Real-world outcomes with durvalumab after chemoradiotherapy in patients with unresectable stage III NSCLC: interim analysis of overall survival from PACIFIC-R.

BACKGROUND: Based on the findings of the PACIFIC trial, consolidation durvalumab following platinum-based chemoradiotherapy (CRT) is a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). An earlier analysis from the ongoing PACIFIC-R study (NCT03798535) demonstrated the effectiveness of this regimen in terms of progression-free survival (PFS). Here, we report the first planned overall survival (OS) analysis. PATIENTS AND METHODS: PACIFIC-R is an observational/non-interventional, retrospective study of patients with unresectable, stage III NSCLC who started durvalumab (10 mg/kg intravenously every 2 weeks) within an AstraZeneca-initiated early access program between September 2017 and December 2018. Primary endpoints are OS and investigator-assessed PFS, estimated using the Kaplan-Meier method. RESULTS: By 30 November 2021, the full analysis set included 1154 participants from 10 countries (median follow-up in censored patients: 38.7 months). Median OS was not reached, and the 3-year OS rate was 63.2% (95% confidence interval 60.3% to 65.9%). Three-year OS rates were numerically higher among patients with programmed death-ligand 1 (PD-L1) expression on ≥1% versus <1% of tumor cells (TCs; 67.0% versus 54.4%) and patients who received concurrent CRT (cCRT) versus sequential CRT (sCRT) (64.8% versus 57.9%). CONCLUSIONS: PACIFIC-R data continue to provide evidence for the effectiveness of consolidation durvalumab after CRT in a large, diverse, real-world population. Better outcomes were observed among patients with PD-L1 TCs ≥1% and patients who received cCRT. Nevertheless, encouraging outcomes were still observed among patients with TCs <1% and patients who received sCRT, supporting use of consolidation durvalumab in a broad population of patients with unresectable, stage III NSCLC.

Transarterial chemoembolization followed by moderately hypofractionated radiotherapy in hepatocellular carcinoma: Long-term results of RTF3 regimen.

PURPOSE: In early-stage hepatocellular carcinoma (HCC) patients merely fit for surgery, transarterial chemoembolization (TACE) achieve low long-term disease control. We evaluated the efficacy and safety of its combination with moderately hypofractionated radiotherapy (hRT) using RTF3 regimen. MATERIAL AND METHODS: Between 2006 and 2016, 61 consecutive patients treated in our single expert center for a Barcelona Clinic Liver Cancer (BCLC) A HCC by TACE followed by hRT 3Gy/fraction were retrospectively included. RESULTS: Sixty of the 61 included presented Child-Pugh A cirrhosis (A5, n=41, 67.2%; A6: n=19, 31.1%). Fourteen patients (22.9%) were already treated for a HCC, mainly by radiofrequency (n=12). All patient received a TACE followed by 3Gy per fraction hRT. Mean radiation dose was 54Gy (range: 48-60). After a median follow-up of 118 months, median time-to-progression, progression-free survival (PFS) and overall survival (OS) was 21.3, 18.1, and 31.5 months, respectively. In univariate analysis, PFS was related to dose > 54Gy (HR: 2, P=0.036), and OS was correlated to Child-Pugh A6 or B7 (HR: 1.93, P=0.03) and overall hRT time (HR: 1.06, P=0.015). At progression, orthotopic liver transplantation was performed in 8 patients (13.1%). Severe symptomatic adverse events occurred in 12 patients (19.7%), mainly ascites (n=7). CONCLUSION: In BCLC-A Child-Pugh A HCC patients ineligible to surgery or thermoablation, TACE-hRT is a safe and effective treatment. Prospective studies are needed to compare this association with radioembolization, TACE-stereotactic radiotherapy, and systemic treatments combinations.

Final results of the IFCT-0803 study, a phase II study of cetuximab, pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced, unresectable, stage III, non-squamous, non-small-cell lung cancer.

