Multiple Ground-glass Nodules Research Articles

A case of pulmonary nodular lymphoid hyperplasia with multiple ground-glass nodules

A case of pulmonary nodular lymphoid hyperplasia with multiple ground-glass nodules

Chinese expert consensus: multidisciplinary diagnosis and treatment of multiple ground-glass nodule like lung cancer (2024 edition)

Multiple ground glass nodules (GGN) like lung cancer is a special type of synchronous multiple primary lung cancer, with two or more lesions present simultaneously. It has characteristics such as"indolent"development, less lymph node or distant metastasis, identical or different pathological stages, differential driving gene mutations, diverse imaging manifestations, and good prognosis. In order to standardize the diagnosis and treatment behavior of multiple GGN-like lung cancer, reduce issues such as over diagnosis and insufficient treatment, relevant domestic experts are organized by The Lung Cancer Medical Education Committee of the Chinese Medical Education Association, Lung Cancer Alliance of Chinese Thoracic Surgery, the Society of Tumor Ablation Therapy of the Chinese Anti-Cancer Association, the Tumor Ablation Expert Committee of the Chinese Society of Clinical Oncology, the Tumor Ablation Expert Group of the Chinese College of Interventionalists, The Chinese Expert Consensus:Multidisciplinary Diagnosis and Treatment of Multiple Ground-Glass Nodule Like Lung Cancer (2024 Edition) was discussed and formulated. The main content includes: follow-up strategies, differential diagnosis, diagnosis and staging, treatment methods, and post treatment follow-up for multiple GGN-like lung cancer.

Pathological diagnosis and immunohistochemical analysis of minute pulmonary meningothelial-like nodules: A case report

BACKGROUND Minute Pulmonary Meningothelial-like Nodules (MPMNs) are rare benign pulmonary nodules, which are more common in elderly women and have a higher detection rate in lung tissues of patients with lung malignant diseases. Its origin is not yet clear. At present, there are few reports on the diagnostic methods such as imaging and pathological manifestations of MPMNs. This article reports a 70-year-old female patient with pulmonary adenocarcinoma combined with MPMNs and reviews of the relevant literature. CASE SUMMARY A 70-year-old women was admitted to our institution with feeling sour in her back and occasional cough for more than 2 mo. Computerized electronic scanning scan and 3D reconstruction images in our institution showed there were multiple ground-glass nodules in both of her two lungs. The biggest one was in the apicoposterior segment of left upper lobe, about 2.5 mm × 9 mm in size. We performed thoracoscopic resection of the left upper lung apicoposterior segment of the patient, and the final pathological report was minimally invasive adenocarcinoma. Re-examination of high resolution computed tomography 21 mo after surgery showed multiple ground-glass nodules in both lungs, and a new ground-glass nodule was found in the superior segment of the right lower lobe. We took pathological biopsy of the right upper lung and right lower lung nodules for the patient under thoracoscopy. The histomorphology of the right lower lobe nodule showed multiple lesions in the lung tissue, and the small foci in the alveolar septum were distributed in mild form of the aggregation of short spindle cells. The immunohistochemistry showed that the lesion was epithelial membrane antigen (EMA) (+), somatostatin receptor 2a (SSTR2a) (+), S-100 (-), chromogranin A (-), Syn (-), cytokeratin (-) and HMB-45 (-). The final diagnosis was minimally invasive adenocarcinoma, accompanied by MPMNs. We recommend that patients continue to receive treatment after surgery and to do regular follow-up observations. CONCLUSION The imaging manifestations of MPMNs are atypical, histomorphology and immunohistochemistry can assist in its diagnosis. This article reviews the relevant literature of MPMNs immunohistochemistry and shows that MPMNs are positive for EMA, SSTR2a, and progesterone receptor.

Development of predictive models for assessing the progression and invasiveness of satellite lesions in patients with multiple pulmonary ground glass nodules

Development of predictive models for assessing the progression and invasiveness of satellite lesions in patients with multiple pulmonary ground glass nodules

European guidelines for the surgical management of pure ground-glass opacities and part-solid nodules: Task Force of the European Association of Cardio-Thoracic Surgery and the European Society of Thoracic Surgeons.

