Pignat's vertical partial laryngectomy with crico-hyoido-epiglotto-plasty.

PURPOSE: Pignat's partial laryngectomy with crico-hyoido-epiglotto-plasty (CHEPL) is a vertical laryngectomy with resection of the anterior portion of the thyroid cartilage and reconstruction with a wires net and the subhyoid muscles. The aim of this retrospective study was to evaluate and analyze oncologic and functional outcomes in patients affected by laryngeal squamous cell carcinoma and treated with Pignat's partial laryngectomy. METHODS: Seventy patients with cT1-cT3 glottic cancer were surgically treated with Pignat's technique. EXCLUSION CRITERIA: invasion of posterior cricoid arch, more than 3 mm under glottis, of more than one arytenoid, of posterior portion of thyroid cartilage, of the suprahyoid epiglottis. Overall survival, disease free survival, rates of decannulation and enteral feeding were analyzed. RESULTS: 23 (32.9%) pT1, 37 (52.9%) pT2, 5 (7.1%) pT3, 5 (7.1%) pT4a, 64 (91.5%) pN0, 5 (7.1%) pN1, 1 (1.4%) pN2. Adjuvant treatment was administered to 13 patients (18.6%). All patients had tracheotomy. Five year OS and DFS were 81.66 and 77.95%, respectively. A statistically significant DFS difference was observed between early and late stages. Five year local control was 81.16%. Five year larynx preservation rate was 89.16%. Median decannulation time was 12 days. Median duration of enteral nutrition was 16 days. All patients achieved efficient phonation. CONCLUSION: Pignat's partial laryngectomy with CHEPL can represent an alternative to horizontal supracricoid laryngectomy to achieve laryngeal preservation. Good oncologic and functional outcomes are possible as long as indications are followed.

Resection and reconstruction of the carotid artery for head and neck squamous cell carcinoma: a GETTEC study.

OBJECTIVES: Main: To describe 1-year overall survival (OS) after primary or salvage management of head and neck squamous cell carcinoma (HNSCC) invading the common or internal carotid artery (CCA/ICA). Secondary: To assess disease control rate, treatment morbidity, and radio-anatomopathologic correlation. METHODS: Retrospective study of 67 patients, treated between 1999 and 2020 for N3bM0 HNSCC invading the CCA/ICA as identified by CT-scan. Tumors that could not have been resected with a complete en-bloc resection sacrificing and reconstructing the CCA/ICA were excluded. Patients were separated into two groups (primary or salvage treatment) and studied according to the type of treatment they received: radiotherapy/radiochemotherapy (RT/RCT), surgery, or systemic therapy (ST). RESULTS: For newly treated patients, the 1-year OS was significantly better after RT/RCT (73%) than after surgery (40%, p < 0.0001). In the salvage setting, the 1-year OS after surgery (40%) was better than after ST (14%, statistically suggestive difference with p = 0.0241). Surgery improved cervical control, but distant metastases occurred in more than 50% of cases regardless of treatment. No neurological complication occurred after carotid reconstruction. Perioperative mortality was 7% (1/15). The carotid invasion was confirmed by pathological examination in all five patients with an arterial deformation on CT-scan, in seven among eight patients with CCA/ICA encasement greater than 270°, and in four out of seven patients with CCA/ICA encasement between 180° and 270°. CONCLUSION: Neck dissection with carotid resection and reconstruction is technically feasible with acceptable neurovascular morbidity. For newly treated patients, survival is better after RT/RCT. For salvage treatment, surgery could be proposed to selected patients.

Mortality of patients with solid and haematological cancers presenting with symptoms of COVID-19 with vs without detectable SARS-COV-2: a French nationwide prospective cohort study.

