Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART): an open-label, randomised, phase 3 trial.

BACKGROUND: In patients with non-small-cell lung cancer (NSCLC), the use of postoperative radiotherapy (PORT) has been controversial since 1998, because of one meta-analysis showing a deleterious effect on survival in patients with pN0 and pN1, but with an unclear effect in patients with pN2 NSCLC. Because many changes have occurred in the management of patients with NSCLC, the role of three-dimensional (3D) conformal PORT warrants further investigation in patients with stage IIIAN2 NSCLC. The aim of this study was to establish whether PORT should be part of their standard treatment. METHODS: Lung ART is an open-label, randomised, phase 3, superiority trial comparing mediastinal PORT to no PORT in patients with NSCLC with complete resection, nodal exploration, and cytologically or histologically proven N2 involvement. Previous neoadjuvant or adjuvant chemotherapy was allowed. Patients aged 18 years or older, with an WHO performance status of 0-2, were recruited from 64 hospitals and cancer centres in five countries (France, UK, Germany, Switzerland, and Belgium). Patients were randomly assigned (1:1) to either the PORT or no PORT (control) groups via a web randomisation system, and minimisation factors were the institution, administration of chemotherapy, number of mediastinal lymph node stations involved, histology, and use of pre-treatment PET scan. Patients received PORT at a dose of 54 Gy in 27 or 30 daily fractions, on five consecutive days a week. Three dimensional conformal radiotherapy was mandatory, and intensity-modulated radiotherapy was permitted in centres with expertise. The primary endpoint was disease-free survival, analysed by intention to treat at 3 years; patients from the PORT group who did not receive radiotherapy and patients from the control group with no follow-up were excluded from the safety analyses. This trial is now closed. This trial is registered with ClinicalTrials.gov number, NCT00410683. FINDINGS: Between Aug 7, 2007, and July 17, 2018, 501 patients, predominantly staged with 18F-fluorodeoxyglucose (18F-FDG) PET (456 [91%]; 232 (92%) in the PORT group and 224 (90%) in the control group), were enrolled and randomly assigned to receive PORT (252 patients) or no PORT (249 patients). At the cutoff date of May 31, 2019, median follow-up was 4·8 years (IQR 2·9-7·0). 3-year disease-free survival was 47% (95% CI 40-54) with PORT versus 44% (37-51) without PORT, and the median disease-free survival was 30·5 months (95% CI 24-49) in the PORT group and 22·8 months (17-37) in the control group (hazard ratio 0·86; 95% CI 0·68-1·08; p=0·18). The most common grade 3-4 adverse events were pneumonitis (13 [5%] of 241 patients in the PORT group vs one [<1%] of 246 in the control group), lymphopenia (nine [4%] vs 0), and fatigue (six [3%] vs one [<1%]). Late-grade 3-4 cardiopulmonary toxicity was reported in 26 patients (11%) in the PORT group versus 12 (5%) in the control group. Two patients died from pneumonitis, partly related to radiotherapy and infection, and one patient died due to chemotherapy toxicity (sepsis) that was deemed to be treatment-related, all of whom were in the PORT group. INTERPRETATION: Lung ART evaluated 3D conformal PORT after complete resection in patients who predominantly had been staged using (18F-FDG PET-CT and received neoadjuvant or adjuvant chemotherapy. 3-year disease-free survival was higher than expected in both groups, but PORT was not associated with an increased disease-free survival compared with no PORT. Conformal PORT cannot be recommended as the standard of care in patients with stage IIIAN2 NSCLC. FUNDING: French National Cancer Institute, Programme Hospitalier de Recherche Clinique from the French Health Ministry, Gustave Roussy, Cancer Research UK, Swiss State Secretary for Education, Research, and Innovation, Swiss Cancer Research Foundation, Swiss Cancer League.

18F-FDG PET/CT heterogeneity quantification through textural features in the era of harmonisation programs: a focus on lung cancer.

