Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study.

BACKGROUND: Cetuximab in combination with platinum and 5-fluorouracil is the standard of care in the first-line treatment of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Cetuximab and taxane combinations have shown promising activity. This study evaluated the efficacy and safety of four cycles of docetaxel associated with cisplatin and cetuximab (TPEx), followed by maintenance with cetuximab every 2 weeks. PATIENTS AND METHODS: Patients with a histologically confirmed HNSCC with metastasis or recurrence unsuitable for locoregional curative treatment received docetaxel and cisplatin (75 mg/m(2) both) at day 1 and weekly cetuximab 250 mg/m(2) (loading dose of 400 mg/m(2)), repeated every 21 days for four cycles, followed by maintenance cetuximab 500 mg/m(2) every 2 weeks until progression or unacceptable toxicity. Prophylactic administration of granulocyte colony-stimulating factor was done systematically after each chemotherapy cycle. Patients had a good general status (performance status ≤1) and were under 71 years. Prior total doses of cisplatin exceeding 300 mg/m(2) were not allowed. The primary end point was objective response rate (ORR) after four cycles. RESULTS: Fifty-four patients were enrolled. The primary end point was met with an ORR of 44.4% (95% CI 30.9-58.6). Median overall and progression-free survivals were, respectively, 14 months (95% CI 11.3-17.3) and 6.2 months (95% CI 5.4-7.2). The most common grade 3/4 adverse events were skin rash (16.6%) and non-febrile neutropenia (20.4%). There were one pulmonary embolism and two infectious events leading to death. CONCLUSIONS: The TPEx regimen showed promising activity as first-line treatment in fit patients with recurrent/metastatic HNSCC. Further studies are needed to compare the TPEx versus EXTREME regimen in this population. CLINICALTRIALGOV: NCT01289522.

Management of head and neck carcinomas with synchronous or metachronous oligometastatic disease: Role of locoregional radiotherapy and metastasis-directed radiotherapy.

Head and neck carcinomas are initially metastatic in about 15% of cases. Radiotherapy is a cornerstone in the multimodal strategy at the locoregional phase. In patients with head and neck cancer, often heavily pretreated and with comorbidities, who relapse locoregionally or at distant sites, radiotherapy has also become increasingly important at the metastatic phase. Data on the optimal sequence of systemic treatments and metastasis-directed treatments including stereotactic irradiation are still lacking. Several randomized head and neck trials have been initiated that should provide important answers, including one recent GORTEC trial.

Metastases-directed radiotherapy in castration resistant oligo metastatic prostate cancer: A multicentric retrospective study from the French group COLib.

Oligometastases are defined as a number of detectable metastases less or equal to 5. In castrate-resistant oligo metastatic prostate Cancer (CR oligoM PC), Metastases-Directed Ablative radiotherapy (MDRT) is poorly investigated. Our study retrospectively reviewed the cases of CR oligoM PC treated with MDRT in 8 French high-volume radiotherapy centers. OS and PFS are defined as the delay between the first day of MDRT and death (OS) or progression according to PCWG criteria (PFS). OS and PFS are evaluated according to Kaplan Meyer, curves are compared with log rank test. Logistic regression was used to identify predictive factors for outcome: bone versus node metastasis, ISUP grade, PSA doubling Time (PSADT) at the time of MDRT, time to castration resistance. 107 patients were included in the study, among those 197 metastases received MDRT. For the overall population, the median follow-up was 25.2 months (1,4-145). OS was 93 % at 2 years and 81,4% at 3 years. At 2 years, 100 % of patients with node-only metastasis were alive versus 88,7% among those who have bone metastases (p = 0,72). The median PFS was 12,6 months (IC 95 % [9,6; 17]), with no difference among patients with node only disease versus the rest of the cohort. The PFS was 18,2 months (10,0; 32,4) in patients with PSADT >6 months versus 10,7 months (8,9; 14,3) when PSADT was inferior to 6 months. However, this difference did not reach significant. We did not find a correlation neither between ISUP grade (1-2 versus 3-4-5) and PFS, nor between hormone-sensitivity duration and PFS. Patients receiving MDRT for CR oligoM PC have a good prognosis with 81,6% OS at 3 years. PSA DT longer than 6 months could be related to better PFS. MDRT strategy could postpone the onset of new systemic treatment with median PFS >1 year.

