[Place of stereotactic radiotherapy in oligoprogressive non-small cell lung cancer]. / Place de la radiothérapie stéréotaxique dans le cancer du poumon non à petites cellules en oligoprogression.

This review of the literature provides an overview of the combination of stereotactic radiotherapy (SBRT) with immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) in oligo-progressive non-small cell lung neoplasia. This combination showed local control of 76-100% and distant response rates of 8-60%. They reported progression-free survival of 2.7-24 months and overall survival of 13.4-41.2 months. All-grade toxicity rates ranged from 0% to 42%, with grade≥3 toxicity ranging from 0% to 14%. The combination of SBRT with ICI or TKIs exhibits a safe profile with high rates of local control with this combination. This could delay the use of a new line of systemic therapy in these patients with often limited therapeutic resources.

Cette revue de la littérature réalise un état des lieux de l'association de la radiothérapie stéréotaxique (SBRT) aux inhibiteurs de points de contrôle immunitaire (IPCI) et inhibiteurs de la tyrosine kinase (ITK) dans les néoplasies pulmonaires non à petites cellules en oligoprogression. Cette association montrait un contrôle local entre 76 et 100 % et un taux de réponse à distance entre 8 et 60 %. Elle était associée à une survie sans progression de 2,7 à 24 mois et une survie globale de 13,4 à 41,2 mois. Les taux de toxicité tous grades confondus étaient de 0 à 42 %, dont ceux de grade ≥ 3 entre 0 et 14 %. L'association de la SBRT aux IPCI ou ITK arbore un profil de sécurité avec des taux élevés de contrôle local avec cette combinaison. Cela pourrait retarder le recours à une nouvelle ligne de traitement systémique chez ces patients aux ressources thérapeutiques souvent limitées.

Localized Non-melanoma Skin Cancer: Risk Factors of Post-surgical Relapse and Role of Postoperative Radiotherapy.

OPINION STATEMENT: The mainstay treatment of localized non-melanoma skin cancer (NMSC) is surgical excision or Mohs surgery. However, approximately 5% of patients with NMSC harbor high-risk clinicopathologic features for loco-regional recurrence, and distant metastasis. Prognostic factors such as close or positive margins, tumor size ≥ 2 cm, poor tumor differentiation, perineural invasion, depth of invasion, and immunosuppression have all been associated with increased loco-regional recurrence and impaired survival rates. In these patients more aggressive treatments are needed and radiotherapy (RT) is often discussed as adjuvant therapy after surgical resection. Due to the retrospective setting and the heterogeneity of the available studies, indications for adjuvant RT in patients with localized resected NMSC harboring high-risk features remain debated. Studies highlighting the limitations of our current understanding of the independent prognosis of each risk factor are needed to better define the role of adjuvant RT on outcome of localized NMSC and standardize its indications in the clinical setting.

Role of irradiation for patients over 80 years old with glioblastoma: a retrospective cohort study.

To assess efficacy and safety of hypofractionated radiation therapy (HRT) in patients over 80 years old with newly diagnosed glioblastoma (GBM). Between June 2009 and September 2015, patients in this population with a recommendation for radiation therapy from a multidisciplinary tumor board, and a Karnofsky performance status (KPS) ≥60 as assessed by a radiation oncologist, who received HRT (40 Gy/15 fractions) ± concomitant and adjuvant temozolomide (TMZ) were retrospectively analyzed. A total of 21 patients fulfilled the criteria for eligibility. Median KPS was 80 (60-90). After a median follow-up of 5.8 months (IQR 3.7-13.1 months), median overall survival (OS) was 7.5 months (95 % CI 4.5-19.1) and the 1-year and 2-year OS were 39.5 % (95 % CI 21.9-71.2 %) and 6.6 % (95 % CI 1.0- 43.3 %), respectively. Median progression-free survival (PFS) was 5.8 months (95 % CI 3.9-7.7 months), 1-year and 2-year PFS were 15.2 % (95 % CI 4.4-52.4) and 0 %, respectively. Overall, 16 (76.2 %) patients presented a recurrence. Overall seven patients (33.3 %) needed to be hospitalized during treatment. On univariate analysis, hospitalization was the only variable that correlated with less favourable outcome in terms of both OS (12.2 months versus 3.8 months, p < 0.010) and PFS (5.8 months versus 3.4 months, p = 0.002). Our study suggests that HRT is feasible with acceptable tolerance among "very elderly" patients affected by GBM. Patients 80 and older should be considered for management based on RT.

