Single Lung Lesion Research Articles

PD-L1 Positron Emission Tomography Imaging in Patients With Non-Small Cell Lung Cancer: Preliminary Results of the ImmunoPET Phase 0 Study

ImmunoPET is a multicenter, single arm, phase 0-1 study of 89Zr-DFO-Sq-durvalumab (89Zr-durvalumab), a novel PET tracer, designed to interrogate the expression of PD-L1 in patients with NSCLC. Clinically relevant findings from phase 0 are presented here. Phase 0 was designed to investigate tracer biodistribution and safety in patients with metastatic NSCLC with PD-L1 expression >25%. After 60MBq/70kg 89Zr-durvalumab infusion, PET/CT images were acquired at days 0, 1, 3 or 5 ± 24h. Baseline FDG PET/CT was performed prior to PD-L1 PET imaging. All five patients recruited to phase 0 completed the full imaging protocol. The only reported adverse event was a transient asymptomatic increase in respiratory rate. At the time of PD-L1 imaging, two patients were in complete remission on FDG-PET after treatment with osimertinib and pembrolizumab; neither showed PD-L1 tracer uptake in previous tumor sites. All three patients with active tumor had received radiotherapy to some or all disease sites prior to PD-L1 imaging. With the exception of a single disease site, specific uptake of 89Zr-durvalumab uptake was seen in tumours, with increasing uptake in tumor seen up to Day 5 post-injection. Patient 1, who had multiple metastases, including brain and bone, showed more intense 89Zr-durvalumab uptake in recently irradiated bone lesions than un-irradiated lesions and uptake was also observed in treated brain metastases.. One patient, who experienced rapid growth of a single lung lesion that had acquired resistance to pembrolizumab, showed no significant 89Zr-durvalumab in that lesion, despite recent radiotherapy. In patient 5, 89Zr-durvalumab uptake was observed in the viable rim of a large, recently irradiated adrenal oligometastasis. 89Zr- durvalumab imaging was safe and detected known viable tumor at multiple sites. Recently irradiated tumours showed the highest uptake and in another, a single site of immunotherapy resistant disease showed minimal tracer uptake. PD-L1 imaging may have utility in patients with NSCLC treated with radiotherapy.

Multiple primary lung cancer: Updates of clinical management and genomic features.

In recent decades, multiple primary lung cancer (MPLC) has been increasingly prevalent in clinical practice. However, many details about MPLC have not been completely settled, such as understanding the driving force, clinical management, pathological mechanisms, and genomic architectures of this disease. From the perspective of diagnosis and treatment, distinguishing MPLC from lung cancer intrapulmonary metastasis (IPM) has been a clinical hotpot for years. Besides, compared to patients with single lung lesion, the treatment for MPLC patients is more individualized, and non-operative therapies, such as ablation and stereotactic ablative radiotherapy (SABR), are prevailing. The emergence of next-generation sequencing has fueled a wave of research about the molecular features of MPLC and advanced the NCCN guidelines. In this review, we generalized the latest updates on MPLC from definition, etiology and epidemiology, clinical management, and genomic updates. We summarized the different perspectives and aimed to offer novel insights into the management of MPLC.

An unusual biphasic pulmonary lesion: late metastasis from a mandibular ameloblastoma

