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Kristiaan Nakaerts



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    ES23 - Optimal Management of N2 Disease in the Era Of IO (ID 26)

    • Event: WCLC 2019
    • Type: Educational Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
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      ES23.04 - Optimal Supportive Care During and After Concurrent Chemoradiotherapy and I/O (Now Available) (ID 3284)

      11:30 - 13:00  |  Author(s): Kristiaan Nakaerts

      • Abstract
      • Presentation
      • Slides

      Abstract

      Concurrent chemotherapy and radiotherapy (CCRT) is the treatment of choice for most fit patients with locally advanced NSCLC. Recently, adjuvant durvalumab has improved the overall survival further.

      However, CCRT is a toxic treatment. Treatment-related deaths occur in a few percent of patients and many suffer severe side effects that require medical interventions and even in-patient care.

      In contrast to extensive research on infections and emesis, most data on other important side effects are scant.

      Two examples of this are acute esophagitis and cough and dyspnea.

      Correlation between dysphagia and endoscopic findings

      In a prospective trial with 38 patients receiving radiotherapy alone for lung cancer, an endoscopy was done during radiotherapy when patients had received a dose of 30-40 Gy on the esophagus. Eighteen patients (47 %) had dysphagia of any grade, but only in 12 of them (67 %) endoscopy showed esophagitis. Of the remaining 20 patients without complaints, 5 (25 %) had endoscopic signs of esophagitis. Gastritis was found in 18 patients (47 %), with or without esophagitis.

      In another study, 82 NSCLC patients were evaluated by endoscopy. There was a good correlation between the RTOG clinical score for dysphagia and the endoscopic findings (Spearman rank correlation coefficient 0.428; p< 0.0001). All patients with clinical grade 3 dysphagia had endoscopic grade 2 or 3 esophagitis. Also in case of RTOG grade 2 dysphagia, all patients had endoscopic esophagitis, although 40 % had endoscopic grade 1 and 27 % had endoscopic grade 3 esophagitis. Of patients with or without only mild (grade 1) dysphagia, 11 % showed grade 3 endoscopic esophagitis. Sixteen percent of patients has esophageal candidiasis, but its relation with dysphagia or endoscopic grade of esophagitis was not reported. No data on the incidence of gastritis were given.

      Effect of radiotherapy on esophageal motility

      An impaired esophageal motility may also lead to dysphagia.

      The esophageal transit time (ETT) before and during (10 Gy and 30 Gy) radiotherapy alone was evaluated in 11 patients. An increase in the ETT was seen in 9 of 11 patients (82%) (p<0.05).

      The ETT was also investigated in 18 breast cancer patients receiving radiotherapy to the inner quadrants of the breast using a dose of 50 Gy/ 25 fractions. The cranial part of the esophagus received a mean dose of 6 Gy/ 25 fractions, and the distal two-thirds a mean dose of 15.3 Gy/ 25 fractions. Comparing the ETT before and after radiotherapy, for the upper third and the distal two-thirds of the esophagus, the ETT increased from 4.77 ± 1.08 sec. to 6.92 ± 2.15 sec., from 11.22 ± 2.85 sec to 23.30 ± 5.65 sec. and from 11.61 ± 2.97 sec. to 23.74 ± 5.70 sec., respectively (p<0.001).

      Because of the motility impairment even at very low radiotherapy doses, the use of proton pump inhibitors is logical.

      Prevention and treatment of acute esophagitis

      In a randomized study with advanced NSCLC patients, treated with radiotherapy alone or radiotherapy plus amifostine, amifostine reduced the incidence of esophagitis in week 4 during radiotherapy from 42 % (31/73) to 4 % (3/73) (p<0.001), without decreasing the tumor response 2 months after treatment. In a larger randomized series of the RTOG, 243 stage II-III NSCLC patients were enrolled and randomized between carboplatin-paclitaxel concurrent chemo-radiotherapy with or without amifostine. No significant differences between the arms regarding overall survival, disease-free survival or long-term toxicity were observed.

      In another study, 60 stage III NSCLC patients were randomized between concurrent carboplatin-paclitaxel and radiotherapy with or without amifostine. No significant difference in esophagitis was observed.

      Therefore, amifostine has no consistently proven effect of preventing acute radiation-induced esophagitis.

      In a small double-blind study, 14 stage III NSCLC patients were randomized between placebo or prophylactic indomethacin. Endoscopically-assessed esophagitis seemed to be milder, but no firm conclusions could be drawn.

      Another small, placebo-controlled randomized trial, investigated naproxen in 28 stage III NSCLC patients receiving radiotherapy alone. There were no differences in clinical or endoscopic esophagitis rates. Eight patients (29 %) developed esophageal candidiasis, with no difference between the groups.

      A placebo-controlled randomized trial could not demonstrate a beneficial effect of sucralfate on dysphagia.

      In NRG/ RTOG 1012, patients were randomized between prophylactic Manuka honey, either in liquid or in lozenge form, and standard supportive care during concurrent chemo-radiotherapy for NSCLC. Standard supportive care consisted of a compound containing viscous lidocaine, an antacid such as magnesium aluminum oxide, and liquid or solid oxycodone, 5–10 mg, every 3 hours as needed. The primary endpoint was patient-reported pain on swallowing utilizing an eleven point (0–10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). Fifty-three patients were randomized to supportive care, 54 randomized to liquid honey and 56 to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms (p=0.03), with 52 % vs. 67 % of patients experiencing no pain with liquid honey. No difference was observed with lozenge honey. with more patients on the supportive care arm taking opioids. However, the differences were only observed at 4 weeks and not at the end of radiotherapy.

