The prognostic impact of combined pulmonary fibrosis and emphysema in patients with clinical stage IA non-small cell lung cancer.

PURPOSE: We evaluated the long-term outcomes of clinical stage IA non-small cell lung cancer (NSCLC) patients with combined pulmonary fibrosis and emphysema (CPFE) who underwent lobectomy. METHODS: We reviewed the chest computed tomography (CT) findings and divided the patients into normal, fibrosis, emphysema and CPFE groups. We evaluated the relationships among the CT findings, the clinicopathological findings and postoperative survival. RESULTS: The patients were classified into the following groups based on the preoperative chest CT findings: normal lung, n = 187; emphysema, n = 62; fibrosis, n = 8; and CPFE, n = 17. The patients with CPFE were significantly older, more likely to be men and smokers, had a higher KL-6 level and lower FEV 1.0% value and had a higher rate of squamous cell carcinoma. The 5-year overall survival (OS) and disease-free survival rates were as follows: normal group, 82.5 and 76.8%; emphysema group, 80.0 and 74.9%; fibrosis group, 46.9 and 50%; and CPFE group, 36.9 and 27.9%, respectively (p < 0.01). A univariate and multivariate analysis determined that the pathological stage and CT findings were associated with OS. CONCLUSIONS: CPFE is a significantly unfavorable prognostic factor after lobectomy, even in early-stage NSCLC patients with a preserved lung function.

Osimertinib reactivated immune-related colitis after treatment with anti-PD1 antibody for non-small cell lung cancer.

We reported a case of relapsing immune-related colitis (initially caused by nivolumab) following osimertinib therapy for lung adenocarcinoma. A 45-year-old female who had never smoked was diagnosed with adenocarcinoma of the lung and underwent surgical resection. Four years after surgical resection, she was diagnosed with recurrent disease and was eventually treated with nivolumab as third-line therapy. One month after the completion of nivolumab therapy, the patient reported abdominal pain and frequent diarrhea. We diagnosed immune-related colitis and started oral prednisolone. However, the steroid therapy was ineffective, so the patient was administered infliximab and an increased dose of prednisolone. Her symptoms subsequently resolved, and her mucosal lesions improved. Six months after the last administration of nivolumab, osimertinib was initiated as fourth-line therapy, but 3 days later, the patient developed blood in the stool and frequent diarrhea. Osimertinib treatment was discontinued, given the possibility that it had reactivated the patient's immune-related colitis. We subsequently re-administered oral prednisolone (2 mg/kg/day), and the colitis resolved within a few weeks.

Clinicopathological Features and Outcome of Lung Cancer Patients with Hematological Malignancy.

PURPOSE: The aim of this study was to report the incidence of lung cancer in patients with hematological malignancy (HM), as well as patient characteristics and outcome. METHODS: We investigated 1503 consecutive patients treated for HM and 1208 patients who underwent surgical resection for lung cancer. RESULTS: Lung cancer with HM was observed in 12 patients (0.8 % of HM cases and 1.0 % of lung cancer cases), including eight men who were smokers and four women who had never smoked. The average Brinkman index was 1010, which suggested heavy smokers. In synchronous cases, all four patients preceded to HM treatment; however, three patients died from HM. In metachronous cases, during a mean 52.7 months after treatment of lung cancer, three patients had HM. At a mean 41.4 months after HM treatment, five patients had lung cancer and underwent surgery without serious postoperative events. CONCLUSIONS: A second cancer tended to be detected within 5 years after treatment of the first cancer. Men with a history of heavy smoking might be at risk for combined lung cancer and HM. Careful follow-up is recommended within 5 years after treatment of the first cancer. Most lung cancer detected synchronously with HM had poor prognosis. In metachronous cases, surgical resection of lung cancer after treatment of HM was feasible and safe.

Outcome of surgical resection as a first line therapy in T3 non-small cell lung cancer patients.