BACKGROUND: Over 30 million COVID-19 cases have been diagnosed worldwide from late 2019. Among frail persons, cancer patients are at high risk of death from COVID-19. METHODS: The French prospective cohort ONCOVID-19 enrolled patients with solid or haematological tumour, receiving anticancer treatment and presenting with clinical symptoms suggestive of COVID-19. COVID-19 was confirmed through detectable SARS-CoV2 by RT-PCR (repeated twice if negative first) and/or specific CT-scan. The study aims to assess the 28-day mortality rate after the first COVID test. RESULTS: From March 1st to May 21st 2020, 23 French cancer centres and hospitals enrolled 1230 cancer patients with suspicion of COVID-19, including 1162 (94.5%) matching the inclusion criteria. We identified 425 (36.6%) COVID-19 positive patients including 155 (13.3%) diagnosed with CT-scan only, while 737 (63.4%) patients were COVID-19 negative. Death at day-28 occurred in 116/425 (27.8%) COVID-19 positive patients, and in 118/737 (16.3%) COVID-19 negative patients (p < 0·0001). With a median follow-up of 2.1 (1.6-2.4) months, 310 (26.7%) deaths were reported including 143 (33.6%) in the COVID-19 positive population, and 167 (22.7%) in the COVID-19 negative patients. Male gender, age, metastatic disease, immunosuppressive treatments, lymphopenia, COVID-19 diagnosis and diabetes were independent risk factors for death. CONCLUSION: Patients with solid and haematological cancers presenting COVID-19 symptoms with SARS-CoV-2 RT-PCR confirmed or not are both at high-risk of early mortality. COVID-19 is reported as the cause of death in 50% of COVID-19 positive patients with cancer. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT04363632.

Systematic screening for occupations and occupational exposures in head and neck squamous cell carcinoma patients.

PURPOSE: The importance of occupational exposures in patients with head and neck squamous cell carcinomas (HNSCC) has received little attention. METHODS: In a single-center study, we prospectively characterized occupational exposures in 154 HNSCC cancer patients in a systematic occupational consultation and examined the association between most frequent exposures, HNSCC stage and localization. RESULTS: Patients occupied a mean of 3.3 different positions during their working life. The prevalence of asbestos, the most frequent exposure (46 patients; 29.9%) was higher than in the French population > 50 years. Other frequent exposures were solvents (n = 26; 16.9%) and silica (n = 19; 12.3%). For 37 patients (24%) a possible link was identified between occupational exposures and HNSCC. Duration of asbestos exposure was significantly higher (p = 0.04) in patients with hypopharyngeal and laryngeal cancer compared to other localizations. CONCLUSIONS: Occupational exposures are frequent in patients with HNSCC and should receive increased attention by physicians.

Can Early Dissection of Cervical Lymph Nodes Improve Prognosis in Squamous Cell Carcinomas of the Hard Palate.

Squamous cell carcinomas of the hard palate and maxillary alveolar ridge are rare tumours with a poor prognosis. Lymph node dissection is recommended for tumours with nodal involvement, and is rarely performed in the absence of adenopathy. We report a series of patients with squamous cell carcinomas and evaluate the rate of lymph node invasion and its impact on survival. This is a retrospective study of 72 patients treated for squamous cell carcinoma of the hard palate and maxillary alveolar ridge between January 1, 1998 and December 31, 2008 in two cancer centres. Using clinical and radiological assessment, tumours were classified as T1-T2 in 25 patients (34.7%) and T3-T4 in 47 patients (65.3%). At diagnosis, 16 (22.2%) patients had clinical and/or radiological nodal involvement and 7 patients (9.7%) distal metastasis. Among N0 patients, 13 (18%) experienced isolated lymph node recurrence. Two-year global survival was 60%; 5-year survival was 34%. The rate of lymph node invasion observed in squamous cell carcinoma of the hard palate and maxillary alveolar ridge does not differ from other oral cavity sites. Because nodal recurrence worsens the prognosis of such a patient, lymph node dissection should be considered at an early stage, even among N0 patients.

An effective and well-tolerated strategy in recurrent and/or metastatic head and neck cancer: successive lines of active chemotherapeutic agents.