Efficacy and safety of helical tomotherapy with daily image guidance in anal canal cancer patients.

Background and purpose Intensity-modulated radiotherapy (IMRT), also using volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) techniques, has been only recently introduced for treating anal cancer patients. We report efficacy and safety HT, and daily image-guided RT (IGRT) for anal cancer. Materials and methods We retrospectively analyzed efficacy and toxicity of HT with or without chemotherapy for anal cancer patients. Local control (LC) and grade 3 or more toxicity rate (CTC-AE v.4.0) were the primary endpoints. Overall (OS), disease-free (DFS), and colostomy-free survival (CFS) are also reported. Results Between October 2007 and May 2014, 78 patients were treated. Fifty patients presented a stage II or stage IIIA (UICC 2002), and 33 presented a N1-3 disease. Radiotherapy consisted of 36 Gy (1.8 Gy/fraction) delivered on the pelvis and on the anal canal, with a sequential boost up to 59.4 Gy (1.8 Gy/fraction) delivered to the anal and to nodal gross tumor volumes. Concomitant chemotherapy was delivered in 73 patients, mainly using mitomycin C and 5-fluorouracil (n = 30) or mitomycin C and capecitabine combination (n = 37). After a median follow-up period of 47 months (range 3-75), the five-year LC rate was 83.8% (95% CI 76.2-91.4%). Seven patients underwent a colostomy because of local recurrence (n = 5) or pretreatment dysfunction (n = 2). Overall incidence of grade 3 acute toxicity was 24%, mainly as erythema (n = 15/19) or diarrhea (n = 7/19). Two patients presented a late grade 3 gastrointestinal toxicity (anal incontinence). No grade 4 acute or late toxicity was recorded. Conclusions HT with daily IGRT is efficacious and safe in the treatment of anal canal cancer patients, and is considered in our department standard of care in this clinical setting.

Impact of Neck Dissection in Head and Neck Squamous Cell Carcinomas of Unknown Primary.

PURPOSE: Management of head and neck cancers of unknown primary (HNCUP) combines neck dissection (ND) and radiotherapy, with or without chemotherapy. The prognostic value of ND has hardly been studied in HNCUP. METHODS: A retrospective multicentric study assessed the impact of ND extent (adenectomy, selective ND, radical/radical-modified ND) on nodal relapse, progression-free survival (PFS) or survival, taking into account nodal stage. RESULTS: 53 patients (16.5%) had no ND, 33 (10.2%) had lymphadenectomy, 116 (36.0%) underwent selective ND and 120 underwent radical/radical-modified ND (37.3%), 15 of which received radical ND (4.7%). With a 34-month median follow-up, the 3-year incidence of nodal relapse was 12.5% and progression-free survival (PFS) 69.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective or radical/modified ND, but survival rates were similar. Patients undergoing lymphadenectomy or ND had a better PFS and lowered nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND. CONCLUSION: In HNCUP, ND improves PFS, regardless of nodal stage. The magnitude of the benefit of ND does not appear to depend on ND extent and decreases with a more advanced nodal stage.

Complete response of leptomeningeal carcinomatosis secondary to breast cancer.

Leptomeningeal carcinomatosis (LC) is an unmet medical need associated with death in 4-6 weeks without treatment, delayed by 4 months in some patients with favorable prognosis and aggressive multimodal therapy. Unfortunately, most clinical trials excluded patients with LC, and the best management remains unknown. Here we present the first report of a LC secondary to HR positive breast cancer with a complete response to CDK4/6 inhibitors abemaciclib, letrozole and hippocampal-avoidance whole-brain radiotherapy.

