Effect of lymphoid volume irradiation on radiation-induced lymphopenia in head and neck cancers.

PURPOSE: Radiotherapy induces significant and prolonged lymphopenia in head and neck cancer patients with poorer outcomes and reduced survival. Irradiated volumes may be correlated with lymphopenia with a potential impact on immunotherapy efficacy. We assessed associations between volumes treated with radiotherapy and the nadir of the lymphocyte count in patients with head and neck cancer. MATERIALS AND METHODS: We conducted a monocentric retrospective study in patients with head and neck cancer treated with radiation. Univariate analysis used regression analysis to model nadir lymphocyte count and radiotherapy volumes; multivariate analysis then modelled factors associated with nadir lymphocyte count. RESULTS: Of the 77 included patients, 97% presented lymphopenia during radiotherapy with an average nadir of 431 cells/mm3 at a median of 40 days after the beginning of treatment. The volume of high-risk radiotherapy and gross tumour volume were correlated with nadir lymphocyte count with a Spearman coefficient of -0.267 (P=0.019) and -0.387 (P=0.001), respectively. After multivariate linear regression, high-risk radiotherapy was significantly associated with nadir lymphocyte count with a regression coefficient of -0.32 (per cubic centimetre) [95% CI=-0.60; -0.03] (P=0.028). CONCLUSION: High-risk radiotherapy was significantly associated with nadir lymphocyte count in patients with head and neck cancer treated with radiation. Sparing lymphoid volumes from irradiation by elective nodal irradiation or proton therapy may limit lymphopenia and needs to be investigated in combination with immunotherapy.

Radiation therapy on primary tumour of synchronous metastatic head and neck squamous cell carcinomas.

PURPOSE: Patients with synchronous metastatic head and neck squamous cell carcinomas often present associated locoregional symptoms and a risk of life-threatening primary tumour progression. Few data have been published about the use of radiation therapy in the management of newly diagnosed metastatic disease associated with advanced locoregional disease. In this article, we aim to determine the role of radiation therapy of the primary tumour in the overall therapeutic strategy for these diseases. We further address radiation therapy modalities (technique, volumes, and fractionation) in such a context. MATERIAL AND METHODS: We conducted a literature survey on locoregional radiotherapy for newly diagnosed metastatic head and neck squamous cell carcinomas. RESULTS: Several retrospective studies have reported that locoregional radiotherapy is associated with improved overall survival of patients with synchronous metastatic head and neck squamous cell carcinomas. However, data about modalities such as timing of radiotherapy in the overall strategy, dose, fractionation and delineation volumes are scarce. Two schematic situations can be distinguished with respect to prognosis and treatment adaptations: polymetastatic/bulky or oligometastatic disease. In polymetastic/bulky disease associated with poor prognosis, standard-of-care is systemic therapy, but locoregional radiotherapy can be discussed either upfront, mainly for symptomatic palliation, or as consolidation after downsizing obtained by systemic therapy. As for oligometastatic disease, with the rise in use of efficacious and well-tolerated local ablative treatments of metastases, aggressive curative-intent locoregional radiotherapy can be considered with or without systemic therapy. CONCLUSION: Because locoregional disease is a major cause of disease failure in patients with synchronous metastatic head and neck squamous cell carcinomas, aggressive locoregional radiation therapy to the primary tumour may be discussed in the initial management of the disease where systemic therapy alone may not induce sufficient primary tumour reduction. With recent technological advances in radiotherapy, the delivery of radiotherapy is safe and feasible even in metastatic setting. Clinical trials assessing radiotherapy use for metastatic head and neck squamous cell carcinomas are warranted.

Routine feasibility of postoperative chemoradiotherapy in head and neck squamous cell carcinoma at high risk of recurrence.

OBJECTIVE: To assess the feasibility in routine practice of postoperative chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC) at high risk of recurrence. METHOD: A single-center retrospective study recruited all patients receiving postoperative cisplatin chemoradiotherapy for HNSCC at high risk of recurrence. The main endpoints were the rate of complete postoperative chemoradiotherapy and the impact of various clinical factors. Secondary endpoints comprised the impact of completion of therapy on survival and on acute and late toxicity. RESULTS: One hundred and six patients were included. 24.5% showed severe comorbidity. Chemoradiotherapy was complete in 61 patients (57.5%). Radiation therapy was interrupted for >3 days in 16 patients (15.1%). The 3rd concomitant cisplatin course could not be implemented in 34 patients (32.1%). Low pre-treatment glomerular filtration rate was significantly associated (p=0.003) with treatment interruption; >5% weight-loss during treatment showed suggestive association (p=0.026). Completion of treatment was not associated with any significant difference in overall survival (p=0.441) or progression-free survival (p=0.81). 14.9% of patients showed post-treatment kidney failure; there were 10 cases of osteoradionecrosis (9.4%). CONCLUSION: The rate of complete postoperative chemoradiotherapy was comparable to that reported in clinical trials, despite frequent comorbidity and poor nutritional status. Early nutritional support is a key factor for treatment under optimal conditions.