BACKGROUND: The combination platinum, 5-fluorouracil (5-FU) and cetuximab is the standard first-line regimen of recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). Due to the toxicity of this treatment, alternative therapies are often offered to patients. The aim of this study was to evaluate the overall survival obtained with a first line chemotherapy adapted to patients functional status and the administration of all active drugs within successive lines of chemotherapy. METHODS: This series included a total of 194 patients with recurrent and/or metastatic HNSCC treated from 2006 to 2011 in a single institution where the administration of successive lines of chemotherapies has been the standard clinical approach. Treatment was administered according to clinical practice guidelines. RESULTS: Most patients received at least two treatment lines. Only 11 patients (6%) were treated with a combination of cisplatin, 5-FU and cetuximab in front line, but most patients received at least one platinum-based regimen (n = 154 patients, 78%); 162 (82%) received taxanes, 36 (18%) received 5-FU, 27 (14%) received capecitabine, 67 (34%) received methotrexate and 134 (68%) received cetuximab. The median overall survival was 9.8 months (95% CI: 8.1-11.4 months) and reached 13.1 months among the subgroup of 131 patients eligible for inclusion in a clinical trial. CONCLUSION: The survival outcomes of patients treated in the first-line setting with chemotherapy regimens adapted to their functional status, followed by several subsequent regimens were comparable with published outcomes of patients treated by platinum, 5-FU and cetuximab.

A pyriform sinus cancer organ preservation strategy comprising induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil, followed by potentiated radiotherapy: a multicenter, retrospective study.

No specific study has evaluated the role of neoadjuvant DCF (docetaxel, cisplatin, 5-fluorouracil) followed by radiotherapy in pyriform sinus cancer, which are often included in studies focusing on laryngeal and hypopharyngeal cancer. We assessed the proportion of patients treated sequentially for a pyriform sinus cancer with a preserved larynx. Overall survival, event-free survival (EFS), survival with 'local control', and treatment tolerance were assessed as well. We retrospectively reviewed 88 patients with advanced pyriform sinus squamous cell carcinoma treated with DCF between 2005 and 2010. After induction, radiation could be potentiated with cetuximab or cisplatin. Most patients (82%) had been treated with organ preservation intent. The response rate to DCF was 85%, including 42% with complete response. Primary tumor was operated in 13 patients (eight with total laryngectomy). Radiotherapy had been delivered to 78 (89%) patients (30 with cisplatin, 39 with cetuximab). Potentiation had been achieved as planned in 52 and 79% of patients treated with cisplatin and cetuximab, respectively. Twenty-three local and three neck recurrences were found. Median overall survival was 16.8 months and 38.3% at 3 years. EFS at 3 years was 29.1% with a hazard ratio for partial responders versus nonresponders of 0.18 (P<0.001), and 0.13 (P<0.001) for complete responders versus nonresponders. Thirty-five percent of patients were alive with their larynx preserved at 3 years. This study confirms the efficacy of induction followed by chemoradiation for pyriform sinus cancer and that response to DCF is predictive of EFS.

Gingiva squamous-cell carcinoma in a non-smoking patient with occupational exposure to solvent siphoning using mouth: case report and literature review.

Background: While overall head and neck cancer incidence decreases due to reduced tobacco and alcohol consumption, the incidence of HPV negative oral cavity squamous cell carcinoma (SCC) is raising in several industrialized countries, especially in non-smoking and non-drinking patients. Case presentation: We document a case of gingiva SCC in a 56 years old never-smoker patient reporting low alcohol consumption and unusual occupational solvent exposure. The HPV-negative lesion was surgically removed in 2018, and the patient remains in complete remission 4 years after recurrent surgery in 2019. In 2021, the patient was referred to the occupational cancer consultation. The patient worked as screen printer for 18 years. He reported mouth siphoning every 2-3 days to transfer organic solvents (mainly aromatic hydrocarbons and ketones) from containers into smaller recipients, with regular passage of solvents into his mouth. Conclusion: According to the literature, the frequency of solvent siphoning using mouth is likely to be underestimated. While our review did not find studies reporting longterm consequences to the oral cavity of mouth siphoning, current evidence supports a positive association of upper aero digestive tract SCC with occupational exposures to organic solvents and printing processes. In absence of major extraprofessional factors, the HPV-negative gingiva SCC of this patient might be attributable to the regular occupational oral solvent exposure. While the available evidence remains limited to formally establish a causal relationship, clinicians should investigate this hazardous work practice in patients with OSCC and history of solvent exposures.

