Background

The research on the benefits of surgical resection for patients with stage N2 small-cell lung cancer (SCLC) remains relatively limited. Our study was to analyse the recurrence patterns and survival of this population, especially their relationship with lymph node status, in order to explore whether these patients could benefit from surgery in addition to chemoradiotherapy.

Methods

We retrospectively reviewed completely resected pathological stage N2 SCLC patients at Shanghai Chest Hospital from July 2005 to June 2015.

Results

A total of 171 patients were included in this study. The first recurrence was mainly outside the chest cavity (54.8%) and mainly blood tract (67.4%). Patients with liver metastasis had the worst prognosis (median DFS 9.367 months, median OS 11.900 months). The median DFS of patients with single and multiple metastatic involved lymph nodes were 19.233 and 9.367months(P = 0.001); the median OS of patients with single and multiple metastatic involved lymph nodes were 43.033 and 17.100 months(P < 0.001). The median DFS of patients with single- and multiple-station metastatic involved lymph nodes were 18.067 and 8.100 months(P < 0.001); the median OS of patients with single- and multiple-station metastatic involved lymph nodes were 34.667 and 14.767 months(P < 0.001).

Conclusions

In patients with p-N2 small-cell lung cancer who had undergone radical surgery +chemotherapy +radiotherapy, the first progression was mainly extra-thoracic recurrence in the form of hematogenous metastasis. What's more, if N2 SCLC with single lymph node metastasis can be identified preoperatively, surgery is also a treatment option.

Legal entity responsible for the study

The authors.

Funding

The Science and Technology Innovation program of Shanghai [grant number 20Y11913800].

Disclosure

All authors have declared no conflicts of interest.

Background

Durvalumab plus EP (etoposide with cisplatin or carboplatin) had demonstrated a significant OS benefit compared to EP alone in the 1^st-line treatment naïve ES-SCLC patients in CASPIAN study. However, there is limited safety data with the durvalumab plus EP regimen in a larger cohort of Chinese ES-SCLC patients in clinical practice including in PS 2 patients and with more flexible cycles of EP.

Trial design

This study is an open-label, single-arm, multicenter, phase IIIb study to determine the safety of durvalumab + etoposide and cisplatin or carboplatin as first-line treatment in Chinese patients with ES-SCLC. About 300 eligible patients will be enrolled. Eligibility include age ≥18, histologically or cytologically documented extensive stage SCLC, ECOG performance status 0–2. Patients with PS 2 will be limited to 20% of the total study population. Patients enrolled will receive treatment with durvalumab + etoposide with either cisplatin or carboplatin (EP) for 4 to 6 cycles per investigators’ clinical decision. Durvalumab will be administered at a dose of 1500 mg every 3 weeks (Q3W) with first-line chemotherapy (EP) and will continue to be administered as monotherapy every 4 weeks (Q4W) post-chemotherapy until progressive disease (PD) or intolerable toxicity. Prophylactic cranial irradiation (PCI) is allowed at the investigators’ discretion. The primary endpoints are incidence of Grade ≥3 AE and incidence of imAE. Secondary endpoints include: PFS, proportion of patients alive and progression free at 12 months (APF12), ORR, DoR, OS, OS12, and incidence of AE, SAE, AESI, AE resulting in treatment discontinuation. There will be no formal interim analysis in this study. Enrollment is ongoing.

Clinical trial identification

NCT04449861.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca

Disclosure

M. Gao: Full/Part-time employment: Astrazeneca. All other authors have declared no conflicts of interest.

Background

Around 30% of patients with non-small cell lung cancer (NSCLC) present with early-stage disease (stage I–IIIA), the primary treatment for which is curative-intent complete surgical resection. Adjuvant chemotherapy is standard of care in patients with resected stage II–III and selected high-risk stage IB, but recurrence rates are high. This study examines the association between EGFRm and all-cause mortality by stage at diagnosis and surgery in patients with stage IB–IIIA NSCLC in Denmark.

Methods

Historical cohort study in patients aged ≥18 years with stage IB–IIIA NSCLC from the Danish Lung Cancer Registry (2013–2018). Hazard ratios (aHRs) for EGFRm status and all-cause mortality rates were estimated using Cox proportional-hazards regression and stratified by disease stage at diagnosis or surgery, adjusted for sex, age, lung function, ECOG, comorbidity, and surgery (if relevant).