BACKGROUND: The T3 category of the 7th Edition of the TNM classification of non-small cell lung cancer (NSCLC) has added two factors that do not appear in the 6th Edition, large tumor size (>7 cm) and pulmonary metastasis of the same lobe. These factors are considered to have different biological and clinical features. In the present study we assessed the outcome of surgical resection as a first line therapy for T3 NSCLC. METHODS: A total of 145 patients who were diagnosed according to the TNM 7th Edition with pathologic T3 NSCLC received surgical resection in our institution as a first line treatment. The outcomes of their treatment were analyzed. RESULTS: The 5-year survival rate was 46.9 %. On the basis of the 6th TNM Edition, the 5-year survival rate was 63.1 % for patients diagnosed with T2 disease (large tumor size), 44.3 % for patients diagnosed with T3 disease, and 33.1 % for patients diagnosed with T4 disease (pulmonary metastasis of the same lobe). There were no significant correlations between these categories and overall survival (OS). Nevertheless, 6th Edition T factors were found to be significantly correlated with lymph node status (p < 0.01). The univariate analyses showed that age, lymph node metastasis, and curative resection had significant effects on OS. In addition, the multivariate analysis identified age and N factor as independent prognostic factors in this cohort. CONCLUSIONS: Indications for surgical resection as a first line therapy in T3 NSCLC should be based on N factors and patient age. Lymph node metastasis, especially N2 disease, was increasingly frequent in patients with 6th Edition T classifications.

Impact of the pretreatment prognostic nutritional index on the survival after first-line immunotherapy in non-small-cell lung cancer patients.

BACKGROUND: Immunotherapy has become a standard-of-care for patients with non-small-cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death-1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first-line ICI combined with or without chemotherapy. MATERIALS AND METHODS: Two-hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first-line therapy. Cutoff value of the pretreatment PNI was set as 42.17. RESULTS: Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression-free survival (PFS; hazard ratio [HR] = 0.67, 95% confidence interval [CI]: 0.51-0.88, p = 0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32-0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p = 0.0011) and OS (p < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively). CONCLUSION: The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first-line ICI therapy.

Lung CT: Part 1, Mimickers of lung cancer--spectrum of CT findings with pathologic correlation.

OBJECTIVE: The purpose of this article is to describe CT findings of miscellaneous pulmonary conditions that mimic lung cancers, especially primary cancers, to improve diagnosis of pulmonary lesions. Brief descriptions of patient clinical information and pathologic findings will be included and correlated with imaging findings in actual cases. CONCLUSION: A wide variety of pulmonary conditions present imaging features that mimic those of primary lung cancers and are difficult to differentiate from cancer. Awareness of these conditions with an understanding of their pathologic background and careful attention to the clinical information will help achieve correct diagnoses.

Results of a surgical resection of pulmonary metastasis from hepatocellular carcinoma: prognostic impact of the preoperative serum alpha-fetoprotein level.

PURPOSE: Pulmonary metastasis is the most common type of extrahepatic recurrence of hepatocellular carcinoma (HCC). The outcome of pulmonary metastasectomy of HCC has not yet been thoroughly investigated. The outcomes of surgical treatment of pulmonary metastases from HCC were reviewed in order to analyze the postoperative survival and the relevant prognostic factors. METHODS: This study retrospectively reviewed 20 patients who underwent pulmonary metastasectomy from an HCC between 1990 and 2007 at two institutions. The surgical outcome was evaluated by both the overall survival and cancer-specific survival after pulmonary resection. The association between various clinico-pathological factors and the survival outcome was analyzed. RESULTS: The overall survival rate after the initial pulmonary metastasectomy was 46.9% at 5 years, and the cancer-specific 5-year survival rate was 63.2%. One patient died of surgery-related events 19 days after the pulmonary resection. The preoperative AFP (alpha-fetoprotein) level was found to be a significant prognostic factor for both overall and cancer-specific survival for patients undergoing pulmonary metastasectomy. Both the overall and cancer-specific survival rates were significantly worse for the patients with AFP ≥ 500 ng/ml in comparison to those with AFP < 500 ng/ml (p < 0.05). No other factors were associated with the survival after pulmonary metastasectomy. CONCLUSION: The serum level of AFP might be a valuable predictor for the outcome of pulmonary metastasectomy required for metastasis of HCC.

Robot-assisted thoracic surgery for intercostal cavernous hemangioma.