Pulmonary nodules are often encountered by respiratory physicians, radiologists, and thoracic surgeons alike. The European Society of Thoracic Surgery (ESTS) and European Association of Cardiothoracic Surgery (EACTS) established a multidisciplinary collaboration of clinicians with expertise in managing pulmonary nodules with the aim of producing the first joint comprehensive review of the scientific literature, with a specific focus on the management of pure ground glass opacities and part-solid nodules. The scope of the document has been defined by the EACTS and ESTS governing bodies and focuses on six areas of main interest agreed upon by the Task Force. These include: management of solitary and multiple pure ground glass nodules, solitary part-solid nodules, identifying the non-palpable lesion, the role of minimally invasive surgery and the decision making behind sub-lobar versus lobar resection. The literature revealed that with the increasing use of incidental CT scans and CT lung cancer screening programs, the detection of early-stage lung cancer is going to rise with a higher number of potential cancers presenting on the ground glass and part-solid nodule spectrum. Given that the gold standard for improved survival is surgical resection, there is an urgent need for comprehensive characterisation of these nodules and guidelines that are directed towards their surgical management. It is recommended that standard decision-making tools are used to determine the risk of malignancy and thus guide referral for surgical management and decisions for surgical resection are made in a multidisciplinary setting with equitable consideration given to radiological characteristics, the evolution of the lesion, presence of solid component, patient fitness and co-morbidities. Given the recent surge in robust level I data comparing sublobar and lobar resection with the release of JCOG0802 and CALGB140503 data, a global overview of an individual case must be adopted into clinical practice. This set of recommendations are based on the available literature; however, close collaboration in the design and conduct of randomized controlled trials is still of utmost importance to answer further questions in this rapidly evolving field.

Value of direct immunohistochemical staining in assisting intraoperative frozen diagnosis of bronchiolar adenoma

Objective: To explore the feasibility and application value of intraoperative direct immunohistochemical (IHC) staining in improving the diagnosis accuracy in difficult cases of bronchiolar adenoma (BA). Methods: Nineteen cases with single or multiple pulmonary ground-glass nodules or solid nodules indicated by imaging in Cancer Hospital of Chinese Academy of Medical Sciences from January to July 2021 and with difficulty in differential diagnosis at frozen HE sections were selected. In the experimental group, direct IHC staining of cytokeratin 5/6 (CK5/6) and p63 was performed on frozen sections to assist the differentiation of BA from in situ/micro-invasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the control group, two pathologists performed routine frozen HE section diagnosis on these 19 cases. The diagnostic results of paraffin sections were used as the gold standard. The sensitivity and specificity of BA diagnosis, consistency with paraffin diagnosis and time used for frozen diagnosis were compared between the experimental group and the control group. Results: The basal cells of BA were highlighted by CK5/6 and p63 staining. There were no basal cells in the in situ/microinvasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the experimental group, the sensitivity and specificity with aid of direct IHC staining for BA were 100% and 86.7%, respectively, and the Kappa value of frozen and paraffin diagnosis was 0.732, and these were significantly higher than those in the control group (P<0.05). The average time consumption in the experimental group (32.4 min) was only 7 min longer than that in the control group (25.4 min). Conclusions: Direct IHC staining can improve the accuracy of BA diagnosis intraoperatively and reduce the risk of misdiagnosis, but require significantly longer time. Thus frozen direct IHC staining should be restricted to cases with difficulty in differentiating benign from malignant diseases, especially when the surgical modalities differ based on the frozen diagnosis.

Osimertinib showed efficacy on contralateral multiple ground-glass nodules after segmentectomy for lung adenocarcinoma harboring primary EGFR-T790M mutation: a case report and review of the literature

BackgroundMultiple ground-glass nodules (mGGNs) in the lung has been defined as synchronous multiple primary lung cancer (SMPLC), it is has been very difficult challenging to differentiate SMPLC from intrapulmonary metastases, and its treatment remains controversial.Case presentationWe report a case simultaneously involving mGGNs and lung adenocarcinoma harboring primary EGFR-T790M mutation, in which the patient underwent the radical resection of lesions in the left upper lung, and continued the osimertinib treatment for the residual mGGNs in all lobes of the right lung. These mGGNs displayed different responses to osimertinib.ConclusionsWe reported a successful strategy on the postoperative treatment for mGGNs. For those that cannot be completely resected, the chemotherapy, radiotherapy, stereotactic body radiation therapy, immunotherapy and targeted therapy have been performed instead. The EGFR-TKI therapy strategy showed significant advantages, but how to achieve even better therapeutic effect needs more researches.