Results

Of 21282 NSCLC patients, 5478 (26%) had stage IB–IIIA disease, and EGFR test results were available for 2468/5478 patients (45%); of these, 195 (8%) tested positive (EGFRm). In patients with an available test result, 1402 (57%) were female and 1754 (71%) aged 60–79 yrs. EGFRm prevalence was 11/5/7/7% in stage IB/IIA/IIB/IIIA, respectively. Among EGFRm patients, surgery was recorded for 124 (64%), and 56/124 (45%) received adjuvant chemotherapy/radiotherapy. Among EGFR mutation-negative patients 1208 (53%) had record of surgery and 497/1208 (41%) received adjuvant chemotherapy/radiotherapy. Table shows aHRs for EGFR status associated with 1-year and 5-year all-cause mortality.

Conclusions

In this real-world Danish cohort study, EGFRm prevalence was 8% (range 5–11%) in patients with stage IB–IIIA NSCLC, and over half of EGFR-tested patients had surgery. EGFRm was associated with lower mortality, although due to small population sizes, most subgroup estimates should be interpreted with caution.

Editorial acknowledgement

We acknowledge and thank Katrine Eriksen and Bianka Darvalics for substantial input to this work. We thank Clare McCleverty PhD, contractor for Ashfield Healthcare Communications, Macclesfield, UK, part of UDG Healthcare plc, who provided medical writing support funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

E. Jakobsen: Research grant/Funding (self), AstraZeneca sponsored this research: AstraZeneca. A. Taylor: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. V. Ehrenstein: Research grant/Funding (institution): AstraZeneca; Full/Part-time employment: Aarhus University.

Background

The preferred treatment for early stage NSCLC (stage I–IIIA) is curative-intent complete surgical resection, with adjuvant chemotherapy as standard of care in resected stage II–III and selected IB. Adjuvant osimertinib showed improved disease-free survival vs placebo in resected early stage EGFR mutation (EGFRm) positive NSCLC, highlighting a need for EGFR testing. Retrospective analysis of patients with stage I–III NSCLC and evidence of EGFRm testing, using the CLQD database (de-identified electronic health record data from 47 US oncology organisations).

Methods

Patients aged ≥18 years (yrs) with primary diagnosis of stage I–III (A and B inclusive) NSCLC 01/01/2014–31/12/2018 (index date) were included. Primary objectives were to describe frequency of EGFRm testing, patient characteristics, EGFRm prevalence and overall survival (OS). OS was defined as time from NSCLC diagnosis to death and summarised by Kaplan-Meier analysis. Patients without death events had OS censored at their last clinic encounter on/before 30/09/2020.

Results

Of 14452 eligible patients with stage I–III NSCLC, 3121 patients (22%) had record of an EGFR test ≤30 days before or any time after index; 493 (16%) were EGFRm positive (Table). Median (IQR) follow-up was 23.3 (11.2, 39.7) months (mo). In the 3121 patients with a recorded EGFR test, median OS was 72.0 mo (95% CI 56.4, NC) in stage I, 55.5 mo (95% CI 45.9, NC) in stage II and 29.5 mo (95% CI 27.4, 33.6) in stage III. One-yr, 2-yr and 5-yr survival rates in EGFRm-positive patients were 97%, 85% and 54% respectively, vs 83%, 64% and 38% in EGFR-negative patients, respectively.

Conclusions

In this large US analysis, 22% of patients with stage I–III NSCLC had record of an EGFR test; 16% tested were EGFRm positive. Survival rates were higher in EGFRm-positive patients vs EGFR-negative. These results reinforce the need for early diagnosis and EGFR testing to identify patients for EGFR-TKI therapy to maximise survival outcomes.

Editorial acknowledgement

We thank Sally Cotterill, PhD, CMPP, from iMed Comms, an Ashfield Company, part of UDG Healthcare plc, who provided medical writing support funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

D. Potter: Research grant/Funding (self), Shareholder/Stockholder/Stock options: AstraZeneca. P. Sun: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. J. Li: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. L. Luo: Full/Part-time employment: AstraZeneca. A. Taylor: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca.

Background

Recently presented ADAURA study shows there is a potential indication for EGFR TKIs to be offered in an adjuvant setting for early stage resected EGFR mutant NSCLC that may improve long term outcomes for patients. We conducted a regional audit to collect clinical outcomes for EGFR positive stage I-III resected NSCLC patients.

Methods

We used a database sourced by our pathology department who identified all resected specimens with adenocarcinoma histology over a 10 year period. Those with EGFR mutation positive histology were identified and post resection treatment and clinical outcomes were obtained retrospectively from their clinical records.