A multi-centric dataset on patient-individual pathological lymph node involvement in head and neck squamous cell carcinoma.

Dataset: We provide a dataset on lymph node metastases in 968 patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC). All patients received neck dissection and we report the number of metastatic versus investigated lymph nodes per lymph node level (LNL) for every individual patient. Additionally, clinicopathological factors including T-category, primary tumor subsite (ICD-O-3 code), age, and sex are reported for all patients. The data is provided as three datasets: Dataset 1 contains 373 HNSCC patients treated at Centre Léon Bérard (CLB), France, with primary tumor location in the oral cavity, oropharynx, hypopharynx, and larynx. Dataset 2 contains 332 HNSCC patients treated at the Inselspital, Bern University Hospital (ISB), Switzerland with primary tumor location in the oral cavity, oropharynx, hypopharynx, and larynx. For these patients, additional information is provided including lateralization of the primary tumor, size and location of the largest metastases, and clinical involvement based on computed tomography (CT), magnetic resonance imaging (MRI), and/or 18FDG-positron emission tomography (PET/CT) imaging. Dataset 3 consists of 263 oropharyngeal SCC patients underlying a previous publication by Bauwens et al. [1], which were treated at CLB. For these patients, additional information including HPV status, lateralization of the primary tumor and clinically diagnosed lymph node involvement is provided. Reuse Potential: The data may be used to quantify the probability of occult lymph node metastases in each LNL, depending on an individual patient's characteristics of the primary tumor and the location of clinically diagnosed lymph node metastases. As such, the data may contribute to further personalize the elective treatment of the neck for HNSCC patients, i.e. definition of the elective clinical target volume (CTV-N) in radiotherapy (RT) and the extent of neck dissection (ND) in surgery. There exists only one similar publicly available dataset that reports clinical involvement per LNL in 287 oropharyngeal SCC patients [2]. The data presented in this article substantially extends the available data, it additionally includes pathologically assessed involvement per LNL, and it provides data for multiple subsites in the head and neck region.

An Integrated Cancer Prevention Strategy: the Viewpoint of the Leon Berard Comprehensive Cancer Center Lyon, France.

This article describes some of the key prevention services in the Leon Berard Comprehensive Cancer Center (CLB) Lyon, France, which are based on clinical prevention services, outreach activities, and collaboration with professional and territorial health communities. In addition, research is embedded at all stages of the prevention continuum, from understanding cancer causes through to the implementation of prevention interventions during and after cancer. Health promotion activities in the community and dedicated outpatient primary cancer prevention services for individuals at increased risk have been implemented. The CLB's experience illustrates how prevention can be integrated into the comprehensive mission of cancer centers, and how in turn, the cancer centers may contribute to bridging the current fragmentation between cancer care and the different components of primary, secondary, and tertiary prevention. With increasing cancer incidence, the shift toward integrated prevention-centered cancer care is not only key for improving population health, but this may also provide a response to the shortage of hospital staff and overcrowding in cancer services, as well as offer opportunities to reduce carbon emissions from cancer care.

Neoadjuvant TPF in locally advanced head and neck cancer can be followed by radiotherapy combined with cisplatin or cetuximab: a study of 157 patients.

Neoadjuvant TPF (docetaxel, cisplatin, 5-fluorouracil), followed by radiotherapy or chemoradiotherapy with weekly carboplatin, increases overall survival and organ preservation. We assessed whether TPF could be used in routine practice and whether radiotherapy potentiated with cisplatin or cetuximab was feasible and could increase survival. We retrospectively reviewed 157 patients with advanced head and neck squamous cell carcinoma treated with TPF in four French institutions between May 2005 and March 2009. After induction, operable patients had undergone surgery and were irradiated, and potentiated in some cases with cetuximab or cisplatin. Most patients (79%) had been treated with organ preservation strategies. The two most common sites were the hypopharynx (34%) and the oropharynx (30%). The response rate to TPF was 84%, including 26% with a complete response. Radiotherapy had been provided to 144 (92%) patients (of whom 17 had received radiotherapy alone, 46 had received q3w cisplatin, 30 had received q1w cisplatin, and 37 had received cetuximab). Potentiation had been achieved as planned in 59, 63, and 62% of patients treated with q3w cisplatin, q1w cisplatin, and cetuximab, respectively. After a median follow-up of 39.9 months, the median overall survival was 43 months. No significant difference was observed in progression-free survival or overall survival according to the type of potentiation. This study confirms the efficacy and tolerability of TPF induction, followed by chemoradiation, with outcomes similar to those for patients irradiated without induction. The best potentiation of radiotherapy after induction has not yet been determined.

