Le cancer broncho-pulmonaire du non-fumeur (caractéristiques cliniques et moléculaires d'une série niçoise)

Le cancer broncho-pulmonaire du non-fumeur (CPNF) se place au septième rang de la mortalité par cancer dans le monde. Il représente 10% des cancers du poumon en Europe, contre 30% en Asie. Les caractéristiques cliniques et moléculaires sont mal définies. Cette étude de cas témoin a inclus tous les patients non-fumeurs pris en charge pour un cancer broncho-pulmonaire dans les services de chirurgie thoracique et de pneumologie de l hôpital Pasteur et/ou dans le centre de lutte contre le cancer Antoine Lacassagne à Nice pendant la période de janvier 2008 à décembre 2011. Tous les patients non-fumeurs présentant un adénocarcinome pulmonaire et dont les prélèvements histologiques permettaient des analyses moléculaires ont été appariés selon l âge, le sexe et le stade TNM à des patients fumeurs issus de la même base de données sur la même période. Les caractéristiques cliniques et moléculaires (mutation EGFR, KRAS, BRAF et le réarrangement EML4-ALK) ont été comparées dans les 2 groupes. Nous retrouvons 166 non-fumeurs sur 1823 patients atteints d un cancer du poumon (9.1%) dont 35 non-fumeurs sur 1266 hommes (2.8%) et 131 non-fumeuses sur 557 femmes (23.5%). La moyenne d âge est de 65,3 ans. On retrouve une majorité de femmes (78.9%). L histologie principale est l adénocarcinome (69%). Parmi ces 166 non-fumeurs, 58 patients ont pu bénéficier de l analyse moléculaire et ont été comparés à 58 patients fumeurs. Chez les non-fumeurs, il existe une plus grande fréquence des mutations de l EGFR (38% vs 14%, p=0.006) et du réarrangement EML4-ALK (12% vs 2%, p=0.061) et une fréquence moins importante des mutations KRAS (12% vs 29%, p=0.03) par rapport aux fumeurs. Aucune différence de survie n est retrouvée selon le statut tabagique. Nous pouvons conclure que le CPNF se distingue comme une entité à part entière tant sur le plan clinique que sur le plan moléculaire et que la recherche moléculaire est essentielle dans la prise en charge de ces patients qui peuvent bénéficier plus fréquemment de thérapies ciblées.NICE-BU Médecine Odontologie (060882102) / SudocSudocFranceF

Valeur pronostique de la réponse précoce dans les cancers broncho-pulmonaires non à petites cellules localement avancés, traité par radiochimiothérapie

NICE-BU Médecine Odontologie (060882102) / SudocSudocFranceF

Rôle de l'endoscopie bronchique dans la mise en place de marqueurs fiduciaires en vue de l'irradiation des tumeurs pulmonaires par Cyberknife

NICE-BU Médecine Odontologie (060882102) / SudocSudocFranceF

Multidisciplinary Management of Lung Cancer: How to Test Its Efficacy?

The multidisciplinary management of lung cancer has been universally accepted. In France, the multidisciplinary approach for cancer patients is established by law. However, the efficacy of this approach remains theoretical, given that no evaluation criteria have been made available and no previous reports have been published on the prospective follow-up of these patients. The Groupe d' Oncologie Thoracique Azuréen carried out a 1-year prospective study on patients discussed during its multidisciplinary weekly meetings, to analyze the concordance between the proposed and administered treatment, the delay of treatment, and the 1-year actuarial survival. Of the 344 patients discussed during the period considered, the therapeutic decision was chemotherapy in 183 patients, surgery in 93, radiochemotherapy in 42, radiotherapy in 14, and supportive care 12. Therapeutic discordance between the planned and the administered treatment was recorded in 15 cases (4.4%), mainly for patient's refusal (seven cases) or poor performance status (five cases). The median delay of treatment was 20 days, shorter for chemotherapy (16 days), and longer for radiotherapy (27 days). The overall 1-year survival rate was 51.4%: 80.4% for stage I, 50.3% for stage II, 37.5% for stage III, and 27.2% for stage IV. For patients for whom discordance of treatment was recorded, a lower survival rate was recorded, without reaching statistical significance (0.07). In conclusion, the efficacy of the Groupe d' Oncologie Thoracique Azuréen multidisciplinary management was confirmed, as we believe that a discordant rate of less than 5% and a delay of treatment of 4 weeks can be considered acceptable. Furthermore, a periodic survival evaluation of the population as a whole could provide additional useful information for multidisciplinary groups

