To compare the efficacy and safety of induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) or bioradiotherapy (BRT) for larynx preservation (LP).
Previously untreated patients with stage ...III to IV larynx/hypopharynx squamous cell carcinoma received three cycles of ICT-docetaxel and cisplatin 75 mg/m(2) each on day 1 and fluorouracil 750 mg/m(2) per day on days 1 through 5. Poor responders (< 50% response) underwent salvage surgery. Responders (≥ 50% response) were randomly assigned to conventional radiotherapy (RT; 70 Gy) with concurrent cisplatin 100 mg/m(2) per day on days 1, 22, and 43 of RT (arm A) or concurrent cetuximab 400 mg/m(2) loading dose and 250 mg/m(2) per week during RT (arm B). Primary end point was LP at 3 months. Secondary end points were larynx function preservation (LFP) and overall survival (OS) at 18 months.
Of the 153 enrolled patients, 116 were randomly assigned after ICT (60, arm A; 56, arm B). Overall toxicity of both CRT and BRT was substantial following ICT. However, treatment compliance was higher in the BRT arm. In an intent-to-treat analysis, there was no significant difference in LP at 3 months between arms A and B (95% and 93%, respectively), LFP (87% and 82%, respectively), and OS at 18 months (92% and 89%, respectively). There were fewer local treatment failures in arm A than in arm B; salvage surgery was feasible in arm B only.
There is no evidence that one treatment was superior to the other or could improve the outcome reported with ICT followed by RT alone (French Groupe Oncologie Radiothérapie Tête et Cou GORTEC 2000-01 trial Induction CT by Cisplatin, 5FU With or Without Docetaxel in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma). The protocol that can best compare with RT alone after ICT is still to be determined.
This article looks into the ways women lawyers worked during the Algerian Independence War from a gender perspective. These women lawyers were members of an anti-colonial lawyers group of the FLN ...(Front de Libération Nationale). Contrary to their male counterparts, they remained invisible in History even if they had also taken part in the practice of cause lawyering, mainly in metropolitan France. These women lawyers developed their own arguments and strategies. Therfore, they should also be written in the feminist law History as well as the anti-colonial History.
Background
The nasopharyngeal and parapharyngeal spaces are difficult for surgeons to access. Of the various external routes described, the maxillary swing has emerged as the gold standard because of ...its simplicity. However, its morbidity has led to the development of less invasive techniques. The purpose of our study was to compare the surgical anatomy of the maxillary swing with that of the endoscopic endonasal approach.
Methods
Each procedure was performed on 10 anatomic specimens. The exposure and the limits obtained were evaluated. A CT scan analysis was performed.
Results
The endoscopic endonasal approach extended the limits, offering wider exposure. The endoscopic endonasal approach made possible better visualization of deep structures and precise dissection of the parapharyngeal spaces. However, the maxillary swing provided better access to the oropharynx and could be completed 3 times faster.
Conclusion
The endoscopic endonasal approach provides excellent exposure, a wide dissection range, and precise definition of anatomic structures, making it an alternative of choice rather than the maxillary swing approach.
Radiotherapy is one of the cornerstones of the treatment of Head and Neck Squamous Cell Carcinomas (HNSCC). However, radioresistance is associated with a high risk of recurrence. To propose ...strategies (such as combinations with drugs) that could over intrinsic radioresistance, it is crucial to predict the response to treatment. Patient-Derived Tumor Organoids (PDTO) are in vitro tridimensional microtumors obtained from patient' own cancer samples. They have been shown to serve as reliable surrogates of the tumor response in patients.
The ORGAVADS study is a multicenter observational trial conducted to investigate the feasibility of generating and testing PDTO derived from HNSCC for the evaluation of sensitivity to treatments. PDTO are obtained after dissociation of resected tumors remaining from tissues necessary for the diagnosis. Embedding of tumor cells is then performed in extracellular matrix and culture in medium supplemented with growth factors and inhibitors. Histological and immunohistochemical characterizations are performed to validate the resemblance between PDTO and their original tumor. Response of PDTO to chemotherapy, radiotherapy and innovating combinations are assessed, as well as response to immunotherapy using co-cultures of PDTO with autologous immune cells collected from patient blood samples. Transcriptomic and genetic analyses of PDTO allow validation of the models compared to patients' own tumor and identification of potential predictive biomarkers.