From data strategy to implementation to advance cancer research and cancer care: A French comprehensive cancer center experience.

In a comprehensive cancer center, effective data strategies are essential to evaluate practices, and outcome, understanding the disease and prognostic factors, identifying disparities in cancer care, and overall developing better treatments. To achieve these goals, the Center Léon Bérard (CLB) considers various data collection strategies, including electronic medical records (EMRs), clinical trial data, and research projects. Advanced data analysis techniques like natural language processing (NLP) can be used to extract and categorize information from these sources to provide a more complete description of patient data. Data sharing is also crucial for collaboration across comprehensive cancer centers, but it must be done securely and in compliance with regulations like GDPR. To ensure data is shared appropriately, CLB should develop clear data sharing policies and share data in a controlled, standardized format like OSIRIS RWD, OMOP and FHIR. The UNICANCER initiative has launched the CONSORE project to support the development of a structured and standardized repository of patient data to improve cancer research and patient outcomes. Real-world data (RWD) studies are vital in cancer research as they provide a comprehensive and accurate picture of patient outcomes and treatment patterns. By incorporating RWD into data collection, analysis, and sharing strategies, comprehensive cancer centers can take a more comprehensive and patient-centered approach to cancer research. In conclusion, comprehensive cancer centers must take an integrated approach to data collection, analysis, and sharing to enhance their understanding of cancer and improve patient outcomes. Leveraging advanced data analytics techniques and developing effective data sharing policies can help cancer centers effectively harness the power of data to drive progress in cancer research.

Predicting acute severe toxicity for head and neck squamous cell carcinomas by combining dosimetry with a radiosensitivity biomarker: a pilot study.

OBJECTIVE: Radiotherapy (RT) against head and neck squamous cell carcinomas (HNSCC) may lead to severe toxicity in 30-40% of patients. The normal tissue complication probability (NTCP) models, based on dosimetric data refined the normal tissue dose/volume tolerance guidelines. In parallel, the radiation-induced nucleoshuttling (RIANS) of the Ataxia-Telangiectasia Mutated protein (pATM) is a predictive approach of individual intrinsic radiosensitivity. Here, we combined NTCP with RADIODTECT©, a blood assay derived from the RIANS model, to predict RT toxicity in HNSCC patients. METHODS: RADIODTECT© cutoff values (i.e. 57.8 ng/mL for grade⩾2 toxicity and 46 ng/mL for grade⩾3 toxicity) have been previously assessed. Validation was performed on a prospective cohort of 36 HNSCC patients treated with postoperative RT. Toxicity was graded with the Common Terminology Criteria for Adverse Events (CTCAE) scale and two criteria were considered: grade⩾2 oral mucositis (OM2), grade⩾3 mucositis (OM3) and grade⩾2 dysphagia (DY2), grade⩾3 dysphagia (DY3). pATM quantification was assessed in lymphocytes of HNSCC patients. The discrimination power of the pATM assay was evaluated through the Area Under the Receiver Operator Characteristics Curve (AUC-ROC). Two previously described NTCP models were considered, including the dose to the oral cavity and the mean dose to the parotid glands (OM2 and OM3) and the dose to the oral cavity, to the larynx and the volume of pharyngeal constrictor muscles (DY2 and DY3). RESULTS: Combining NTCP models with RADIODTECT© blood test improved the AUC-ROC. Considering the prediction of mucositis, AUC-ROCNTCP+RADIODTECT©=0.80 was for OM2, and AUC-ROCNTCP+RADIODTECT©=0.78 for OM3. Considering the prediction of acute dysphagia, AUC-ROCNTCP+RADIODTECT©=0.71 for DY2 and for DY3. CONCLUSIONS: Combining NTCP models with a radiosensitivity biomarker might significantly improve the prediction of toxicities for HNSCC patients.