Diffuse Pulmonary Meningotheliomatosis: A Case Report

Abstract Introduction/Objective Diffuse pulmonary meningotheliomatosis (DPM) is a pulmonary disease characterized by the presence of widespread bilateral minute pulmonary meningothelial-like nodules (MPMNs). It is exceedingly rare and predominantly seen in females. The nodules are typically asymptomatic and detected incidentally on imaging. Methods/Case Report We present a case of a 57-year-old woman with a history of chronic cough and CT imaging findings of bilateral multiple ground-glass nodules. Wedge resections from the right upper and right lower lobes were obtained, which revealed gross changes suggestive of interstitial lung disease. Histologic evaluation of the wedges showed similar morphology, consisting of discrete areas with variable interstitial expansion of the stroma with ovoid/spindle cells, collagen, elastosis, and mild chronic inflammatory cells, in a somewhat perivascular pattern. Some areas were also cystic. This appeared in a background of emphysematous change and focal foreign body giant cell reaction to non-polarizable material. Immunohistochemical stains were diffusely positive for vimentin, EMA , and PR, and CD163 highlighted increased cells that were S100 and CD1a negative. Additionally, the ovoid/spindle cells were negative for desmin, SMM, HMB-45, HHV8, pan-CK, chromogranin, and multiplex SOX10-MART1. Results (if a Case Study enter NA) NA Conclusion Diffuse pulmonary meningotheliomatosis is a rare entity that requires sufficient histological evaluation to identify the ovoid/spindle cell component histologically and immunohistochemically. This disease should be considered in the differential for cases of diffuse interstitial pulmonary infiltrates. Few cases have been reported in the literature, requiring further research to understand the mechanisms of this disease and its clinical significance.

CT imaging features regarding ground-glass nodules and solid lesions reflect prognostication of synchronous multiple lung adenocarcinoma.

The prognosis of synchronous multiple lung adenocarcinoma (SMLA) dramatically differs due to its nature of multiple primaries or intrapulmonary metastases. This study aimed to assess computed tomography (CT)-reflected SMLA features regarding ground-glass nodules (GGNs) and solid lesions and their correlation with prognostication. One seventy eight SMLA patients who underwent surgical resection were reviewed. According to preoperative CT features, patients were categorized as: multiple GGN (MG) group: MGs without solid lesions; solid plus GGN (SPG) group: one solid lesion and at least one GGN; multiple solid (MS) group: MS lesions, with or without GGNs. Clinical characteristics, disease-free survival (DFS), and overall survival (OS) were retrieved. Largest tumor size (P < .001) and lymph-node metastasis prevalence (P < .001) were different among three groups, which were highest in the MS group, followed by the SPG group, and lowest in the MG group. Besides, the dominant tumor subtype also varied among the three groups (P < .001), while no difference in other clinical characteristics was discovered. DFS was more deteriorative in the MS group compared to the SPG group (P = .017) and MG group (P < .001), while of no difference between the SPG group and MG group (P = .128). Meanwhile, OS exhibited similar treads among the three groups. Besides, after multivariate Cox analyses adjustment, MS versus MG independently correlated with DFS (P = .030) and OS (P = .027), but SPG versus MG did not. In conclusion, preoperative CT-imaging MS lesions reflect advanced disease features and poor prognosis compared to MG and solid lesion plus GGN in SMLA patients who underwent surgical resection.