PURPOSE: Quantification of tumour heterogeneity in PET images has recently gained interest, but has been shown to be dependent on image reconstruction. This study aimed to evaluate the impact of the EANM/EARL accreditation program on selected 18F-FDG heterogeneity metrics. METHODS: To carry out our study, we prospectively analysed 71 tumours in 60 biopsy-proven lung cancer patient acquisitions reconstructed with unfiltered point spread function (PSF) positron emission tomography (PET) images (optimised for diagnostic purposes), PSF-reconstructed images with a 7-mm Gaussian filter (PSF7) chosen to meet European Association of Nuclear Medicine (EANM) 1.0 harmonising standards, and EANM Research Ltd. (EARL)-compliant ordered subset expectation maximisation (OSEM) images. Delineation was performed with fuzzy locally adaptive Bayesian (FLAB) algorithm on PSF images and reported on PSF7 and OSEM ones, and with a 50 % standardised uptake values (SUV)max threshold (SUVmax50%) applied independently to each image. Robust and repeatable heterogeneity metrics including 1st-order [area under the curve of the cumulative histogram (CHAUC)], 2nd-order (entropy, correlation, and dissimilarity), and 3rd-order [high-intensity larger area emphasis (HILAE) and zone percentage (ZP)] textural features (TF) were statistically compared. RESULTS: Volumes obtained with SUVmax50% were significantly smaller than FLAB-derived ones, and were significantly smaller in PSF images compared to OSEM and PSF7 images. PSF-reconstructed images showed significantly higher SUVmax and SUVmean values, as well as heterogeneity for CHAUC, dissimilarity, correlation, and HILAE, and a wider range of heterogeneity values than OSEM images for most of the metrics considered, especially when analysing larger tumours. Histological subtypes had no impact on TF distribution. No significant difference was observed between any of the considered metrics (SUV or heterogeneity features) that we extracted from OSEM and PSF7 reconstructions. Furthermore, the distributions of TF for OSEM and PSF7 reconstructions according to tumour volumes were similar for all ranges of volumes. CONCLUSION: PSF reconstruction with Gaussian filtering chosen to meet harmonising standards resulted in similar SUV values and heterogeneity information as compared to OSEM images, which validates its use within the harmonisation strategy context. However, unfiltered PSF-reconstructed images also showed higher heterogeneity according to some metrics, as well as a wider range of heterogeneity values than OSEM images for most of the metrics considered, especially when analysing larger tumours. This suggests that, whenever available, unfiltered PSF images should also be exploited to obtain the most discriminative quantitative heterogeneity features.

Outcome of Patients With Resected Early-Stage Non-small Cell Lung Cancer and EGFR Mutations: Results From the IFCT Biomarkers France Study.

INTRODUCTION: Molecular profile of resected stage I-II non-small cell lung cancer (NSCLC) would help refine prognosis and personalize induction or adjuvant strategies. We sought to report the molecular profile of resected stage I-II NSCLC and analyzed the impact of epidermal growth factor receptor (EGFR) mutations on outcomes in a Western population. PATIENTS AND METHODS: Surgical cases were identified from Biomarkers France study, a nationwide prospective study including NSCLC patients screened for EGFR, HER2, KRAS, BRAF, PIK3CA, ALK alterations from 2012 to 2013. Among surgical patients, clinical charts of the largest centers were reviewed in order to analyze the prognostic impact of EGFR mutations. RESULTS: In the BMF database (n = 17.636), surgical patients (n = 854) were characterized by a higher proportion of EGFR mutations than nonsurgical patients (12.9% vs. 10.2%, P = .025), while the other molecular alterations did not differ. The proportion of EGFR mutations was 27% in women undergoing surgery. In the study group (n = 293; EGFR wild type, n = 235; usual mutation, n = 50; rare mutation, n = 8), after a median follow-up of 67 months, 215 patients (74.4%) had not relapsed. No difference was found between EGFR-mutant and EGFR-wt tumors regarding recurrence site, disease-free survival, and overall survival. The 5-year disease-free survival and overall survival after surgical resection of stage I-II EGFR-mutated tumors were 65% and 75%, respectively. CONCLUSION: In resected stage I to II NSCLC, EGFR mutations were found in 12.9% of cases, associated with a 5-year overall survival of 75%, with no impact on recurrence site, disease-free survival, and overall survival.

Molecular Alterations in Malignant Pleural Mesothelioma: A Hope for Effective Treatment by Targeting YAP.