Baseline metabolic tumor volume as a strong predictive and prognostic biomarker in patients with non-small cell lung cancer treated with PD1 inhibitors: a prospective study

International audienc

Long term efficacy and toxicity after stereotactic ablative reirradiation in locally relapsed stage III non-small cell lung cancer

Abstract Background In stage III non-small cell lung cancer (NSCLC) treated with concomitant chemoradiotherapy, there is a high rate of relapse. Some of these relapses are only local and can be treated by stereotactic ablative radiation therapy (SABR). Previous studies reporting outcome after SABR reirradiation of the thorax consisted of a heterogeneous population of various lung cancer stages or even different types of cancer. The purpose of study is to evaluate toxicity and outcome of this strategy in locally relapsed stage III NSCLC only. Methods From February 2007 to November 2015, 46 Stage III NSCLC patients treated with SABR, for lung recurrence following conventionally fractionated radiation therapy (CFRT), were retrospectively analyzed. Results Median follow-up was 47.3 months (1–76.9). The 2 and 4-year progression-free survival (PFS), and overall survival (OS) were of 25.5%/8.6 and 48.9%/30.8%, respectively. Highest presenting toxicity in patients (grade 1 through 5) was: 13 (28.3%), 7 (15.2%), 1 (2.2%), 0 and 2 (4.4%), with deaths due to hemoptysis (n = 1) and alveolitis (n = 1). Although the Biological Effective Dose (at Planning Tumor Volume isocenter) was lower for central tumors treated for an in-field relapse (n = 21, 116 Gy versus 168 Gy, p = 0.005), they had no significant difference in OS than the remaining cohort, but with a higher rate of grade 2–5 toxicities (OR = 0.22, [0.06–0.8], p = 0.02). Conclusion Reirradiation with SABR for local relapse in patients previously treated for stage III NSCLC, is feasible and associated with good outcome. This is also true for central tumors treated for an in-field relapse, but should be radiated with caution to mitigate toxicity

In-House Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-Small Cell Lung Cancer and Melanoma Patients

International audienceTumor mutational burden (TMB) has emerged as an important potential biomarker for prediction of response to immune-checkpoint inhibitors (ICIs), notably in non-small cell lung cancer (NSCLC). However, its in-house assessment in routine clinical practice is currently challenging and validation is urgently needed. We have analyzed sixty NSCLC and thirty-six melanoma patients with ICI treatment, using the FoundationOne test (FO) in addition to in-house testing using the Oncomine TML (OTML) panel and evaluated the durable clinical benefit (DCB), defined by >6 months without progressive disease. Comparison of TMB values obtained by both tests demonstrated a high correlation in NSCLC (R 2 = 0.73) and melanoma (R 2 = 0.94). The association of TMB with DCB was comparable between OTML (area-under the curve (AUC) = 0.67) and FO (AUC = 0.71) in NSCLC. Median TMB was higher in the DCB cohort and progression-free survival (PFS) was prolonged in patients with high TMB (OTML HR = 0.35; FO HR = 0.45). In contrast, we detected no differences in PFS and median TMB in our melanoma cohort. Combining TMB with PD-L1 and CD8-expression by immunohistochemistry improved the predictive value. We conclude that in our cohort both approaches are equally able to assess TMB and to predict DCB in NSCLC

Multicenter Evaluation of a Novel ROS1 Immunohistochemistry Assay (SP384) for Detection of ROS1 Rearrangements in a Large Cohort of Lung Adenocarcinoma Patients

International audienceINTRODUCTION:The detection of a ROS1 rearrangement in advanced and metastatic lung adenocarcinoma (LUAD) led to a targeted treatment with tyrosine kinase inhibitors with favorable progression-free survival and overall survival of the patients. Thus, it is mandatory to screen for the ROS1 rearrangement in all these patients. ROS1 rearrangements can be detected using break-apart fluorescence in situ hybridization (FISH), which is the gold standard; however, ROS1 immunohistochemistry (IHC) can be used as a screening test because it is widely available, easy and rapid to perform, and cost-effective.METHODS:We evaluated the diagnostic accuracy and interpathologist agreement of two anti-ROS1 IHC clones, SP384 (Ventana, Tucson, Arizona) and D4D6 (Cell Signaling, Danvers, Massachusetts), in a training cohort of 51 positive ROS1 FISH LUAD cases, and then in a large validation cohort of 714 consecutive cases of LUAD from six routine molecular pathology platforms.RESULTS:In the two cohorts, the SP384 and D4D6 clones show variable sensitivity and specificity rates on the basis of two cutoff points greater than or equal to 1+ (all % tumor cells) and greater than or equal to 2+ (>30% stained tumor cells). In the validation cohort, the D4D6 yielded the best accuracy for the presence of a ROS1 rearrangement by FISH. Interpathologist agreement was moderate to good (interclass correlation 0.722-0.874) for the D4D6 clone and good to excellent (interclass correlation: 0.830-0.956) for the SP384 clone.CONCLUSIONS:ROS1 IHC is an effective screening tool for the presence of ROS1 rearrangements. However, users must be acutely aware of the variable diagnostic performance of different anti-ROS1 antibodies before implementation into routine clinical practice

