoma, for age, sex, primary tumor location and delay after radiation. RILA was prospectively assessed from blood samples using flow cytometry. RESULTS: Three hundred and forty-seven patients were analyzed (118 RIS patients and 229 matched control patients). A majority (74%) were initially treated by RT for breast cancer. The mean RT dose was comparable with a similar mean (± standard deviation) for RIS (53.7 ±â€¯16.0 Gy) and control patients (57.1 ±â€¯15.1 Gy) (p = .053). Median RILA values were significantly lower in RIS than in control patients with respectively 18.5% [5.5-55.7] and 22.3% [3.8-52.2] (p = .0008). Thus, patients with a RILA >21.3% are less likely to develop RIS (p < .0001, OR: 0.358, 95%CI [0.221-0.599]. CONCLUSION: RILA is a promising indicator to predict an individual risk of developing RIS. Our results should be followed up and compared with molecular and genomic testing in order to better identify patients at risk. A dedicated strategy could be developed to define and inform high-risk patients who require a specific approach for primary tumor treatment and long term follow-up.

[Radiation-induced sequelae: toward an individual profile]. / Séquelles radio-induites et tests prédictifs.

The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the targeted volume. Nevertheless, the dose delivery is limited by the tolerated dose of the surrounding healthy tissues. Two different side effects (acute and late) can occur during and after radiotherapy. Of particular interest are the radiation-induced sequelae due to their irreversibility and the potential impact on daily quality of life. In a population treated in one center with the same technique, it appears that individual radiosensitivity clearly exists. In the hypothesis that genetic is involved in this area of research, lymphocytes seem to be the tissue of choice due to easy accessibility. Recently, low percentage of CD4 and CD8 lymphocyte apoptosis were shown to be correlated with high grade of sequelae. In addition, recent data suggest that patients with severe radiation-induced late side effects possess four or more SNP in candidate genes (ATM, SOD2, TGFB1, XRCC1 et XRCC3) and low radiation-induced CD8 lymphocyte apoptosis in vitro.

[Ductal carcinoma in situ: role of the boost]. / Radiothérapie des carcinomes canalaires in situ: impact du complément d'irradiation du lit tumoral.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

[Image-guided radiotherapy]. / Radiothérapie guidée par l'image.

Recent advances in radiation oncology are based on improvement in dose distribution thanks to IMRT and improvement in target definition through new diagnostic imaging such as spectroscopic or functional MRI or PET. However, anatomic variations may occur during treatment decreasing the benefit of such optimization. Image-guided radiotherapy reduces geometric uncertainties occurring during treatment and therefore should reduce dose delivered to healthy tissues and enable dose escalation to enhance tumour control. However, IGRT experience is still limited, while a wide panel of IGRT modalities is available. A strong quality control is required for safety and proper evaluation of the clinical benefit of IGRT combined or not with IMRT.

[Prostate localization systems for prostate radiotherapy]. / Dispositifs de repositionnement prostatique sous l'accélérateur linéaire.

The development of sophisticated conformal radiation therapy techniques for prostate cancer, such as intensity-modulated radiotherapy, implies precise and accurate targeting. Inter- and intrafraction prostate motion can be significant and should be characterized, unless the target volume may occasionally be missed. Indeed, bony landmark-based portal imaging does not provide the positional information for soft-tissue targets (prostate and seminal vesicles) or critical organs (rectum and bladder). In this article, we describe various prostate localization systems used before or during the fraction: rectal balloon, intraprostatic fiducials, ultrasound-based localization, integrated CT/linear accelerator system, megavoltage or kilovoltage cone-beam CT, Calypso 4D localization system tomotherapy, Cyberknife and Exactrac X-Ray 6D. The clinical benefit in using such prostate localization tools is not proven by randomized studies and the feasibility has just been established for some of these techniques. Nevertheless, these systems should improve local control by a more accurate delivery of an increased prescribed dose in a reduced planning target volume.

[Radiotherapy of bone metastases]. / Radiothérapie des métastases osseuses.

Radiotherapy plays a major role in palliative treatment of bone metastases. Recent developments of stereotactic radiotherapy and intensity modulated radiation therapy give the possibility to treat oligometastatic diseases. The objective of this paper is to report indications and treatment modalities of radiotherapy in these situations.

[Symptomatic extramedullary haematopoiesis in ß-thalassemia: A retrospective single centre study]. / Hématopoïèse extra-médullaire symptomatique au cours des ß-thalassémies: étude rétrospective monocentrique.