Ameloblastoma is mostly a benign odontogenic tumour most frequently arising within the mandible and maxilla. Although ameloblastoma can be locally aggressive and prone to local recurrence, metastasis is a rare (and usually late) complication. We report a case of a metastatic ameloblastoma to the lung following an original presentation with a traumatic jaw fracture through what was thought to be a mandibular odontogenic cyst in 1988. The definitive diagnosis of ameloblastoma was not reached until a local recurrence occurred ten years later; this was managed with hemimandibulectomy and post-operative radiotherapy. A single lung lesion was identified incidentally 33 years after the original presentation: it demonstrated typical morphological features of ameloblastoma and FOXP1 immunostaining was confirmatory. Recent advances in understanding the genetic pathogenesis of ameloblastoma demonstrate frequent BRAFV600E mutations as well as mutations in other MAP kinase pathway genes such as KRAS, NRAS, HRAS and FGFR2.1 Several case reports have indicated promising results with BRAF inhibitor therapy in metastatic ameloblastoma.2 1.Brown N, Betz B. Ameloblastoma: a review of recent molecular pathogenetic discoveries. Biomark Cancer 2015; 7 (Suppl 2): 19–24.2.González-González R, López-Verdín S, Lavalle-Carrasco J, et al. Current concepts in ameloblastoma-targeted therapies in B-raf proto-oncogene serine/threonine kinase V600E mutation: Systematic review. World J Clin Oncol 2020; 11: 31–42.

The Impact of Biopsy Tool Choice and Rapid On-Site Evaluation on Diagnostic Accuracy for Malignant Lesions in the Prospective: Multicenter NAVIGATE Study.

Background:The diagnostic yield of electromagnetic navigation bronchoscopy (ENB) is impacted by biopsy tool strategy and rapid on-site evaluation (ROSE) use. This analysis evaluates usage patterns, accuracy, and safety of tool strategy and ROSE in a multicenter study.Methods:NAVIGATE (NCT02410837) evaluates ENB using the superDimension navigation system (versions 6.3 to 7.1). The 1-year analysis included 1215 prospectively enrolled subjects at 29 United States sites. Included herein are 416 subjects who underwent ENB-aided biopsy of a single lung lesion positive for malignancy at 1 year. Use of a restricted number of tools (only biopsy forceps, standard cytology brush, and/or bronchoalveolar lavage) was compared with an extensive multimodal strategy (biopsy forceps, cytology brush, aspirating needle, triple needle cytology brush, needle-tipped cytology brush, core biopsy system, and bronchoalveolar lavage).Results:Of malignant cases, 86.8% (361/416) of true positive diagnoses were obtained using extensive multimodal strategies. ROSE was used in 300/416 cases. The finding of malignancy by ROSE reduced the total number of tools used. A malignant ROSE call was obtained in 71% (212/300), most (88.7%; 188/212) by the first tool used (49.5% with aspirating needle, 20.2% with cytology brush, 17.0% with forceps). True positive rates were highest for the biopsy forceps (86.9%) and aspirating needle (86.6%). Use of extensive tool strategies did not increase the rates of pneumothorax (5.5% restricted, 2.8% extensive) or bronchopulmonary hemorrhage (3.6% restricted, 1.1% extensive).Conclusion:These results suggest that extensive biopsy tool strategies, including the aspirating needle, may provide higher true positive rates for detecting lung cancer without increasing complications.

Clinical analysis in immunocompetent and immunocompromised patients with pulmonary cryptococcosis in western China

Cryptococcosis is a systemic infection and it may occur in immunocompromised and immunocompetent hosts. In order to better understand the clinical characteristics of patients with PC in different immune status, we retrospectively investigated the clinical, radiological, and treatment profiles of immunocompetent and immunocompromised patients with PC during a 10-year period (2008–2017). As a result, out of 136 patients, 94 (69.1%) were immunocompromised hosts. For the PC patients without CNS involvement, higher percentage of immunocompetent patients (39.5%, 15/38) had asymptomatic presentation than immunocompromised patients (6.3%, 3/48) (P < 0.05). Multiple pulmonary nodules (72.7%, 56/77), ground-glass attenuation/interstitial changes (94.4%, 17/18) and cavitation (88.6%, 31/35) were significantly frequent in immunocompromised patients (P < 0.05). A total of 47 patients were misdiagnosed as tuberculosis or tumors based on CT signs. PC was likely to be misdiagnosed as tuberculosis in immunocompromised patients (88.2%, 15/17), and tumor was more likely to be considered in immunocompetent patients (43.3%, 13/30). Immunocompetent patients accounted for 80% (24/30) of patients with definite diagnosis on surgical lung biopsy. Fluconazole monotherapy can achieve good clinical outcome in most PC patients without central nervous system (CNS) involvement (91.5%, 54/59). After 3 months of treatment, 92.7% (38/41) patients have improved imaging findings. In conclusion, PC has diverse imaging manifestations and it is easily misdiagnosed. Lobectomy should be carefully selected in immunocompetent patients with a single lung lesion. Fluconazole monotherapy is preferred for PC patients without CNS involvement.