Intercostal cavernous hemangioma is extremely rare among benign vascular tumors. Achieving a definitive diagnosis preoperatively by radiographic examination alone is difficult; surgical resection is usually needed. Occasional cases are found as giant tumors, and some grow substantially during observation without treatment. Such tumors require extended surgical resection; however, small tumors can be completely resected by tumor extirpation alone. Thus, immediate surgical resection while the tumor is small might help to avoid invasive surgery. We herein describe cases of intercostal cavernous hemangioma with no invasion to the surrounding tissues, successfully treated by complete tumor resection using robot-assisted thoracic surgery.

Induction immunotherapy followed by surgery for hilar unicentric Castleman disease.

Castleman disease is a rare disease borne of a B cell lymphoproliferative disorder of uncertain cause. Standard therapy for the unicentric type of Castleman disease localized as a single mass or single lymph-node station is surgical extirpation. Nevertheless, in the thoracic cavity, unresectable cases or cases of incomplete extirpation of the tumor without lung scarring owing to tumor size/location have been noted. In such cases, lung resection (e.g., lobectomy, pneumonectomy) or additional therapy (immunotherapy, chemotherapy, radiotherapy) after resection is required. However, few instances of patients receiving induction immunotherapy or chemotherapy followed by surgery have been reported. Here, we describe a 21-year-old woman with unicentric Castleman disease originating from the left hilum. The tumor seemed to involve/be in contact with the pulmonary vein and bronchus. Tumor location indicated that initial resection was necessary to sacrifice upper and lower pulmonary lobes. To avoid these pulmonary resections, induction therapy followed by surgery was selected. Induction therapy using rituximab was very efficacious. Resection after induction therapy was completed only by tumor extirpation, and resulted in preservation of pulmonary function. Thoracic surgeons might consider induction therapy followed by resection if the tumor is resectable UCAD, but initial resection is needed and sacrifices a large amount of pulmonary function.

Resection of Pulmonary Metastases 12 Years after Initial Surgery for a Benign Pheochromocytoma.

We describe a rare case of newly discovered pulmonary metastases and surgical confirmation 12 years after initial surgery for a pheochromocytoma. A 61-year-old asymptomatic man was referred because of an abnormal shadow in the right lung field upon chest radiography. Computed tomography (CT) showed two well-demarcated tumors in the basal segment of the right lung. Twelve years previously, he underwent right adrenalectomy and was pathologically diagnosed as having a benign pheochromocytoma. Thereafter, he received a medical check-up annually. To confirm the diagnosis of two pulmonary tumors, video-assisted thoracic surgery was done and wedge resection of the right lower lobe completed. Pathology studies revealed these tumors as pulmonary metastases from the pheochromocytoma, which indicated that the true diagnosis was a malignant pheochromocytoma. Patients with a benign pheochromocytoma should continue to undergo careful monitoring for a long time after the initial surgical procedure. Thoracic surgeons should be aware of the possibility of pulmonary metastases even if >10 years have passed since initial resection of a benign pheochromocytoma.

Oncological issues in staging mediastinal lymph node metastasis for left lung cancer.

OBJECTIVE: We aimed to discuss the underlying oncological issues in staging of mediastinal lymph node metastasis in patients with left lung cancer who underwent extended radical lymphadenectomy (ERL). METHODS: This multi-institutional retrospective study analyzed 116 patients with left non-small-cell lung cancer who underwent bilateral paratracheal lymph node dissection (ERL) via median sternotomy. The clinicopathological records of patients with mediastinal lymph node metastasis were examined for prognostic factors, including age, sex, histology, tumor size, cN number, preoperative data, metastatic stations (number and distribution), pT, and adjuvant chemotherapy. RESULTS: Mediastinal lymph node metastases were found in 43 patients, and right paratracheal lymph node metastases (pN3) were found in 13 patients. The 5-year overall survival rate was 25.2% in patients with pN3 tumors (n = 13) and 23.1% in patients with pN2 tumors (n = 30). The prognosis did not differ between patients with pN3 and pN2. Univariate analyses showed that histology, cN, and adjuvant chemotherapy were significant prognostic factors in patients with mediastinal lymph node metastasis. In these 43 patients, cN and adjuvant chemotherapy were significant independent prognostic factors in multivariate analysis. CONCLUSIONS: The prognostic factors for left lung cancer with mediastinal lymph node metastasis were cN status and adjuvant chemotherapy, and not pN status (pN2 or pN3). We hope that the study results, which suggest that there may be no difference in prognosis between pN2 and pN3, would broaden the discussion of oncological issues in the staging of mediastinal lymph node metastasis of left lung cancer.