Malignant pleural mesothelioma is a rare and aggressive neoplasm, which has primarily been attributed to the exposure to asbestos fibers (83% of cases); yet, despite a ban of using asbestos in many countries, the incidence of malignant pleural mesothelioma failed to decline worldwide. While little progress has been made in malignant pleural mesothelioma diagnosis, bevacizumab at first, then followed by double immunotherapy (nivolumab plus ipilumumab), were all shown to improve survival in large phase III randomized trials. The morphological analysis of the histological subtyping remains the primary indicator for therapeutic decision making at an advanced disease stage, while a platinum-based chemotherapy regimen combined with pemetrexed, either with or without bevacizumab, is still the main treatment option. Consequently, malignant pleural mesothelioma still represents a significant health concern owing to poor median survival (12-18 months). Given this context, both diagnosis and therapy improvements require better knowledge of the molecular mechanisms underlying malignant pleural mesothelioma's carcinogenesis and progression. Hence, the Hippo pathway in malignant pleural mesothelioma initiation and progression has recently received increasing attention, as the aberrant expression of its core components may be closely related to patient prognosis. The purpose of this review was to provide a critical analysis of our current knowledge on these topics, the main focus being on the available evidence concerning the role of each Hippo pathway's member as a promising biomarker, enabling detection of the disease at earlier stages and thus improving prognosis.

Phase II study of afatinib plus pembrolizumab in patients with squamous cell carcinoma of the lung following progression during or after first-line chemotherapy (LUX-Lung-IO).

INTRODUCTION: Afatinib and pembrolizumab have separately shown survival benefit in patients with squamous cell carcinoma (SqCC) of the lung, and there is biological rationale for concurrent inhibition of the programmed death ligand-1 and epidermal growth factor receptor (EGFR) pathways in this patient population. MATERIALS AND METHODS: This open-label, single-arm study enrolled patients with SqCC of the lung who had progressed during/after first-line chemotherapy and comprised two parts: a safety run-in to establish the recommended phase II dose (RP2D; afatinib 40 mg or 30 mg once daily with pembrolizumab 200 mg every 3 weeks); and the main part assessing efficacy and safety of the RP2D. The primary endpoint was objective response rate (ORR); secondary endpoints included the RP2D, progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty-four patients were treated in the safety run-in (afatinib 40 mg/30 mg cohorts: n = 12/12). Median age was 63.5 years; 79.2% of patients were male. All patients discontinued afatinib and pembrolizumab, most commonly due to disease progression (58.3% and 75.0%, respectively) or adverse events (AEs; 37.5% and 25.0%, respectively). The study was discontinued early after completion of the safety run-in, and no patients entered the main part. ORR was 12.5%; median PFS and OS were 13.1 and 29.3 weeks, respectively. All patients had ≥ 1 drug-related AE (grade ≥ 3: 45.8%). CONCLUSION: While there were no new or unexpected safety findings, exploratory analysis of antitumor activity indicated limited efficacy with afatinib plus pembrolizumab in patients with SqCC of the lung who had progressed during/after first-line chemotherapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT03157089.

Combination of Trastuzumab, Pertuzumab, and Docetaxel in Patients With Advanced Non-Small-Cell Lung Cancer Harboring HER2 Mutations: Results From the IFCT-1703 R2D2 Trial.