PURPOSE: Roughly 20% of patients with non-small-cell lung cancer exhibit locally advanced, unresectable, stage III disease. Concurrent platinum-based chemoradiotherapy is the backbone treatment, which is followed by maintenance immunotherapy, yet with poor long-term prognosis. This phase II trial (IFCT-0803) sought to evaluate whether adding cetuximab to cisplatin and pemetrexed chemoradiotherapy would improve its efficacy in these patients. MATERIALS AND METHODS: Eligible patients received weekly cetuximab (loading dose 400mg/m2 day 1; subsequent weekly 250mg/m2 doses until two weeks postradiotherapy). Chemotherapy comprised cisplatin (75mg/m2) and pemetrexed (500mg/m2), both delivered on day 1 of a 21-day cycle of maximally four. Irradiation with maximally 66Gy started on day 22. Disease control rate at week 16 was the primary endpoint. RESULTS: One hundred and six patients were included (99 eligible patients). Compliance exceeded 95% for day 1 of chemotherapy cycles 1 to 4, with 76% patients receiving the 12 planned cetuximab doses. Maximal grade 3 toxicity occurred in 63% patients, and maximal grade 4 in 9.6%. The primary endpoint involving the first 95 eligible patients comprised two (2.1%) complete responses, 57 (60.0%) partial responses, and 27 (28.4%) stable diseases. This 90.5% disease control rate (95% confidence interval [95% CI]: 84.6%-96.4%) was achieved at week 16. After median 63.0-month follow-up, one-year and two-year survival rates were 75.8% and 59.5%. Median overall survival was 35.8months (95% CI: 23.5-NR), and median progression-free survival 14.4months (95% CI: 11.2-18.8), with one-year and two-year progression-free survival rates of 57.6% and 34.3%. CONCLUSION: These survival rates compare favourably with published data, thus justifying further development of cetuximab-based induction chemoradiotherapy.

Radiotherapy for patient with cardiac implantable electronic device, consensus from French radiation oncology society.

Radiotherapy in patients with cardiac implantable electronic device such as pacemakers or defibrillators, is a clinical situation that is becoming increasingly common. There is a risk of interaction between the magnetic field induced by accelerators and the cardiac implantable electronic device, but also a risk of device dysfunction due to direct and/or indirect irradiation if the cardiac implantable electronic device is in the field of treatment. The risk can be dose-dependent, but it is most often independent of the total dose and occurs randomly in case of neutron production (stochastic effect). The presence of this type of device is therefore described as a contraindication for radiotherapy by the French national agency for the safety of medicines and health products (Agence nationale de sécurité du médicament et des produits de santé, ANSM). Nevertheless, since radiotherapy is often possible, it is advisable to respect the recommendations of good practice, in particular the eligibility criteria, the monitoring modalities before, during and after irradiation according to the type of treatment, the dose and the characteristics of the cardiac implantable electronic device. It is sometimes necessary to discuss repositioning the device and/or modifying the treatment plan to minimize the risk of cardiac implantable electronic device dysfunction. We present the update of the recommendations of the French society of oncological radiotherapy on in patients with cardiac implantable electronic device.

[Radiation therapy of hepatic haemangiomas: Review from a case report]. / Radiothérapie externe des angiomes hépatiques : revue de la littérature, à partir d'un cas.

Haemangioma is the most frequent benign hepatic tumour. Haemangioma is generally asymptomatic but it can sometimes cause disabling symptoms depending on its size and location. Surgery and interventional radiology are the cornerstone of the treatment in this situation. Radiation therapy, already used with good efficacy and safety to treat hepatic malignant lesions as hepatocarcinoma and metastases, is a relevant option in case of contraindication to surgery because of multiple or very large lesions. In this context, we report the case of a patient presenting with multiple symptomatic hepatic haemangiomas, successfully treated by radiation therapy in our department. These good results justified a review of the literature to report series of patients treated in this indication and to describe the main treatment regimens used.

Radiation therapy of pancreatic cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy of pancreatic tumors. Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In the adjuvant setting, the standard treatment is six months of chemotherapy with 5-fluorouracile, irinotecan and oxaliplatin. Chemoradiation may improve the survival of patients with incompletely resected tumours (R1). This remains to be confirmed by a prospective trial. Neoadjuvant chemoradiation is a promising treatment especially for patients with borderline resectable tumours. For patients with locally advanced tumours, there is no standard. An induction chemotherapy followed by chemoradiation for non progressive patients reduces the rate of local relapse. Whereas in the first trials of chemoradiation large fields were used, the treated volumes have been reduced to improve tolerance. Tumour movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique has poor evidence-based recommendation. Stereotactic body radiation therapy is also being studied, as a neoadjuvant or exclusive treatment.

Radiotherapy for primary lung cancer.

Herein are presented the recommendations from the Société française de radiothérapie oncologique regarding indications and modalities of lung cancer radiotherapy. The recommendations for delineation of the target volumes and organs at risk are detailed.

Hepatic tumours and radiotherapy.