Neck management in head and neck squamous cell carcinomas: where do we stand?

Head and neck squamous-cell carcinomas (HNSCCs) have a significant lymph node tropism. This varies considerably depending on the primary tumor site and the Human Papillomavirus (HPV) status of the disease. The best therapeutic option, between up-front lymph node dissection and chemoradiotherapy (CRT) +/- followed by lymph node dissection in case of persistent lymphadenopathy or regional relapse, remains unclear. The purpose of this review is to discuss the pros and cons related to the different approaches of the neck management in HNSCC. A narrative review of the management of the cervical lymph nodes was undertaken. Searches of PubMed database were performed using the terms 'neck management' OR 'cervical lymphadenopathies' AND 'head and neck neoplasms'. Recent advances in imaging, pathological analysis, surgery and radiotherapy let to personalize the type of lymph node dissection and, the volumes of radiation therapy. Excluding inoperable patients and unresectable diseases, N3 lymphadenopathies, as well as bulky N2 stages, specifically HPV- or necrotic nodes, would be in favor of an up-front surgical approach, while HPV+ diseases, and lymphadenopathies of unknown primary would support CRT first. However, efficacy of such strategies is challenged by a significant morbidity in the medium and long terms. In the absence of higher level of evidence, the decision-making tools for the neck dissection before or after the CRT are based on the Mehanna's trial and retrospective studies with significant biases. Consequently, the approaches and the ensuing outcomes remain not homogenous depending on the centers' experience, in the context of limited data, especially for N2-3 HPV- HNSCC.

Selection of lymph node target volumes for definitive head and neck radiation therapy: a 2019 Update.

BACKGROUND AND PURPOSE: In 2000, a panel of experts published a proposal for the selection of lymph node target volumes for definitive head and neck radiation therapy (Radiother Oncol, 2000; 56: 135-150). Hereunder, this selection is updated and extended to also cover primary sites not previously covered. PATIENTS AND METHODS: The lymphatic spread of head and neck cancers into neck lymph nodes was comprehensively reviewed based on radiological, surgical and pathological literature regarding both initial involvement and patterns of failure. Then a panel of worldwide head and neck radiotherapy experts agreed on a consensus for the selection of both high- and low-risk lymph node target volumes for the node negative and the node positive neck. RESULTS: An updated selection of lymph node target volumes is reported for oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses, nasal cavity and carcinoma of unknown primary as a function of the nodal staging (UICC 8th edition). CONCLUSIONS: The selection of lymph node target volumes for head and neck cancers treated with IMRT/VMAT or other highly conformal techniques (e.g. proton therapy) requires a rigorous approach. This updated proposal of selection should help clinicians for the selection of lymph nodes target volumes and contribute to increase consistency.

Stereotactic Radiation Therapy for Renal Cell Carcinoma Brain Metastases in the Tyrosine Kinase Inhibitors Era: Outcomes of 120 Patients.

BACKGROUND: The objective of the study was to evaluate the outcomes in terms of efficacy and safety of a large consecutive series of 362 patients with renal cell carcinoma (RCC) brain metastases treated using stereotactic radiosurgery (SRS) in the tyrosine kinase inhibitor (TKI) era. PATIENTS AND METHODS: From 2005 to 2015, 362 consecutive patients with brain metastases from RCC were treated using SRS in 1 fraction: 226 metastases (61 patients) using Gamma-Knife at a median of 18 Gy (50% isodose line); 136 metastases (63 patients) using linear accelerator at a median of 16 Gy (70% isodose line). The median patient age was 58 years. At the first SRS, 37 patients (31%) received a systemic treatment. Among systemic therapies, TKIs were the most common (65%). RESULTS: The local control rates were 94% and 92% at 12 and 36 months, respectively. In multivariate analysis, a minimal dose >17 Gy and concomitant TKI treatment were associated with higher rates of local control. The overall survival rates at 12 and 36 months were 52% and 29%, respectively. In multivariate analysis, factors associated with poor survival included age ≥65 years, lower score index for SRS, concomitant lung metastases, time between RCC diagnosis and first systemic metastasis ≤4 months, occurrence during treatment with a systemic therapy, no history of neurosurgery, and persistence or occurrence of neurological symptoms at 3 months after SRS. Seventeen patients had Grade III/IV adverse effects of whom 3 patients presented a symptomatic radionecrosis. CONCLUSION: SRS is highly effective in patients with brain metastases from RCC. Its association with TKIs does not suggest higher risk of neurologic toxicity.

