Treatment of supraglottic squamous cell carcinoma with advanced technologies: observational prospective evaluation of oncological outcomes, functional outcomes, quality of life and cost-effectiveness (SUPRA-QoL).

BACKGROUND: Over the past decade, therapeutic options in head and neck supraglottic squamous cell carcinoma have constantly evolved. The classical total laryngectomy has been partially replaced by alternative organ- and function-sparing techniques with the same prognosis but less morbidity, such as Radiotherapy, Transoral Laser Microsurgery (TLM) and Trans-Oral Robotic Surgery (TORS). Up to now, a prospective comparison of these innovant techniques has not been conducted. METHODS/DESIGN: We will conduct an original international multicentric prospective nonrandomized clinical trial to compare the efficacy between these treatments (Arm 1: Radiotherapy ± chemotherapy; Arm 2: TLM and Arm 3: TORS) with 4 classes of outcomes: quality of life (QoL), oncological outcomes, functional outcomes and economic resources. The population will include cT1-T2 /cN0-N1/M0 supraglottic squamous cell carcinoma. The primary outcome is a Clinical Dysphagia QoL evaluation assessed by the MD Anderson Dysphagia questionnaire. Secondary outcomes include others QoL evaluation, oncological and functional measures and cost parameters. The sample size needs to reach 36 patients per arm (total 108). DISCUSSION: In the current literature, no prospective head-to-head trials are available to compare objectively these different treatments. With the increase of highly efficient treatments and the increase of oncological survival, it is imperative also to develop management strategies that optimize QoL and functional results. We will conduct this innovate prospective trial in order to obtain objective data in these two main issues. TRIAL REGISTRATION: NCT05611515 posted on 10/11/2022 (clinicaltrial.fgov).

Cellular and molecular features related to exceptional therapy response and extreme long-term survival in glioblastoma.

Glioblastoma Multiforme (GBM) remains the most common malignant primary brain tumor with a dismal prognosis that rarely exceeds beyond 2 years despite extensive therapy, which consists of maximal safe surgical resection, radiotherapy, and/or chemotherapy. Recently, it has become clear that GBM is not one homogeneous entity and that both intra-and intertumoral heterogeneity contributes significantly to differences in tumoral behavior which may consequently be responsible for differences in survival. Strikingly and in spite of its dismal prognosis, small fractions of GBM patients seem to display extremely long survival, defined as surviving over 10 years after diagnosis, compared to the large majority of patients. Although the underlying mechanisms for this peculiarity remain largely unknown, emerging data suggest that still poorly characterized both cellular and molecular factors of the tumor microenvironment and their interplay probably play an important role. We hereby give an extensive overview of what is yet known about these cellular and molecular features shaping extreme long survival in GBM.

Long-term volumetric analysis of vestibular schwannomas following stereotactic radiotherapy: Practical implications for follow-up.

BACKGROUND AND PURPOSE: Transient tumor swelling is a well-known phenomenon following radiotherapy for vestibular schwannomas (VS). We analyzed the long-term volumetric changes of VS after LINAC radiosurgery, in order to determine a time interval during which a true tumor progression can be distinguished from a pseudoprogression. METHODS: Among 63 patients with VS treated by one fraction or fractionated radiotherapy, we selected 52 of them who had a minimal follow-up of 5 years. Maximal axial diameter and three-dimensional tumor volume were measured on each MRI scan. Volume changes were interpreted using different error margins ranging from 10 to 20%. Patients were categorized according to the tumor evolution pattern over time. RESULTS: Median follow-up was 83 months. One tumor (1.9%) remained stable and 26.9% had continuous shrinkage. Applying an error margin of 13%, a transient tumor enlargement was observed in 63.5% of patients, with a first peak at 6-12 months and a late peak at 3-4 years. A true progression was suspected in 4 (7.7%) patients, tumor regrowth starting after the 3rd or 4th year post-treatment. Only one patient required salvage radiotherapy. CONCLUSION: Transient swelling of VS following radiotherapy is generally an early phenomenon but may occur late. In the first 5 years, a true tumor progression cannot be differentiated from a pseudoprogression. A significant tumor expansion observed on 3 sequential MRI scans after the 3rd year may be suggestive of treatment failure. Long-term follow-up is therefore mandatory and no decision of salvage treatment should be made until the 6th year.