Results

Conclusions

Within our cohort of patients, approximately a quarter of our patients received adjuvant chemotherapy, relatively similar to what was observed in the ADAURA study. The majority of our patients had stage I disease which would explain the low numbers of patients receiving adjuvant treatment. Our 2 year disease free survival was 51.6% which was highly comparable to the control arm seen in ADAURA study. Pending licensing and reimbursement of Osimertinib in the adjuvant settting for EGFR positive NSCLC patients, the treatment landscape for this subgroup will change dramatically. Although our data shows consistency with the ADAURA study control arm, the interpretation is limited by the small sample size and the retrospective data collection methodology.

Legal entity responsible for the study

Rachel Powell.

Funding

Has not received any funding.

Disclosure

R.L. Powell: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol Myers Squibb; Speaker Bureau/Expert testimony: Boehringer Ingelheim. Q. Ghafoor: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca. S. Baijal: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer. All other authors have declared no conflicts of interest.

Background

Several randomized controlled trials have suggested that adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were associated with prolonged disease-free survival (DFS) in EGFR-mutated NSCLC patients after radical resection, comparing with chemotherapy or placebo. Herein, we aimed to compare the effectiveness of different first-generation EGFR-TKIs as adjuvant treatment in real-world setting.

Methods

Early stage EGFR mutated NSCLC patients who underwent radical resection and treated with first-generation EGFR-TKIs (gefitinib, erlotinib, icotinib) as adjuvant therapy between Feb 2006 and Jan 2019 were retrieved from a prospectively-maintained database in our center. The primary endpoint was DFS in stage II/III (TNM 8th) patients with exploratory endpoint regarding DFS in stage I patients. Sensitivity analyses were based on propensity score matched (PSM) cohorts. Treatment failure pattens between different TKIs were also compared.

Results

Of 588 eligible patients, 198 patients (33.7%) received gefitinib, 106 patients (17.9%) received erlotinib, and 284 patients (48.2%) received icotinib. The median DFS of stage II/III patients in the gefitinib, erlotinib and icotinib group were 36.1 months (95% CI, 23.9–49.4), 42.8 months (95% CI, 29.6–97.8), and 32.5 months (95% CI, 23.9–49.4), respectively, with no significant difference (log-rank test P = 0.22). There was also no significant difference in DFS among stage I patients receiving different TKIs (P = 0.12). PSM adjustments and multivariate analyses adjusting for other confounders revealed similar results. In addition, there was no significant differences in treatment failure pattens in different EGFR-TKI arms, especially in terms of brain metastases (6.1% in gefitinb, 7.5% in erlotinib, 3.9% in icotinib) and bone metastases(8.6% in gefitinb, 9.4% in erlotinib, 7.0% in icotinib).

Conclusions

This first and largest real-world study showed that gefitinib, erlotinib, and icotinib demonstrated comparable clinical effectiveness as adjuvant therapy in completely resected patients with EGFR mutated NSCLC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

For patients with early stage NSCLC unfit or unwilling to undergo surgical resection, stereotactic body radiation therapy (SBRT) is considered the election treatment. Our purpose is to analyze outcomes and toxicity in primary-lung tumors treated with SBRT at our institution.

Methods

Data from 177 patients with 203 NSCLC irradiated from May 2012 to November 2018 at a single institution were retrospectively collected. Tumors were classified into central and non-central (medial or peripheral) and we reported local control (LC), overall survival (OS) and toxicity scored with CTCAE v4.03. Internal Target Volume (ITV) was defined by 4D RPM-Varian™ and expanding it uniformly 5 mm for Planning Target Volume (PTV). Biologically Effective Dose (BED) prescription was always over 100 Gy₁₀ in 3-5-8 fractions following a risk-adapted protocol. Treatments were performed with volumetric-modulated-arc-therapy planning (VMAT), 4D Cone beam CT and 4D-RPM were used to control intra-fraction movement. Follow-up was performed with PET-CT or CT. Statistical analysis was conducted with R program.