We present the update of the recommendations of the French society of oncological radiotherapy on hepatic tumours. Recent technological progress led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumours, as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. The tumour volume, its liver location close to the organs at risk determine the irradiation technique (repositioning method, total dose delivered, dose fractionation regimens). Tumour (and liver) breathing related motions should be taken into account. Strict dosimetric criteria must be observed with particular attention to the dose-volume histograms of non-tumoral liver as well as of the hollow organs, particularly in case of hypofractionated high dose radiotherapy "under stereotaxic conditions". Stereotactic body radiotherapy is being evaluated and is often preferred to radiofrequency for primary or secondary tumours (usually less than 5cm). An adaptation can be proposed, with a conformal fractionated irradiation protocol with or without intensity modulation, for hepatocellular carcinomas larger than 5cm.

Lung metastases radiation therapy.

We present an update of the French society of oncological radiotherapy recommendation regarding indication, doses, and technique of radiotherapy for intrathoracic metastases. The recommendations for delineation of the target volumes and critical organs are detailed.

[The 30th anniversary of SFRO, the French society of oncological radiotherapy]. / Les 30 ans de la SFRO.

The French society of oncological radiotherapy (Société française de radiothérapie oncologique, SFRO) was created in 1990. On the occasion of its thirtieth annual congress, in October 2019, a session was devoted to it, with the objective of exposing its functioning, its actions and its productions during these three decades during which radiotherapy and oncology have undergone unprecedented transformations. We propose in this article to outline the content of this session.

[Stereotactic radiotherapy of stage I non-small cell lung cancer. State of the art in 2019 and recommendations: Stereotaxy as an alternative to surgery?] / Radiothérapie stéréotaxique du cancer bronchique non à petites cellules de stade I. État de l'art en 2019 et recommandations : la stéréotaxie comme alternative à la chirurgie ?

Stereotactic radiotherapy (or Stereotactic body radiotherapy [SBRT]) is a technique currently well established in the therapeutic arsenal for the management of bronchial cancers. It represents the standard treatment for inoperable patients or who refuses surgery. It is well tolerated, especially in elderly and frail patients, and the current issue is to define its indications in operated patients, based on retrospective and randomized trials comparing stereotactic radiotherapy and surgery, with results equivalents. This work analyzes in detail the different aspects of pulmonary stereotactic radiotherapy and suggests arguments that help in the therapeutic choice between surgery and stereotaxic irradiation. In all cases, the therapeutic decision must be discussed in a multidisciplinary consultation meeting, while informing the patient of the possible therapeutic options.

Prevalence of burnout, depression and job satisfaction among French senior and resident radiation oncologists.

PURPOSE: Cancer caregivers are at high risk of burn-out, with potential severe consequences on professionals' health and on patients' care. We have investigated the prevalence of burn-out and its impact in terms of psychological morbidity among French radiation oncologists. METHODS AND MATERIALS: An anonymous online questionnaire was advertised in all French senior radiation oncologists and residents, including demographical data, job-related stress factors, drug use, the Maslach Burn-out Inventory (MBI) and the General Health Questionnaire (GHQ-12). RESULTS: The response rates were 37% (76 out of 204) for radiation oncologists and 22% (166 out of 751) for residents. Sixty-four (84%) radiation oncology residents and 104 (63%) radiation oncologists met criteria for moderate/severe burn-out (odd ratio 2.1 [95% confidence interval 1.0-4.8], P=0.03). Radiation oncology residents were more prone to depersonalization (P<0.001) and lower personal accomplishment (P<0.001). Burn-out was more frequent in radiation oncologists working for public facilities. Symptoms of depression (GHQ-12≥4) were reported by 42% of residents and 36% of radiation oncologists (P=0.40). Psychological morbidity, suicidal ideation and anxiolytic consumption were more frequent in burnt out responders. CONCLUSION: Our figures are in the highest range of published data. Active screening and prevention of burn-out should be implemented and particularly aimed at radiation oncology residents.

[Siriade 2.0: An e-learning platform for radiation oncology contouring]. / Siriade 2.0 : outil de formation en ligne à la délinéation en radiothérapie.

PURPOSE: In 2008, the French national society of radiation oncology (SFRO) and the association for radiation oncology continued education (AFCOR) created Siriade, an e-learning website dedicated to contouring. MATERIAL AND METHODS: Between 2015 and 2017, this platform was updated using the latest digital online tools available. Two main sections were needed: a theoretical part and another section of online workshops. RESULTS: Teaching courses are available as online commented videos, available on demand. The practical section of the website is an online contouring workshop that automatically generates a report quantifying the quality of the user's delineation compared with the experts'. CONCLUSION: Siriade 2.0 is an innovating digital tool for radiation oncology initial and continuous education.

[Reference bases of radiotherapy under stereotaxic conditions for bronchopulmonary, hepatic, prostatic, upper aero-digestive, cerebral and bone tumors or metastases]. / Bases référentielles de la radiothérapie en conditions stéréotaxiques pour les tumeurs ou métastases bronchopulmonaires, hépatiques, prostatiques, des voies aérodigestives supérieures, cérébrales et osseuses.