Application of a multi-institutional nomogram predicting salvage whole brain radiation-free survival to patients treated with postoperative stereotactic radiotherapy for brain metastases.

PURPOSE: The ultimate goal of stereotactic radiotherapy (SRT) of brain metastases (BM) is to avoid or postpone whole brain radiotherapy (WBRT). A nomogram based on multi-institutional data was developed by Gorovets, et al. to estimate the 6 and 12-months WBRT-free survival (WFS). The aim of the current retrospective study was to validate the nomogram in a cohort of postoperative BM patients treated with adjuvant SRT. MATERIAL AND METHODS: We reviewed the data of 68 patients treated between 2008-2017 with postoperative SRT for BM. The primary endpoint was the WFS. The receiver operating characteristic curve and area under the curve (AUC) were calculated for both 6- and 12-months time points. RESULTS: After a median follow-up of 64 months, the 1-year cumulative incidence of local and distant brain relapse rates were 15% [95% CI=8-26%] and 34% [95% CI=24-48%], respectively. At recurrence, repeated SRT or salvage WBRT were applied in 33% and 57% cases, respectively. The WFS rates at 6 and 12 months were 88% [95% CI=81-97%] and 67% [95% CI=56-81%], respectively. Using the Gorovets nomogram, the 6 months rates were overestimated while they were accurate at 12 months. AUC values were 0.47 and 0.62 for the 6- and 12-months respectively. Overall, Harrell's concordance index was 0.54. CONCLUSION: This nomogram-predicted well the 12 months WFS but its discriminative power was quite low. This underlines the limits of this kind of predictive tool and leads us to consider the use of big data analysis in the future.

Randomized Clinical Trial on Reduction of Radiotherapy Dose to the Elective Neck in Head and Neck Squamous Cell Carcinoma: Results on the Quality of Life.

PURPOSE: A randomized trial was initiated to investigate whether a reduction of the dose to the elective nodal sites would result in less toxicity and improvement in Quality of Life (QoL) without compromising tumor control. This paper aimed to compare QoL in both treatment arms. METHODS: Two-hundred head and neck cancer patients treated with radiotherapy (RT) or chemo-RT were randomized (all stages, mean age: 60 years, M/F: 82%/18%). The elective nodal volumes of patients randomized in the experimental arm were treated up to a 40 Gy equivalent dose. In the standard arm, the elective nodal volumes were treated up to a 50 Gy equivalent dose. The QoL data were collected using The European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and the EORTC Head and Neck Cancer module (H&N35). RESULTS: A trend toward less decline in QoL during treatment was observed in the 40 Gy arm compared to the 50 Gy arm. Statistically significant differences for global health status, physical functioning, emotional functioning, speech problems, and trouble with social eating in favor of the 40 Gy arm were observed. A clinically relevant better outcome in the 40 Gy arm was found for physical functioning at the end of therapy. CONCLUSION: QoL during RT for head and neck cancer tends to be less impaired in the 40 Gy arm. However, reducing the dose only on the elective neck does not result in clinically relevant improvement of QoL. Therefore, additional treatment strategies must be examined to further improve the QoL of HNSCC patients.

Surgical bed stereotactic radiotherapy of brain metastases: Clinical outcome and predictors of local and distant brain failure.

PURPOSE: To retrospectively analyze the outcomes of stereotactic radiotherapy (SRT) targeted at surgical bed of brain metastases (BM) and identify patterns of local/distant brain relapses (LR/DBR). PATIENTS/METHODS: Seventy patients were treated with SRT between 2008-2017. Marginal dose prescription on the 70% isodose line depended on the maximal diameter of the target volume and range between 15-18Gy for single fraction radiosurgery and 23.1-26Gy in 3-5 fractions for fractionated SRT. RESULTS: At 12 months, the overall survival (OS) was 69% [CI 95%=59%-81%]. At 6 and 12 months, the cumulative incidence functions (CIF) of local relapse were 4% [1%-13%] and 15% [8%-26%], respectively. According to univariate analysis, factors associated with LR were an initial volume larger than 7cc (hazard ratio: 4.6 [1.0-20.8], P=0.046) and a positive resection margin [hazard ratio: 3.6 [1.1-12.0], P=0.037. DBR occurred in 54.3% of patients with a median time of 8 months. None of the variables tested (histology, location or number of lesions) were found correlated with the DBR. Leptomeningeal disease occurred in 12.9% of cases. Salvage whole brain radiotherapy (WBRT) was required in 45.7% of patients and delayed by a median time of 9.6 months. Symptomatic radionecrosis (RN) occurred in 7.1%. CONCLUSIONS: Adjuvant SRT was an effective and well-tolerated treatment to control the postoperative risk of recurrence of BM without compromising OS. Positive resection margins and large volumes were predictors factor of local relapse.

