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Alex Martinez-Marti
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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: 5
- Now Available
- Moderators:Alex Martinez-Marti, Hong-Xu Liu
- Coordinates: 9/10/2019, 11:30 - 13:00, Hilton Head (1978)
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ES23.01 - Mediastinoscopy with Invasive Staging: Are They Still Crucial? (Now Available) (ID 3281)
11:30 - 13:00 | Presenting Author(s): Akif Turna
- Abstract
- Presentation
Abstract
There are more multiple treatment strategies for non-small cell lung cancer(NSCLC) that should be selected based on staging of the disease. Nodal status indicates N component of staging and studies invariably show that upfront surgical resection of patients with mediastinal lymph node involvement (i.e., N2 or N3) is not recommended. Evidence suggest that, T1-4N2-3M0-1c patients should firstly receive oncological treatment; otherwise, surgical treatment could be deemed to be futile.
Accordingly, mediastinal lymph node involvement prediction as accurate as possible is recommended before any treatment planning. PET-CT, Endobronchial ultrasonography-transbronchial aspiration (EBUS-TBNA), endoscopic ultrasound-guided-fine-needle aspiration(EUS-FNB) have all inherent limitations. Mediastinoscopy has been defined to be gold standard for preoperative disclosure of mediastinal lymph node metastasis. However, small biopsy material due to being an incisional biopsy, practically low number of explored mediastinal stations (usually median number of 2 or 3) led to approximately 10% of false negativity rate. Also studies showed that, even the fact that, mediastinoscopy has been recommended to be performed in all patients except the patients with non-discrete lymph node involvement or in the patients with peripheral cT1a-cN0M0 patients, a fraction of thoracic surgeons prefer to comply with the published guidelines.
Video-assisted mediastinoscopy lymphadenectomy(VAMLA) was developed to reduce the false negativity rate below statistically non-significant levels (below 5%). It involves dissection of at least 5 lymph nodes stations and some evidence suggest that, VAMLA is associated with better survival rate beyond selection bias phenomenon. Transcervical extended mediastinal lymphadenectomy (TEMLA) is a technically more advanced mediastinal lymph node dissection procedure that is a definition of a resection of lymph nodes from #1-9 bilaterally including aorticopulmonary and anterior mediastinal lymph nodes. The accuracy of TEMLA has been reported to be 98.4%. Taking all those achievements into consideration, VAMLA or TEMLA or at least video-mediastinoscopy should be performed before selecting a therapeutical option in a patient with potentially resectable operable NSCLC.
However, recent advancements in computational science could propose us that, possibly, there is enough information for us to predict mediastinal lymph node positivity without performing any invasive procedure. Artificial Intelligence (AI) is accomplished by computers that use algorithms, pattern matching, rules, deep learning and cognitive computing to approximate conclusions using previously defined analog or digital parameters. AI aimed to mimic the brain’s neural networks. It uses multiple layers of non-linear processing units to teach itself how to understand data classifying the record or making predictions.
In a study, we aimed to evaluate the value of artificial neural network(ANN) for mediastinal nodal metastasis, by using only clinical and radiologic data. In our data set, ANN predicted mediastinal nodal involvement perfectly (AUC:1) in both training and test groups. When we used ‘traditional’ univariate and multivariate analyses, younger age (<65) (AUC:0.59) and higher SUVmax (>2.5)(AUC:0.67) were associated to be mediastinal nodal involvement. ANN prediction was better and it was even more sensitive than VAMLA! However, specificity of ANN resulted to be less than 0.9 in some training analyses.
The major limitations of ANN include its variability, non-transparency and non-consistency. Nevertheless, there is a possibility that, ANN could provide better predictions and it may help us to identify and narrow down the patients who need invasive staging. However, the usage of ANN in medicine has been continuously expanding. Future studies are needed to understand the exact place of ANN in mediastinal staging.