Challenges and advances in cervix cancer treatment in elder women.

With population ageing, cancer treatments in elder patients is becoming a true public health care issue. There is an authentic dilemma between patient's frailty, residual life expectancy and the toll that take anticancer treatments. Since elder patients are almost always excluded from clinical trials, it is hard to get robust scientific data on the tolerability of oncologic treatments and to set in place recommendations. Cervix cancer is traditionally diagnosed in younger women but it has a 2nd incidence peak between 60 and 70 years old. Cervix cancer in elder patients is a subject to many questions in terms of screening and is a therapeutic challenge. This article reviews literature data on these different aspects, from screening to surgery, from radiotherapy to brachytherapy, from chemotherapy to supportive care, from immunotherapy to geriatric assessment. We tried to show how modern therapeutic innovations may benefit elder patients. Expected benefits in terms of efficacy and toxicity may overcome the long-lasting tendency to undertreatment in elder patients and improve their quality of life after cancer treatment. In 2020, there seems to be less and less reasons justifying that elder women with cervix cancer may not receive the appropriate treatment.

Impact of locoregional irradiation in patients with upfront metastatic head and neck squamous cell carcinoma.

OBJECTIVE: To evaluate the frequency of use, modalities and potential interest of locoregional irradiation (LRT) in patients with upfront metastatic head and neck squamous cell carcinoma (HNSCC). METHODS: Retrospective multicentric study. Were included all patients presenting an upfront metastatic HNSCC treated by platin-5FU- cetuximab based regimen, from 2008 to 2016. Patients with past history of cervical irradiation or HNSCC within the 5 years before metastasis diagnosis were excluded. RESULTS: 65 patients were included. 25 patients (38%) presented a response or stable disease with chemotherapy. Forty-one patients (63%) underwent a locoregional irradiation: 5 patients before chemotherapy (upfront RT), 13 patients with stable disease or response after chemotherapy (consolidation RT), and 23 patients with progressive disease. Median overall survival (OS) was 11.6 months, median progression free survival was 7.9 months. OS was significantly improved for patients who underwent LRT (median OS 16.1 vs 7.5 months, p < 0.01). Among patients who received LRT, OS trended to be better if LRT was performed as consolidation RT compared to upfront RT (median OS of 22.1 vs 15.5 months, p = 0.11). Among patients with stable disease or response after chemotherapy, there was a non-significant better OS for the 13 patients treated by LRT (median OS 22.1 vs 11.8 months, p = 0.21)). Radical dose was not associated with better locoregional control compared to palliative dose (p = 0.37). CONCLUSION: LRT is frequently performed during management of upfront metastatic HNSCC and associated with better OS. Non-progressive disease after firs-line chemotherapy seems a good way to select patients who would benefit from radical LRT.

Platinum rechallenge in recurrent head and neck squamous cell carcinoma after primary chemoradiation.

OBJECTIVE: To evaluate platinum rechallenge efficacy and tolerance in patients presenting recurrent head and neck squamous cell carcinoma (HNSCC) after platinum-based chemoradiation. MATERIALS AND METHODS: We retrospectively included all patients treated from 2007 to 2016 by platinum-based polychemotherapy for recurrence of HNSCC previously treated by primary or postsurgical platinum-based chemoradiation. The primary end-point was disease control rate (DCR) on platinum rechallenge. RESULTS: Forty-five patients were included. Median disease-free interval (DFI) after chemoradiation was 5.7 months. DCR on platinum rechallenge was 40%. Progression-free survival at recurrence was 3.7 months and overall survival 5.0 months. DCR in patients with recurrence within 6 months of chemoradiotherapy was 47.8%. DFI>4.5 months was associated with better DCR: 28.5% versus 54.8%; P=0.0311. CONCLUSION: Platinum rechallenge provided good DCR in recurrent HNSCC after chemoradiation.