This study is designed to develop PDTO models from HNSCC. It will allow comparing the response of PDTO to treatment and the clinical response of the patients from whom they are derived. Our aim is to study the PDTO ability to predict the clinical response to treatment for each patient in view of a personalized medicine as well as to establish a collection of HNSCC models that will be useful for future innovative strategies evaluation.
NCT04261192, registered February 7, 2020, last amendment v4 accepted on June, 2021.
Head and neck cancers have a very poor prognosis and are common in France. They are subject to various recommendations for early detection and management, but there is no detailed data in the French ...general population to fuel the public health debate on it.A high-resolution population-based study about cancer management was conducted, using cancers registries in the north-west of France, on 1729 tumors diagnosed between 2008 and 2010.The tumors were diagnosed late (70.3% stage III-IV), mainly after the onset of symptoms (93.2%). After adjustment, advanced stages were more frequent in patients with hypopharyngeal adjusted odds ratio (ORa): 4.68; 95% confidence interval CI 3.11-7.05 and oropharyngeal tumors (ORa: 2.84; 95% CI 2.02-3.99) compared with oral cavity ones. They were also more frequent in patients with moderate (ORa 1.68; 95% CI 1.12-2.52) or severe comorbidities (ORa 1.86; 95% CI: 1.23-2.80). A multidisciplinary meeting (MM) had taken place in 96.9% of cases. The assessment included a panendoscopy in 80.3% of cases, a cervical computerized tomography (CT) scan in 89.3% and a chest CT scan in 87.3%. The vast majority of patients (90.7%) had received treatment, with surgery in 48.7% of cases and/or radiotherapy in 76.9%.Despite the recommendations for early detection, diagnoses are often made late, even for tumors that can be detected by a direct visual and tactile examination of the oral cavity. However, the major risk of advanced stage concerns deep tumors and the most weakened subjects. Otherwise, diagnostic assessment is broadly consistent with the recommendations, and multidisciplinary treatment decisions are widespread.
In patients with differentiated thyroid cancer (DTC), tumor burden of persistent disease (PD) is a variable that could affect therapy efficiency. Our aim was to assess its correlation with the 2015 ...American Thyroid Association (ATA) risk-stratification system, and its impact on response to initial therapy and outcome.
This retrospective cohort study included 618 consecutive DTC patients referred for postoperative radioiodine (RAI) treatment. Patients were risk-stratified using the 2015 ATA guidelines according to postoperative data, before RAI treatment. Tumor burden of PD was classified into three categories, i.e. very small-, small- and large-volume PD. Very small-volume PD was defined by the presence of abnormal foci on post-RAI scintigraphy with SPECT/CT or
FDG PET/CT without identifiable lesions on anatomic imaging. Small- and large-volume PD were defined by lesions with a largest size < 10 or ≥ 10 mm respectively.
PD was evidenced in 107 patients (17%). Mean follow-up for patients with PD was 7 ± 3 years. The percentage of large-volume PD increased with the ATA risk (18, 56 and 89% in low-, intermediate- and high-risk patients, respectively, p < 0.0001). There was a significant trend for a decrease in excellent response rate from the very small-, small- to large-volume PD groups at 9-12 months after initial therapy (71, 20 and 7%, respectively; p = 0.01) and at last follow-up visit (75, 28 and 16%, respectively; p = 0.04). On multivariate analysis, age ≥ 45 years, distant and/or thyroid bed disease, small-volume or large-volume tumor burden and
FDG-positive PD were independent risk factors for indeterminate or incomplete response at last follow-up visit.
The tumor burden of PD correlates with the ATA risk-stratification, affects the response to initial therapy and is an independent predictor of residual disease after a mean 7-yr follow-up. This variable might be taken into account in addition to the postoperative ATA risk-stratification to refine outcome prognostication after initial treatment.
Objective: To determine risk factors and evaluate the treatment of ethmoid adenocarcinoma. Epidemiologic data were recorded and compared with the literature.
Materials and Methods: A multicenter and ...retrospective study. The medical records of 418 patients who had presented with ethmoid adenocarcinoma at 11 French hospitals from 1976 to 2001 were analyzed to determine the clinical characteristics and treatment of the disease.