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ES23.02 - Which N2 Patients Are Candidates to Surgery in the Era If I/O? (Now Available) (ID 3282)
11:30 - 13:00 | Presenting Author(s): Eric Vallieres
- Abstract
- Presentation
Abstract
The role of surgery in patients with pre-resection documented N2 disease remains a subject of controversy. In some institutions, any clinical N2 disease identified preoperatively is considered non-surgical and these patients are offered upfront definitive chemoradiation therapy (DefCRT) without planned resection. In other institutions, a selective approach to N2 patients will consider surgery as part of a multimodality approach where surgery may be offered first followed by adjuvant cytotoxic chemotherapy (AC) with or without sequential post-operative radiation therapy (PORT), or where surgery will be offered after induction chemotherapy or induction chemoradiation therapy. Due to variability in N2 disease presentation, factors determining this selective approach vary between institutions and may include the bulk of N2 nodal involvement (size), extent of N2 involvement (single vs multistation, microscopic vs macroscopic), the presence or absence of extracapsular nodal involvement, the need to perform a pneumonectomy or not, and mediastinal sterilization after induction therapy. Historically, response to induction therapy with clearance of N2 nodal involvement following induction therapy has been shown to bode for a better prognosis after surgical resection. Unfortunately, even after complete resection following induction therapy, many patients develop distant metastases, with brain metastases prevailing.
In 2018, the PACIFIC trial showed that adding an immune checkpoint inhibitor (IO) durvalumab for up to one year after completion of DefCRT in non-surgical stages cIIIa and cIIIB patients led to a significant and unprecedented overall survival in this population of patients. (Antonia, NEJM 2018) In patients with resectable NSCLC (cIIIA and less), recent small phase I clinical trials of either single-agent induction IO (Forde, NEJM 2018) or concurrent induction chemoimmunotherapy (Provencio, JTO abst. 2018) given before surgery have demonstrated feasibility, acceptable toxicity, and unprecedented pathological response rates. It remains to be seen if these pathologic responses will translate into improved overall survival in this patient population.
Extrapolating from these early observations, one may think that induction IO (likely with concurrent cytotoxic chemotherapy) may possibly allow us to offer surgery to a larger proportion of patients with clinical N2 disease in the future as we observe higher response rates to induction therapies which may translate in better survival. Others may want to extrapolate from the Pacific trial results and hypothesize that surgery followed by adjuvant IO may become a desirable option. Though encouraging, there is a paucity of data to help guide us in the incorporation of IO therapy perioperatively for patients with clinical N2 disease. As such, the role for IO in multimodality treatment for N2 disease remains undefined. Unknown are the true impacts of periop IOs in this patient population and what is the optimal combination and timing of these multimodality treatments. There are more unanswered questions than established guidelines: (1) whether “IO first then surgery” is superior to “surgery first then adjuvant IO”, (2) whether an induction IO strategy followed by resection would be superior to DefCRT followed by IO in this population of potentially resectable cN2 IIIA patients, (3) if induction IO is shown to be superior, how many cycles preop, (4) do we need to continue IOs post op, if so, for how long, (5) whether there will be a role for surgery after major response to IO, and (6) how will we select patients for resection when major pathological response rates will be in the 80% range (7) do we need to utilize biomarkers, tumor mutation burden, or genotyping in patient selection, (8) What is the best biomarker to predict response, among other questions .
The easy answer at this stage is to treat these patients on trials where the impact of IOs can be rigorously studied. Ideally, I personally would want to compare: (1) Induction vs adjuvant IOs for surgical patients with cN+ disease, (2) Induction IO followed by resection vs DefCRT followed by IO. The duration of periop IO also needs to be evaluated and these studies should include cost analysis as well. For the surgeons, as systemic treatments improve, our duty is to perform sound oncological surgery with minimal morbidity and minimal to absent mortality. I believe that preop IO may allow us to consider surgical resection for a larger proportion of cIIIA N2 patients in the future.
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ES23.03 - Is CT/RT Followed by I/O the Standard of Care for All N2 and Selected N3 Patients? (Now Available) (ID 3283)
11:30 - 13:00 | Presenting Author(s): Wilfried Ernst Erich Eberhardt
- Abstract
- Presentation
Abstract
Background: Immunotherapy consolidation with PD-L1-Ab has changed the current standard treatment for unresectable patients with stage III NSCLC (in Europe with PD-L1-exp by IHC > or = 1%) who are not progressing following definitive chemoradiotherapy1,2,3. More and more issue comes up for which patients this new strategy should be adopted, and for whom these data do not represent the new standard. Here we will try to analyze current evidence of stage selection for this multimodality approach.