Addictions, Social Deprivation and Cessation Failure in Head and Neck Squamous Cell Carcinoma Survivors.

AIM: To evaluate the evolution of addictions (tobacco and alcohol) and social precarity in head and neck squamous cell carcinoma survivors when these factors are addressed from the time of diagnosis. METHODS: Addictions and social precarity in patients with a new diagnosis of HNSCC were assessed through the EPICES score, the Fagerström score, and the CAGE questionnaire. When identified as precarious/dependent, patients were referred to relevant addiction/social services. RESULTS: One hundred and eighty-two patients were included. At the time of diagnosis, an active tobacco consumption was associated with alcohol drinking (Fisher's exact test, p < 0.001). Active smokers were more socially deprived (mean EPICES score = mES = 36.2 [±22.1]) than former smokers (mES = 22.8 [±17.8]) and never smokers (mES = 18.9 [±14.5]; Kruskal-Wallis, p < 0.001). The EPICES score was correlated to the Fagerström score (Kruskal-Wallis, p < 0.001). Active drinkers (mES = 34.1 [±21.9]) and former drinkers (mES = 32.7 [±21]) were more likely to be socially deprived than those who never drank (mES = 20.8 [±17.1]; Krukal-Wallis, p < 0.001). A Fagerström score improvement at one year was associated to a CAGE score improvement (Fisher's exact test, p < 0.001). Tobacco and alcohol consumption were more than halved one year after treatment. Patients who continued to smoke one year after diagnosis were significantly more likely to continue to drink (Fisher's exact test, p < 0.001) and had a significantly higher initial EPICES score (Kruskal-Wallis, p < 0.001). CONCLUSIONS: At one year, addictions and social deprivation tend to improve when taken care of from the diagnosis. The most dependent patients and those with multiple frailties are at highest risk of cessation failure.

Randomized phase II study of preoperative afatinib in untreated head and neck cancers: predictive and pharmacodynamic biomarkers of activity.

There is no strong and reliable predictive biomarker in head and neck squamous cell carcinoma (HNSCC) for EGFR inhibitors. We aimed to identify predictive and pharmacodynamic biomarkers of efficacy of afatinib, a pan-HER tyrosine kinase inhibitor, in a window-of-opportunity trial (NCT01415674). Multi-omics analyses were carried out on pre-treatment biopsy and surgical specimen for biological assessment of afatinib activity. Sixty-one treatment-naïve and operable HNSCC patients were randomised to afatinib 40 mg/day for 21-28 days versus no treatment. Afatinib produced a high rate of metabolic response. Responders had a higher expression of pERK1/2 (P = 0.02) and lower expressions of pHER4 (P = 0.03) and pRB1 (P = 0.002) in pre-treatment biopsy compared to non-responders. At the cellular level, responders displayed an enrichment of tumor-infiltrating B cells under afatinib (P = 0.02). At the molecular level, NF-kappa B signaling was over-represented among upregulated genes in non-responders (P < 0.001; FDR = 0.01). Although exploratory, phosphoproteomics-based biomarkers deserve further investigations as predictors of afatinib efficacy.

Efficacy and safety of capecitabine in heavily pretreated recurrent/metastatic head and neck squamous cell carcinoma.

UNLABELLED: The objective of this study was to evaluate the efficacy and tolerability of capecitabine as a single agent in the treatment of recurrent/metastatic head and neck squamous cell carcinoma. Patients were treated with oral capecitabine according to good clinical practice. Efficacy and safety outcomes were analyzed retrospectively. The response and adverse events rates and their exact confidence intervals (CIs) were calculated. Survival distributions were estimated using the Kaplan-Meier method. Twenty-nine patients were included in the study. Twenty-five patients (86%) had received at least three previous lines of chemotherapy. The disease control rate was 48% (95% CI: 29-67%). The median progression-free survival was 2.0 months (95% CI: 0.1-3.9 months) and the median overall survival was 7.0 months (95% CI: 4.1-9.9 months). Hand-foot syndrome, fatigue, and mucositis were the most frequent severe side effects. No patient died, and only three patients discontinued treatment because of side effects. Capecitabine seems to be an active and well-tolerated regimen, even in heavily pretreated, frail patients. LEVEL OF EVIDENCE: 2C 'Outcomes Research'.