Chronological analysis of the gut microbiome for efficacy of atezolizumab-based immunotherapy in non-small cell lung cancer: Protocol for a multicenter prospective observational study.

BACKGROUND: Cancer immunotherapy with immune checkpoint inhibitors (ICIs) is an innovative treatment for non-small cell lung cancer (NSCLC). Recently, the specific composition of the gut microbiome before initiation of cancer immunotherapy has been highlighted as a predictive biomarker in patients undergoing cancer immunotherapy, mainly in the US or Europe. However, the fact gut microbiome status is completely different in races or countries has been revealed. In addition, how the microbiome composition and diversity chronologically change during cancer immunotherapy is still unclear. METHODS: This multicenter, prospective observational study will analyze the association between the gut microbiome and therapeutic response in NSCLC patients who received atezolizumab-based immunotherapy. The aim of the present study is to clarify not only how the specific composition of the gut microbiome influences clinical response in NSCLC patients but the chronological changes of gut microbiota during atezolizumab-based immunotherapy. The gut microbiota will be analyzed using 16S rRNA gene sequencing. The main inclusion criteria are as follows: (1) Pathologically- or cytologically-confirmed stage IV or postoperative recurrent NSCLC. (2) Patients ≥20 years old at the time of informed consent. (3) Planned to treat with atezolizumab-based immunotherapy combined with platinum-based chemotherapy (cohort 1) and monotherapy (cohort 2) as a first immunotherapy. (4) Patients to provide fecal samples. A total of 60 patients will be enrolled prospectively. Enrollment will begin in 2020 and the final analyses will be completed by 2024. DISCUSSION: This trial will provide more evidence of how gut microbiota composition and diversity chronologically change during cancer immunotherapy and contribute to the development of biomarkers to predict ICI response as well as biotic therapies which enhance the ICI response.

Thymic basaloid carcinoma with aggressive invasion of the lung and pericardium: report of a case.

We report a case of basaloid carcinoma of the thymus, invading the lung and pericardium. The patient was a 72-year-old man who suffered thoracic trauma in a fall and was taken to his family physician. Computed tomography revealed a huge mediastinal tumor with cystic components, pressing into the lung. He was referred to our hospital, where magnetic resonance imaging showed suspicious invasion of the pericardium and mediastinum. We made an assumed diagnosis of a mediastinal malignancy and performed mediastinal tumor resection. The tumor was adherent to the lung, pericardium, and left innominate vein. The final pathological diagnosis was a basaloid carcinoma of the thymus. Basaloid carcinoma is often a component of a multiloculated thymic cyst (MTC) and should be considered when MTC is identified within an anterior mediastinal tumor.

Results of a pulmonary metastasectomy in patients with colorectal cancer.

PURPOSE: The lung is one of the key sites of hematogenous metastasis in patients with colorectal cancer. A metastasectomy of the lung is reported to improve the prognosis of colorectal cancer. We reviewed our experience in evaluating the surgical outcomes in colorectal cancer patients who have undergone a pulmonary metastasectomy. METHODS: A single-center retrospective evaluation of clinical prognostic factors (1996-2008) related to a pulmonary metastasectomy of patients with colorectal cancer was conducted. Fifty-seven consecutive patients in our hospital who had undergone a resection of pulmonary metastasis from colorectal cancer were retrospectively investigated. RESULTS: The mean age of the patients who underwent an initial pulmonary metastasectomy was 63.8 years. The average number of pulmonary metastases was 3.8. Pulmonary metastasectomy was performed an average of 1.6 times per head. A total of 32 patients had undergone a liver metastasectomy, and the 5-year survival of these 32 patients was 43.1%. The 5-year survival of the time from first pulmonary metastasectomy was 53.9%. There were no statistical differences with regard to the disease-free interval, interval from primary resection, or the number of pulmonary metastasectomies. CONCLUSIONS: A pulmonary resection for colorectal pulmonary metastases is therefore considered to be a favorable treatment for long-term survival even in the presence of liver metastases. Thoracic surgeons should therefore aggressively perform a pulmonary metastasectomy of colorectal cancer.

The results of surgery under general anesthesia in patients with lung cancer.