INTRODUCTION: Symptomatic extramedullary hematopoiesis (EH) is a rare but potentially severe phenomenon which occurs in ß-thalassemia. There are no treatment guidelines. METHODS: Retrospective single centre study including the cases of symptomatic EH encountered between 1997 and 2014 in a unit specialised in red blood cell genetic disorders. Description of clinical, biological and radiological characteristics of the patients, treatments received, and outcomes. RESULTS: Among 182 ß-thalassemia patients followed during the study period, 7 cases of symptomatic EH were diagnosed. They were 5 men and 2 women, and their mean age was 37 years. Four patients were splenectomised, two patients were regularly transfused, and four patients had already received erythropoietin. EH was localised in intravertebral areas and responsible for dorsal spinal cord compression in 5 patients, in paravertebral dorsal area in 1 patient, and in presacral area in 1 patient. The mean hemoglobin level at diagnosis was 7.9 g/dL. Treatment administered included: red cell transfusion in 6 cases, associated with hydroxyurea in 5 cases and/or radiotherapy in 3 patients. One patient was treated with surgery and HU. After a median follow-up of 41 months, clinical recovery was complete in 2 patients and partial in 5 patients. CONCLUSION: EH must be suspected in ß-thalassemia in patients presenting clinical signs of organ compression, and a typical radiological aspect. The functional prognosis depends on the rapidity of treatment, which includes red blood cell transfusion, hydroxyurea, radiotherapy, and rarely surgery. Long-term outcome is uncertain.

[Repeated radiation dose effect and DNA repair: Importance of the individual factor and the time interval between the doses]. / Effets de répétitions de doses d'irradiation et réparation de l'ADN : importance du facteur individuel et de l'intervalle de temps entre les doses.

The dose fractionation effect is a recurrent question of radiation biology research that remains unsolved since no model predicts the clinical effect only with the cumulated dose and the radiobiology of irradiated tissues. Such an important question is differentially answered in radioprotection, radiotherapy, radiology or epidemiology. A better understanding of the molecular response to radiation makes possible today a novel approach to identify the parameters that condition the fractionation effect. Particularly, the time between doses appears to be a key factor since it will permit, or not, the repair of certain radiation-induced DNA damages whose repair rates are of the order of seconds, minutes or hours: the fractionation effect will therefore vary according to the functionality of the different repair pathways, whatever for tumor or normal tissues.

[Radiotherapy of bladder cancer]. / Radiothérapie des cancers de vessie.

Surgery (radical cystectomy) is the standard treatment of muscle-invasive bladder cancer. Radiochemotherapy has risen as an alternative treatment option to surgery as part as organ-sparing combined modality treatment or for patients unfit for surgery. Radiochemotherapy achieves 5-year bladder intact survival of 40 to 65% and 5-year overall survival of 40 to 50% with excellent quality of life. This article introduces the French recommendations for radiotherapy of bladder cancer: indications, exams, technique, dosimetry, delivery and image guidance.

Endogenous phosphorylation of soluble enzymes in human red cells. Cyclic 3',5'-AMP-dependent phosphorylation of phosphofructokinase without detectable regulatory effect.

ATP-depleted human red cells have been incubated in a glucose-containing medium with [32P]orthophosphate in the presence and in the absence of cyclic 3',5'-AMP and dibutyril cyclic 3',5'-AMP. Spectrin, pyruvate kinase, phosphofructokinase, glucose-6-phosphate dehydrogenase and hemoglobin A1 have been purified and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein-bound radioactivity has been measured from the sodium dodecyl sulfate polyacrylamide gels and the trichloroacetic acid-precipitated proteins. In the cytosol, the most intense phosphorylation was found for pyruvate kinase whose, in the presence of cyclic AMP, specific radioactivity was comparable to that of the membrane protein and spectrin. In the absence of cyclic nucleotides it was five times less phosphorylated. Phosphofructokinase was only phosphorylated when the red cells were incubated with cyclic nucleotides; the extent of phosphorylation was four times less than for pyruvate kinase. Hemoglobin, glucose-6-phosphate dehydrogenase and a contaminant protein copurified with phosphofructokinase were not phosphorylated: the 'background' of the radioactivity found for these proteins was 100 times less than for pyruvate kinase and spectrin, and 20 times less than for phosphofructokinase (+cyclic AMP).