      From this example, already, it is clear that more in-depth knowledge of the physiopathology of radiation injury is needed. A joint task force between ESTRO and ESMO members will address a spectrum of supportive care interventions in patients receiving concurrent chemotherapy and radiotherapy for lung cancer.

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    IBS06 - Multimodality Treatment - Realtime Data from National Registries (Ticketed Session) (ID 37)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      IBS06.01 - Realtime Data from Europe ETOP / ESTS Database (Now Available) (ID 3331)

      07:00 - 08:00  |  Author(s): Kristiaan Nakaerts

      • Abstract
      • Presentation
      • Slides

      Abstract

      Title: Mesothelioma Realtime Data from Europe - ETOP Mesoscape / ESTS Database

      Introduction:

      Malignant pleural mesothelioma (MPM) is an aggressive malignancy with increasing prevalence and poor prognosis. Despite a still increase in incidence, it remains an orphan disease and studying limited numbers of MPM cases hampers the derivation of solid conclusions.

      The combination of two databases including clinical as well as pathological information will allow researchers to improve the knowledge and facilitate decision-making in patients with MPM.

      The European Thoracic Oncology Platform (ETOP) Mesoscape project and the European Society of Thoracic Surgeons’ (ESTS) database are designed to address clinical, pathological, and molecular characteristics of mesothelioma patients and their impact on outcome. The joined analysis of both databases is a unique approach to real-time data reflecting the reality of mesothelioma characteristics, treatment and prognosis in Europe.

      Materials and Methods:

      A decentralized biobank with fully annotated tissue samples is established for ETOP Mesoscape. Selection criteria for participating centers included sufficient number of cases, and documented ethical approval. Patient selection is based on availability of comprehensive clinical data with adequate follow-up, and adequate quantity and quality of formalin-fixed tissue.
      The ESTS database is a clinical database with pre-operative, intra-operative and post-operative data. A minimum set of data is captured, including demographic, histology, treatment, staging and follow up data.

      The characteristics between the two databases are compared using the Fisher’s exact test (for categorical variables) and Mann-Whitney test (for continuous variables), while Kaplan-Meier method (with log-rank test).

      Results:

      Up to 29 May 2019, the ETOP Mesoscape included information on 497 patients from 10 centers, diagnosed between 1999-2018. In the ESTS database, as of April 2019, 2269 patients are included, diagnosed between 1989-2019.

      Patients in both databases are primarily men (84% in the ETOP, 71% in the ESTS), of 0/1 ECOG Performance status (46/46% and 59/29% in ETOP and ESTS respectively), with known previous exposure to asbestos (75% and 93%) and median ages 64 and 67 years old.

      Significant differences are detected between the two data sources with respect to gender, exposure to asbestos and age (p-value <0.001).

      The primary histology of patients is epithelioid (72% in ETOP and 70% in ESTS), followed by biphasic (22%; 17%) and sarcomatoid (6%; 9%) (not significantly different between the two databases).

      Clinical staging is available for 77% of the patients in ETOP, but only for the 28% in the ESTS database. The stage distribution (I/II/III/IV) is 14/29/42/15% in the ETOP and 23/21/41/16% in the ESTS (significantly difference p<0.001).

      Among the biomarkers common in both data sources, Calretinin and WT1 are detected in the vast majority of patients tested (Calretinin: 97% in both cases; WT1: 89% and 87% in the ETOP and ESTS database respectively).

      For the ETOP cases 90% (of those tested) are CK5/6 positive, 91% D2-40 positive and 97% Pan-CK positive.

      Palliative treatment has been administered in 41% of the ETOP cases. Among them, 84% received palliative chemotherapy (with the vast majority 92%, using multiple agents). Palliative surgery was undertaken in 32% (62 of 194 patients with available information) and palliative radiotherapy for 13% of the patients.

      Complete resection has been performed in 59% of the ETOP Mesoscape patients. This was combined with induction chemotherapy (81%), while adjuvant chemotherapy and radiotherapy was administered in 4% and 37% respectively.

      The surgical approach adopted for the ESTS patients was either video-assisted thoracoscopic surgery (VATS) (59%) or thoracotomy (41%) based on a subset of 887 patients with available information. Post-operation treatment information is available for 620 ESTS patients. Among them, 71% received chemotherapy, 54% underwent surgery and 15% radiotherapy.

      Conclusion:

      We present the combined results from the ETOP Mesoscape and the ESTS database, one of the largest databases. These two series allow us to report on mesothelioma epidemiology and treatment.

      Up to now, the comparison of the baseline characteristics of the patients of the two data sources revealed some statistically significant differences with respect to gender, age, exposure to asbestos and clinical stage.

      As tissue from all ETOP Mesoscape patients is preserved locally and is available for detailed molecular investigations, Mesoscape provides an excellent basis to evaluate the influence of molecular parameters on the disease outcome, besides providing an overview of the molecular landscape.

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