Unilateral or bilateral irradiation in cervical lymph node metastases of unknown primary? A retrospective cohort study.

INTRODUCTION: Patients with cervical lymphadenopathy of unknown primary carcinoma (CUP) usually undergo neck dissection and irradiation. There is an ongoing controversy regarding the extent of nodal and mucosal volumes to be irradiated. We assessed outcomes after bilateral or unilateral nodal irradiation. METHODS: This retrospective multicentre study included patients with CUP and squamous cellular carcinoma who underwent radiotherapy (RT) between 2000 and 2015. RESULTS: Of 350 patients, 74.5% had unilateral disease and 25.5% had bilateral disease. Of 297 patients with available data on disease and irradiation sides, 61 (20.5%) patients had unilateral disease and unilateral irradiation, 155 (52.2%), unilateral disease and bilateral irradiation and 81 (27.3%), bilateral disease and bilateral irradiation. Thirty-four (9.7%) and 217 (62.0%) patients received neoadjuvant and/or concomitant chemotherapy, respectively. Median follow-up was 37 months. Three-year local, regional, locoregional failure rates and CUP-specific survival were 5.6%, 11.7%, 15.0% and 84.7%, respectively. In patients with unilateral disease, the 3-year cumulative incidence of regional/local relapse was 7.7%/4.3% after bilateral irradiation versus 16.9%/11.1% after unilateral irradiation (hazard ratio = 0.56/0.61, p = 0.17/0.32). The cumulative incidence of CUP-specific deaths was 9.2% after bilateral irradiation and 15.5% after unilateral irradiation (p = 0.92). In multivariate analysis, mucosal irradiation was associated with better local control, whereas no neck dissection, ≥N2b and interruption of RT for more than 4 days were associated with poorer regional control. Toxicity was higher after bilateral irradiation (p < 0.05). No positron-emission tomography-computed tomography, largest node diameter, ≥N2b, neoadjuvant chemotherapy and interruption of RT were associated with poorer cause-specific survival. CONCLUSION: Bilateral nodal irradiation yielded non-significant better nodal and mucosal control rates but was associated with higher rates of severe toxicity.

Management of locally advanced anal canal carcinoma with intensity-modulated radiotherapy and concurrent chemotherapy.

The best curative option for locally advanced (stages II-III) squamous-cell carcinomas of the anal canal (SCCAC) is concurrent chemo-radiotherapy delivering 36-45 Gy to the prophylactic planning target volume with an additional boost of 14-20 Gy to the gross tumor volume with or without a gap-period between these two sequences. Although 3-dimensional conformal radiotherapy led to suboptimal tumor coverage because of field junctions, this modality remains a standard of care. Recently, intensity-modulated radiotherapy (IMRT) techniques improved tumor coverage while decreasing doses delivered to organs at risk. Sparing healthy tissues results in fewer severe acute toxicities. Consequently, IMRT could potentially avoid a gap-period that may increase the risk of local failure. Furthermore, these modalities reduce severe late toxicities of the gastrointestinal tract as well as better functional conservation of anorectal sphincter. This report aims to critically review contemporary trends in the management of locally advanced SCCAC using IMRT and concurrent chemotherapy.

[Advances in the management of cervical lymphadenopathies of unknown primary: advances in diagnostic imaging and surgical modalities and new international staging system]. / Évolutions dans la prise en charge des métastases ganglionnaires cervicales sans cancer primitif retrouvé : avancées diagnostiques et nouvelle classification TNM.

