Second cancer among cancer survivors : incidence and impact on survival

Les objectifs de cette thèse étaient d’étudier les tendances du risque de second cancer primitif (SPC) selon l’année de diagnostic d’un premier cancer des voies aéro-digestives supérieures (VADS) dans le Bas-Rhin, de produire les premières estimations de l’incidence des SPC à l’échelle nationale en France et d’estimer la survie des patients atteints d’un cancer des VADS selon la présence d’antécédents de cancer. Ce travail a montré que : 1) L’excès de risque de SPC des VADS et de l’œsophage a diminué de 53% entre 1975 et 2006 dans le Bas-Rhin, mais que le risque de SPC du poumon est resté stable ; 2) Le risque de SPC en France est augmenté de 36% chez les patients atteints de cancer par rapport à la population générale ; 3) La survie des hommes atteints d’un cancer des VADS était fortement associée à la présence d’antécédents de cancer. Des perspectives se dégagent de ce travail en termes de recherche épidémiologique, de recherche clinique et de politiques de santé publique.The objectives of this PhD thesis were: to study the trends of the risk of second primary cancer (SPC) among patients with a head and neck (HNSCC) cancer in Bas-Rhin, to provide first nationwide estimates of the risk of SPC in France and to assess the survival of patients with a HNSCC depending on their history of cancer. This work showed that : 1) The excess risk of SPC of head and neck and esophagus sites decreased by 53% over three decades among patients with a HNSCC, and that the excess risk of SPC of the lung did not change significantly. 2) The risk of SPC among cancer survivors in France was increased by 36% compared to the general population. 3) History of cancer was strongly associated with survival among HNSCC patients. Several epidemiological and clinical research perspectives can be established based on this work. These results also present an interest in a public health perspective in the framework of the third cancer plan

Second cancer among cancer survivors : incidence and impact on survival

Les objectifs de cette thèse étaient d’étudier les tendances du risque de second cancer primitif (SPC) selon l’année de diagnostic d’un premier cancer des voies aéro-digestives supérieures (VADS) dans le Bas-Rhin, de produire les premières estimations de l’incidence des SPC à l’échelle nationale en France et d’estimer la survie des patients atteints d’un cancer des VADS selon la présence d’antécédents de cancer. Ce travail a montré que : 1) L’excès de risque de SPC des VADS et de l’œsophage a diminué de 53% entre 1975 et 2006 dans le Bas-Rhin, mais que le risque de SPC du poumon est resté stable ; 2) Le risque de SPC en France est augmenté de 36% chez les patients atteints de cancer par rapport à la population générale ; 3) La survie des hommes atteints d’un cancer des VADS était fortement associée à la présence d’antécédents de cancer. Des perspectives se dégagent de ce travail en termes de recherche épidémiologique, de recherche clinique et de politiques de santé publique.The objectives of this PhD thesis were: to study the trends of the risk of second primary cancer (SPC) among patients with a head and neck (HNSCC) cancer in Bas-Rhin, to provide first nationwide estimates of the risk of SPC in France and to assess the survival of patients with a HNSCC depending on their history of cancer. This work showed that : 1) The excess risk of SPC of head and neck and esophagus sites decreased by 53% over three decades among patients with a HNSCC, and that the excess risk of SPC of the lung did not change significantly. 2) The risk of SPC among cancer survivors in France was increased by 36% compared to the general population. 3) History of cancer was strongly associated with survival among HNSCC patients. Several epidemiological and clinical research perspectives can be established based on this work. These results also present an interest in a public health perspective in the framework of the third cancer plan

Cancer ultérieur chez les survivants d'un premier cancer : incidence et impact sur la survie

The objectives of this PhD thesis were: to study the trends of the risk of second primary cancer (SPC) among patients with a head and neck (HNSCC) cancer in Bas-Rhin, to provide first nationwide estimates of the risk of SPC in France and to assess the survival of patients with a HNSCC depending on their history of cancer. This work showed that : 1) The excess risk of SPC of head and neck and esophagus sites decreased by 53% over three decades among patients with a HNSCC, and that the excess risk of SPC of the lung did not change significantly. 2) The risk of SPC among cancer survivors in France was increased by 36% compared to the general population. 3) History of cancer was strongly associated with survival among HNSCC patients. Several epidemiological and clinical research perspectives can be established based on this work. These results also present an interest in a public health perspective in the framework of the third cancer plan.Les objectifs de cette thèse étaient d’étudier les tendances du risque de second cancer primitif (SPC) selon l’année de diagnostic d’un premier cancer des voies aéro-digestives supérieures (VADS) dans le Bas-Rhin, de produire les premières estimations de l’incidence des SPC à l’échelle nationale en France et d’estimer la survie des patients atteints d’un cancer des VADS selon la présence d’antécédents de cancer. Ce travail a montré que : 1) L’excès de risque de SPC des VADS et de l’œsophage a diminué de 53% entre 1975 et 2006 dans le Bas-Rhin, mais que le risque de SPC du poumon est resté stable ; 2) Le risque de SPC en France est augmenté de 36% chez les patients atteints de cancer par rapport à la population générale ; 3) La survie des hommes atteints d’un cancer des VADS était fortement associée à la présence d’antécédents de cancer. Des perspectives se dégagent de ce travail en termes de recherche épidémiologique, de recherche clinique et de politiques de santé publique