Stereotactic body radiation therapy for adrenal gland metastases: A multi-institutional outcome analysis.

Aim: The adrenal gland is a common site of metastasis with a rate of up to 27% in autopsy series. The incidence of these metastases is increasing due to greater use of Positron Emission Tomography scans and improved overall survival of patients with metastatic cancers. Stereotactic body radiation therapy (SBRT) is a non-invasive treatment option for metastasis. The aim of this study is to assess prognostic factors influencing local control, progression-free and overall survival in oligometastatic patients treated with SBRT for an adrenal metastasis. Methods: In this multicentric retrospective study, we included patients with adrenal metastases treated with SBRT between 2010 and 2021 in eleven french centers. All primary tumors were included. Results: A total of 110 patients treated for 121 adrenal lesions were included. Non-small-cell lung cancer was the predominant histologic type (55.4 %). Eighty-two percent of patients had at least 2 metastatic sites. The median Planning Target Volume was 70 cm3 with a median prescription dose of 40 Gray (Gy). The mean Biologically Effective Dose (BED) 10 dose was 74.2 Gy. Local control at 1 and 2 years was 85.9 % and 72.5 % respectively. The median overall survival and progression-free survival were 31.6 and 8.5 months respectively. Local control was significantly improved by systemic treatment one month before or after SBRT (p = 0.009) and by a BED10 greater than or equal to 50 Gy (p = 0.003).In multivariate analysis, oligometastatic presentation (p = 0.009) and a metachronous metastatic presentation (p = 0.008) were independent factors for progression-free survival.Tolerance was excellent, no grade 3 and 4 toxicities were described due to SBRT. Conclusion: Stereotactic radiotherapy of adrenal metastases makes possible a local control of more than 85% at one year and was well tolerated. The factors influencing survival in oligometastatic patients still need to be found in order to better select those who benefit the most from this type of treatment.

[Proposal for the delineation of postoperative primary clinical target volumes in maxillary sinus and nasal cavity cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers du sinus maxillaire et des cavités nasales.

In this article, we propose a consensus delineation of postoperative clinical target volumes for the primary tumour in maxillary sinus and nasal cavity cancers. These guidelines are developed based on radioanatomy and the natural history of those cancers. They require the fusion of the planning CT with preoperative imaging for accurate positioning of the initial GTV and the combined use of the geometric and anatomical concepts for the delineation of clinical target volume for the primary tumour. This article does not discuss the indications of external radiotherapy (nor concurrent systemic treatment) but focuses on target volumes when there is an indication for radiotherapy.

Stereotactic body radiotherapy for mediastinal lymph node with CyberKnife®: Efficacy and toxicity.

PUPRPOSE: Stereotactic body radiotherapy is more and more used for treatment of oligometastatic mediastinal lymph nodes. The objective of this single-centre study was to evaluate its efficacy in patients with either a locoregional recurrence of a pulmonary or oesophageal cancer or with distant metastases of extrathoracic tumours. PATIENTS AND METHODS: Patients with oligometastatic mediastinal lymph nodes treated with CyberKnife from June 2010 to September 2020 were screened. The primary endpoint was to assess local progression free survival and induced toxicity. Secondary endpoints were overall survival and progression free survival. The delay before introduction of systemic treatment in the subgroup of patients who did not receive systemic therapy for previous progression was also evaluated. RESULTS: Fifty patients were included: 15 with a locoregional progression of a thoracic primary tumour (87% pulmonary) and 35 with mediastinal metastasis of especially renal tumour (29%). Median follow-up was 27 months (6-110 months). Local progression free survival at 6, 12 and 18 months was respectively 94, 88 and 72%. The rate of local progression was significantly lower in patients who received 36Gy in six fractions (66% of the cohort) versus other treatment schemes. Two grade 1 acute oesophagitis and one late grade 2 pulmonary fibrosis were described. Overall survival at 12, 18 and 24 months was respectively 94, 85 and 82%. Median progression free survival was 13 months. Twenty-one patients were treated by stereotactic body irradiation alone without previous history of systemic treatment. Among this subgroup, 11 patients (52%) received a systemic treatment following stereotactic body radiotherapy with a median introduction time of 17 months (5-52 months) and 24% did not progress. CONCLUSION: Stereotactic body irradiation as treatment of oligometastatic mediastinal lymph nodes is a well-tolerated targeted irradiation that leads to a high control rate and delay the introduction of systemic therapy in selected patients.