Results

Median age was 75 years old. The median GTV/PTV size was 5.6/23.7cc. Median follow-up was 17 months. Estimated global local control was 96.8% (89.9–99), 87.8% (76.5–93.9) and 69.2% (40.5–86.1) at 24, 30 and 54 months. For central tumors: 89.1% (70–96.4) and 80% (66–89) at 24 and 30 months. For non-central tumors: 96.6% (89.4–99) and 87.1% (75.2–93.5) at 24 and 30 months. Estimated global overall survival was 84.7% (78.2–89.4), 60.1% (50.9–68.2) and 50.5% (40.7–59.6) at 6, 24 and 30 months. For central tumors: 85.4% (77.2–89.6) and 55.8% (34.1–72.9) at 12 and 24 months. For non-central tumors: 84.5% (77.2–89.6) and 58.3% (48.7–66.8) at 12 and 24 months. From the 72 patients deceased, 27.8% were cancer-specific deaths whilst 72.2% were attributed to other causes, mostly by cardiovascular or respiratory underlying comorbidities. Cough, dermitis or dyspnea were described as mild (G1) acute toxicity in 7 patients. Chronic toxicity was G1 pneumonitis or fibrosis in 11 patients and one patient developed G5 hemoptysis in a local relapse context.

Conclusions

Primary lung cancer VMAT based SBRT achieves good local control rates with a tolerable toxicity. Overall survival may be influenced by patient selection.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

Organs at risk (OARs) are prone to the same movements of target volumes induced by respiratory, cardiac, and gastrointestinal motion. OAR's contouring usually does not consider their movements, thus there are uncertainties regarding OAR dose estimation, toxicity evaluation, and dose-toxicity relationship. OARs can be propagated to obtain an internal organ at risk volume (IRV), although IRVs were never tested in a clinical setting. This work aims at studying the IRVs in a retrospective database of lung SABR.

Methods

Sixty patients that underwent 4DCT between August 2018 and January 2020 were included. These patients underwent radiotherapy for either primary NSCLC or metastatic malignancies. All patients’ clinical and pathological data, collected before RT, were recorded. For each patient, OARs (heart, esophagus, trachea, spinal cord and great vessels) were contoured using contouring atlases and international guidelines and were deformably propagated across phases for obtaining IRVs using MIM Maestro software, a commercially deformable image registration tool (MIM Software Inc., Cleveland, OH, US). We correlated the volumes of OARs with the volumes of IRVs, with the Wilcoxon sign correlation test. A p-value ≤ 0.05 was considered as statistically significant. We also calculated whether IRVs still respected the dosimetric dose constraints. The respect of dose constraints was finally correlated with the lesions’ localization (central vs peripheral), with the Chi-Square test.

Results

All the patients respected SABR dose constraints for standard OARs (21). Conversely, the IRVs not respecting the dose constraints were, respectively, 7/60 (11,7%) for Heart IRV, 7/60 (11,7%) for Esophagus IRV, 11/60 (18,3%) for Trachea IRV, 16/60 (26,6%) for Bronchial Tree IRV and 0/60 (0%) for great vessel IRV and spinal cord IRV. In the subset (n.38) of central targets, the percentage of the IRVs not complying with the dose constraints are 18,4% for Heart IRV, 18,4% for Esophagus IRV, 28,9% for Trachea IRV and 42% for Bronchial Tree IRV.

Conclusions

In our analysis, IRVs do not respect dose constraints in a significant percentage of patients, which is even higher in central lesions (up to 42%). The correlation of IRVs with clinical parameters and toxicity deserves future investigation.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Aim – To identify the incidence and risk factors of chest wall toxicity in patients who have undergone stereotactic radiotherapy for early stage lung cancers at the Edinburgh Cancer Centre between 2014 and 2019, particularly focusing on osteoporotic risk.

Methods

Retrospective data was collected from radiotherapy physics records to assess dose to chest wall (V30). Patient were divided into two cohorts. We identified 62 patients with a chest wall V30 > 30 Gy as our high-risk cohort and selected 58 patients as a random sample with a V30 of <30 Gy. Patient electronic notes and radiological scans were also used to collect information regarding patient demographics, pre-treatment tumour characteristics and post-treatment complications. Chest wall toxicity was defined and graded as per CTCAE v5.0. To investigate a correlation with osteoporotic risk factors we used the FRAX clinical scoring tool, scores were generated using factors at time of treatment.

Results

We identified 22 patients out of 120 with chest wall toxicity grade 1 or above. 8 from 58 in low-risk cohort (14%, V30 < 30 Gy) and 14 of 62 (23%, V30 > 30 Gy). Radiologically reported rib fractures were found in 8 of 62 patients in the high-risk cohort (12.9%, V30 > 30 Gy); and 4 of 58 (6.89%) in the lower-risk cohort. Patient factors related to chest wall pain/rib fractures after treatment included advanced age and female sex (81.8% of those affected were female). Tumour factors included larger sized tumours and proximity to the chest wall. We calculated FRAX scores for all 120 patients and 14/22(68%) with CWT were below the treatment threshold. Using a chi square test (p = 0.47) no significant correlation was found between median 10-year osteoporotic fracture and hip fracture probability in patients with chest wall toxicity compared to the entire study cohort.

