Jérémie Jégu

Trends over three decades of the risk of second primary cancer among patients with head and neck cancer

OBJECTIVES Patients with a head and neck squamous cell carcinoma (HNSCC) carry a high risk of second primary cancer (SPC). In recent years, a rise in incidence of human papillomavirus (HPV)-associated HNSCC has been recorded. Moreover, tobacco and alcohol consumption levels have changed and major advances have been made in radiation treatment approaches. This raises the question of a modification to the risk of SPC, taking into account variations of patient characteristics related to the HPV-cancer epidemic. MATERIALS AND METHODS All patients with a first HNSCC diagnosed between 1975 and 2006 in the French Bas-Rhin region were followed up for 10 years. Multivariate Poisson regression models were used to model standardized incidence rates and excess absolute risks (EARs) over years of diagnosis, taking into account confounders such as sex, age, subsite of first HNSCC and follow-up. RESULTS Among these 6258 patients, 1326 presented with a SPC. High EAR values were observed for SPC of lung, head and neck, and esophagus sites (EAR of 172.8, 159.3 and 72.5 excess cancers per 10,000 person-years, respectively). Multivariate analysis showed that the excess risk of SPC of head and neck (P<.001) and esophagus (P=.029) sites decreased, with 53% lower EARs values in 2000-2006 compared to 1975-1979. In contrast, the excess risk of SPC of the lung did not change significantly (P=.174). CONCLUSIONS Efforts made by public health policy-makers and oncology care providers should be sustained to develop effective smoking cessation interventions, as the excess risk of lung SPC remains high and unchanged.

The effect of patient characteristics on second primary cancer risk in France

BackgroundAlthough cancer survivors are known to be at greater risk of developing second primary cancer (SPC), SPC incidence estimates in France are thus far lacking. We used a multivariate approach to compute these estimates and analyzed the effect of patient characteristics (gender, age at diagnosis, first cancer site, year of diagnosis and follow-up) on SPC risk.MethodsData from ten French population-based cancer registries were used to establish a cohort of all patients diagnosed with a first cancer between 1989 and 2004 and followed up until December 31, 2007. The person-year approach was used to estimate standardized incidence ratios (SIRs) and excess absolute risks (EARs) of metachronous SPC. Multivariate Poisson regression models were then used to model SIRs and EARs separately by gender, adjusting for age, year of diagnosis, follow-up and first cancer site.ResultsAmong the 289,967 followed-up patients with a first primary cancer, 21,226 developed a SPC. The SIR was of 1.36 (95% CI, 1.35-1.38) and the EAR was of 39.4 excess cancers per 10,000 person-years (95% CI, 37.4-41.3). Among male and female patients, multivariate analyses showed that age, year of diagnosis, follow-up and first cancer site were often independently associated with SIRs and EARs. Moreover, the EAR of SPC remained elevated during patient follow-up.ConclusionsFrench cancer survivors face a dramatically increased risk of SPC which is probably related to the high rate of tobacco and alcohol consumption in France. Multivariate modeling of SPC risk will facilitate the construction of a tailored prediction tool to optimize SPC prevention and early detection strategies.

Risk of second primary cancer after a first potentially-human papillomavirus-related cancer: A population-based study

Human papillomaviruses (HPV) are involved in the development of anogenital and head and neck cancers. The purpose of this study was to assess the risk of developing a second primary cancer (SPC) after a first potentially-HPV-related cancer, and to analyze the sites where SPCs most frequently occurred in these patients. All patients with a first cancer diagnosed between 1989 and 2004, as recorded by 10 French cancer registries, were followed up until December 31, 2007. Only invasive potentially-HPV-related cancers (namely, cervical, vagina, vulva, anal canal, penile, oropharynx, tongue and tonsil) were included. Standardized Incidence Ratios (SIRs) were calculated to assess the risk of SPC. A multivariate Poisson regression model was used to model SIRs separately by gender, adjusted for the characteristics of the first cancer. 10,127 patients presented a first potentially-HPV-related cancer. The overall SIR was 2.48 (95% CI, 2.34-2.63). The SIR was 3.59 (95% CI, 3.33-3.86) and 1.61 (95% CI, 1.46-1.78) in men and women respectively. The relative risk of potentially-HPV-related SPC was high among these patients (SIR=13.74; 95% CI, 8.80-20.45 and 6.78; 95% CI, 4.61-9.63 for men and women, respectively). Women diagnosed in the most recent period (2000-2004) showed a 40% increase of their relative risk of SPC as compared with women diagnosed between 1989 and 1994 (ratio of SIRs=1.40; 95% CI, 1.06-1.85). HPV cancer survivors face an increased risk of SPC, especially second cancer. Clinicians may consider this increased risk of developing HPV-related SPC during follow-up to improve subsequent cancer prevention in these patients.