Targeted Assessment of the EGFR Status as Reflex Testing in Treatment-Naive Non-Squamous Cell Lung Carcinoma Patients: A Single Laboratory Experience (LPCE, Nice, France)

Background: Assessment of actionable EGFR mutations is mandatory for treatment-naïve advanced or metastatic non-squamous lung carcinoma (NSLC), but the results need to be obtained in less than 10 working days. For rapid EGFR testing, an EGFR-specific polymerase chain reaction (PCR) assay is an alternative and simple approach compared to next generation sequencing (NGS). Here, we describe how a rapid EGFR-specific PCR assay can be implemented in a single laboratory center (LPCE, Nice, France) as reflex testing in treatment-naïve NSLC. Methods: A total of 901 biopsies from NSLC with more than 10% of tumor cells were prospectively and consecutively evaluated for EGFR mutation status between November 2017 and December 2019 using the Idylla system (Biocartis NV, Mechelen, Belgium). NGS was performed for nonsmokers with NSLC wild type for EGFR, ALK, ROS1, and BRAF and with less than 50% PD-L1 positive cells using the Hotspot panel (Thermo Fisher Scientific, Waltham, MA, USA). Results: Results were obtained from 889/901 (97%) biopsies with detection of EGFR mutations in 114/889 (13%) cases using the Idylla system. Among the 562 EGFR wild type tumors identified with Idylla, NGS detected one actionable and one nonactionable EGFR mutation. Conclusions: Rapid and targeted assessment of EGFR mutations in treatment-naïve NSLC can be implemented in routine clinical practice. However, it is mandatory to integrate this approach into a molecular algorithm that allows evaluation of potentially actionable genomic alterations other than EGFR mutations

Cost-utility analysis of maintenance therapy with gemcitabine or erlotinib vs observation with predefined second-line treatment after cisplatin–gemcitabine induction chemotherapy for advanced NSCLC: IFCT-GFPC 0502-Eco phase III study

on behalf of the IFCT-GFPC investigatorsInternational audienceBackground: The IFCT-GFPC 0502 phase III study reported prolongation of progression-free survival with gemcitabine or erlotinib maintenance vs. observation after cisplatin–gemcitabine induction chemotherapy for advanced non-small-cell lung cancer (NSCLC). This analysis was undertaken to assess the incremental cost-effectiveness ratio (ICER) of these strategies for the global population and pre-specified subgroups.Methods: A cost-utility analysis evaluated the ICER of gemcitabine or erlotinib maintenance therapy vs. observation, from randomization until the end of follow-up. Direct medical costs (including drugs, hospitalization, follow-up examinations, second-line treatments and palliative care) were prospectively collected per patient during the trial, until death, from the primary health-insurance provider's perspective. Utility data were extracted from literature. Sensitivity analyses were conducted.Results: The ICERs for gemcitabine or erlotinib maintenance therapy were respectively 76,625 and 184,733 euros per quality-adjusted life year (QALY). Gemcitabine continuation maintenance therapy had a favourable ICER in patients with PS = 0 (52,213 €/QALY), in responders to induction chemotherapy (64,296 €/QALY), regardless of histology (adenocarcinoma, 62,292 €/QALY, non adenocarcinoma, 83,291 €/QALY). Erlotinib maintenance showed a favourable ICER in patients with PS = 0 (94,908 €/QALY), in patients with adenocarcinoma (97,160 €/QALY) and in patient with objective response to induction (101,186 €/QALY), but it is not cost-effective in patients with PS =1, in patients with non-adenocarcinoma or with stable disease after induction chemotherapy.Conclusion: Gemcitabine-or erlotinib-maintenance therapy had ICERs that varied as a function of histology, PS and response to first-line chemotherapy