Results: The gender ratio was 2.8 men per 1 woman. Toxic exposure was classic for this lesion, exposure to wood and leather for most cases. The mean age was 63 years (range 31–91). Symptoms were nonspecific and based on clinical rhinologic signs. Nasal endoscopy after mucosal retraction was found useful to evaluate the extension of the lesion and to perform biopsies. Computed tomography scan and magnetic resonance imagery must be carried out prior to treatment to define extra nasal extension. The survival rate was significantly influenced by the size of the lesion (T4, N+) and extension to brain or dura. Surgery with postoperative radiotherapy remains the treatment of choice. Total excision must be a major priority, as confirmed in our series.
Conclusion: This retrospective study was, to our knowledge, the largest ever reported in the literature. This series confirmed the risk factor of this lesion as well as the lesion's influence on the survival rate. Surgery is the most important part of the treatment. Local recurrences were responsible for the poor prognosis of this lesion.
Head and neck cancers (HNC) have a poor prognosis and a long treatment delay may have a negative impact on this. Some studies have investigated the determinants of this delay but not in the general ...population and rarely taking into account socio-economic factors. A high-resolution population-based study about cancer management was conducted, using registries in the north-west of France, on HNC diagnosed between 2008 and 2010. The median time between diagnosis and multidisciplinary team meeting (DMI) (
N
= 1631) was 14 days (Q1: 7 to Q3: 26). The median time between diagnosis and first treatment (DTI) (
N
= 1519) was 35 days (Q1: 21 to Q3: 54). When the first treatment was radiotherapy, the interval was 54.5 days (Q1: 40 to Q3: 71). In multivariate analysis, DTI was associated with the type of first treatment and place of treatment. For advanced stage HNC, DTI was associated with comorbidities, topography of the cancer and socio-economic status, underprivileged patients being treated later than privileged ones. Given the French governmental cancer plans which set out to coordinate care pathways via nursing coordinators and to improve the availability of radiotherapy, the waiting times observed in this study still seem long. The optimal care pathway should include adapted social management but the DTI was still longer for underprivileged patients.
Aim
Cetuximab is an anti‐epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated ...with cetuximab use. The aim of the study was to evaluate the utility of anti‐cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab.
Methods
We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti‐cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti‐cetuximab IgE levels (≤29 IgE arbitrary units) subgroup with that in a historical cohort of 213 patients extracted from a previous study.
Results
Of the 301 assessable patients (mean age: 60.9 ± 9.3 years, head‐and‐neck cancer: 77%), 66 patients (22%) had high anti‐cetuximab IgE levels, and 247 patients received cetuximab (including 38 with high anti‐cetuximab levels). Severe HSRs occurred in eight patients (five grade 3 and three grade 4). The proportion of severe HSRs was lower in the low anti‐cetuximab IgE levels subgroup vs. the historical cohort (3/209 1.4% vs. 11/213 5.2%, odds ratio, 0.27, 95% confidence interval, 0.07–0.97), and higher in high vs. low anti‐cetuximab IgE levels subgroup (5/38 13.2% vs. 3/209 1.4%; odds ratio, 10.4, 95% confidence interval, 2.4–45.6). Patients with severe HSRs had higher anti‐cetuximab IgE levels than patients without reaction (median, 45 vs. 2 IgE arbitrary units, P = 0.006).
Conclusions
Detection of pretreatment anti‐cetuximab IgE is feasible and helpful to identify patients at risk of severe cetuximab‐induced HSRs.
Radiotherapy associated with cetuximab (Cet-RT) is an alternative treatment to platinum-based chemoradiotherapy in locally advanced head and neck carcinoma (LAHNC). Reviews suggest that the use of ...cetuximab is associated with poorer tolerance in patients unfit for chemotherapy than in pivotal trial. We retrospectively studied patients first treated by Cet-RT for LAHNC presenting contraindications to chemoradiotherapy. Objectives were treated population description, acute tolerance, progression-free survival (PFS), overall survival (OS), and 3-month clinical response. Eighty-eight patients were included. Treatment was completed without delay for 43 patients. Grade 3–4 acute toxicity was described in 44.3%: mucositis (
n
= 20), radiodermatitis (
n
= 25) folliculitis (
n
= 10), and anaphylaxis (
n
= 6). Fourteen patients died during treatment. Median PFS and OS were 6.3 and 18.7 months, respectively. We confirm that Cet-RT tolerance in unfit patients is poorer than that in trials. Survival data illustrate patients’ frailty and suggest that balanced use of Cet-RT is required in this population.
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