Since decades, stereotactic radiotherapy has spread out worldwide. Published results are very numerous. To clarify obviousness among all the publications, this recommendation review was written. Voluntarily, authors limited analysis of international best evidence literature on malignant tumors of lung, liver, prostate, head and neck, and metastasis of bone and brain. These data could be used to advance standardization and quality improvement of treatments performed in the nationwide radiotherapy departments and can provide useful guidance for centers worldwide.

[Doses to organs at risk in conformational and stereotactic body radiation therapy: Liver]. / Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie stéréotaxique : le foie.

The liver is an essential organ that ensures many vital functions such as metabolism of bilirubin, glucose, lipids, synthesis of coagulation factors, destruction of many toxins, etc. The hepatic parenchyma can be irradiated during the management of digestive tumors, right basithoracic, esophagus, abdomen in toto or TBI. In addition, radiotherapy of the hepatic area, which is mainly stereotactic, now occupies a central place in the management of primary or secondary hepatic tumors. Irradiation of the whole liver, or part of it, may be complicated by radiation-induced hepatitis. It is therefore necessary to respect strict dosimetric constraints both in stereotactic and in conformational irradiation in order to limit the undesired irradiation of the hepatic parenchyma which may vary according to the treatment techniques, the basic hepatic function or the lesion size. The liver is an organ with a parallel architecture, so the average tolerable dose in the whole liver should be considered rather than the maximum tolerable dose at one point. The purpose of this article is to propose a development of dose recommendations during conformation or stereotactic radiotherapy of the liver.

[Stereotactic body radiotherapy for liver tumors: State of the art]. / Radiothérapie en conditions stéréotaxiques des tumeurs hépatiques : état de l'art.

Thanks to the improvement in radiotherapy physics, biology, computing and imaging, patients presenting with liver tumors can be efficiently treated by radiation. Radiotherapy has been included in liver tumors treatment guidelines at all disease stages. Liver stereotactic radiotherapy has to be preferred to standard fractionated radiotherapy whenever possible, as potentially more efficient because of higher biological equivalent dose. Liver stereotactic radiotherapy planning and delivery require extensive experience and optimal treatment quality at every step, thus limiting its availability to specialized centres. Multicentre studies are difficult to develop due to a large technical heterogeneity. Respiratory management, image guidance and immobilization are considerations as important as machine type. The use of multimodal planning imaging is compulsory to achieve expected contouring quality. Treatment efficacy is difficult to assess following liver stereotactic radiotherapy, but local control is high and toxicity unusual. As a consequence, liver stereotactic radiotherapy is part of multimodal and multidisciplinary management of liver tumors.

[Immunotherapy and radiotherapy]. / Immunothérapie et radiothérapie.

Radiotherapy, primarily known for its cytotoxic effect on the tumor cells, via the induction of DNA damages, has the ability to induce a systemic antitumoral response. By an immunologic cell death, tumor cells exposed to radiation release a large amount of neoantigenes and pro-inflammatory mediators, acting as an in situ vaccine, resulting in an tumor regression within the primary irradiated site, but also in the distant "out of field" secondary tumors. However, this phenomenon is extremly rare with radiotherapy alone, suggesting that the radiation-induced antitumor immunity is not sufficient for overcoming the tumor's and its microenvironnement immunosuppressing effect. Over the last years, many scientific data and preclinical studies have demonstrated that the combination of local irradiation with immune therapy has a synergistic action in inducing an antitumoral immunity, thus enhancing an abscopal effect. In this article, we summarize the main mechanisms cancer harnesses to evade the control of the immune system and how ionising radiations can induce an antitumor immunity. A focus reports then on recent preclinical and clinical research built on this background of combined radiation and immune therapy, which bear the great potential to further improve anticancer therapies.

[Radiotherapy and targeted therapy/immunotherapy]. / Radiothérapie et thérapies ciblées/immunothérapie.

Thanks to recent advances achieved in oncologic systemic and local ablative treatment, the treatments become more and more efficient in term of local control and overall survival. Thus, the targeted therapies, immunotherapy or stereotactic radiotherapy have modified the management of patients, especially in case of oligometastatic disease. Many questions are raised by these innovations, particularly the diagnosis and management of new side effects or that of the combination of these different treatments, depending on the type of primary tumor. Fundamental data are available, while clinical data are still limited. Ongoing trials should help to clarify the clinical management protocols. This manuscript is a review of the combination of radiotherapy and targeted therapy/immunotherapy.