[Clinical research in private sector: Which strategic analysis?] / Recherche clinique en structure libérale : quelle analyse stratégique ?

Clinical research in private practice has significantly increased in recent years and has become crucial for the attractiveness of centres both for patients who can access innovative treatments and molecules and for participating physicians. The responsiveness, the size and reduced number of interlocutors, flexibility, and decision-making autonomy of private practitioners are strengths in the strategic analysis of clinical research in the private sector. However, the varied medical activity allowing for broader recruitment, location of practice, and administrative time related leadership roles can become weakness in terms of quality and time dedicated to this research activity, which still relies heavily on strong individual involvement. Collaborations, which develop when clinical research in private centres is dynamic, are sources of opportunities, growth, and progress, allowing participation in various ambitious projects that can benefit patients in these facilities. Recent administrative and legislative complexities for trial integration and competition with academic structures can threaten this important clinical research activity for private practices, requiring reflection on its valorisation and promotion to ensure its sustainability.

[Clinical research in general hospital centres in France, strengths and weaknesses]. / Recherche clinique au sein des centres hospitaliers généraux en France, forces et faiblesses.

Clinical research is an essential activity in cancer care. Both for patients, who can gain access to innovative therapies, and for practitioners, who can maintain their skills and stay at the forefront of new treatment approaches. First developed in university hospitals, clinical research is now established in general hospitals and private health institutions. The number of patient inclusions in clinical trials has doubled over the last ten years, thus reflecting the dynamism of it. Strengths and weaknesses, opportunities and threats concerning clinical research, and more specifically clinical research in general hospitals, are exposed in this article.

[French careers in oncology radiotherapy: Crossing views]. / Carrières en oncologie radiothérapie : réflexions croisées SFjRO-SFRO-SNRO.

The French Society of Young Radiation Oncologists (SFjRO), the National Union of Radiation Oncologists (SNRO) and the French Society of Oncological Radiotherapy (SFRO) aim to reconcile career opportunities and demographic needs in oncology. In 2021, 932 radiation oncologists (RO) are in regular activity in France, this represents an increase of more than 20% in ten years. Physician distribution is changing in public hospitals, cancer centers and private clinics. Currently one third of ROs works in each sector. In addition, fifteen percent of ROs have a mixed activity. In 2021, 180 young RO (trainees and residents) were questioned by SFjRO board about their training, internship, coaching and career guidance. An interactive communication was organized during the 32nd SFRO Meeting in 2021. It was an opportunity to bring the results of this study. More than 70% RO interviewed answered to the survey, for 55% among them, career choice was difficult. In order to help young ROs in their professional approach, three RO made an oral presentation during this session, about radiotherapy in public hospitals, private centers or with a mixed practice. The aim of this article is to summarize the highlights of the last SFjRO/SFRO session: expectations of young RO, career prospects and trends.

[Hematological pathologies: the most successful model of de-escalation in radiotherapy]. / Pathologie hématologique : le modèle le plus abouti de désescalade en radiothérapie.

The proportion of patients irradiated in the context of malignant hematological pathologies decreased over the last decades. The main causes are the late side effects of the historical series and the new therapeutic strategies aiming to relay radiotherapy to the rank of option. At the same time, radiotherapy has been modernised, target volumes and total doses have been drastically reduced. Hodgkin's lymphomas, indolent follicular lymphomas and primary cerebral lymphomas are the main witnesses of this therapeutic deflation.

[Immuno-radiotherapy: A review of the rationale, recent clinical developments and future prospects]. / Immuno-radiothérapie : une revue du rationnel, développements cliniques récents et perspectives futures.

Thanks to the success of checkpoint inhibitors, immunotherapy now plays a major role in the management of a large number of solid tumors, while the number of indications continues to grow and new combinations could, in the near future, further modify treatment standards. However, the response rates of immunotherapies as monotherapy are modest and their use is increasingly considered in combination with other cancer treatments (chemotherapy, surgery, radiotherapy or certain targeted therapies). Combinations with radiotherapy seem particularly attractive because there is a strong experimental rationale linking part of the efficacy of ionizing radiation to an induced stimulation of both of the innate and adaptive response. Many early phases and a number of large randomized combination trials have published efficacy and safety results, while important trials are still ongoing and will provide answers in the near future. This short review recalls the experimental biological rationale for immuno-radiotherapy and highlights some of the fundamental directions being explored, then presents the clinical efficacy and safety results available to date, those expected in the near future, and finally outlines the outlook in this rapidly evolving field.