PURPOSE: HER2 exon 20 insertions and point mutations are oncogenic drivers found in 1%-2% of patients with non-small-cell lung cancer (NSCLC). No targeted therapy is approved for this subset of patients. We prospectively evaluated the effectiveness of the combination of two antibodies against human epidermal growth factor 2 (HER2 [HER2] trastuzumab and pertuzumab with docetaxel; trastuzumab and pertuzumab) and docetaxel. METHODS: The IFCT 1703-R2D2 trial is a multicenter, nonrandomized phase II study. Patients with HER2-mutated, advanced NSCLC who progressed after ≥ 1 platinum-based treatment were enrolled. Patients received pertuzumab at a loading dose of 840 mg and 420 mg thereafter; trastuzumab at an 8 mg/kg loading dose and 6 mg/kg thereafter; and docetaxel at a dose of 75 mg/m2 every 3 weeks. The primary outcome was the objective response rate (ORR). Other end points included the duration of response, progression-free survival, and safety (NCT03845270). RESULTS: Forty-five patients were enrolled and treated. The median age was 64.5 years (range, 31-84 years), 35% were smokers, 72% were females, 15% had an Eastern Cooperative Oncology Group performance status of 2, and 30% had brain metastases. The objective response rate was 29% (n = 13), and 58% had stable disease (n = 26). The median progression-free survival was 6.8 months (95% CI, 4.0 to 8.5). The median duration of response in patients with a confirmed response (n = 13) was 11 months (95% CI, 2.9 to 14.9). Grade 3/4 treatment-related adverse events were observed in 64% of the patients. No patient discontinued treatment because of toxicity. The most frequent grade ≥ 3 treatment-related adverse events were neutropenia (33%), diarrhea (13%), and anemia (9%). CONCLUSION: Triple therapy with trastuzumab, pertuzumab, and docetaxel is feasible and effective for HER2-mutated pretreated advanced NSCLC. These results highlight the effectiveness of the HER2 antibody-based strategy, which should be considered for these patients.

Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitor (ICI)-associated early cardiac adverse events (CAEs), mostly acute and fulminant myocarditis, have been well characterized and mainly occur during the first 90 days after ICI therapy initiation. ICI-associated late CAEs (occurring after the first 90 days of treatment) have not yet been described. METHODS: First, we compared characteristics of a cohort involving early (defined as a CAE time to onset (TTO) of <90 days after ICI therapy initiation) and late (defined as a CAE TTO of ≥90 days after ICI therapy initiation) ICI-associated CAE consecutive cases who were referred to three French cardio-oncology units. Second, ICI-associated CAE cases were searched in VigiBase, the WHO global individual case safety report database, and early and late ICI-associated CAEs were compared. RESULTS: In the cohort study, compared with early CAE cases (n=19, median TTO of 14 days), late ICI-associated CAE cases (n=19, median TTO of 304 days) exhibited significantly more left ventricular systolic dysfunction (LVSD) and heart failure (HF) and less frequent supraventricular arrhythmias. In VigiBase, compared with early cases (n=437, 73.3%, median TTO 21 days), the late ICI-associated CAE reports (n=159, 26.7%, median TTO 178 days) had significantly more frequent HF (21.1% vs 31.4%, respectively, p=0.01). Early and late ICI-associated CAE cases had similarly high mortality rates (40.0% vs 44.4% in the cohort and 30.0% vs 27.0% in VigiBase, respectively). CONCLUSIONS: Late CAEs could occur with ICI therapy and were mainly revealed to be HF with LVSD. TRIAL REGISTRATION NUMBERS: NCT03678337, NCT03882580, and NCT03492528.

Switch maintenance chemotherapy versus observation after carboplatin and weekly paclitaxel doublet chemotherapy in elderly patients with advanced non-small cell lung cancer: IFCT-1201 MODEL trial.

PURPOSE: Maintenance chemotherapy is a reasonable choice for patients with metastatic non-small cell lung carcinoma (NSCLC) not progressing after induction therapy with a platinum-based doublet. Nevertheless, there have been no studies dedicated to elderly patients. PATIENTS AND METHODS: We conducted a randomised trial in patients aged 70-89 years, with advanced NSCLC (with neither EGFR mutation nor ALK rearrangement), who had not progressed after four cycles of monthly carboplatin and weekly paclitaxel in order to compare maintenance with either pemetrexed (500 mg/m2 d1, 22) in patients with non-squamous cell carcinoma or gemcitabine (1,150 mg/m2 d1, 8, 22) in squamous cell carcinoma to simple observation. The patients were required to have a performance status (PS) 0-2, mini-mental score >23, and creatinine clearance ≥45 mL/min. The primary end-point was overall survival (OS). RESULTS: 632 patients were enrolled from May 2013 to October 2016. Of the 328 (52.3%) patients randomised after induction therapy, 166 patients were assigned to the observation arm, versus 162 to the switch maintenance arm, 119 of whom received pemetrexed and 43 gemcitabine. The median OS from randomisation was 14.1 months (95% confidence interval [CI]: 12.0-17.0) in the observation arm and 14 months (95% CI: 10.9-16.9) in the maintenance arm (p = 0.72). The median progression-free survival (PFS) from randomisation was 2.7 months (95% CI: 2.6-3.1) in the observation arm versus 5.7 months (95% CI: 4.8-7.1) in the maintenance arm (p < 0.001). CONCLUSION: Switch maintenance therapy significantly prolonged PFS but not OS and, thus, should not be proposed to elderly patients with advanced NSCLC.