Methods: We analyzed the existing evidence on outcome results of stage III NSCLC subsets based on the new 8th-version of the IASLC/UICC staging classification and expert consensus4,5 and current outcome data on stage III subsets within large landmark randomized trials,6,7,8,9,10 and possible permutations of chosen multimodality treatment approaches.
Results: The PACIFIC Trial included only unresectable patients with stage IIIA and stage IIIB (based on the old UICC7 staging classification)1,2,3. No detailed data on T- and N-subgroups as well as transferring the data to the new UICC8 stage subsets IIIA/IIIB/IIIC were given in the manuscript1. Definition of "unresectable stage IIIA and IIIB" was probably best carried out as "individual local descision within tumor boards including thoracic surgeons to define disease resectability status". Nevertheless, no clear definition on selection for unresectable disease is given in the trial description of the PACIFIC publication. The overall two- and three-year-survival results were excellent and showed a significant and clinically meaningful benefit for patients receiving PD-1-antibody consolidation for one year2,3. Based on current evidence and consensus4,5 about 15 to 20% of stage III patients are still ocnsidered to be potentially resectable. The majority of these belong to the IIIA(N2) diasease subset. Only one recently published clinical phase-III trial included subgroups with T4N0 (stage IIIB UICC7/stage IIIA/UICC8)8. Outside of multimodality groups with specific expertise, stage IIIB(UICC8) and stage IIIC(UICC8) are considered unresectable and would definitely be put on definitive chemoradiotherapy protocols. Only three large randomized trials6,7,8 included resectable patients subsets of stage IIIA(N2)-disease (INTERGROUP 0137, SAKK, ESPATUE). The treatment strategies within these trials were induction chemotherapy followed by surgery versus induction chemotherapy followed by radiation and followed by surgery6, induction chemoradiotherapy followed by surgery versus definitive chemoradiotherapy7or induction chemotherapy followed by concurrent chemoradiotherapy and surgery versus induction chemotherapy followed by concurrent chemoradiotherapy and definitive chemoradiation boost8. All three trials including surgery in at least one of the randomization arms gave a detailed description of T- and N-subgroups in their overall patient characteristics. All three clinical trials had PET-CT and detailed mediastinal staging techniques included into the initial patient selection descision (either mediastinoscopy or recently EBUS). All three trials had excellent overall survival outcomes in each of their randomization arms. Five-year survival results were somewhere betweeen 20% and 44% observed in the three randomized trials. In all three trials no significant difference was noted for OS between the different randomization arms while the OS results in all treatment groups of the studies can be considered excellent. However, in all three trials a low accrual rate was generally noted, and the overall duration of the clinical trials was around six to eight years in all three, pointing to a considerable selection procedure of patient inclusion. The two large randomized clinical phase-III trials investigating modern chemoradiation techniques9,10 included per definition only "unresectable stage IIIA and IIIB patients subsets" (following the old UICC7/UICC6 classification). However, in both trials (PROCLAIM and RTOG 0617) no detailed TN-subgroups were given, but they included rather IIIA and IIIB definitions based on PET-CT staging as well as biopsy confirmation of N2- or N3-tumor-positive lymph nodes at staging work-up. FIve-year overall survival data turned out somewhere around 30% of the initially included patient groups within the two trials. The only group that showed a significantly worse outcome was that with the higher total radiation dose of 74 Gy in the RTOG study (no comment on this issue here). Nevertheless, all survival outcomes showed overall excellent five-year survival data in these two chemoradiation trials, too. Median OS data were between 25 and 29 months observed. There are considerable difficulties to compare all six randomized trials (PACIFIC, RTOG 0617, PROCLAIM, SAKK-TRIAL, INTERGROUP 0139, ESPATUE) based on the difficulties to compare patient selection and included TN-subgroups. Thus the above mentioned relevant differences in patient selection and accrual between the pure chemoradiation trials and the randomized trials including surgical arms cannot be overcome by comparing TN-data from these studies. All three definitive chemoradiation trials did only give IIIA and IIIB subset numbers of their patient population. However, patient accrual was much faster in all three definitive chemoradiation studies, pointing to a less selective patient inclusion into these trials. Some of the differences in the observed OS and PFS results noted could in fact be based on these different patient selection procedures rather than on differences between the individual treatment strategies.