СИНДРОМ ГУДПАСЧЕРА С УМЕРЕННЫМ ПОРАЖЕНИЕМ ПОЧЕК И ТОРПИДНЫМ ТЕЧЕНИЕМ ЛЁГОЧНОГО ПРОЦЕССА: КЛИНИЧЕСКИЙ СЛУЧАЙ

Anti-GBM antibody disease (Goodpasture syndromee) is a rare immunecomlpex vasculitis, affecting small vessels, and characterized by rapidly progressive glomerulonephritis and alveolitis. Causative mechanism is defined by the hyperproduction of autoantibodies against the α3-chain of type IV collagen (Goodpasture antigen) with immune complex formation on the glomerular and alveolar basement membrane. Typically patients with fnti-GBM antibody disease present with rapidly progressive (crescentic) glomerulonephritis, more than in half of cases associated with alveolar hemorrhage. Cases of Anti-GBM antibody disease with atypical clinical presentation have been reported. We report a case of atypical clinical presentation anti-GBM antibody disease with mild renal damage and slow progression of pulmonary involvement. Main CT signs were multiple centrilobular ground glass nodules. This case report demonstrates that CT with disseminated pulmonary process associated with even mild kidney involvement in patients with high anti-GBM antibodies titers gives a clue to the diagnosis of anti-GBM antibody disease.

Correlation Analysis of Computed Tomography Features and Pathological Types of Multifocal Ground-Glass Nodular Lung Adenocarcinoma.

To investigate the correlation between computed tomography (CT) image characteristics of multiple lung ground-glass nodules (GGNs) and pathological classification, the CT image data of multiple lung GGN patients confirmed by pathology (n = 132) in our hospital were collected. The imaging features of GGNs were analyzed by qualified physicians, including lesion size (diameter, volume, and mass), location, CT values (mean and relative CT values), lesion morphology (round and irregular), marginal structure (pagination and burr), internal structure (bronchial inflation sign), and adjacent structure (pleural depression). CT imaging analysis was performed for the subtype of infiltrating adenocarcinoma (IAC). In CT findings, GGNs were greatly different from adenomatous hyperplasia (AAH), pure GGN adenocarcinoma in situ (AIS), and microinvasive adenocarcinoma (MIA) in terms of marginal structure, lesion morphology, internal structure, adjacent structure, and size (P < 0.05). The mean and relative CT values of mural adenocarcinoma, acinar adenocarcinoma, and papillary adenocarcinoma of IAC subtypes were greatly different from those of AAH/AIS/MIA (P < 0.05). In summary, the CT images of GGNs can be used as the basis for the differentiation of AAH, AIS, and MIA early noninvasive types and IAC invasive types, and the CT value of the IAC subtype can be used as the basis for the classification and differentiation of IAC pathological subtypes.

Application Value of PET/CT and MRI in the Diagnosis and Treatment of Patients With Synchronous Multiple Pulmonary Ground-Glass Nodules.

BackgroundSynchronous multiple ground-glass nodules (SMGGNs) in synchronous multiple lung cancers are associated with specific imaging findings. It is difficult to distinguish whether multiple nodules are primary tumors or metastatic lesions in the lungs. The need for PET/CT and contrast-enhanced brain MRI for these patients remains unclear. This study investigated the necessity of these two imaging examinations for SMGGN patients by means of retrospective analysis.MethodsSMGGN patients who were diagnosed and treated in our hospital from October 2017 to May 2020 and underwent whole-body PET/CT(Cranial excepted) and/or contrast-enhanced brain MRI+DWI were enrolled in this study. We analyzed the imaging and clinical characteristics of these patients to evaluate SMGGN patients’ need to undergo whole-body PET/CT and brain MRI examination.ResultsA total of 87 SMGGN patients were enrolled. 51 patients underwent whole-body PET/CT examinations and did not show signs of primary tumors in other organs, metastatic foci in other organs, or metastasis to surrounding lymph nodes. 87 patients underwent whole-brain MRI, which did not reveal brain metastases but did detect an old cerebral infarction in 23 patients and a new cerebral infarction in one patient. 87 patients underwent surgical treatment in which 219 nodules were removed. All nodules were diagnosed as adenocarcinoma or atypical adenomatous hyperplasia. No lymph node metastasis was noted.ConclusionFor SMGGN patients, PET/CT and enhanced cranial MRI are unnecessary for SMGGNs patients, but from the perspective of perioperative patient safety, preoperative MRI+DWI examination is recommended for SMGGNs patients.