THE IMPACT OF BIOPSY TOOL CHOICE AND RAPID ON-SITE EVALUATION ON THE DIAGNOSTIC ACCURACY FOR MALIGNANT LESIONS IN THE PROSPECTIVE, MULTICENTER NAVIGATE STUDY

THE IMPACT OF BIOPSY TOOL CHOICE AND RAPID ON-SITE EVALUATION ON THE DIAGNOSTIC ACCURACY FOR MALIGNANT LESIONS IN THE PROSPECTIVE, MULTICENTER NAVIGATE STUDY

P3-13-2 - Feasibility of Stereotactic Body Radiation Therapy with Concurrent Chemotherapy for Metachronous Primary Lung Cancer

Background: Patients with lung cancer may develop a second primary lung cancer after treatment of the initial lesion (metachronous PLC). In those cases, it is difficult to distinguish primary lung cancer from lung metastasis. Therefore, we need both local therapy for a single lung lesion, and systemic therapy for micrometastasis. Stereotactic body radiation therapy (SBRT) is now the standard treatment for patients with inoperable Stage I non-small-cell lung cancer (NSCLC). However SBRT with concurrent chemotherapy may be feasible and effective for selected patients with NSCLC. This retrospective study was aimed at evaluating the safety and tolerability of concurrent SBRT and chemotherapy in patients with metachronous primary lung cancer.Methods: We reviewed the records of 10 patients with metachronous primary lung cancer treated with SBRT and concurrent chemotherapy with curative intent from 2007 to 2013. All patients had T1 tumor. The median age was 65 years with a range of 58 to 79 years. The median delivered radiation dose was 48 Gy in 4 fractions. Concurrent chemotherapy regimen was cisplatin plus docetaxel, cisplatin plus vinorelbine, nedaplatin plus docetaxel, carboplatin plus docetaxel, and carboplatin plus paclitaxel, carboplatin plus docetaxel.Results: All patients received SBRT on schedule. Concurrent chemotherapy was successfully accomplished as originally planned in 10 patients. Initial effect of SBRT plus chemotherapy could be evaluated in all cases. Complete local remission was achieved in 9 patients and Partial local remission was achieved in one patient. Local recurrence were not observed in any patient. Only one patient alone had distant metastases. A grade 3 or 4 neutrophil count decreased occurred in 7 patients, grade 3 febrile neutropenia in 2 patients, and grade3 anemia in one patient. No treatment-related deaths were observed.Conclusion: Our study showed good feasibility and safety of SBRT and concurrent chemotherapy.

Double KRAS and BRAF mutations in colorectal cancer in a single oncologic department series.