PURPOSE: There are few reports of surgical complications for underweight patients. This study evaluated the complications associated with lung cancer surgery and anesthesia in underweight patients in a comparison with obese ones. METHODS: A single-center retrospective evaluation of perioperative complications was conducted in 756 patients who underwent thoracic surgery under general anesthesia between 1996 and 2006. The body mass index showed that 39 were extremely underweight (<17.2 kg/m(2)), 45 were underweight (17.2-18.4 kg/m(2)), 513 were normal (18.5-24.9 kg/m(2)), and 159 were obese (>24.9 kg/m(2)). RESULTS: Extremely underweight patients had the most preoperative thoracic disease such as emphysema, whereas obese patients had the most preoperative cardiovascular disease such as hypertension. The postresection-predicted pulmonary function showed no difference among the four groups. Extremely underweight patients had an increased incidence of intraoperative hypotension and arrhythmia in comparison to underweight patients. On the other hand, obese patients had the majority of intraoperative thoracic complications such as hypoxia. Extremely underweight patients had more postoperative thoracic complications, especially pneumonia and pulmonary air leakage, than other patients. CONCLUSIONS: Extremely underweight patients as well as obese patients had a high risk of perioperative complications, especially postoperative thoracic complications. Extremely underweight patients should therefore be carefully observed with regard to respiratory management.

Impact of Preoperative Immunonutritional Support in Patients Undergoing Elective Thoracic Surgery.

INTRODUCTION: Several immunonutritional supplements have recently been developed. However, improvements in preoperative immunonutritional conditions using these supplements have not been analyzed in patients undergoing thoracic surgery. METHODS: This prospective, single-arm, single-institution pilot study involved patients planning to undergo thoracic surgery. Forty adults with a poor preoperative immunonutritional status were enrolled. The patients freely selected one of three oral immunonutritional supplements (IMPACTⓇ, MEINⓇ, or AboundⓇ) and started taking it on an outpatient basis from 7 to 14 days before thoracic surgery. The primary endpoint was the rate of improvement in three immunonutritional parameters on the hospitalization day: body mass index (BMI), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI). These improvement rates were compared with those of a matched historical control group. RESULTS: The PNI and GNRI improvement rates were significantly higher in the immunonutritional support group than in the control group (PNI: 103.1% ± 0.6% vs. 98.9% ± 1.3%, p = 0.0391; GNRI: 101.7% ± 0.8% vs. 99.3% ± 0.8%, p = 0.0266), although there was no significant difference in the BMI improvement rate (101.0% ± 0.6% vs. 100.2% ± 0.7%, p = 0.3626). The PNI and GNRI improvement rates were significantly higher in the IMPACTⓇ support group than in the control group (PNI: 104.5% ± 2.4% vs. 98.9% ± 1.3%, p = 0.0212; GNRI: 101.6% ± 1.1% vs. 99.3% ± 0.8%, p = 0.0415). CONCLUSIONS: The present study revealed that short-term preoperative immunonutritional support can actually improve immunonutritional parameters immediately before surgery. In particular, preoperative immunonutritional support using IMPACTⓇ supplementation might be the most promising agent in patients with a poor immunonutritional condition undergoing elective thoracic surgery. TRIAL REGISTRATION: University Hospital Medical Information Network 000035851.

Cumulative experience of the anterior approach in robot-assisted thoracic surgery for lung cancer patients.

BACKGROUND: Robot-assisted thoracic surgery (RATS) lobectomy for lung cancer is now performed all around the world. The camera and robotic devices are generally inserted from a low position via the thorax. We previously reported our original anterior approach (AA) for performing RATS lobectomy with a camera and robotic devices inserted via the anterior chest wall. However, whether AA is comparable or superior to the conventional approach (CA) remains unclear. METHODS: A total of 108 patients who underwent RATS lobectomy were included in the current study. We compared the AA with the CA for performing RATS lobectomy in terms of the operative and postoperative features, such as total operation/console time, blood loss and postoperative complications. RESULTS: Eighty-seven and 21 patients underwent the AA and CA in RATS lobectomy, respectively. The console and total operation time were significantly shorter in the AA group than in the CA group for RATS lobectomy (median console time: AA vs. CA, 112 vs. 148 min, P=0.0001; median total operation time: AA vs. CA, 193 vs. 243 min, P=0.0002), especially left upper lobectomy. Intraoperative blood loss and the frequency of postoperative complications were significantly reduced in the AA group compared with the CA group (median intraoperative blood loss: AA vs. CA, 20 vs. 105 mL, P<0.0001; postoperative complications: AA vs. CA, 8.0% vs. 28.6%, P=0.0088). CONCLUSIONS: These results suggest that our AA of RATS lobectomy can be very easily and safely performed.