Utility of whole exome sequencing analysis in differentiating intrapulmonary metastatic multiple ground-glass nodules (GGNs) from multiple primary GGNs

PurposeClinical evidence of metastasis with ground-glass nodules (GGNs) has been reported, including pulmonary metastasis and distant metastasis. However, the clonal relationships of multiple GGNs at the genetic level remain unclear.Experimental designSixty tissue specimens were obtained from 19 patients with multiple GGN lung cancer who underwent surgery in 2019. Whole exome sequencing (WES) was performed on tissue samples, and genomic profiling and clone evolution analysis were conducted to investigate the genetic characteristics and clonality of multiple GGNs.ResultsA total of 15,435 nonsynonymous mutations were identified by WES, and GGNs with shared nonsynonymous mutations were observed in seven patients. Copy number variant (CNV) analysis showed that GGNs in ten patients had at least one shared arm-level CNV. Mutational spectrum analysis showed that GGNs in three patients had similar six substitution profiles and GGNs in fou patients had similar 96 substitution profiles. According to the clone evolution analysis, we found that GGNs in five patients had shared clonal driver gene mutations. Taken together, we identified that 5 patients may have multiple primary GGNs without any similar genetic features, 2 patients may have intrapulmonary metastatic GGNs with ≥ 3 similar genetic features, and the other 12 patients cannot be determined due to insufficient evidences in our cohort.ConclusionsOur findings suggest that the intrapulmonary metastasis exist in multiple GGNs, but the number of GGNs was not associated with the probability of metastasis. Application of genomic profiling may prove to be important to precise management of patients with multiple GGNs.

Comparison of Clinical and Pathological Characteristics Between Extremely Multiple GGNs and Single GGNs

ObjectiveThis study aims to compare the clinical and pathological characteristics between patients undergoing surgery for extremely multiple ground-glass nodules (GGNs) and those for single GGN.MethodsWe defined extremely multiple GGNs as follows: (i) number of GGNs ≥3, (ii) GGN diameter between 3 and 30 mm, and (iii) no less than three nodules that were surgically removed and pathologically diagnosed. Patients with extremely multiple GGNs and single GGNs who underwent surgery at the same time were retrospectively analyzed. The patients were divided into three groups according to the number of nodules: exceedingly multiple nodules (EMN) group (>10), highly multiple nodules (HMN) group (three to 10), and single nodule (SN) group. The clinical and pathological characteristics, surgical methods and prognosis were analyzed.ResultsNinety-nine patients with single nodules and 102 patients with extremely multiple nodules were enrolled. Among the patients with extremely multiple nodules, 43 (42.2%) had >10 nodules. There were no significant differences in demographic characteristics, such as age, sex, and smoking history, between the groups, but there were differences in tumor characteristics. All patients with >10 nodules showed bilateral pulmonary nodules and presented with both pure and mixed GGNs. The single GGNs were smaller in diameter, and the proportion of mixed GGNs and pathologically invasive adenocarcinoma was lower than that of the primary nodules in the exceedingly multiple GGNs group (p < 0.05). However, the proportion of both mixed GGNs and malignant nodules decreased significantly with the increasing number of total lesions. During postoperative follow-up, one patient in the highly multiple nodules group had a local recurrence, and 16 (15.7%) patients in the extremely multiple GGNs group and 10 (9.8%) patients in the single GGN group had enlarged unresected GGNs or additional GGNs.ConclusionsOur study revealed the clinical and pathologic characteristics, surgical methods, and prognosis of patients with extremely multiple GGNs and compared them with those of patients with a single GGN. Although the primary nodules in extremely multiple GGNs may have higher malignancy than those in the single nodule group, the proportion of both mGGNs and malignant nodules decreased significantly with the increasing number of lesions, and the prognosis of patients with extremely multiple GGNs was satisfied.

Tuberous sclerosis complex for the pulmonologist.

Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder affecting almost all organs with no sex predominance. TSC has an autosomal-dominant inheritance and is caused by a heterozygous mutation in either the TSC1 or TSC2 gene leading to hyperactivation of the mammalian target of rapamycin (mTOR). TSC is associated with several pulmonary manifestations including lymphangioleiomyomatosis (LAM), multifocal micronodular pneumocyte hyperplasia (MMPH) and chylous effusions. LAM is a multisystem disorder characterised by cystic destruction of lung parenchyma, and may occur in either the setting of TSC (TSC-LAM) or sporadically (S-LAM). LAM occurs in 30-40% of adult females with TSC at childbearing age and is considered a nonmalignant metastatic neoplasm of unknown origin. TSC-LAM is generally milder and, unlike S-LAM, may occur in males. It manifests as multiple, bilateral, diffuse and thin-walled cysts with normal intervening lung parenchyma on chest computed tomography. LAM is complicated by spontaneous pneumothoraces in up to 70% of patients, with a high recurrence rate. mTOR inhibitors are the treatment of choice for LAM with moderately impaired lung function or chylous effusion. MMPH, manifesting as multiple solid and ground-glass nodules on high-resolution computed tomography, is usually harmless with no need for treatment.

Utility of Whole Exome Sequencing Analysis in Differentiating Intrapulmonary Metastatic Multiple Ground-Glass Nodules (GGNs) from Multiple Primary GGNs

Utility of Whole Exome Sequencing Analysis in Differentiating Intrapulmonary Metastatic Multiple Ground-Glass Nodules (GGNs) from Multiple Primary GGNs

Primary pulmonary diffuse large B-cell lymphoma with multiple ground-glass nodules as the primary manifestation

Introduction:Primary pulmonary lymphoma (PPL) is a rare extranodal lymphoma. Only 5% to 20% of patients suffering from PPL have diffuse large β-cell lymphoma (DLBCL), and their chest computed tomography (CT) findings show single- or double-lung patchy or flocculated shadows, isolated or multifocal nodules, or masses. In this research paper, we report an older woman having multiple ground-glass nodules, who was eventually diagnosed with primary pulmonary diffuse large β-cell lymphoma (PPDLBCL).Patient concerns:A 69-year-old woman suffering from cough was admitted to the Second Hospital of Jilin University.Diagnoses:A chest CT scan showed multiple ground-glass nodules. She had received 2 weeks of antibiotic treatment, but the multiple ground-glass nodules were still present. Lung biopsy was performed by tracheoscopy, which showed non-Hodgkin diffuse large β-cell lymphoma.Interventions:The patient received R-CHOP-21 chemotherapy.Outcomes:The multiple ground-glass nodules were absorbed.Conclusion:The current study shows that spotting multiple ground-glass nodules in the lungs is a clear indication of the presence of PPDLBCL. It is important to spread awareness of PPDLBCL, which needs timely diagnosis and management.

Risk Factors for The Growth of Residual Nodule in Surgical Patients with Adenocarcinoma Presenting as Multifocal Ground-glass Nodules

PurposeWe aim to investigate the risk factors influencing the growth of residual nodule (RN) in surgical patients with adenocarcinoma presenting as multifocal ground-glass nodules (GGNs). MethodFrom January 2014 to June 2018, we enrolled 238 patients with multiple GGNs in a retrospective review. Patients were categorized into growth group 63 (26.5%), and non-growth group 175 (73.5%). The median follow-up time was 28.2 months (range, 6.3-73.0 months). To obtain the time of RN growth and find the risk factors for growth, data such as age, gender, history of smoking, history of malignancy, type of surgery, pathology and radiological characteristics were analyzed to use Kaplan-Meier method with the log-rank test and Cox regression analysis. ResultsThe median growth time of RN was 56.0 months (95% CI, 45.0-67.0 months) in all 238 patients. Roundness (HR 4.62, 95% CI 2.20-9.68), part-solid nodule (CTR ≥ 50%) (HR 4.39, 95% CI 2.29-8.45), vascular convergence sign (HR 2.32, 95% CI 1.36-3.96) of RN, and age (HR 1.04, 95% CI 1.01-1.07) were independent predictors of further nodule growth. However, radiological characteristics and pathology of domain tumour (DT) cannot be used as indicators to predict RN growth. ConclusionsRN showed an indolent growth pattern in surgical patients with multifocal GGNs. RN with a higher roundness, presence of vascular convergence sign, more solid component, and in the elder was likely to grow. However, the growth of RN showed no association with the radiological features and pathology of DT.