Constitutive or Induced HIF-2 Addiction is Involved in Resistance to Anti-EGFR Treatment and Radiation Therapy in HNSCC

International audienceBACKGROUND:management of head and neck squamous cell carcinomas (HNSCC) include anti-Epidermal Growth Factor Receptor (EGFR) antibodies and radiotherapy, but resistance emerges in most patients. RAS mutations lead to primary resistance to EGFR blockade in metastatic colorectal cancer but are infrequent in HNSCC, suggesting that other mechanisms are implicated. Since hypoxia and Hypoxia Inducible Factor-1 (HIF-1) have been associated with treatment failure and tumor progression, we hypothesized that EGFR/mammalian Target Of Rapamycin (mTOR)/HIF-1 axis inhibition could radiosensitize HNSCC.METHODS:We treated the radiosensitive Cal27 used as control, and radioresistant SQ20B and UD-SCC1 cells, in vivo and in vitro, with rapamycin and cetuximab before irradiation and evaluated tumor progression and clonogenic survival.RESULTS:Rapamycin and cetuximab inhibited the mTOR/HIF-1α axis, and sensitized the SQ20B cell line to EGFR-inhibition. However, concomitant delivery of radiation to SQ20B xenografts increased tumor relapse frequency, despite effective HIF-1 inhibition. Treatment failure was associated with the induction of HIF-2α expression by cetuximab and radiotherapy. Strikingly, SQ20B and UD-SCC1 cells clonogenic survival dropped <30% after HIF-2α silencing, suggesting a HIF-2-dependent mechanism of oncogenic addiction.CONCLUSIONS:altogether, our data suggest that resistance to EGFR inhibition combined with radiotherapy in HNSCC may depend on tumor HIF-2 expression and underline the urgent need to develop novel HIF-2 targeted treatments

Should we screen patients for carotid artery disease before lung cancer resection?

International audienceBackground: Postoperative stroke is a rare complication after lung cancer surgery but has a high mortality rate. No strategy has been recommended to detect carotid artery disease preoperatively in lung cancer patients. The main objective of this study was to evaluate whether a routine carotid duplex ultrasound (DUS) altered the preoperative management of these patients.Methods: We performed a single-centre, retrospective study of all patients referred for lung cancer resection over a two-year period and reviewed the available carotid DUS results. We quantified the number of carotid artery disease diagnosis, the severity of the disease according to DUS results, and the number of treatments initiated preoperatively. We examined relationships between cardiovascular history and preoperative carotid artery disease diagnosis.Results: Among the 398 consecutive lung surgery patients, 6% had a preoperative history of stroke or transient ischemic attack, and one developed a postoperative stroke, of cardioembolic origin. Three hundred and seven patients (77%) had preoperative carotid DUS. Carotid DUS results elicited anti-platelet therapy initiation or endarterectomy before lung resection in 7 out of these 307 patients (2.3%). One hundred and seventy-one carotid DUS were retrospectively reviewed by an expert, who diagnosed carotid stenosis >50% and occlusion in 2.3% and 1.2% of patients, respectively. Abnormal carotid DUS was associated with history of lower extremity artery disease (P<0.001), diabetes mellitus (P<0.05) and dyslipidemia (P<0.05).Conclusions: This retrospective observational study showed that routine preoperative carotid DUS led to few carotid stenosis detection and few perioperative management alterations. Carotid artery disease diagnosis was associated with cardiovascular history and risk factors. Future studies should examine how to select patients who will benefit from a preoperative carotid DUS

Biomechanical effects of osteoplasty with or without Kirschner wire augmentation on long bone diaphyses undergoing bending stress: implications for percutaneous imaging-guided consolidation in cancer patients