Conclusion: Based on a differential analysis of the recent five largest randomized phase-III trials with multimodality treatment of stage III NSCLC, we cannot readily compare the patient selection for "pure" concurrent chemoradiotherapy trials on one hand, to that within multimodality trials including surgery in at least one trial arm on the other side. This strongly points to the fact, that we cannot currently widen up any indication for an inclusion of immunotherapy for subsets of patients with potentiallly resectable stage III NSCLC. Patient with resectable stage III (mostly IIIA) should either be treated within multimodality protocols including surgery (based on the local expertise) or should be offered to participate within clinical trials that try to implement immunotherapy with PD-1 or PD-L1 antibodies into this multimodality setting including surgery. Several clinical studies wirth induction chemoimmunotherapy followed by surgery or induction chemoimmunotherapy/chemoradiationimmunotherapy followed by surgery are currenlty being performed by different multimodality treatment groups. The practice-changing results of the PACIFIC trial for unresectable stage III disease leave us very enthusiastic, that this new approach could also improve the results for potentially resectable stage III patients groups in NSCLC.
1Antonia, NEJM 2017 2 Antonia, NEJM 2018 3 Gray, ASCO 2019 4Goldstraw, J Thorac Oncol 2016 5Eberhardt, Ann Oncol 2015 6Pless, Lancet 2015 7Albain, Lancet 2009 8Eberhardt, J Clin Oncol 2015 9Senan, J Clin Oncol 2016 10 Bradley, Lancet Oncol 2015
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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 | Presenting Author(s): Dirk De Ruysscher | Author(s): Kristiaan Nakaerts
- Abstract
- Presentation
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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ES23.05 - The Future of Systemic Therapy in Stage III (Now Available) (ID 3285)
11:30 - 13:00 | Presenting Author(s): Pilar Garrido
- Abstract
- Presentation
Abstract
Stage III NSCLC comprises a very heterogeneous group of patients with regard to tumor extent, prognosis, and treatment options. It represents between 25-30% of NSCLCs and the majority of them are unresectable. Potentially curative treatment of unresectable stage III necessitates adequate locoregional control as well as control of the micrometastatic disease that is likely to be present in most patients. Several randomized clinical trials dating back as far as 20 years and metanalysis have shown the superiority of cisplatin-based chemotherapy and radiotherapy over radiotherapy alone. Sequential versus concomitant approach has been directly compared in several trials; almost all of them showed a trend in favor of concomitant treatment. These results clearly supported the use of concomitant chemoradiotherapy as standard of care for these patients1 fit enough to tolerate the risk of severe toxicity, particularly grade 3-4 esophagitis that is the most common adverse effect of the concomitant approach.
Attempts to improve outcomes have included studies of radiotherapy dose escalation and new chemotherapy combinations, as well as adding biological agents and cancer vaccines to existing regimens. Technical radiotherapy modifications, including intensity-modulated radiotherapy and particle beam therapy, have also been investigated. In spite of it, the long-term survival has remained largely unchanged for many years, with only 15% of patients are alive at 5 years.
In the last years, immune-checkpoints blockade revolutionized the standard of care of metastatic NSCLC. The PACIFIC study is an randomized, double-blind, placebo-controlled, multi-centre, phase 3 study to evaluate the efficacy and safety of durvalumab compared with placebo, as sequential therapy in patients with locally advanced, unresectable stage III NSCLC who have not progressed following definitive, concurrent platinum-based chemotherapy and thoracic RT. The study was positive for both primary endpoints progression- free survival (HR=0.51; 95%CI: 0.41-0.63)) and overall survival (HR=0.68; 95%CI: 0.49-0.99; p=0.00251)2. This benefit was observed in both non-squamous and squamous histology as well as in both stages IIIA and IIIB NSCLC. Based on this study, there is a new standard of care for unresectable stage III NSCLC patients. Nevertheless, improving outcomes for patients with stage III disease remains a challenge and many questions have to address in well-designed clinical trials.