INTRODUCTION: Cervical lymphadenopathies of unknown primary represent 3 % of head and neck cancers. Their diagnostic work up has largely changed in recent years. This review provides an update on diagnostic developments and their potential therapeutic impact. MATERIALS AND METHODS: This is a systematic review of the literature. RESULTS: In recent years, changes in epidemiology-based prognostic factors such as human papilloma virus (HPV) cancers, advances in imaging and minimally invasive surgery have been integrated in the management of cervical lymphadenopathies of unknown primary. In particular, systematic use of PET scanner and increasing practice of robotic or laser surgery have contributed to increasing detection rate of primary cancers. These allow more adapted and personalized treatments. The impact of changes in the eighth TNM staging system is discussed. CONCLUSION: The management of cervical lymphadenopathies of unknown primary cancer has changed significantly in the last 10 years. On the other hand, practice changes will have to be assessed.

Adaptive radiation therapy in head and neck cancer for clinical practice: state of the art and practical challenges.

Modern radiation therapy techniques are characterized by high conformality to tumor volumes and steep dose gradients to spare normal organs. These techniques require accurate clinical target volume definitions and rigorous assessment of set up uncertainties using image guidance, a concept called image-guided radiation therapy. Due to alteration of patient anatomy, changes in tissue density/volumes and tumor shrinkage over the course of treatment, treatment accuracy may be challenged. This may result in excessive irradiation of organs at risk/healthy tissues and undercoverage of target volumes with a significant risk of locoregional failure. Adaptive radiation therapy (ART) is a concept allowing the clinician to reconsider the planned dose based on potential changes to accurately delivering the remaining radiation dose to the tumor while optimally minimizing irradiation of healthy tissues. There is little consensus on how to apply this concept in clinical practice. The current review investigates the current ART issues, including patient selection, clinical/dosimetric criteria and timing for re-planning, and practical technical issues. A practical algorithm is proposed for patient management in cases where ART is required.

[Mucosal melanomas of the head and neck: State of the art and current controversies]. / Mélanomes muqueux de la tête et du cou : état actuel des pratiques et controverses.

Mucosal melanomas of the head and neck (sinonasal and oral cavity) account for 1% of neoplasms, 4% of all melanomas and over 50% of all mucosal melanomas. They have a high metastatic potential. Five-year overall survival does not exceed 30%. Diagnosis may be difficult and includes adequate immunohistochemical staining. Risk factors, presentation and molecular biology are different from those of cutaneous melanomas. The mainstay of treatment is surgery and postoperative radiotherapy. Endoscopic surgery should be evaluated prospectively. Neck dissection is recommended for N0 oral cavity melanomas, while it can generally be omitted for sinonasal melanomas. Inoperable tumors can be treated with exclusive radiotherapy. Molecular guidance for metastatic cases is a relevant option despite low level of evidence, based on the rarity of disease and low response rates to chemotherapy. c-KIT inhibitors and immunotherapy appear promising.

[Lymph node metastases from squamous cell carcinoma of unknown primary site. Is it time to change of paradigm?]. / Les adénopathies métastatiques d'un carcinome épidermoïde sans porte d'entrée. Quelle est l'attitude actuelle ?

The diagnosis of carcinoma of unknown primary (CUP) is made after exclusion of the presence of a mucosal primary. There are two mains options for the primary treatment of CUP, either a neck node dissection followed by postoperative radiotherapy or chemo-radiotherapy, or a primary radiotherapy or chemo-radiotherapy depending on the nodal stage followed in case of residual neck disease by a selective neck dissection. There is no data to suggest the superiority of one over the other. For radiotherapy, unilateral neck or bilateral neck, including the upper aerodigestive tract mucosa are possible options. There is no definite data to demonstrate the superiority of one over the other, but owing the reduced toxicity of unilateral irradiation, and the possibility of salvage treatment in case of emergence of a mucosal primary and/or a contralateral neck node development, the former may be the preferred option. Advances in radiotherapy such as intensity modulated radiation therapy have the potential to spare organs at risk and reduce late toxicity rates. A selective irradiation approach customized on "major" criteria, such as nodal stage and level, HPV and EBV status and accessory criteria, such as histological variants, is under investigation.