e14657 Background: KRAS and BRAF mutations have prognostic and predictive value in colorectal cancer and are predominantly mutually exclusive. Only a few cases of double mutations (DM) have been reported so far but the actual incidence and presumed role in worsening prognosis is still unknown. Here we report on a series of KRAS and BRAF mutations, focusing on three cases of KRAS and BRAF DM. Methods: since May 2010, 316 consecutive colorectal cancer samples were collected by our Oncology Department; ten patients (3%) had high risk localized disease and 306 (97%) metastatic disease. Genome DNA from formalin-fixed paraffin embedded samples with tumor cells &gt; 50% was analyzed by reverse dot blot with KRAS-BRAF StripAssay kit (Nuclear Laser Medicine). Results: KRAS point mutations were found in 141 patients (44.6%): 32% G12V, 30.5% G12D, 14.9% G13D, 6.4% G12S, 5.7% G12C, 4.9% G12A, 4.9% G12R, 0.7% G13C; V600E BRAF point mutation was found in 21 patients (6.6%). Three patients (1%) displayed DM: 2 KRAS G13D + BRAF V600E (A and B) and 1 KRAS G12V + BRAF V600E (C). Patients A and C, both aged 59, presented with metastatic disease. Patient A had a rectal primary, a single lung lesion and mediastinal nodes. He failed first line FOLFOX4 plus bevacizumab and underwent salvage surgery both on primary and metastatic disease. He relapsed in 3 months with liver and brain metastasis and died after one year from diagnosis. Patient B had huge liver lesions at presentation. She progressed after 3 courses of FOLFIRI and died after 6 months from diagnosis. Patient C was operated on for a right colon cancer, G3, pT2N2, stage IIIB with lymph vascular invasion and had adjuvant FOLFOX 4. The 6-month assessment did not show relapse. Conclusions: in our series KRAS mutation incidence was in line with literature, but G12V was far more frequent. KRAS-BRAF DM accounted for 1% of all cases and the 2 patients with metastatic disease had an aggressive course with a much lower than expected survival. To our knowledge no series of DM have been described, hindering the understanding of their biological meaning. According to our experience, metastatic double mutated patients do not respond to standard therapy and should be treated with new drugs combinations in clinical trials.

Case of lung carcinoma revealed by vulvar metastasis associated with systemic scleroderma and literature review

Metastatic carcinoma to the vulva is rare, where the incidence is believed to be between 5% and 8%.However, malignant tumors have been described in 3–11% of systemic scleroderma (SSc) cases.We report the case of one patient, a 66-year-old postmenopausal woman, whose medical history was marked with rheumatic vascular disease (systemic scleroderma) since 1993 without muscular, renal, cardiac lesions or HTA (arterial hypertension) and without tobacco history.The woman presented with a new vulvar mass of the right labia in December 2011 that had progressively enlarged in size.CT scan of the abdominopelvic region demonstrated a lobular mass of the right labia with central necrosis, 7cm on the wide axis, and the rectum and the vaginal wall were normal. No inguinal or iliac lymphadenopathy was noted.An outpatient excisional biopsy revealed a poorly differentiated malignant tumor suggestive of carcinoma.IHC: CK7+/CK20−, estrogen receptors−, AE 1 AE 3+, vimentine+, S100−, Desmina−, CD34−, KI 67: 20%.The thoracic scan revealed a large mass of 4cm×3cm in the right lung base with right paratracheal lymphadenopathy 3cm×2cm.A bronchoscopy revealed discrete stenosis of the mediastinal portion of the right bronchial tree.The bronchial biopsy also revealed poorly differentiated lung carcinoma, non-small cell, which was identical with the vulvar tumor. ConclusionThe presence of the single lung lesion with only one lymphadenopathy paratracheal with pathological and immunohistochemical (IHC) profile similar to the vulvar lesion, and a particular IHC profile with CK7+ and CK20− was detected – that is more specific to the primitive pulmonary cancer, and the presence of only one sarcoma marker vementine+, desmine and actine−. Also the presence of KI 67: 20%, predicted the proliferative and great metastatic power of the lung tumor was observed.Additionally, lung cancer was the most frequent type and may develop in scleroderma as reported in most studies.This allows to conclude for primitive lung carcinoma revealed with vulvar metastasis after elimination of the possibility of vulvar sarcoma.The patient was treated by chemotherapy (Taxol/Platin) with partial response from the lung after 3 cycles and palliative radiotherapy in the vulva with a good response.This case described primary lung carcinoma associated with scleroderma, revealed by a vulvar metastasis, which may be related to the aggressiveness of lung cancer when the lung fibrosis follow-up is not performed well to detect early the development of lung tumors in the patient with systemic scleroderma.