1.- Postmus PE, Kerr KM, Oudkerk M et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; 28 Suppl 4: iv1-iv21.
2.-Antonia SJ, Villegas A, Daniel D et al. Overall survival with Durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med 2018; 379: 2342-50
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OA13 - Ideal Approach to Lung Resection and Novel Perioperative Therapy (ID 146)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:Tomasz Grodzki, Kenji Suzuki
- Coordinates: 9/10/2019, 11:30 - 13:00, Toronto (1985)
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OA13.05 - NADIM Study: Updated Clinical Research and Outcomes (Now Available) (ID 1670)
11:30 - 13:00 | Author(s): Alex Martinez-Marti
- Abstract
- Presentation
Background
Patients with stage IIIA (N2 or T4N0) are potentially curable but median overall survival is only around 15 months
Method
A Phase II, single-arm, open-label multicenter study of resectable stage IIIA N2-NSCLC in adult patients with CT plus IO as neoadjuvant treatment: 3 cycles of nivolumab (NV) 360 mg IV Q3W + paclitaxel 200 mg/m2 + carboplatin AUC 6 IV Q3W followed by adjuvant NV treatment for 1 year. After completing neoadjuvant therapy, all patients underwent tumor assessment prior to surgery. Surgery was performed during the 3rd or 4th week after day 21 of the 3rd neoadjuvant treatment cycle. The study aimed to recruit 46 patients. The primary endpoint was Progression-Free Survival (PFS) at 24 months. Efficacy was explored using objective pathologic response criteria. Here we present the final data on all study patients that underwent surgical assessment.
Result
At the time of submission, the 46 patients had been included. None of the patients were withdrawn from the study preoperatively due to progression or toxicity. 41 patients had undergone surgery and all tumors were deemed resectable with R0 resection in all cases. Intention to treat analysis shows 35 patients (85%; 95% CI, 71; 94%) achieved major pathologic response (MPR) of which 25 (71%; 95% CI, 54; 85%) were complete pathologic responses (CPR). Downstaging was seen in 38 (93%; 95% CI, 80; 98%) of cases. The median follow-up was 13.8 months (P25; P75: 11.7; 16.6 months) for both the whole series and resected patients, and 12 month PFS was 95.7% (95% CI, 84; 99%).
Conclusion
This is the first multicentric study to test CT-IO in the neoadjuvant setting in stage IIIA. Neoadjuvant CT-IO with nivolumab in resectable IIIA NSCLC yields a complete pathologic response rate that is higher than ever seen previously, together with a promising PFS which may translate into increased overall survival. EudraCT Number: 2016-003732-20. Clinical trial information: NCT 03081689.
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P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.16-05 - Incidence and Outcome of Multiple Primary Cancers (MPC) in a Series of Lung Cancer (LC) Patients (ID 1030)
09:45 - 18:00 | Author(s): Alex Martinez-Marti
- Abstract
Background
The number of cancer survivors has increased as a result of significant progress in prevention, diagnosis and treatment of malignant tumors. The risk of developing a second neoplasm, after treatment of an initial primary cancer, is increasing and indeed lung cancer represents a commonly diagnosed second primary malignancy. This study investigates the co-occurrence of MPC among patients (p) diagnosed with lung cancer (LC).