[Stereotactic radiotherapy for localized primary lung tumours of stage T1-T2]. / Intérêt de la radiothérapie stéréotaxique pour les tumeurs primitives du poumon localisées de stade T1-T2.

The historical treatment for stage I non-small cell lung cancer is surgical. Parenchymal amputation is not always possible due to cardiopulmonary comorbidities and stereotactic radiotherapy is one of the alternatives to an invasive procedure. The excellent results observed for inoperable tumors raised the question of this treatment in operable patients. This article presents the data in these two situations and the future perspectives.

[Impact of IMRT for neoadjuvant rectal cancer?] / Quel apport de la modulation d'intensité pour la radiothérapie des cancers du rectum ?

The standard management of locally advanced rectal tumors as cT3-T4 and/or N0/N1 is based on preoperative treatment combining radiotherapy of 45 to 50Gy and chemotherapy based on 5-fluorouracil. Intensity-modulated radiotherapy has already shown its interest compared to conformal radiotherapy in other locations, like in pelvic cancer. The role of intensity-modulated radiotherapy in the pre/postoperative treatment of rectal cancers is not a standard of care. Published studies showed its feasibility with the objective of less toxicity with equivalent efficacy.

Role of radiotherapy in the management of bladder cancer: Recommendations of the French society for radiation oncology.

We present the recommendations of the French society of oncological radiotherapy on the indications and techniques for external beam radiotherapy for bladder cancer.

Radiotherapy for hypopharynx cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy for hypopharynx. Intensity-modulated radiotherapy is the gold standard treatment for hypopharynx cancers. Early T1 and T2 tumors could be treated by exclusive radiotherapy or surgery followed by postoperative radiotherapy in case of high recurrence risk. For locally advanced tumours requiring total pharyngolaryngectomy (T2 or T3) or with significant lymph nodes involvement, induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy were possible. For T4 tumour, surgery must be proposed. The treatment of lymph nodes is based on initial primary tumour treatment. In non-surgical procedure, for 35 fractions, curative dose is 70Gy (2Gy per fraction) and prophylactic dose are 50 to 56Gy (2Gy per fraction in case of sequential radiotherapy or 1.6Gy in case of integrated simultaneous boost) radiotherapy; for 33 fractions, curative dose is 69.96Gy (2.12Gy per fraction) and prophylactic dose is 52.8Gy (1.6Gy per fraction in integrated simultaneous boost radiotherapy or 54Gy in 1.64Gy per fraction); for 30 fractions, curative dose is 66Gy (2.2Gy per fraction) and prophylactic dose is 54Gy (1.8Gy per fraction in integrated simultaneous boost radiotherapy). Doses over 2Gy per fraction could be done when chemotherapy is not used regarding potential larynx toxicity. Postoperatively, radiotherapy is used in locally advanced cancer with dose levels based on pathologic criteria, 60 to 66Gy for R1 resection and 54 to 60Gy for complete resection in bed tumour; 50 to 66Gy in lymph nodes areas regarding extracapsular spread. Volume delineation were based on guidelines cited in this article.

[Challenges and limits of therapeutic de-escalation for papillomavirus-related oropharyngeal cancer]. / Enjeux et limites de la désescalade thérapeutique dans la prise en charge du cancer de l'oropharynx lié au papillomavirus.

The incidence of HPV-related oropharyngeal cancers has been increasing in Western countries for several decades. If they are individualized within the latest TNM classification, the current standards of management do not authorize the management of these patients to be singled out. However, their distinct oncogenesis and their excellent prognosis compared to other patients has allowed the development of several clinical trials based on the question of therapeutic de-escalation. This review of the literature aims to take stock of the elements provided by clinical research in recent years.

Management and work-up procedures of patients with head and neck malignancies treated by radiation.