Conclusions

We found that there was an increased risk of chest wall toxicity in patients who were older with higher rates in female patients and an increase in median chest wall dose with higher rates in the high-risk cohort (V30 > 3000CGy). We assessed the risk of chest wall toxicity and the 10-year probability of major osteoporotic fractures and hip fractures as calculated by the FRAX scoring tool and found no statistically significant correlation.

Legal entity responsible for the study

Edinburgh Cancer Centre.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Thoracic incisions are considered the most painful of all surgical incisions. Even with minimally invasive approaches, pain is the main driver of length of stay after uncomplicated surgery. The most common methods for pain control include epidural catheters and opioid medications. However, many side effects are associated with them, including addiction.

Methods

Analysis of a data base analyzing the impact of a pain management protocol and opioid consumption after robotic lobectomy as part of ERAS pathway. Our protocol begins with admnistration of acetaminophen (1 g po), celecoxib (400 mg po) and gabapentin (600 mg po) 2 hours before anesthesia. Intraoperatively, we utilize cryoanalgesia (T4-T9) and intercostal blockade with bupivacaine (01.25%). At the end of the operation, we give ketorolac (15–30 mg IV) and acetaminophen (1 g IV). Postoperatively patients receive a combination of acetaminophen, ibuprofen, gabapentin and tramadol. Other opioids are prescribed for brakethrough pain as prn medications. Our database and the electronic health record were analyzed looking at the consumption of IV or oral opioids until the time of discharge. The Morphine Milligram Equivalent (MME) was calculated using a standard opioid conversion calculator. Pain scores and length of stay were additionally analyzed.

Results

27 patients (M = 14, F = 13) underwent robotic lobectomy for lung cancer. Mean age was 63 (55–81). Mean length of stay was 1.7 days (1–4). Pain score mean was 1.6 (0–5). Twelve patients did not receive any doses of hydromorphone (IV) or oxycodone (po). Five patients received oxycodone but not hydromorphone. Four patients received hydromorphone but not oxycodone. The remaining six patients received both hydromorphone and oxycodone. Cryoanalgesia was utilized in all patients. The calculated morphine milligram equivalents (MME) were 2 for hydromorphone and 11.75 for oxycodone.

Conclusions

A multimodality protocol for pain management in thoracic surgery patients that includes a variety of medications and techniques (including cryoanalgesia and intercostal blockade), results in a significant reduction or elimination of opioid consumption, while providing excellent pain relief and a short length of stay.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

A positive resection margin is a rather serious factor which negatively affects the survival of patients with locally advanced NSCLC. In spite of this, there is still no consensus on the tactics for management of such patients. In this systematic review, we have summarized the available data of studies.

Methods

We performed a systematic literature search in PubMed, Elibrary, clinicaltrials.gov, and also in references of articles published prior to December 2020, to evaluate the possibility of these treatment methods in indirect comparison in patients with NSCLC 1A-2B stages. In addition, we contacted some experts in this field to clarify the availability of current studies on this topic. We also evaluated the methodological quality of the studies. It was not possible to perform a reliable comparative efficacy analysis due to the study design and the data presentation in the selected studies.

Results

233 published clinical studies were found and 6 retrospective studies were selected from these. The total number of patients was 5707. Most publications had moderate methodological quality. A systematic literature search found no studies evaluating the effectiveness of combining reoperation and chemotherapy. The 3-year OS for post-operative radiation therapy is 67% (p = .86) and 59% (not reported) for reoperation. The 5-year OS is 25% to 32% (p < 0.05) for post-operative radiation therapy groups and 33% to 44% (p ≤ 0.05) for post-operative chemoradiotherapy groups, whereas the 5-year OS for pneumonectomy is 33–43.1% (not reported). There was no difference in efficacy between post-operative radiation therapy and chemoradiotherapy in patients with NSCLC stage 1–2 in the absence of lymph node lesions or with the lymph node lesions.

Conclusions

Thus, we found a lack of high methodological quality randomized controlled trials and works that support the great efficacy of any treatment method. Further large comparative studies are needed to assess the intervention's effectiveness.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.