Association of CTLA4 Gene Polymorphisms with Susceptibility and Pathology Correlation to Pulmonary Tuberculosis in Southern Han Chinese

The cytotoxic T lymphocyte antigen-4 (CTLA4) gene is a key negative regulator of the T lymphocyte immune response. It has been found that CTLA4 +49A>G (rs231775), +6230G>A (rs3087243), and 11430G>A (rs11571319) polymorphisms are associated with susceptibility to many autoimmune diseases, and can down-regulate the inhibition of cellular immune response of CTLA4. Three SNPs in CTLA4 were genotyped by using the PCR and DNA sequencing methods in order to reveal the susceptibility and pathology correlation to pulmonary tuberculosis in Southern Han Chinese. We found that the frequency of CTLA4 +49AG genotype in the pulmonary tuberculosis patients (38.42%) was significantly lower than that of the healthy controls (49.77%), (Pcor=0.038, OR 0.653, 95% CI 0.436-0.978). But, no associations were found between the other 2 SNPs (+6230G>A, 11430G>A) and tuberculosis (P>0.05). Haplotype analysis showed that the frequency of haplotype AGG in the healthy controls group (6.9%) was significantly higher than the pulmonary tuberculosis patients group (1.4%), (global P=0.005, Pcor=0.0002, OR 0.183, 95% CI 0.072-0.468). In addition, haplotype GGA was found to be significantly related to tuberculosis with double lung lesion rather than single lung lesion (Pcor=0.042). This study is the first to report that genetic variants in the CTLA4 gene can be associated with pulmonary tuberculosis in Southern Han Chinese, and CTLA4 +49AG genotype as well as haplotype AGG may reduce the risk of being infected with pulmonary tuberculosis. The GGA haplotype was related to tuberculosis with double lung lesion, which provides a new experimental basis to clarify the pathogenesis of pulmonary tuberculosis.

Survival after Lung Metastasectomy in Colorectal Cancer Patients with Previously Resected Liver Metastases

Resection of hepatic metastases is indicated in selected stage IV colorectal cancer (CRC) patients. A minority will eventually develop pulmonary metastases and may undergo lung surgery with curative intent. The aims of the present study were to assess clinical outcome and identify parameters predicting survival after pulmonary metastasectomy in patients who underwent prior resection of hepatic CRC metastases. We performed a retrospective analysis of 27 consecutive patients (median age 62 years; range: 33-75 years) who underwent resection of pulmonary metastases after previous hepatic metastasectomy from CRC in two institutions from 1996 to 2009. All patients underwent complete resection (R0) for both colorectal and hepatic metastases. Median follow-up was 32 months (range: 3-69 months) after resection of lung metastases and 65 months (range: 19-146 months) after resection of primary CRC. Three- and 5-year overall survival rates after lung surgery were 56 and 39%, respectively, and median survival was 46 months (95% CI 35-57). Median disease-free survival after pulmonary metastasectomy was 13 months (95% CI 5-21). At the time of last follow-up, seven patients (26%) had no evidence of recurrent disease and 6 of these 7 patients presented initially with a single lung metastasis. Resection of lung metastases from CRC patients may result in prolonged survival, even after previous hepatic metastasectomy. Yet, prolonged disease-free survival remains the exception, and seems to occur only in patients with a single lung lesion.

Comparison of outcomes of lung cancer patients treated with surgical resection with 125I lung brachytherapy vs stereotactic hypofractionated radiation therapy for single lung lesions

Purpose: A single lung cancer lesion can be treated with surgical resection (lobectomy or wedge resection) with or without the addition of 125I radiation seeds. Alternatively, inoperable patients may be treated with hypofractionated stereotactic radiation therapy (SRT). The purpose of this study is to evaluate and compare the outcomes of patients with single lung cancer lesions treated at our institute with either surgery plus 125I radiation seeds or SRT.