Dramatic response to pembrolizumab with chemotherapy followed by salvage surgery in a lung cancer patient.

Immune checkpoint inhibitors with chemotherapy have been shown to exhibit remarkable efficacy for advanced non-small-cell lung carcinoma and are under investigation as an induction therapy. However, the significance of preoperative therapy with pembrolizumab + chemotherapy for surgically resectable non-small-cell lung carcinoma still remains unclear. Here, we report a case of stage IIIB non-small-cell lung carcinoma that underwent salvage surgery after three cycles of pembrolizumab + carboplatin + nab-paclitaxel. Computed tomography revealed the remarkable decrease in tumor volume by 81%. A pathological examination showed that viable neoplastic cells were observed in <1% of the total tumorous lesion suggesting near pathological complete response. This case suggests that this regimen might be a good option as induction therapy for non-small-cell lung carcinoma.

ALK-positive lung cancer in a patient with recurrent brain metastases and meningeal dissemination who achieved long-term survival of more than seven years with sequential treatment of five ALK-inhibitors: A case report.

The incidence of central nervous system (CNS) metastases in patients with anaplastic lymphoma kinase (ALK) fusion gene-positive (ALK+) non-small cell lung cancer (NSCLC) is high, ranging from approximately 20%-70%. Although ALK inhibitors (ALKis) are generally effective for CNS metastases in patients with ALK+ NSCLC, relapse with CNS metastases is frequently observed. A 37-year-old woman with a high level of carcinoembryonic antigen was diagnosed with right lung adenocarcinoma (pathological stage IIIA) and underwent right lower lobectomy. Despite the administration of postoperative chemotherapy, her carcinoembryonic antigen (CEA) level remained elevated. Although crizotinib was administered due to the positivity for ALK fusion, brain metastases appeared at 19.0 months after the start of treatment. Treatment with alectinib following crizotinib resulted in the complete disappearance of brain metastases. However, brain metastases relapsed, and meningeal dissemination appeared at 38.3 months after the start of treatment with alectinib. Although ceritinib, brigatinib, and alectinib rechallenge were attempted, the CNS lesions worsened. Lorlatinib was then administered, resulting in the normalization of the CEA level (4.5 ng/ml) 4.1 months after the start of lorlatinib. The brain metastases and meningeal dissemination almost disappeared. The overall time from the start of crizotinib to lorlatinib is 89.5 months at present, and the patient continues to be treated with lorlatinib without relapse. Lorlatinib was effective in this case with brain metastases and meningeal dissemination after resistance to first- and second-generation ALKis. Appropriate sequential treatment with first-, second- and third-generation ALKis can lead to a long-term survival in ALK+ patients with brain metastases and meningeal dissemination.

A deep learning model for the classification of indeterminate lung carcinoma in biopsy whole slide images.

The differentiation between major histological types of lung cancer, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC), and small-cell lung cancer (SCLC) is of crucial importance for determining optimum cancer treatment. Hematoxylin and Eosin (H&E)-stained slides of small transbronchial lung biopsy (TBLB) are one of the primary sources for making a diagnosis; however, a subset of cases present a challenge for pathologists to diagnose from H&E-stained slides alone, and these either require further immunohistochemistry or are deferred to surgical resection for definitive diagnosis. We trained a deep learning model to classify H&E-stained Whole Slide Images of TBLB specimens into ADC, SCC, SCLC, and non-neoplastic using a training set of 579 WSIs. The trained model was capable of classifying an independent test set of 83 challenging indeterminate cases with a receiver operator curve area under the curve (AUC) of 0.99. We further evaluated the model on four independent test sets-one TBLB and three surgical, with combined total of 2407 WSIs-demonstrating highly promising results with AUCs ranging from 0.94 to 0.99.