1232P An exploratory study of a PD-1 inhibitor for high-risk multiple ground-glass nodules (mGGNs) in synchronous stage I non-small cell lung cancer patients

Surgical resection is recommended for stage I NSCLC patients. However, there is a lack of standard therapies for synchronous mGGNs. This study aims to explore the feasibility of a PD-1 inhibitor (sintilimab) in high-risk residual mGGNs in post-surgery synchronous stage I NSCLC patients. This is a single arm phase I trial aiming to recruit 20 subjects. Eligible patients contained at least one high-risk residual mGGN (confirmed by MDT discussion) after surgical resection of stage I NSCLC. Patients received sintilimab (200mg i.v., Q3W) for 10 cycles starting 6 weeks post-surgery. Radiological evaluations were performed every 3 cycles during the treatment period and every 3 months during follow-up. Whether re-operation is needed depends on MDT evaluation. The primary endpoints were safety and overall response rate (ORR). The secondary endpoints included duration of response (DOR), major pathologic response (MPR) of re-operated GGNs, and one-year progression-free survival (PFS). At data cutoff (23 Jan 2020), 20 patients (9 males and 11 females) were enrolled. The pathological results revealed that all had lung adenocarcinoma. The median number of treatment cycles was 6 (range 3 to 10). All lesions were evaluated as stable disease by RECIST 1.1. Six patients underwent re-operation safely and 12 GGNs were resected. Pathology showed that 1 had no residual tumour cells, 4 had 20-35%, and 7 had over 80%. Whole-exome sequencing of 12 GGNs showed 6 harbouring EGFR mutations and 2 harbouring KRAS mutations. Interestingly, 3 out of 6 with EGFR-mut showed less residual tumour cells (23.3%, 30%, and 80%). The highest TMB (15.7 mut/Mb) was observed in the complete response GGN. 65% patients experienced treatment-related 1-2 grade AEs. The PD-1 inhibitor was well tolerated and a certain degree of anti-tumour activity was seen from the pathologic results of re-operated GGNs. Radiological evaluation using RECIST 1.1 might be unsuitable for mGGNs. Further studies are needed to demonstrate the clinical benefits. ChiCTR: 1900022159.

An exploratory study of PD-1 inhibitor for high-risk multiple ground-glass nodules (mGGNs) in synchronous stage I non-small cell lung cancer patients.

e21068 Background: Surgical resection is recommended for the stage I NSCLC patients. However it is lack of standard therapies for synchronous mGGNs. This study aims to explore the feasibility of a PD-1 inhibitor (sintilimab) in high-risk residual mGGNs in post-surgery synchronous stage I NSCLC patients. Methods: This is a single arm phase I trial intending to recruit 20 subjects. Eligible patients contained at least one high-risk residual mGGN (confirmed by MDT discussion) after surgical resection of stage I NSCLC. Patients received sintilimab (200mg i.v., Q3W) for 10 cycles since 6 weeks post-surgery. Radiological evaluations were performed at every 3 cycles in treatment period and every 3 months during follow-up. Whether re-operation is needed depends on MDT evaluation. The primary endpoints were safety and ORR. The secondary endpoints included DOR, MPR of re-operated GGNs, and the one-year PFS. Results: As data cutoff (23 Jan 2020), 20 patients (9 males and 11 females) were enrolled. The pathological results revealed that all were lung adenocarcinoma. The median treatment cycles was 6 (range 3 to 10). All lesions were evaluated as stable disease by RECIST 1.1. Six patients underwent re-operation safely and12 GGNs were resected. Pathology showed that 1 had no tumor cells residue, 4 had 20-35%, and 7 had over 80% residues. Whole-exome sequencing of 12 GGNs showed 6 harboring EGFR and 2 harboring KRAS mutations. Interestingly, 3 out of 6 with EGFR-mut showed less tumor cells residues (23.3%, 30%, and 80%). The highest TMB (15.7 mut/Mb) was observed in the complete response GGN. 65% patients experienced treatment-related 1-2 grade AEs. Conclusions: The PD-1 inhibitor showed well tolerability and a certain degree anti-tumor activity was seen from the pathologic results of re-operated GGNs. Radiological evaluation using RECIST 1.1 might be unsuitable for mGGNs. Further studies are needed to demonstrate the clinical benefits. ChiCTR: 1900022159 Clinical trial information: 1900022159 .