The chest image appearances of penicilliosis marneffei in patients with AIDS

Objective To study the chest image appearances of penicilliosis marneffei(PSM)in patients with acquired immune deficiency syndrome(AIDS).Methods Chest imaging features of PSM in 36 patients with AIDS were retrospectively analyzed.Results Radiographic features of infiltrative lesions and focal lung consolidation were found in 14 cases(38.89%),in which 2 cases were with single lung disease(5.56%)and 12 cases with bilateral lung involvement(33.33%).Eight cases had diffuse lesions (22.22%),10 cases had reticular image patterns(27.78%),9 cases had nodular patterns(25.00%), 7 cases had ground-glass shadows(19.44%),6 cases had diffuse miliary lesions(16.67%),4 cases had enlarged bilar and enlarged mediastinum lymph nodes(11.11%).Cystic lesions was found in 5 cases (13.89%).Four cases had pleural effusion(11.11%),and 2 cases had nodular bump(5.56%). Pericardial effusion and pneumothorax each appeared in 1 case(2.78%).By HRCT,infiltrative lesion and focal lung consolidation were found in 32 patients(88.89%),in which 4 cases were with single lung lesions (11.11%)and 28 cases were with bilateral lung lesions(77.78%).Thirteen cases had diffuse lesions (36.11%),10 cases had pulmonary interstitial hyperplasia(27.78%),9 cases had nodular patterns (25.00%),8 cases had ground-glass shadows(22.22%),9 cases had diffuse miliary lesions(25.00%), 21 cases had enlarged lymph nodes in the mediastinum(58.33%).Cystic lesions were found in 8 cases (22.22%).Thirteen cases had pleural effusion(36.11%),and 2 cases had nodular bump(5.56%). Pericardial effusion and pneumothorax each appeared in 1 case(2.78%).Conclusion The image appearances of PSM in patients with AIDS include infiltrative lesions or focal lung consolidation,ground- glass shadow,enlarged hilar and mediastinum lymph nodes,pleural effusion,interstitial involvement or reticular image pattern(pulmonary interstitial hyperplasia),diffuse miliary lesion,and cystic lesion.

Improved survival with combined modality treatment for stage IV breast cancer

Between November 1974 and March 1977, 85 patients with breast cancer at first postmastectomy relapse were irradiated (Radiation 3500–6000 rad-3/5 weeks) to all clinically evident lesions. Radiation fields were properly shaped to include a maximum 40% active bone marrow. After 3–4 weeks rest, chemotherapy was started as adjuvant therapy for residual or subclinical disease (ADR 30 mg/M 2 Day 1 and 8, 5-FU 400 mg/M 2 Day 1 and 8, CY 100 mg/M 2 Day 1 through 14: repeated after 14 days). ADR was discontinued at 500/M 2 and substituted by MTX 30 mg/M 2 Day 1 and 8 for a total of 2 years. Irradiated sites were chest wall in 35, supraclavicular and internal mammary nodes in 22, bone in 56, single lung lesions in 12, brain in 24. Controls were 52 comparable but non-randomized patients treated with chemotherapy only. Forty days after x-irradiation 68 patients (80%) were free of disease (NED) while in 17 cases (20%) some residual was still present (RED). In 28 of 68 cases (41%) NED after x-irradiation and 13 of 17 (76%) in RED group developed second relapse after a median interval of 26 and 20 mos, respectively. Four of 52 patients (8%) in the control group had complete regression with a median interval to second relapse of 7 mos. Median survival was 30 mos., 24 mos. and 13 mos., respectively, for NED, RED and chemotherapy only. Eighteen patients (269o) are free of disease after 36–48 mos. in the combined modality group; none in the chemotherapy group. Combined treatment cases did not show untolerable mylodepression: in 41 patients (60%) the average chemotherapy dose had to be reduced during the first 4–5 cycles because of marrow depression. In 10 long-surviving patients a marked subcutaneous and skin fibrosis developed because of drug additive effect. Stage IV breast cancers rendered clinically free of disease with x-irradiation and subsequently treated with chemotherapy survive significantly longer than with chemotherapy alone.