Paclitaxel and cetuximab combination efficiency after the failure of a platinum-based chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma.

The addition of cetuximab (CTX) to the combination of cisplatin and 5-fluorouracil increases the overall survival (OS) in recurrent/metastatic head and neck squamous cell carcinoma. Only a few patients are eligible for this treatment because of its toxicity. The combination of CTX and paclitaxel (TXL) could be included in sequential treatment strategies. Patients were treated with CTX (400/250 mg/m) and TXL (60-80 mg/m) weekly until disease progression or unacceptable toxicity. Efficacy and safety outcomes were determined retrospectively. A total of 42 patients were included in this analysis. The overall response rate was 38% [95% confidence interval (CI); 23-53%]. The disease control rate with TXL and CTX combination was 74%. Seven (17%) patients progressed before the first evaluation. The median progression-free survival was 3.9 months [95% CI; 3.1-4.7 months] and the median OS was 7.6 months [95% CI; 5.3-9.9 months]. Neurotoxicity and skin rash were the most frequent grade≥2 toxicities, reported in 17 and 12% of patients, respectively. Previous chemotherapy seems to be associated with a lower response rate and progression-free survival but not with the OS. The combination of CTX and TXL was an active and well-tolerated treatment in this series of patients with a poor prognosis and who were mostly symptomatic.

Survival and risk of COVID-19 after SARS-COV-2 vaccination in a series of 2391 cancer patients.

BACKGROUND: Patients with cancer are at high risk of severe or lethal COVID-19. The impact of SARS-COV-2 vaccination on the risk of developing COVID-19 was investigated in an exhaustive series of patients from a comprehensive cancer center. METHODS: This is a study of the exhaustive population of 2391 cancer patients who were prescribed SARS-COV-2 vaccination until 09/21. Patient characteristics, documented SARS-COV-2 infection with RT-PCR, and survival were collected. The primary endpoint was the rate of COVID-19 after vaccination. Secondary endpoints included risk factors to develop COVID-19 after vaccination, with a comparison with the cohort of vaccinated health care workers (HCW), and risk factors for death. RESULTS: From January to September 2021, among 2391 patients with cancer under active treatment in whom a SARS-COV-2 vaccine was prescribed, 659 (28%), 1498 (63%) and 139 (6%) received 1, 2, and 3 doses, respectively. Ninety five patients received a single dose of vaccine after a previous COVID-19. Two thousand two hundred eighty five health care workers (HCW) received one (N = 17, 0.7%), 2-3 (N = 2026, 88.7%) vaccine doses and one dose after COVID-19 (N = 242, 10.6%). With a median follow-up of 142 and 199 days for patients and HCW, respectively. Thirty nine (1.6%) patients and 35 (1.5%) HCW developed COVID-19 after vaccination. Six of 39 cancer patients and no HCW died because ofCOVID-19 within 50 days after diagnosis. Independent risk factors for COVID-19 in vaccinated patients were age, single dose of vaccine without previous COVID-19 and anti-CD20 treatment in the last three months. Independent risk factors for death included metastatic disease, gender, cancer type, but also documented COVID-19 before vaccination. CONCLUSIONS: Patients receiving two or more doses of COVID-19 vaccine have reduced risk of COVID-19. The risk of death of vaccinated cancer patients presenting COVID-19 remains high. COVID-19 before vaccination is associated with an increased overall risk of death.

Immunologically active phenotype by gene expression profiling is associated with clinical benefit from PD-1/PD-L1 inhibitors in real-world head and neck and lung cancer patients.

INTRODUCTION: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours. METHODS: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. RESULTS: A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis. CONCLUSION: The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors.

Datasets for gene expression profiles of head and neck squamous cell carcinoma and lung cancer treated or not by PD1/PD-L1 inhibitors.

Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1/PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples.