Stage IIIB Non-small Cell Lung Cancer Research Articles

Cemiplimab (Libtayo)

CADTH recommends that Libtayo in combination with platinum-based chemotherapy be reimbursed by public drug plans for the first-line treatment of adults with non–small cell lung cancer (NSCLC) whose tumours have no EGFR, ALK, or ROS1 aberrations and is locally advanced where patients are not candidates for surgical resection or definitive chemoradiation, or for those with metastatic NSCLC, if certain conditions are met. Libtayo in combination with platinum-based chemotherapy should only be covered to treat adults who have stage IIIB or IIIC NSCLC and are not suitable for curative surgery or definitive chemoradiation or have stage IV NSCLC and have not received prior systemic treatment. Patients’ tumours should have no EGFR, ALK, or ROS1 Patients should have a good performance status. Libtayo should only be reimbursed in combination with platinum-based chemotherapy if prescribed by clinicians with expertise and experience in treating NSCLC. The treatment should be delivered in outpatient specialized oncology clinics with expertise in systemic therapy delivery and management of immunotherapy-related side effects. The price of Libtayo should be negotiated so that its use in combination with platinum-based chemotherapy does not exceed the total drug cost of treatment with the least costly immunotherapy reimbursed in the first-line setting.

Immunotherapy or Chemoimmunotherapy in Older Adults With Advanced Non–Small Cell Lung Cancer

Immune checkpoint inhibitor (ICI) plus chemotherapy combination treatment (ICI-chemotherapy) is now a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alterations, but there are few data on ICI-chemotherapy for patients 75 years and older. To inform the choice of first-line drugs in clinical practice and assess the safety and efficacy of ICI-chemotherapy combination treatment in older adult patients with previously untreated advanced NSCLC. This retrospective cohort study included 58 centers in Japan. The cohort consisted of patients 75 years and older with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC. Patients started first-line systemic therapy between December 2018 and March 2021. Those receiving first-line molecular targeted drugs were excluded. The data were analyzed from February 2022 to October 2022. Systemic therapy. The main outcomes were overall survival (OS), progression-free survival (PFS), and safety. A total of 1245 patients (median [range] age, 78 [75-95] years; 967 [78%] male) with NSCLC were included in the cohort. Programmed death ligand-1 (PD-L1) expression of less than 1% occurred in 268 tumors (22%); 1% to 49% in 387 tumors (31%); 50% and higher in 410 tumors (33%), and unknown expression in 180 tumors (14%). Median OS was 20.0 (95% CI, 17.1-23.6) months for the 354 patients receiving ICI-chemotherapy (28%); 19.8 (95% CI, 16.5-23.8) months for the 425 patients receiving ICI alone (34%); 12.8 (95% CI, 10.7-15.6) months for the 311 patients receiving platinum-doublet chemotherapy (25%); and 9.5 (95% CI, 7.4-13.4) months for the 155 patients receiving single-agent chemotherapy (12%). After propensity score matching, no differences in OS and PFS were found between the patients receiving ICI-chemotherapy vs ICI alone. Each group consisted of 118 patients. For PD-L1 expression of 1% and higher the OS hazard ratio (HR) was 0.98 (95% CI, 0.67-1.42; P = .90), and the PFS HR was 0.92 (95% CI, 0.67-1.25; P = .59). Significance was also not reached when separately analyzed for lower or higher PD-L1 expression (1%-49% or ≥50%). However, grade 3 or higher immune-related adverse events occurred in 86 patients (24.3%) treated with ICI-chemotherapy and 76 (17.9%) with ICI alone (P = .03). In this study, ICI-chemotherapy combination treatment did not improve survival and increased the incidence of grade 3 and higher immune-related adverse events compared with ICI alone in patients 75 years and older. Based on these results, ICI alone may be recommended for older adult patients with PD-L1-positive NSCLC.

Deep pathomics: A new image-based tool for predicting response to treatment in stage III non-small cell lung cancer.

Despite the advantages offered by personalized treatments, there is presently no way to predict response to chemoradiotherapy in patients with non-small cell lung cancer (NSCLC). In this exploratory study, we investigated the application of deep learning techniques to histological tissue slides (deep pathomics), with the aim of predicting the response to therapy in stage III NSCLC. We evaluated 35 digitalized tissue slides (biopsies or surgical specimens) obtained from patients with stage IIIA or IIIB NSCLC. Patients were classified as responders (12/35, 34.7%) or non-responders (23/35, 65.7%) based on the target volume reduction shown on weekly CT scans performed during chemoradiation treatment. Digital tissue slides were tested by five pre-trained convolutional neural networks (CNNs)-AlexNet, VGG, MobileNet, GoogLeNet, and ResNet-using a leave-two patient-out cross validation approach, and we evaluated the networks' performances. GoogLeNet was globally found to be the best CNN, correctly classifying 8/12 responders and 10/11 non-responders. Moreover, Deep-Pathomics was found to be highly specific (TNr: 90.1) and quite sensitive (TPr: 0.75). Our data showed that AI could surpass the capabilities of all presently available diagnostic systems, supplying additional information beyond that currently obtainable in clinical practice. The ability to predict a patient's response to treatment could guide the development of new and more effective therapeutic AI-based approaches and could therefore be considered an effective and innovative step forward in personalised medicine.

Traitement standard des stades III non résécables: Standard therapy for unresectable Stage III Non-Small Cell Lung Cancer

Approximately 25% of Non-small Cell Lung Cancer (NSCLC) present with a locally advanced disease. Stage III NSCLC includes heterogeneous diseases in term of initial clinical presentation and therapeutic strategy. An optimal initial staging integrating a PET/CT, EBUS mediastinal nodes exploration and an injected brain imaging is necessary. Pulmonary function test is to be systematically realized. The therapeutic strategy is decided in a multidisciplinary tumor board by an experimented team. Most of the stage IIIB and IIIC NSCLC receive a radio-chemotherapy. A concurrent plan is to be favored to a sequential plan. Platinum doublets comprise most standard chemotherapy regimens and must be started as early as possible. For fail or elderly patients who could not benefit from a concurrent chemotherapy, a sequential normo-fractionnated radiotherapy, or even a single chemotherapy are possible alternatives. After radio-chemotherapy, a consolidation systemic treatment by durvalumab, a checkpoint inhibitor, is currently a standard of care, in patients with a PD-L1 expressing tumor, based on the PACIFIC trial overall survival results.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Randomized, open-label phase II study of brigatinib and carboplatin plus pemetrexed and brigatinib alone for chemotherapy-naive patients with ALK-rearranged non-squamous non-small cell lung cancer: treatment rationale and protocol design of the B-DASH study (WJOG 14720 L)

BackgroundThe ALTA-1L study compared brigatinib with crizotinib in untreated ALK-rearranged non-small cell lung cancer (NSCLC) patients, demonstrating the efficacy of brigatinib. Although the median progression-free survival (PFS) of brigatinib group was 24.0 months, the one-year PFS rate was 70%. In the NEJ009 study, patients with EGFR mutations showed improved outcomes with gefitinib plus chemotherapy compared with gefitinib monotherapy. To evaluate the efficacy of the combination of brigatinib with chemotherapy for patients with ALK-rearranged NSCLC, we designed B-DASH study (WJOG 14720L).MethodsB-DASH study is a multicenter, two-arm, phase II study. Eligible patients have untreated stage IIIB, stage IIIC, stage IV, or postoperative relapse ALK-rearranged nonsquamous NSCLC. Patients will be randomized in a 1:1 ratio to receive brigatinib (180 mg once daily with a 7-day lead-in period at 90 mg) monotherapy or carboplatin (area under the curve = 5 on day 1) plus pemetrexed (500 mg/m2 on day 1) and brigatinib in a 3-week cycle for up to four cycles, followed by pemetrexed and brigatinib as maintenance therapy. The target hazard ratio of 0.62 is set based on the NEJ009 study. With one-sided alpha = 0.20 and power = 0.8, the sample size for the B-DASH study was calculated to be 110, considering the possibility of patients dropping out. The primary endpoint is PFS. The key secondary endpoints are the overall response rate and overall survival. We will evaluate tumor-derived DNA from plasma specimens before treatment, 42 days after administering the study drug, and on the day of progressive disease. Recruitment began in November 2021 and is ongoing.DiscussionThe efficacy of combination therapy with tyrosine kinase inhibitors and cytotoxic chemotherapy was demonstrated in patients with EGFR mutations but remains unclear in patients with ALK-rearranged NSCLC. The B-DASH study is the only trial of brigatinib combined with chemotherapy in patients with untreated ALK-rearranged NSCLC.Trial registrationjRCT identifier: jRCTs041210103.

Neoadjuvant Camrelizumab Plus Platinum-Based Chemotherapy vs Chemotherapy Alone for Chinese Patients With Resectable Stage IIIA or IIIB (T3N2) Non–Small Cell Lung Cancer

The benefit of neoadjuvant camrelizumab plus chemotherapy for resectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) remains unknown. To assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy vs chemotherapy alone for patients with resectable stage IIIA or IIIB NSCLC. In this randomized phase 2 clinical trial conducted at 2 hospitals in China, patients aged 18 to 70 years with resectable stage IIIA or IIIB (T3N2) NSCLC were enrolled between April 7, 2020, and January 12, 2022. Patients were randomly assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m2, and platinum [cisplatin, 75 mg/m2; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m2]) or chemotherapy alone, followed by surgery after 4 to 6 weeks. The primary end point was the pathologic complete response (pCR) rate. Secondary end points included the major pathologic response (MPR) rate, objective response rate (ORR), event-free survival (EFS), and safety. Disease-free survival (DFS, defined as the time from surgery to disease recurrence or death from any cause) was analyzed post hoc. Efficacy was assessed on a modified intention-to-treat basis. Ninety-four Chinese patients were randomized, and 88 (93.6%; median age, 61 years [IQR, 54-65 years]; 74 men [84.1%]) received allocated neoadjuvant treatment (43 received camrelizumab plus chemotherapy, and 45 received chemotherapy alone). Among these 88 patients, the pCR rate was 32.6% (14 of 43; 95% CI, 19.1%-48.5%) with camrelizumab plus chemotherapy vs 8.9% (4 of 45; 95% CI, 2.5%-21.2%) with chemotherapy alone (odds ratio, 4.95; 95% CI, 1.35-22.37; P = .008). The MPR rates were 65.1% (95% CI, 49.1%-79.0%) with camrelizumab plus chemotherapy and 15.6% (95% CI, 6.5%-29.5%) with chemotherapy alone. The radiographic ORRs were 72.1% (95% CI, 56.3%-84.7%) with camrelizumab plus chemotherapy and 53.3% (95% CI, 37.9%-68.3%) with chemotherapy alone. With a median follow-up of 14.1 months (IQR, 9.2-20.9 months), the median EFS and DFS were not reached in either group. The most common neoadjuvant treatment-related adverse events of grade 3 or higher were decreased white blood cell count (6 of 43 [14.0%] in the camrelizumab plus chemotherapy group vs 2 of 45 [4.4%] in the chemotherapy group) and decreased neutrophil count (3 of 43 [7.0%] in the camrelizumab plus chemotherapy group vs 5 of 45 [11.1%] in the chemotherapy group). No treatment-related deaths were reported. This randomized clinical trial found that among patients with resectable stage IIIA or IIIB (T3N2) NSCLC, camrelizumab plus chemotherapy, compared with chemotherapy alone, significantly improved the pCR rate with manageable toxic effects. ClinicalTrials.gov Identifier: NCT04338620.

Neoadjuvant immunotherapy plus chemotherapy and adjuvant targeted therapy in ALK-positive non-small-cell lung cancer.

Neoadjuvant therapy and adjuvant therapy for locally advanced non-small-cell lung cancer (NSCLC) with ALKfusion mutation have not been thoroughly studied. Here, a stage IIIB NSCLC patient with EML4-ALK fusion mutation receiving immunotherapy plus chemotherapy as neoadjuvant treatment followed by lobectomy plus lymph node dissection is reported. The patient achieved a pathological complete responseaccording to pathological evaluation. The patient received adjuvant crizotinib for 3months and achieved a disease-free survival time of 36months.

Safety and efficacy of two-drug combination in elderly patients with locally advanced non-small cell lung cancer and validation of the Charlson Index as a predictor of survival.

The best platinum-based chemotherapy regimen remains to be determined in elderly patients treated with definitive chemoradiotherapy for advanced non-small cell lung cancer (NSCLC). Predictive indexes for toxicity and survival are also needed to give the safest and most effective treatment for this population. This is a retrospective cohort study. Patients with histologically confirmed stage IIIA, IIIB or IIIC NSCLC over 70 years of age, treated with radiotherapy and chemotherapy, were included. Patients from two cancer centers treated between 12/2006 and 08/2019 were included in the data analysis. Fifty-eight patients were enrolled in the study. The median age was 76.6 years [interquartile range (IQR): 71.6-83.4]. Thirty-nine patients were treated with concomitant chemoradiotherapy and 19 with a sequential strategy. The chemotherapy regimen consisted in a combination of platinum and taxanes. At a median follow-up of 52 months (IQR: 7-69), the 2-year progression-free survival (PFS) and overall survival (OS) were 35.5% and 66.9%, respectively. Male sex and a high Charlson index were identified as independent prognostic factors for worse OS. Acute grade 3-5 toxicities occurred in 34.4% of patients, including 1 grade 5 toxicity, and grade 3-4 late toxicities occurred in 17.2% of patients. In the whole cohort a high Charlson index was the only predictive factor for a higher risk of grade 3-5 acute toxicities (statistical trend in the concurrent cohort, P=0.06). The Charlson index correlated with toxicity and survival in elderly patients treated with chemoradiotherapy in locally advanced NSCLC. The addition of taxanes to platinum chemotherapy was safe in the present study and warrants further exploration.

Perioperative Nivolumab and Chemotherapy in Stage III Non–Small-Cell Lung Cancer

BackgroundApproximately 20% of patients with non–small-cell lung cancer (NSCLC) receive a diagnosis of stage III disease. There is no current consensus regarding the most appropriate treatment for these patients.MethodsIn this open-label, phase 2 trial, we randomly assigned patients with resectable stage IIIA or IIIB NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy (experimental group) or chemotherapy alone (control group), followed by surgery. Patients in the experimental group who had R0 resections received adjuvant treatment with nivolumab for 6 months. The primary end point was a pathological complete response (0% viable tumor in resected lung and lymph nodes). Secondary end points included progression-free survival and overall survival at 24 months and safety.ResultsA total of 86 patients underwent randomization; 57 were assigned to the experimental group and 29 were assigned to the control group. A pathological complete response occurred in 37% of the patients in the experimental group and in 7% in the control group (relative risk, 5.34; 95% confidence interval [CI], 1.34 to 21.23; P=0.02). Surgery was performed in 93% of the patients in the experimental group and in 69% in the control group (relative risk, 1.35; 95% CI, 1.05 to 1.74). Kaplan–Meier estimates of progression-free survival at 24 months were 67.2% in the experimental group and 40.9% in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25 to 0.88). Kaplan–Meier estimates of overall survival at 24 months were 85.0% in the experimental group and 63.6% in the control group (hazard ratio for death, 0.43; 95% CI, 0.19 to 0.98). Grade 3 or 4 adverse events occurred in 11 patients in the experimental group (19%; some patients had events of both grades) and 3 patients in the control group (10%).ConclusionsIn patients with resectable stage IIIA or IIIB NSCLC, perioperative treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients with a pathological complete response and longer survival than chemotherapy alone. (Funded by Bristol Myers Squibb and others; NADIM II ClinicalTrials.gov number, NCT03838159; EudraCT number, 2018-004515-45.)

Dosimetric comparison of four radiotherapy techniques for stage III non‑small cell lung cancer.

The present study was implemented to compare the dosimetric parameters of the target dose coverage and critical structures in the treatment planning of four radiotherapy techniques [namely, three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), hybrid IMRT (h-IMRT) and volumetric-modulated arc therapy (VMAT)] for stage III non-small cell lung cancer (NSCLC) qualified plans for medical physicists, therapists and physicians. A total of 40 patients confirmed to have stage IIIA or IIIB NSCLC were enrolled, and four plans were designed for each patient. The prescription dose to the planning target volume (PTV) was assigned as 60 Gy in 30 fractions. The conformity index (CI), heterogeneity index (HI) and parameters of organs at risk (OARs) were calculated. For the PTV, the CI for VMAT was found to be the highest of all the four techniques (P<0.05), whereas the HI for the h-IMRT technique was found to be the lowest (P<0.05). Concerning the OARs, for the percentage of lung volume receiving a dose >5 Gy (lung V5), the highest value was obtained with VMAT (P<0.05), whereas for lung V30 and heart V30, the VMAT and IMRT techniques were found to be better compared with 3D-CRT and h-IMRT (P<0.05). For esophagus V50, the maximal dose (Dmax) and mean dose for the IMRT technique displayed the best results (P<0.05), and in the case of the spinal cord, the Dmax with VMAT showed a significant advantage over the other techniques (P<0.05). The treatment monitor units (MUs) in IMRT were found to be the largest (P<0.05), whereas the treatment time with VMAT was the shortest (P<0.05). For smaller PTVs, VMAT was the technique that provided the optimal dose distribution and sparing of the heart. Compared with 3D-CRT alone, adding 20% IMRT to the 3D-CRT base plan was shown to improve the plan quality, and IMRT and VMAT, as techniques, had better dose coverage and sparing of OARs. Furthermore, for patients in whom the lung V5 could be kept low enough, VMAT potentially offered a good alternative to the technique to IMRT, thereby offering additional possibilities for sparing of other OARs, and decreasing the MUs and treatment time.

Exploration of biomarkers in potentially resectable stage IIIB NSCLC patients receiving neoadjuvant chemoimmunotherapy.

e20591 Background: Non–small cell lung cancer (NSCLC) is one of the main leading causes of cancer mortality in the world. NSCLC is incurable in most patients with potentially resectable locally advanced stage IIIB disease. Numerous studies suggest that advantageous chemoimmunotherapy is a promising treatment for resectable NSCLC. The determination of PD-L1, T-cell receptor (TCR) repertoire and tumor mutational burden (TMB) have been reported to predict the response to immunotherapy. However, the value of pathologic response determination in the context of neoadjuvant chemoimmunotherapy in resectable stage IIIB NSCLC is limited. Therefore, it is necessary to identify biomarkers for the prediction of the benefit from neoadjuvant chemoimmunotherapy in patients with potentially resectable stage IIIB NSCLC. Methods: A total of 15 patients with potentially resectable clinical stage IIIB NSCLC were enrolled into the study receiving neoadjuvant sintilimab (200mg IV Q3W) plus chemotherapy therapies for 4-6 weeks followed by surgery. All peripheral blood and tissue samples were collected and detected by using TCR repertoire sequencing before and after chemoimmunotherapy. The patients were divided into MPR group (n=5) and non-MPR group (n=10) according to MPR (&lt;10% viable tumour at resection) as an index. Furthermore, TMB spectra of 1021-gene panels and PD-L1 immunohistochemical staining were performed in paraffin-embedded human NSCLC tissue before neoadjuvant chemoimmunotherapy. The Pearson correlation coefficient method was used to analyze correlation. The ROC analysis were performed using “pROC” R package. Results: In baseline tissue samples, the levels of TMB and NAD were higher in MPR compared with non-MPR groups (P=0.0328, P=0.015, respectively). The negative correlation was existed between pretreatment tissue TCR richness and TMB in non-MPR group (P=0.028, R=-0.66). In MPR group, TCR clones and evenness showed significant difference (P=0.00237, P=0.04658, respectively). In non-MPR group, the TCR repertoire of tissue in posttreatment showed significant difference compared with those of pretreatment, including clones (P=1.04x10-6), shannon’s diversity (P=0.00142), evenness (P=0.00433), richness (P=0.00591). The clinical data showed that MPR patients with DDR mutation had longer DFS after sintilimab plus chemotherapy therapies (18.4±5.41 months, X-squared=9.8, P=0.02034). DDR mutation, TMB and TCR richness revealed better sensitivity and specificity to classify patients achieving MPR after neoadjuvant chemoimmunotherapy (AUC=1.000, AUC=0.796, AUC=0.773, respectively). Conclusions: This study confirmed the superiority of neoadjuvant chemoimmunotherapy in patients with potentially resectable stage IIIB NSCLC in terms of MPR. TCR repertoire, TMB and DDR mutation were associated with pathologic response to neoadjuvant chemoimmunotherapy as biomarkers for effective anti-tumor immunity. Clinical trial information: ChiCTR2000040673 .

First-line immune checkpoint inhibitors alone or in combination with chemotherapy in real-life elderly patients with advanced non-small cell lung cancer (NEJ057).

9012 Background: Immune checkpoint inhibitor (ICI) plus chemotherapy is now a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alternations. However, the efficacy and safety of ICI plus chemotherapy (ICI-chemo) in 75 years or older patients have not been elucidated. The aim of this study is to reveal the real-world choice of first-line drugs in elderly patients (pts) and evaluate the efficacy and safety of ICI-chemo. Methods: We conducted a multicenter (58 centers in Japan), retrospective cohort study of consecutive 75 years or older pts with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC who started first-line systemic therapy between December 2018 and March 2021. Pts with epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or whose first-line systemic therapy was molecular targeted therapy were excluded. Results: A total of 1245 pts were enrolled: median (range) age 78 (75-95) years; 278 (22%) female; 367 (29%) ECOG PS 0, 680 (55%) PS 1 and 171 (14%) PS 2; 678 (54%) adenocarcinoma; PD-L1 tumor proportion score 268 (22%) &lt;1%, 387 (31%) 1-49% and 410 (34%) ≥50%; 354 (28%) ICI-chemo, 425 (34%) ICI alone, 311 (25%) platinum-doublet chemotherapy and 155 (12%) single agent chemotherapy. The median overall survival (OS) was 20.0 months (95%CI, 17.1–23.6) in the ICI-chemo group, 19.8 months (95%CI, 16.5–23.8) in the ICI alone group, 12.8 months (95%CI, 10.7–15.6) in the platinum-doublet chemotherapy group and 9.5 months (95%CI, 7.4–13.4) in the single agent chemotherapy group, respectively. After propensity score matching, there was no difference in OS and progression-free survival (PFS) between ICI-chemo group (n=96) and ICI alone group (n=95) in PD-L1 ≥1% (OS: HR, 0.98; 95% CI, 0.67-1.42, PFS: HR, 0.92; 95% CI, 0.67-1.25). Regardless of PD-L1 subgroups (1-49% or ≥50%), no significant differences in OS and PFS were observed. Concerning safety, Grade 3 or higher immune-related adverse events (irAEs) occurred in 86 pts (24.3%) in the ICI-chemo group and 76 pts (17.9%) in the ICI alone group (p = 0.03). The number of pts who required steroids for irAEs was 115 (32.5%) in the ICI-chemo group and 105 (24.7%) in the ICI alone group (p = 0.02). Pneumonitis was reported in 83 pts (23.4%) in the ICI-chemo group and 66 pts (15.6%) in the ICI alone group (p = 0.006). Conclusions: In real-world data for pts aged 75 years or older, ICI-chemo did not improve survival and increased the incidence of grade 3 or higher irAEs compared to ICI alone. Based on our results, ICI alone is recommended for elderly pts with PD-L1 positive NSCLC. Clinical trial information: UMIN000046700 .

Characteristics of lung cancer in renal transplant recipients.

e20592 Background: Renal transplant recipients (RTRs) are at a higher risk of developing malignancies primarily due to prolonged immunosuppression. Lung cancer while rare in RTR, is associated with significant morbidity and mortality. The primary objective of our study is to analyze the clinical characteristics and outcomes of RTRs who developed lung cancer at our institution. Methods: We retrospectively reviewed 1998 RTRs who underwent transplantation between January 1, 1999, and December 31, 2019, at our institution and identified patients who were diagnosed with lung cancer after transplant. Baseline demographic variables and information related to the renal transplant, the diagnosis and management of lung cancer were collected. Results: Among 1998 RTRs, 10 patients (0.005%) developed lung cancer. A majority of the lung cancer patients identified as male (n = 8), and the median age was 62.5 years. The races of the patients were white (30%, n = 3), African American (50%, n = 5), Hispanic (10%, n = 1), and Native American (10%, n = 1). Concomitant liver transplant was performed in 2 patients, and a concomitant heart transplant was performed in 1 patient. Median time to lung cancer diagnosis after transplant was 67.5 months (range, 12-168). The histology of the lung cancers found were adenocarcinoma (n = 4), squamous (n = 4), and small cell (n = 2). All patients had a history of smoking, with 90% reporting a &gt; 15 pack-year history of smoking and none of them received lung cancer screening. Among the patients with non-small cell lung cancer (NSCLC), 87.5% (n = 7) had early-stage disease, and 12.5% (n = 1) had locally advanced disease (Stage IIIB). Both patients diagnosed with small cell lung cancer had extensive-stage (es-SCLC) disease at the time of diagnosis. Among patients with NSCLC, 2 had genomic tumor profiling performed. Among patients with early-stage NSCLC, 57% underwent upfront surgery, 14% received radiation alone, 14% received neoadjuvant chemotherapy, and 14% received adjuvant chemotherapy. Around 71% (n = 5) remained alive at the last follow up recorded. The patient with stage IIIB NSCLC received chemotherapy and concomitant radiation but had an overall survival (OS) of only 6 months; that patient died of complications related to cancer progression. Both patients with es-SCLC received front-line chemotherapy with carboplatin and etoposide. To our knowledge, 40% (n = 4) of these patients retained their renal graft function. At 1-year from diagnosis, 40% of patients diagnosed with lung cancer were still alive. Conclusions: Lung cancer in RTRs is rare but is associated with significant morbidity and mortality. With the improving life expectancy of RTRs, the incidence of de novo malignancies including lung cancer is likely to increase. Annual screening for lung cancer in high-risk individuals is an important step for early diagnosis. Surgical resection and chemotherapy are well tolerated in patients with lung cancer.

Comparative Study of Hypofractionated Palliative Radiotherapy 17 Gy in 2 Fractions vs. 30 Gy in 10 Fractions in Lethal Locally Advanced Non-small Cell Lung Cancer

<i>Background</i>: Lung cancer kills the most people worldwide. Most Bangladeshi patients had regionally advanced surgically inoperable Non-Small Cell Lung Cancer (NSCLC), a deadly disease. Radiotherapy to main tumor and regional lymphatics with chemotherapy is conventional treatment. <i>Objective</i>: This study was done to investigate the symptoms relief and treatment related toxicities in hypo fractionated 17 Gy in 2 fractions which is effectively comparable to 30 Gy in 10 fractions. <i>Methods</i>: A total 60 patients were divided equally into Arm A and Arm B with locally advanced stage IIIA, and stage IIIB NSCLC patients with the objective to compare palliation of symptoms and to assess the toxicity profile. This Quasi Experimental study was carried out from January 2018 to December 2018 in the department of Radiation oncology, National Institute of Cancer Research and Hospital. Cases of Arm A were treated with 17 Gy radiotherapy in 2 fractions and those of Arm B were treated with 30 Gy radiotherapy in 10 fractions. <i>Results</i>: The mean age was 49.3±8.8 and 52.2±8.1 years for the Arm- A and the Arm-B respectively. Most patients in both groups were males, 80% in group A and 90% in group B. Adenocarcinoma (Arm A-70%, Arm B- 66.7%) was the most common pathological subtype in both groups, followed by Squamous cell carcinoma (30%, 33.3% respectively). This study showed that there was a significant palliation of these symptoms following radiotherapy as reported by patients and as assessed clinically with no statistically significant difference between two Arms. Hemoptysis had the highest rate of improvement, 100% in both arms and improvement in chest pain by 83.3% in arm A and 70% in Arm B. Cough was improved in 83.3% and 67.7% and dyspnea was palliated in 80.0% and 70.0% of patients in Arm A and Arm B, respectively as per clinical assessment of the patients. The early toxicities in both arms had no significant difference. Patients with locally advanced inoperable NSCLC have poor prognosis and less survival. The first goal was acceptable symptoms control as cough, dyspnoea, haemoptysis and chest pain. <i>Conclusion</i>: The result of this study showed that a significant palliation of symptoms with minimum toxicities improving quality of life following radiotherapy as reported by patients also assessed clinically and radiographically with no statistically significant difference among both arms.

Neoadjuvant Immunotherapy in Oncogene-Positive Non-Small Cell Lung Cancer: A Multicenter Study

BackgroundPreoperative immunotherapy has shed light on the management of resectable non-small cell lung cancer (NSCLC). However, whether neoadjuvant immunotherapy benefits patients with oncogene-positive NSCLC remains unknown. MethodsData were retrieved from 4 institutions in the period from August 2018 to May 2021. Eligible patients were aged ≥18 years with histologically confirmed stage IIA to stage IIIB (T1-2 N1-2 or T3-4 N0-2) NSCLC that was deemed to be surgically resectable. The neoadjuvant regimen included immune checkpoint inhibitors alone or in combination with platinum-based doublets. Surgical resection was performed 4 to 6 weeks after the first day of the last cycle of treatment. The primary end point was major pathologic response (MPR; ≤10% viable tumor cells). Analyses were categorized according to the patients’ oncogene (EGFR, ALK, KRAS, MET, BRAF, ROS1, RET) status. ResultsOverall, 137 patients were identified; 46 (33%) patients had nonsquamous cell cancer, and 114 (83%) had stage IIIA/B disease. Oncogene alterations were identified in 22 (16%) patients, of whom only 2 patients (2/22 [9%]) had an MPR compared with 65 (65/115 [56.5%]) in the oncogene-negative population (P < .001). Similar results were retained after propensity score matching for age, sex, smoking status, histologic type, stage, and cycles of neoadjuvant treatment. Squamous cell carcinoma (odds ratio, 2.54; 95% CI, 1.08-5.99) and positive oncogene status (odds ratio, 0.13; 95% CI, 0.03-0.64) were found to be indicators for MPR by logistic regression. The 1-year event-free survival rate was 75.4% in the oncogene-positive group, which was not significantly different from 85.5% in the oncogene-negative population (P = .23). ConclusionsPatients with stage II-III oncogene-positive NSCLCs respond less than patients with oncogene-negative NSCLCs after neoadjuvant immunotherapy.

The Validation of Predictive Risk Scoring Model of Radiation Pneumonitis (RP) in Lung Cancer Patients

<h3>Purpose/Objective(s)</h3> In our previous research, pulmonary emphysema (PE) was reported as a risk factor of radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC). Subclinical interstitial lung disease (SILD) was associated with severe RP in small cell lung cancer patients. A predictive risk scoring model of RP was developed in stage IIIA or Stage IIIB NSCLC patients receiving radical radiotherapy. The risk score has not been validated using an independent dataset. The aim of this study was to validate the predictive risk score which established in our previous study and evaluate the predictive value of the model. <h3>Materials/Methods</h3> From January 2019 to October 2021,129 lung cancer patients were recruited in study which included in validation group. Those patients were received thoracic radiotherapy with ≥50Gy total radiotherapy dose. The risk scoring model in our previous research as follow: PRS=5 (if subclinical ILD grade≥1) + 3 (if age >68 years) + 3 (if PE grade >1). According to the risk score, the cases in validation group were scored, predictive value of this model were evaluated by receiver operator characteristic curve (ROC) using statistical software. The decision curve analysis was constructed using Stata 17.0 software. <h3>Results</h3> In 129 eligible patients, 13(10.08%, 13/129) developed grade 1 RP, 15(11.62%, 15/129) developed grade 2 RP, grade 3 and grade 4 RP were not observed. 23 (16.60%, 23/129) had PE grade >1. Risk scores of all patients were calculated according to the risk score, 37 had 3 points which incidence of RP ≥2 grade was 13.50%, 2 had 5 points which incidence of RP ≥2 grade was 100.0%, 3 had 6 points which incidence of RP ≥2 grade was 33.33%. ROC curve was plotted according to the risk score of all patients, the area of ROC curve (AUC) was 0.695 (95%CI: 0.541-0.849, P < 0.05). The decision curve indicated that the net benefit of the model was higher in the high-risk threshold of 0.2-0.3. <h3>Conclusion</h3> The previous predictive risk scoring model indicated good discrimination and clinical application value, which can be used in clinical treatment.

Use of Preoperative FDG PET/CT and Survival of Patients with Resectable Non-Small Cell Lung Cancer.

Background The added value of preoperative PET/CT for the overall survival of patients with resectable non-small cell lung cancer (NSCLC) is unknown. Purpose To investigate the association of the use of preoperative PET/CT on survival of patients with resectable stage I-IIIB NSCLC. Materials and Methods In this retrospective study, patients with resectable stage I-IIIB NSCLC who underwent thoracic surgery from January 1, 2009, to December 31, 2018, from the Taiwan Cancer Registry were included. The last follow-up date was December 31, 2019. Patients were categorized into two groups according to whether they underwent preoperative metabolic imaging with fluorine 18 fluorodeoxyglucose PET/CT. Patients who did not undergo preoperative imaging were used as the control group. The primary outcome of interest was all-cause mortality. Patients in both groups were propensity score matched at a ratio of 1:1. Matching variables used were sex, age, histologic findings, American Joint Committee on Cancer clinical stage, cT stage, cN stage, current and past smoker history, adjuvant chemotherapy, adjuvant chemoradiation, Charlson comorbidity index, and hospital type. Survival curves were generated using the Kaplan-Meier method and compared using the log-rank test. Results In the matched cohort, 6754 patients (3349 men, mean age ± SD: 64 years ± 11) underwent PET/CT and 6754 did not (3362 men, mean age: 64 years ± 11). In adjusted analysis, patients with stage IIIA or IIIB NSCLC and preoperative PET/CT had a lower risk of death versus those without PET/CT (for stage IIIA: hazard ratio [HR] = 0.90 [95% CI: 0.79, 0.94], P = .02; for stage IIIB: HR = 0.80 [95% CI: 0.71, 0.90], P < .01). There was no improvement in a lower risk of death for patients with stage I-II NSCLC (after multivariable adjustment, the HR was 1.19 [95% CI: 0.89, 1.30], P = .65). Conclusion Use of preoperative PET/CT was associated with lower risk of death in patients with stage IIIA-IIIB non-small cell lung cancer compared with those without preoperative PET/CT. © RSNA, 2022 Online supplemental material is available for this article.

Necrosis onstaging 18F FDG PET/CT is associated with worse progression-free survival in patients with stage IIIB non-small cell lung cancer.

The presence of pathological necrosis in the tumor is known to be a factor indicating worse survival. Our study defined necrosis in staging 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with stage IIIB non-small-cell lung cancer (NSCLC) to investigate whether this is a poor prognostic marker. A total of 77 patients with NSCLC were evaluated. To evaluate necrosis on 18F FDG PET/CT, we drew a region of interest (ROI) in the area showing visually very low/or no FDG uptake on PET and PET/CT fusion images. If SUVmax was less than blood pool SUVmax and showed significantly less attenuation [10 to 30 Hounsfield units (HUs)] than surrounding tissue on low-dose correlative CT with non-intravenous contrast, we defined it as necrotic (PETNECROSIS). We evaluated the relationship of SUVmax, tumor size, and PETNECROSIS with progression-free survival (PFS) using a Cox proportional hazard regression model. A PFS analysis was performed on 16 patients treated with standard chemoradiotherapy (CRT) regimen. Tumor size ≤42 mm versus >42 mm (P = 0.044, HR: 6.103, 95 CI%: 1.053-35.358) and PETNECROSİS presence/absence (P = 0.027, HR: 6.719, 95 CI%: 1.245-36.264) were independent predictors for PFS. Patients with tumor size ≤42 mm and PETNECROSİS absence were associated with higher 1-year PFS rate than patients with tumor size >42 mm and PETNECROSİS presence (86% vs. 63.5% P = 0.005 and 87.5% vs. 29%, P = 0.001, respectively). PETNECROSİS is helpful to distinguish the patients who would suffer worse survival in stage IIIB NSCLC.

Abstract LBA039: Canakinumab as Adjuvant Therapy in Patients With Completely Resected Non-Small Cell Lung Cancer: CANOPY-A Trial

Abstract Background: In the CANTOS study, canakinumab (selective interleukin 1β inhibitor) treatment was associated with reduced incidence and mortality from non-small cell lung cancer (NSCLC) in stable post–myocardial infarction patients with elevated high-sensitivity C-reactive protein (hs-CRP) levels. The CANOPY-A study was designed to investigate the therapeutic role of canakinumab in NSCLC. Methods: The CANOPY-A study (NCT03447769) is evaluating the efficacy and safety of canakinumab as adjuvant therapy in adult patients with completely resected NSCLC. Patients with American Joint Committee on Cancer/Union for International Cancer Control version 8 stage IIA-IIIA and IIIB (T &amp;gt;5 cm, N2), any histology, completely resected (R0) NSCLC and completion of adjuvant cisplatin-based chemotherapy (≥2 cycles) and radiotherapy (if applicable) are eligible. Patients must not have had prior neoadjuvant chemotherapy or radiotherapy. Patients (~1500) are randomized 1:1 to receive canakinumab (200 mg) or placebo subcutaneously every 3 weeks for 18 cycles or until disease recurrence as determined by investigator, unacceptable toxicity, or treatment discontinuation at the discretion of the investigator. The primary objective is to compare disease-free survival (DFS) in the canakinumab versus placebo arm per local investigator assessment. Secondary objectives are overall survival (OS), lung cancer–specific survival, safety, pharmacokinetics, immunogenicity, and patient-reported outcomes. Adult patients with stage IIA-IIIA and IIIB (T&amp;gt;5 cm, N2 disease only) NSCLC who are candidates for complete resection surgery (and therefore prospective candidates for the main study) will be asked to participate in a biomarker substudy to understand how resection may impact biomarkers involved in the interleukin 1β inflammatory pathway and mutations present in blood. In the substudy, the levels of hs-CRP, other cytokines, and additional biomarkers in blood will be assessed before and after surgery (endpoint: summary statistics of hs-CRP and other pharmacodynamic biomarkers). For patients who will enroll in the main study, possible associations between pre- and post-surgery biomarker levels with canakinumab efficacy will be assessed (endpoint: DFS and OS by hs-CRP and other pharmacodynamic biomarkers). The CANOPY-A study is currently enrolling. As of August 6, 2021, there are 399 study locations. Citation Format: Edward B. Garon, Andrea Ardizzoni, Fabrice Barlesi, Byoung Chul Cho, Pedro De Marchi, Yasushi Goto, Dariusz Kowalski, Shun Lu, David R. Spigel, Michael Thomas, James Chih-Hsin Yang, Sabine Turri, Wen Zhou, Teri Kreisl, Luis Paz-Ares. Canakinumab as Adjuvant Therapy in Patients With Completely Resected Non-Small Cell Lung Cancer: CANOPY-A Trial [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA039.

Role of Modified Frailty Index in Predicting Oncologic Outcomes From Moderately Hypofractionated Radiotherapy for Patients with Stage I-IIB Non-Small Cell Lung Cancer

Moderately hypofractionated regimens have emerged as an alternative to stereotactic body radiotherapy for patients with central/ultracentral non-small cell lung cancer (NSCLC) who are medically inoperable due to age, poor performance status (PS) or associated comorbidity and who may be at a higher risk of severe toxicity. In the present study, we utilize a modified frailty index (mFI) to identify frail patients and hypothesize that frailty could better stratify clinical outcomes in these patients.We retrospectively analyzed 32 consecutive patients with stage I-IIB NSCLC treated with 8-10 fraction hypofractionated radiation therapy (RT) in our multi-site practice. Patients who received prior thoracic RT were excluded. An 11 factor mFI score was calculated based on the following variables: ECOG score ≥ 2, impaired sensorium, diabetes, chronic lung disease, myocardial infarction within 6 months, hospitalization within 6 months for heart failure, coronary/cardiac disease, HTN on medication, history of transient ischemic attack, stroke with deficits, and peripheral vascular disease. Kaplan-Meier (KM) method was used to estimate 1-year overall-survival (OS), local control (LC), freedom from progression (FFP) and severe toxicity (≥ grade 3) with patients stratified by mFI score (0-3 vs ≥ 4), median age (< 78 vs ≥ 78) and ECOG PS (0-1 vs ≥ 2).The patient population was predominantly elderly (median 78 years; range 58-94), 84% Caucasian, with squamous cell carcinoma (50%). Eleven pts (34.3%) had clinical stage II disease; the rest had stage I. Patients were treated with 8-10 fractions with a dose range of 50-70 Gy. The most common regimen was 70 Gy in 10 fractions. At a median follow-up of 16 months, KM estimated 1-year OS for the whole cohort was 86%. When stratified by mFI score (0-3 vs ≥ 4), there was no significant difference in 1-year LC (78% vs 100%), FFP (73% vs 80%), or OS (81% vs 91%), respectively. When stratified by median age (< 78 vs ≥ 78), there was no significant difference in 1-year LC (76% vs 91%), FFP (71% vs 81%), or OS (93% vs 81%), respectively. When stratified by ECOG PS (0-1 vs ≥ 2), there was no significant difference in 1-year LC (84.7% vs 92.3%), FFP (79.4% vs 72.2%), or OS (87.4% vs 85.6%), respectively. Treatment was well-tolerated with only 3 instances of severe grade 3 toxicity (2 pts developed or had worsening of left ventricular systolic function, 1 developed a pneumonia requiring hospitalization), all in the frailer group (mFI score ≥ 4, P = 0.053). Stratification by median age and PS was not significant.Hypofractionated RT for early-stage NSCLC yields similar tumor control and survival whether stratified by frailty, age or PS. Higher frailty score showed a trend towards worse toxicity that was not detected by age and PS alone. Further analyses in larger datasets could evaluate significance of frailty index in this population.