Circulating Tumor DNA as a Prognostic Determinant in Small Cell Lung Cancer Patients Receiving Atezolizumab.

BACKGROUND: The IFCT-1603 trial evaluated atezolizumab in small cell lung cancer (SCLC). The purpose of the present study was to determine whether circulating tumor DNA (ctDNA), prospectively collected at treatment initiation, was associated with the prognosis of SCLC, and whether it identified patients who benefited from atezolizumab. METHODS: 68 patients were included in this study: 46 patients were treated with atezolizumab and 22 with conventional chemotherapy. Circulating DNA was extracted from plasma and NGS (Next Generation Sequencing) looked for mutations in the TP53, RB1, NOTCH1, NOTCH2, and NOTCH3 genes. ctDNA was detectable when at least one somatic mutation was identified, and its relative abundance was quantified by the variant allele fraction (VAF) of the most represented mutation. RESULTS: We found that 49/68 patients (70.6%) had detectable baseline ctDNA. The most frequently identified mutations were TP53 (32/49; 65.3%) and RB1 (25/49; 51.0%). Patients with detectable ctDNA had a significantly lower disease control rate at week 6 compared with patients with no detectable ctDNA, regardless of the nature of the treatment. Detection of ctDNA was associated with a poor OS prognosis. The detection of ctDNA at a relative abundance greater than the median value was significantly associated with poor overall survival (OS) and progression free survival (PFS). Interestingly, the benefit in overall survival (OS) associated with low ctDNA was more pronounced in patients treated with atezolizumab than in patients receiving chemotherapy. Among patients whose relative ctDNA abundance was below the median, those treated with atezolizumab tended to have higher OS than those in the chemotherapy arm. CONCLUSION: ctDNA is strongly associated with the prognosis of SCLC patients treated with second-line immunotherapy. Its analysis seems justified for future SCLC clinical trials.

Real-Life Efficacy of Osimertinib in Pretreated Octogenarian Patients with T790M-Mutated Advanced Non-small Cell Lung Cancer.

BACKGROUND: The resistance mutation T790M is reported in 50-60% of patients pretreated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Osimertinib has been approved in these patients, but data in octogenarians remain rare. OBJECTIVE: The objective of this retrospective analysis was to evaluate in real life the efficacy of osimertinib in a population of octogenarian patients. METHODS: This retrospective multicentric study included pretreated octogenarian patients with EGFR T790M-mutated advanced non-small cell lung cancer (NSCLC) in the setting of the French early access program for osimertinib. The primary endpoints were progression-free survival (PFS) and overall survival (OS) from osimertinib initiation. RESULTS: In total, 43 patients were included (mean age 84.6 years; women 90.7%: adenocarcinoma 100%; never smokers 90.5%; at osimertinib initiation: performance status ≥ 2, 42.4%; stage 4, 93.0%; brain metastases 16.3%). Patients received a median of two lines of treatment before osimertinib initiation, and all received first- or second-generation EGFR TKIs before osimertinib (first line in 79.1%). Osimertinib was used as a second-line treatment in 41.9% of cases and third line or more in 58.1%. Median PFS was 17.5 (95% confidence interval [CI] 12.2-19.0) months for the entire population: 20.6 (95% CI 18.8-not reached) months in patients with brain metastases and 16.7 (95% CI 10.4-18.9) months in patients without (p = 0.1). There was no significant difference for osimertinib treatment as second or third line or more (17.1 vs. 18.6 months, respectively). OS was 22.8 (95% CI 15.7-not reached) months from osimertinib initiation. CONCLUSION: The efficacy of osimertinib as second-line treatment or more in octogenarian pretreated patients with EGFR T790M-mutated advanced NSCLC in a real-life setting was similar to that in randomized controlled trials.