[Stereotactic radiotherapy for brain metastasis]. / Radiothérapie en conditions stéréotaxiques des métastases cérébrales.

Stereotactic radiosurgery is now well implanted in the radiotherapy treatment tools of brain metastasis. The dose can be delivered in one or multiple sessions. Results seem equivalent. CT scan and MRI imaging are required to delineate and calculate dosimetry. Doses are variable according to the size of the metastases, localization, pathology or equipment. Stabilization or reduction of tumour size is the rules after stereotactic treatment. Impact in terms of overall survival is more difficult to apprehend because of the general context of the disease. Many questions remain unresolved, such as the usefulness of whole brain irradiation, adaptation of the treatment schedule to tumour pathophysiology, role of stereotactic treatment after surgery of metastases, etc.

Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer.

BACKGROUND: To assess the safety and preliminary efficacy of concurrent radiotherapy, capecitabine, and cetuximab in the preoperative treatment of patients with rectal cancer. PATIENTS AND METHODS: Forty patients with rectal cancer (T3-T4, and/or N+, endorectal ultrasound) received preoperative radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, three-dimensional conformal technique) in combination with cetuximab [initial dose 400 mg/m(2) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily, second dose level). RESULTS: Four and six patients were treated at the first and second dose level of capecitabine, respectively. No dose-limiting toxicity occurred. Thirty additional patients were treated with capecitabine at 825 mg/m(2) twice daily. The most frequent grade 1/2 side-effects were acneiform rash (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%. Three grade 4 toxic effects were recorded: one myocardial infarction, one pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%) had a pathological complete response. CONCLUSIONS: Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging.

The opinion of general practitioners on the treatment of prostate and breast cancer in elderly people: results of a survey based on clinical models.

AIMS: Several publications have reported age-related differences in the management of people with cancer. Most data have been derived retrospectively from hospital or cancer-centre databases. The aim of the present study was to identify major decisional factors observed in general practitioner (GP) practices, outside the hospital setting, regarding the clinical management of patients with prostate and breast cancer. MATERIALS AND METHODS: During three national GP meetings in Belgium, questionnaires presenting two simulated patient cases were presented to GPs who were asked two questions: one regarding further staging and referral of the case and the second regarding the treatment of the case. A total of 678 questionnaires were distributed. GPs received two randomly selected cases each: a breast cancer history and a prostate cancer history. Three variables were assessed simultaneously: age, performance status and medical history (comorbidity). RESULTS: The analysis indicated that elderly patients were more likely to be referred for non-curative treatment (OR 13.71; 95% CI 5.67-33.12; P < 0.0001 for prostate cancer and OR 17.67; 95% CI 4.04-77.31; P < 0.0001 for breast cancer). The other variables (performance status and medical history) did not affect treatment orientation. However, GPs were prepared to seek assistance from oncologists in both cases, irrespective of the patient's age. CONCLUSION: Age seems to be more important among GPs in deciding how to manage cancer patients than performance status and comorbidity. This is a very common prejudice. They are, nevertheless, inclined to refer people with cancer to oncologists independently of the patient's age.

[Selection and delineation of lymph node target volumes in head and neck neoplasms]. / Sélection et délimitation des volumes-cibles anatomocliniques ganglionnaires dans les tumeurs de la sphère cervico-maxillo-faciale.

This article reviews all clinical and pathological data available in the literature supporting the concept of selectivity in the neck nodes to be included in the Clinical Target Volume for head and neck squamous cell carcinoma. Using the terminology of neck node levels and the guidelines for the surgical delineation of these levels proposed by the Committee for Head and Neck Surgery and Oncology of the American Academy for Otolaryngology-Head and Neck Surgery, recommendations are proposed for both the selection and the delineation of lymph node target volumes.