Number: 1 PMID: 30693406BACKGROUND: Osteoplasty has been discouraged in long bones. However, despite a substantial lack of pre-clinical biomechanical tests, multiple clinical studies have implemented a wide range of techniques to optimise long bone osteoplasty. The aim of the present study is to evaluate the biomechanical properties of osteoplasty alone and in combination with Kirschner wires (K-wires) in a cadaveric human diaphyseal model undergoing 3-point bending stress. METHODS: Thirty unpaired human cadaveric hemi-tibia specimens were randomly assigned to receive no consolidation (group 1, n = 10), osteoplasty alone (group 2, n = 10), or K-wires augmented osteoplasty (group 3, n = 10). Specimens were tested on a dedicated servo-hydraulic machine using a 3-point bending test. Fracture load was calculated for each specimen; two-sample Wilcoxon rank-sum tests were used to assess differences between groups. RESULTS: Median volume of polymethyl methacrylate injected was 18 mL for group 2 (25th-50th percentile 15-21 mL) and 19 mL for group 3 (25th-50th percentile 17-21). There were no significant differences in fracture load between groups 1 and 2 (z = - 0.793; p = 0.430), between groups 1 and 3 (z = - 0.944; p = 0.347), and between groups 2 and 3 (z = - 0.454; p = 0.650). Fractures through the cement occurred in 4 of 30 cases (13.3%); there were no K-wires fractures. CONCLUSIONS: Osteoplasty with or without K-wires augmentation does not improve the resistance of diaphyseal bone to bending stresses

Incidence of solitary pulmonary nodules in Northeastern France: a population-based study in five regions

IF 2.766International audienceBackground: The discovery of a solitary pulmonary nodule (SPN) on a chest imaging exam is of major clinical concern. However, the incidence rates of SPNs in a general population have not been estimated. The objective of this study was to provide incidence estimates of SPNs in a general population in 5 northeastern regions of France.Methods: This population-based study was undertaken in 5 regions of northeastern France in May 2002-March 2003 and May 2004-June 2005. SPNs were identified by chest CT reports collected from all radiology centres in the study area by trained readers using a standardised procedure. All reports for patients at least 18 years old, without a previous history of cancer and showing an SPN between 1 and 3 cm, were included.Results: A total of 11,705 and 20,075 chest CT reports were collected for the 2002-2003 and 2004-2005 periods, respectively. Among them, 154 and 297 reports showing a SPN were included, respectively for each period. The age-standardised incidence rate (IR) was 10.2 per 100,000 person-years (95% confidence interval 8.5-11.9) for 2002-2003 and 12.6 (11.0-14.2) for 2004-2005. From 2002 to 2005, the age-standardised IR evolved for men from 16.4 (13.2-19.6) to 17.7 (15.0-20.4) and for women from 4.9 (3.2-6.6) to 8.2 (6.4-10.0). In multivariate Poisson regression analysis, gender, age, region and period were significantly associated with incidence variation.Conclusions: This study provides reference incidence rates of SPN in France. Incidence was higher for men than women, increased with age for both gender and with time for women. Trends in smoking prevalence and improvement in radiological equipment may be related to incidence variations

Conformity to Clinical Practice Guidelines at Initial Management in Adult Soft Tissue and Visceral Tumors since the Implementation of the NetSarc Network in Eastern France

Number: 8 PMID: 31073021 PMCID: PMC6693707BACKGROUND: Soft tissue sarcomas are rare and heterogenous tumors that are hard to diagnose. The aim of this study was to evaluate local practices and conformity to clinical practice guidelines (CPGs) for their initial diagnostic management. MATERIALS AND METHODS: Patients were carriers of a soft tissue or visceral tumor, presented at a sarcoma tumor board (STB) between 2010 and 2016. Conformity to CPGs was evaluated using ten criteria designed for this purpose. Associations between different factors and conformity to composite criteria, reflecting the three main diagnostic steps (imaging, biopsy and histological report) were analyzed. RESULTS: A total of 643 patients were included. A preoperative tumor imaging assessment and a biopsy were performed according to CPGs in 80.8% and 36.8% of the cases, respectively. When done, the first surgical resection was R0 in 30.3% of cases, R1 in 28.6%, and R2 in 10.9%. The rest of the operated patients with sarcoma had a second surgical excision (11.4%), an intraoperative fragmentation (4.3%), or margins were unknown (14.4%). Six of the ten quality criteria presented a conformity rate higher than 70%. Two criteria with a conformity rate lower than 20% were the most controversial: presentation at a STB before biopsy and freezing of a tumor fragment. A multivariate analysis revealed that the common predictor of nonconformity to composite criteria was the initial management in a nonexpert center. CONCLUSION: Initial diagnostic management requires improvement, especially outside of specialized centers. IMPLICATIONS FOR PRACTICE: This article supports the essential need to refer patients with soft tissue tumors to specialized centers to improve the management of sarcomas beginning at the diagnostic phase. Indeed, the reported data were very similar to those already described at the national level of the NetSarc network and indicate the necessity to keep raising awareness about this simple issue: early referral to reference centers will save lives