Afatinib With Pembrolizumab for Treatment of Patients With Locally Advanced/Metastatic Squamous Cell Carcinoma of the Lung: The LUX-Lung IO/KEYNOTE 497 Study Protocol.

BACKGROUND: Afatinib is a selective, irreversible ErbB family blocker that has shown survival benefit in lung squamous-cell carcinoma (SCC) patients. Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody to the programmed cell death 1 (PD-1) receptor, has also shown survival benefit in lung SCC. Concurrent inhibition of the PD-1 and epidermal growth factor receptor (EGFR) pathways represents a rational approach to improve responses and delay the onset of treatment resistance in lung SCC. TRIAL DESIGN: This phase II, open-label, single-arm study (NCT03157089) is designed to assess the efficacy and safety of afatinib in combination with pembrolizumab in patients with stage IIIB/IV lung SCC that has progressed during/after first-line platinum-based chemotherapy. Eligible patients must have ≥1 target lesion (as per Response Evaluation Criteria in Solid Tumors version 1.1) and must have not received previous immune checkpoint inhibitor/EGFR-targeted therapy. The recommended phase II dose (RP2D) and safety profile will be determined during a safety run-in with oral afatinib (starting dose, 40 mg/d) with intravenous pembrolizumab (200 mg every 3 weeks). In the main study, all patients will receive afatinib at the RP2D with pembrolizumab until disease progression, unacceptable toxicity, or for up to 35 cycles. The primary end point is objective response (complete + partial response). Other end points include disease control, duration of objective response, progression-free survival, overall survival, tumor shrinkage, RP2D, and pharmacokinetics. Exploratory biomarker analysis will be performed. This study is being conducted in the United States, Spain, France, South Korea, and Turkey. Enrollment commenced in September 2017, with a target of 50 to 62 patients.

A Randomized Non-Comparative Phase II Study of Anti-Programmed Cell Death-Ligand 1 Atezolizumab or Chemotherapy as Second-Line Therapy in Patients With Small Cell Lung Cancer: Results From the IFCT-1603 Trial.

INTRODUCTION: This randomized phase II trial aimed at evaluating the engineered programmed cell death ligand 1 (PD-L1) antibody atezolizumab in SCLC progressing after first-line platinum-etoposide chemotherapy. METHODS: Patients were randomized 2:1 to atezolizumab (1200 mg intravenously every 3 weeks) until progression or unacceptable toxicity, or conventional chemotherapy (up to 6 cycles of topotecan or re-induction of initial chemotherapy). Patients were not selected based on PD-L1 tissue expression. The primary endpoint was objective response rate at 6 weeks. A two-stage design with 2:1 randomization and O'Brien-Fleming stopping rules was used. The null hypothesis was rejected if more than 12 of 45 patients were responders. RESULTS: Overall, 73 patients were randomized (atezolizumab n = 49; chemotherapy n = 24). At 6 weeks, 1 of 43 eligible atezolizumab patients achieved an objective response (2.3%, 95% confidence interval [CI]: 0.0-6.8), whereas 8 others had stable disease (20.9% disease control rate; 95% CI: 8.8-33.1). Among eligible chemotherapy patients (n = 20), 10% achieved an objective response (65% disease control rate). Median progression-free survival was 1.4 months (95% CI: 1.2-1.5) with atezolizumab and 4.3 months (95% CI: 1.5-5.9) with chemotherapy. Overall survival did not significantly differ between groups. Median overall survival was 9.5 months versus 8.7 months for the atezolizumab and the chemotherapy group, respectively (adjusted hazard ratioatezolizumab : 0.84, 95% CI: 0.45-1.58; p = 0.60). Two atezolizumab patients (4.2%) experienced grade 3 fatigue, and two others grade 1 dysthyroidism. Among 53 evaluable specimens, only 1 (2%) had positive immunohistochemical PD-L1 staining (SP142 clone). CONCLUSIONS: Atezolizumab monotherapy in relapsed SCLC failed to show significant efficacy. No unexpected safety concerns were observed.

Generating harmonized SUV within the EANM EARL accreditation program: software approach versus EARL-compliant reconstruction.