Method
Review of clinical data of all consecutive patients with histologically confirmed LC visited at our institution between October 2017 and August 2018
Result
Out of 1386 p with LC, two primary cancers occurred in 206 cases (15%), including 41 p (3%) with three primary cancers. Patients with MPC were predominantly males (67%), smokers (88%), statin users (40%) and 28% had known family history. Second cancer was detected in a routine follow-up in 62%, whereas 27% were symptomatic patients. Median age at the first tumor diagnosis was 61 years (27-85). LC occurred as first neoplasm in 34% of the cases, as subsequent neoplasm in 41% and as two consecutive primary neoplasm in 25%. The most common primary cancer was LC in 34%, followed by breast (16%), colorectal (15%), prostate (9%), bladder (8%) and head and neck (6%). Treatment received for the first cancer included surgery in 80%, chemotherapy in 47% and radiotherapy in 32%. As a second tumor LC represented 41%, followed by bladder (19%), colorectal (10%), prostate (9%) and breast (7%). Surgery was performed in 70% of the cases with a second cancer. Regarding only patients with LC as two primary tumours (first and second tumour), 25 pts (89%) were not metastatic at second tumour, surgery was performed in 82% and 7 pts (24%) developed a third tumour. Overall, median time of diagnosis between the first and the second neoplasm was 4.2 years (CI95% 3.2-5.2), without significant differences if primary tumor was LC or another neoplasm (p=0.82). Smoking was associated with a shorter time of the second neoplasm diagnosis (3.8 years vs 7.9 years for non-smokers, p=0.09), whereas taking statins exhibited longer time of diagnosis of the second neoplasm (5.1 vs 3.3 year, p=0.05). With a median follow up of 7.3 years after diagnosis of the first neoplasm, the 5-year survival rate was 97.2% (94.8-99.7%).
Conclusion
In our series, the frequency of the MPC co-occurrence among LC p is 15%, indicating that surveillance strategies are recommended. Many p are treated with curative intent. Moreover, smoking and taking statins influences the time interval between tumors
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-10 - Biomarkers of Pathological Response on Neo-Adjuvant Chemo-Immunotherapy Treatment for Resectable Stage IIIA NSCLC Patients (ID 1466)
10:15 - 18:15 | Author(s): Alex Martinez-Marti
- Abstract
Background
PD1/PDL1 treatments have become the main therapy in advanced stages of NSCLC due to its significant increase in overall survival (OS), but recently, combination with chemotherapy in locally advanced stages is showing promising results. Many studies have described peripheral blood immune cells parameters as biomarkers of response to immunotherapy. In our study, we described the effect of neo-adjuvant chemo-immunotherapy treatment in Complete Blood Count (CBC) and Peripheral Blood Mononuclear Cells (PBMCs) phenotype, as well as, the association of these parameters with the degree of pathological response.
Method
Immune cell populations of 46 resectable stage IIIA NSCLC patients treated with neo-adjuvant chemo-immunotherapy from NADIM clinical trial were analysed. Samples were extracted before initiating the neo-adjuvant treatment with nivolumab plus carboplatin and at the third cycle before patients underwent surgery. We classified patients in 3 subgroups of pathological response assessed in the resection specimen: complete response (pCR), major response (<10% viable tumour) and incomplete response (>10% viable tumour, pIR). Wilcoxon and Mann-Whitney U statistic test were used to evaluate differences between pre and post treatment and between pathological responses groups respectively.
Result
From 46 patients, 5 patients did not undergo surgery, so they were excluded from the analysis. Absolute numbers of Leucocytes, Eosinophil, Monocytes, Neutrophils, Haemoglobin and Platelets from hemograms were significantly reduced after neo-adjuvant treatment. However, no changes were observed for Lymphocytes, Basophils, LDH levels or the Lung Immune Prognostic Index (LIPI). Additionally, post-treatment Neutrophil-to-Lymphocyte (NLR), Myeloid-to-Lymphoid lineage (M:L) and Platelets-to-Lymphocytes (PLR) ratios were decreased. Remarkably, from all the CBC absolute numbers and ratios, only PLR variation showed differences between pCR and pIR.
On the other hand, percentages of PBMCs (T cells, B cells, NK cells and macrophages) did not vary after neo-adjuvant treatment, however activation of CD4 T cells and NK cells as well as PD-1 receptor expression on immune cells were downregulated after neo-adjuvant chemo-immunotherapy. Interestingly, these variations correlate with pCR.
Conclusion
In our study, PLR, PD-1 expression, CD4 T cells and NK cells activation are predictive biomarkers of response to treatment. Thus, a higher decrease on PLR post neo-adjuvant treatment is associated to pCR. Moreover, a decrease of PD-1 expression in CD4, CD8 and NK cells, as well as, a reduction of CD4 T cells and NK cells activation after neo-adjuvant treatment, are associated to pCR.