Radiotherapy alone or in association with systemic treatment plays a major role in the treatment of head and neck tumours, either as a primary treatment or as a postoperative modality. The management of these tumours is multidisciplinary, requiring particular care at every treatment step. We present the update of the recommendations of the French Society of Radiation Oncology on the radiotherapy of head and neck tumours from the imaging work-up needed for optimal selection of treatment volume, to optimization of the dose distribution and delivery.

Radiotherapy for laryngeal cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy of laryngeal cancers. Intensity modulated radiotherapy is the standard of care radiotherapy for the management of laryngeal cancers. Early stage T1 or T2 tumours can be treated either by radiotherapy or conservative surgery. For tumours requiring total laryngectomy (T2 or T3), an organ preservation strategy by either induction chemotherapy followed by radiotherapy or chemoradiotherapy with cisplatin is recommended. For T4 tumours, a total laryngectomy followed by radiotherapy is recommended when feasible. Dose regimens for definitive and postoperative radiotherapy are detailed in this article, as well as the selection and delineation of tumour and lymph node target volumes.

[Molecular-integrated risk profile: An opportunity for therapeutic de-escalation in intermediate and high-intermediate risk endometrial cancer]. / Cancer de l'endomètre de stade localisé : la perspective d'une désescalade thérapeutique guidée par la classification moléculaire.

In Europe, endometrial cancer is the fourth most common cancer among women. The majority of patients are diagnosed at a localized stage. For these patients, the standard of care is based on an hysterectomy with salpingo oophorectomy±lymph node staging. Through the assessment of histopathologic features, risk groups are determined: low, intermediate, high-intermediate, and high risk. Adjuvant strategies are guided by these risk groups. While the prognosis of low-risk and high-risk is well known, that of intermediate and high-intermediate risk is more heterogeneous, and the therapeutic index of adjuvant treatments is more questionable. Several trials (PORTEC [Post Operative Radiation Therapy in Endometrial Carcinoma] I, GOG [Gynecologic Oncology Group] 99, ASTEC [A Study in the Treatment of Endometrial Cancer] EN.5, PORTEC II, Sorbe et al trial) have assessed observation, vaginal cuff brachytherapy and/or pelvic external beam radiotherapy in this population. Vaginal cuff brachytherapy reduces the local recurrence rate, and pelvic external beam radiotherapy the pelvic recurrence rate. However, no benefit in terms of overall survival or occurrence of distant metastases is highlighted. Compared to observation, brachytherapy and above all external beam radiotherapy are associated with an increased morbidity, and with a decreased quality of life. In order to improve the therapeutic ratio and to optimize medico-economic decisions, therapeutic de-escalation strategies, based on the molecular profiles, are emerging in clinical trials, and in the recommendations for the management of intermediate and high-intermediate risk endometrial cancers. The four main molecular profiles highlighted by the genomic analyzes of The Cancer Genome Atlas (TCGA) - POLE (polymerase epsilon) mutation, non-specific molecular profile, MMR (MisMatch repair) deficiency, and p53 mutation - but also the quantification of lymphovascular space invasion (absent, focal or substantial), and the assessment of L1CAM (L1 cell adhesion molecule) overexpression represent growing concerns. Thus, the use of molecular-integrated risk profile to determine the best adjuvant treatment represent a major way to personalize adjuvant treatment of endometrial cancers, with therapeutic de-escalation opportunity for around half of the high-intermediate risks. However, in the absence of prospective data, inclusion in clinical trials assessing molecular profile-based treatment remains the best therapeutic opportunity.

[Clinical research in radiotherapy oncology in private sector: A reality with a possible future?] / Recherche clinique en oncologie radiothérapie dans le secteur libéral : une réalité avec un avenir possible ?

Clinical research is one of the activities of medical practice, particularly in oncology including radiotherapy. It was developed in the public sector and then in the liberal sector, in compliance with regulatory institutions, resulting in a doubling of inclusions over the last decade. Setting up and developing clinical research in the liberal sector are major axes in terms of interests: improving the proposition of care, access to innovation, to keep patients, intellectual stimulation, encouraging recruitment, activity of scientific publications, financial valorisation, quality of visibility… An inventory on French national territory via the national union of iadiotherapists oncologists (SNRO) and the club of liberal oncologists (Colib) is reported in this article, as well as examples of structuring and organization.