BACKGROUND: Evolutions in hardware and software PET technology, such as point spread function (PSF) reconstruction, have been shown to improve diagnostic performance, but can also lead to important device-dependent and reconstruction-dependent variations in standardized uptake values (SUVs). This may preclude the multicentre use of SUVs as a prognostic or diagnostic tool or as a biomarker of the early response to antineoplastic treatments. This study compared two SUV harmonization strategies using a newer reconstruction algorithm that improves lesion detection while maintaining comparability with older systems: (1) the use of a second reconstruction compliant with harmonization standards and (2) the use of a proprietary software tool (EQ.PET). METHODS: PET data from 50 consecutive non-small cell lung cancer patients were reconstructed with PSF reconstruction for optimal tumor detection and an ordered subset expectation maximization (OSEM3D) reconstruction to mimic a former generation PET. An additional PSF reconstruction was performed with a 7 mm Gaussian filter (PSF7, first method), and, post-reconstruction, the EQ filter (same Gaussian filter) was applied to the PSF data (PSFEQ, second method) for harmonization purposes. The 7 mm kernel filter was chosen to comply with the European Association of Nuclear Medicine (EANM) standards. SUVs for all reconstructions were compared with regression analyses and/or Bland-Altman plots. RESULTS: Overall, 171 lesions were analyzed: 55 lung lesions (32.2%), 87 lymph nodes (50.9%), and 29 metastases (16.9%). In these lesions, the mean PSF7/OSEM3D ratios for SUVmax and SUVpeak were 1.02 (95% CI: 0.93-1.11) and 1.04 (95% CI: 0.95-1.14), respectively. The mean PSFEQ/OSEM3D ratios for SUVmax and SUVpeak were 1.01 (95% CI: 0.91-1.11) and 1.04 (95% CI: 0.94-1.14), respectively. When comparing PSF7 and PSFEQ, Bland-Altman analysis showed that the mean PSF7/PSFEQ ratios for SUVmax and SUVpeak were 1.01 (95% CI: 0.96-1.06) and 1.01 (95% CI: 0.97-1.04), respectively. CONCLUSION: The issue of reconstruction dependency in SUV values that hampers the comparison of data between different PET systems can be overcome using two reconstructions for harmonized quantification and optimal diagnosis or using the EQ.PET technology. Both technologies produce similar results, EQ.PET sparing reconstruction and interpretation time. Other manufacturers are encouraged to either emulate this solution or to produce a vendor-neutral approach.

Nivolumab Causing a Polymyalgia Rheumatica in a Patient With a Squamous Non-Small Cell Lung Cancer.

The anti-programmed cell-death-1 antibody, nivolumab, has been recently approved for the treatment of advanced non-small cell lung cancer. Although, today, immune-related adverse effects such as dermatologic, digestive, hepatic, and endocrine toxicities are well-known with immune checkpoint inhibitors, rheumatic diseases are less well described. Herein, we report the case of a patient without a history of arthritis who developed polymyalgia rheumatica after 13 cycles of nivolumab used for the treatment of advanced non-small cell lung cancer. Laboratory evidence of inflammatory syndrome, articular echography, and clinical presentation with classical symptoms and also distal manifestations were suggestive of this chronic inflammatory disorder. Because of a relevant pain, clinicians were forced to suspend immunotherapy. Nevertheless, due to glucocorticoid therapy, the patient's symptoms have decreased progressively. Moreover, nivolumab was reintroduced 8 weeks later, whereas prednisone (10 mg) was continued, without any recurrence symptoms. To conclude, our case suggests that polymyalgia rheumatica might be a very disabling anti-programmed cell-death-1 immune-related adverse effect.

[Hydration of patients treated with cisplatin: practical investigation and establishment of a protocol]. / Hydratation des patients sous cisplatine: enquête de pratiques et elaboration d'un protocole.

BACKGROUND: Administration of cisplatin requires hyperhydration of the patient to prevent nephrotoxic effects of this molecule. MATERIALS AND METHODS: A survey done in different hospitals - university hospitals, general hospitals and cancer institutes--has shown a large variability in the hydration protocols. A multidisciplinary group was set up in our university hospital comprising oncologists, nephrologists and pharmacists. This group has developed a consensual local protocol from a bibliographic analysis (Medline) and from the personal experience of each member. CONCLUSION: This protocol was approved by our hospital's Committee of Drugs and Medical Devices.