Risk assessment of second primary cancer according to histological subtype of non-Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of diseases that are known to carry a considerable risk of second primary cancer (SPC). However, little attention has been paid to SPC risk assessment according to NHL subtypes. Data from 10 French population-based cancer registries were used to establish a cohort of 7546 patients with a first diagnosis of NHL (eight subtypes) between 1989 and 2004. Standardized incidence ratios (SIRs) of metachronous SPC were estimated. Among the 7546 patients diagnosed with a NHL, the overall SPC risk was 25% higher than that in the reference population (SIR = 1.25, 95% confidence interval 1.15–1.36). In univariate analysis, the SPC risk differed by lymphoma subtype. Interestingly, multivariate analysis showed that SPC risk did not differ significantly across NHL subtypes after adjustment for the other covariates (p = 0.786). Patients with NHL have an increased risk of SPC that is not influenced by the histological NHL subtype.

Trends in the risk of second primary cancer among bladder cancer survivors: a population-based cohort of 10 047 patients

To determine whether the risk of second primary cancer (SPC) among patients with bladder cancer (BCa) has changed over past years.

Development of a model to predict the 10-year cumulative risk of second primary cancer among cancer survivors

BACKGROUND To develop a prediction model to quantify the cumulative risk of Second Primary Cancer (SPC) among cancer patients given that they survive their disease. METHODS A cohort of 293,435 patients based on data from twelve French cancer registries was analyzed. For five first cancer sites, SPC incidence rates were estimated using Poisson regression models. The cumulative risks of SPC were computed for different follow-up times. For comparison purpose, the same method was used to estimate the probability of cancer in the general population. RESULTS In this population-based cohort, 27,320 patients presented with a SPC. The cumulative risk of SPC varied depending on first cancer site, with a 10-year cumulative probability of SPC ranging from 6.2% for women with breast cancer to 44.0% for men with head and neck cancer. Compared with the general population, the 10-year cumulative risk of SPC was dramatically elevated for tobacco-related first cancers, with an increase of +7.3% for men aged 55 to 64 with a first lung cancer and +35.6% for men aged 45 to 54 with a first head and neck cancer. Lower differences were observed among patients diagnosed with a first prostate cancer (+5.5% among men aged 55 to 64), colorectal (+4.1% for women aged 55 to 64 and +6.3% for men aged 55 to 64), and breast (+2.0% among females aged 75 and older) cancers. CONCLUSION This study provides physicians with a practical estimate to assess the risk of SPC of their patients more accurately.

Methodological issues of assessing the risk of a second cancer occurring in the same site as a first cancer using registry data

OBJECTIVE To present methodological issues that can arise with the assessment of the risk of a second primary cancer (SPC) occurring in the same site as a first cancer using registry data. MATERIAL AND METHODS Data from ten French cancer registries were used, including data for patients with a first prostate cancer (in males), breast cancer (in females), and colon, lung and kidney cancer (in both sexes) diagnosed between 1989 and 2004. Standardized incidence ratios (SIRs) of SPC were computed by excluding, or not, the risk of an SPC at the same site. RESULTS For prostate cancer, the SIR dropped from 1.11 to 0.72 when the risk of SPC of the prostate was included. SIRs increased from 1.36 to 1.45, from 1.14 to 1.21, from 1.57 to 2.01, and from 1.37 to 1.51 for breast, colon, lung, and kidney respectively. CONCLUSION The inclusion, or not, of an SPC at the same site can impact on SPC risk estimates.

Modern Treatments in Advanced Non–Small-Cell Lung Cancer: Temporal Trends and Effect on Survival. A French Population-Based Study

UNLABELLED Extrapolation of clinical trials results to the general population is always challenging. We analysed 1047 patients diagnosed with an advanced stage disease between 1998 and 2005 in a french administrative department and found a good spread of modern chemotherapy since 1998 and targeted therapy since 2002. Moreover, the outcomes in patients treated according to guidelines are very proximal from those obtained in clinical trials. BACKGROUND Management of metastatic non-small-cell lung cancer has considerably evolved during the past 2 decades. In this study we aimed to assess how treatments have spread at a population-based level and their effect on survival. PATIENTS AND METHODS Medical records of patients diagnosed from 1998 to 2005 in the French department of Bas-Rhin were checked to collect data on patient characteristics and treatments received. Multivariate analysis of survival was performed using pretherapeutic and therapeutic factors including targeted therapies received as third-line treatment. RESULTS We included 1047 patients with stage IIIB to IV non-small-cell lung cancer. The proportion of patients who underwent chemotherapy increased from 373/471 (79.2%) to 491/576 (85.2%) over the 1998 to 2001 and 2002 to 2005 periods, and there was an increased use of third-generation drugs associated with platin. Third-line treatment was gefitinib or erlotinib in 73/155 (47.1%) of the cases among patients diagnosed from 2002 to 2005. Compared with older agents, targeted therapy administered as third-line treatment was associated with a longer survival but there was no significant difference in survival with recent chemotherapy agents in multivariate analyses (hazard ratio, 0.773; 95% confidence interval, 0.445-1.343). CONCLUSION Results of our study showed a good spread of modern chemotherapy and targeted therapy use at a population-based level. However, even if the general outcomes were improved along the years, the results observed in real clinical practice were slightly different from those reported in clinical trials.

Epidemiology of Merkel cell carcinoma. A population-based study from 1985 to 2013, in northeastern of France: Epidemiology of Merkel cell carcinoma

Merkel Cell Carcinoma (MCC) is an aggressive skin cancer with an increasing incidence. Population‐based epidemiologic data about MCC in France are rare. Our study aims to describe the epidemiology of MCC in Bas‐Rhin, Northeastern of France, between 1985 and 2013. Data were collected from the Bas‐Rhin Cancer Registry. We measured age‐adjusted incidence rates (per 100,000 person‐years) and effect of age, sex and period of diagnosis on survival. The world age‐standardized incidence rate was 0.17 and it quadrupled between 1985 and 2013. Cases (n = 111) occurred mostly in women (60%) and in persons ≥70 years of age (74%). Incidence rates was close for men (0.18) and women (0.16) and was 25‐time higher in people ≥70 years of age but incidence rate similarly increased between 1985 and 2013 in persons older and younger than 70 years. Net 5‐year survival was 48.5%; female sex and younger age were positive predictors of survival. Given the low number of cases, incidence and survival data should be interpreted with caution. Incidence of MCC in Bas‐Rhin quadrupled between 1985 and 2013. The highest incidence rate was observed in people ≥70 years. Better survival was associated with female sex and younger age. We hypothesize that MCC will still increase and be diagnosed in increasingly younger patients in next generations.

SNAI2 and TWIST1 in lymph node progression in early stages of NSCLC patients

Lymph node metastasis is an important prognosis factor in non‐small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the role of epithelial to mesenchymal transition (EMT) in lymph node progression in the early stages of NSCLC. We studied a retrospective cohort of 160 consecutive surgically treated NSCLC patients with available frozen tumor samples for expression of EMT markers (CDH1, CTNNB1, CDH2, and VIMENTIN), inducers (TGFB1, c‐MET, and CAIX), and transcription factors (EMT‐TF: SNAI1, SNAI2, ZEB1, TWIST1, and TWIST2). Partial EMT was more frequent in N1‐2 (N+) vs N0 patients (P < .01). TGFB1 (P = .02) as well as SNAI2 (P < .01) and TWIST1 (P = .04) were the most differentially expressed genes in N+ tumors. In this group, ZEB1 was correlated with all EMT inducers and other EMT‐TFs were overexpressed depending on the inducers. CAIX was an independent prognostic factor for overall survival (IC 95% HR: 1.10‐5.14, P = .03). Partial EMT is involved in lymph node progression of NSCLC patients and depends on the TGFβ pathway. EMT‐TFs are differentially expressed depending on EMT inducers. CAIX might be a relevant prognostic marker in early stage NSCLC.