Immunotherapy With Radiotherapy for Brain Metastases in Patients With NSCLC: NEJ060.

Introduction: Immune checkpoint inhibitor (ICI)-based treatment has become standard treatment for patients with advanced NSCLC. We aimed to determine the survival benefit of upfront radiotherapy for brain metastases (BMs) in patients with NSCLC who received ICI alone (ICI-alone) or with chemotherapy (ICI-chemo). Methods: This study included consecutive patients with NSCLC having BMs who received ICI alone or ICI-chemo at 50 institutes between February 2017 and September 2021. The presence of BMs was confirmed by imaging before treatment. Treatment outcomes were compared between patients who did and did not receive upfront radiotherapy for BMs. Potential confounding factors were adjusted between the groups through inverse probability treatment weighting (IPTW) analysis and overlap weighting (OW) analysis with propensity scores. Results: Patients were grouped as ICI-alone cohort, 224 patients (upfront-radiotherapy group, 135 patients; no-radiotherapy group, 89 patients) and ICI-chemo cohort, 367 patients (upfront-radiotherapy group, 212 patients; no-radiotherapy group, 155 patients). In the ICI-alone cohort, the overall survival of the upfront-radiotherapy group was significantly longer than that of the no-radiotherapy group (IPTW-adjusted hazards ratio [HR] = 0.45 [95% confidence interval [CI]: 0.29-0.72], OW-adjusted HR = 0.52 [95% CI: 0.35-0.77]). In contrast, in the ICI-chemo cohort, the OS of the upfront-radiotherapy group was not significantly different from that of the no-radiotherapy group (IPTW-adjusted HR = 1.02 [95% CI: 0.70-1.48], OW-adjusted HR = 0.93 [95% CI: 0.65-1.33]). Conclusions: Upfront radiotherapy for BMs was associated with longer overall survival in patients with NSCLC who received ICI alone; however, it did not exhibit survival benefits in the patients who received ICI-chemo.

Texture Features of 18F-Fluorodeoxyglucose Positron Emission Tomography for Predicting Programmed Death-Ligand-1 Levels in Non-Small Cell Lung Cancer.

Background: Identifying programmed death-ligand-1 (PD-L1) expression is crucial for optimizing treatment strategies involving immune checkpoint inhibitors. However, the role of intratumoral metabolic heterogeneity specifically derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images in predicting PD-L1 expression in patients with newly diagnosed non-small cell lung cancer (NSCLC) remains unexplored. Here, we investigated the association between FDG PET texture features and PD-L1 expression by retrospectively analyzing the data of patients newly diagnosed with NSCLC who underwent FDG PET/CT scans and PD-L1 immunohistochemical staining before treatment. Methods: Patients were categorized based on their tumor proportion scores (TPSs) into negative-, low-, and high-PD-L1 expression groups. We computed the maximum standardized uptake value and 31 texture features for the primary tumor from PET images and compared differences in parameters among the groups. Results: Of the 83 patients, 12, 45, and 26 were assigned to the negative-, low-, and high-PD-L1 expression groups, respectively. Six specific texture features (low gray-level run emphasis, short-run low gray-level emphasis, long-run high gray-level emphasis, low gray-level zone emphasis, high gray-level zone emphasis, and short-zone low gray-level emphasis) helped distinguish among all possible combinations. Conclusions: Our findings revealed that FDG PET texture features are potential imaging biomarkers for predicting PD-L1 expression in patients newly diagnosed with NSCLC.

Clinical characteristics of patients treated with immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: CS-Lung-003 prospective observational registry study.

PURPOSE: Immune checkpoint inhibitors (ICIs) are ineffective against epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics of patients who were treated or not treated with ICIs, and of those who benefit from immunotherapy in EGFR-mutant NSCLC. METHODS: We analyzed patients with unresectable stage III/IV or recurrent NSCLC harboring EGFR mutations using a prospective umbrella-type lung cancer registry (CS-Lung-003). RESULTS: A total of 303 patients who met the eligibility criteria were analyzed. The median age was 69 years; 116 patients were male, 289 had adenocarcinoma, 273 had major mutations, and 67 were treated with ICIs. The duration of EGFR-TKI treatment was longer in the Non-ICI group than in the ICI group (17.1 vs. 12.7 months, p < 0.001). Patients who received ICIs for more than 6 months were categorized into the durable clinical benefit (DCB) group (24 patients), and those who received ICIs for less than 6 months into the Non-DCB group (43 patients). The overall survival in the DCB group exhibited longer than the Non-DCB group (69.3 vs. 47.1 months), and an equivalent compared to that in the Non-ICI group (69.3 vs. 68.9 months). Multivariate analysis for time to next treatment (TTNT) of ICIs showed that a poor PS was associated with a shorter TTNT [hazard ratio (HR) 3.309; p < 0.001]. Patients who were treated with ICIs and chemotherapy combination were associated with a longer TTNT (HR 0.389; p = 0.003). In addition, minor EGFR mutation was associated with a long TTNT (HR 0.450; p = 0.046). CONCLUSION: ICIs were administered to only 22% of patients with EGFR-mutated lung cancer, and they had shorter TTNT of EGFR-TKI compared to other patients. ICI treatment should be avoided in EGFR mutated lung cancer with poor PS but can be considered for lung cancer with EGFR minor mutations. Pathological biomarker to predict long-term responders to ICI are needed.

Efficacy and Safety of Re-administration of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) After EGFR-TKI-Induced Interstitial Lung Disease (CS-Lung-005).

PURPOSE: This study investigated the safety and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) re-administration after recovery from EGFR-TKI-induced interstitial lung disease (ILD). METHODS: This multicenter retrospective study collected data from consecutive advanced NSCLC patients who underwent EGFR-TKI re-administration after recovery from EGFR-TKI-induced ILD. RESULTS: Fifty-eight patients were registered. The grades of initial TKI-induced ILD were grade 1 to 4. TKIs used for re-administration were erlotinib for 15 patients, osimertinib for 15, gefitinib for 14, afatinib for 13 patients, and dacomitinib for 1 patient. ILD recurred in 13 patients (22.4%), comprising 3 patients with grade 1, 6 patients with grade 2, and 4 patients with grade 3. No significant associations were found between ILD recurrence and age, smoking history, performance status, time from initial ILD to TKI re-administration, or concomitant corticosteroid use. However, the incidence of ILD recurrence was high in cases of repeated use of gefitinib or erlotinib or first time use of osimertinib at TKI re-administration. The ILD recurrence rate was lowest in patients treated with first time use of gefitinib (8%) or erlotinib (8%), followed by patients treated with repeated use of osimertinib (9%). The response rate, median progression-free survival by TKI re-administration, and median overall survival were 55%, 9.6 and 84.8 months, respectively. CONCLUSION: This study showed that EGFR-TKI re-administration is a feasible and effective treatment for patients who recovered from EGFR-TKI-induced ILD. Our results indicate that re-administration of EGFR-TKI is an important option for long-term prognosis after recovery from EGFR-TKI-induced ILD.

A randomized phase II study of afatinib alone or combined with bevacizumab for treating chemo-naïve patients with non-small cell lung cancer harboring EGFR mutations.

BACKGROUND: Adding bevacizumab to first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) prolonged the progression-free survival (PFS), but limited data are available for second-generation EGFR-TKIs. AfaBev-CS is a randomized, phase II trial comparing afatinib plus bevacizumab and afatinib alone as first-line treatment. PATIENTS AND METHODS: Untreated patients with non-squamous non-small cell lung cancer (NSCLC) harboring EGFR mutations (Del19 or L858R) were enrolled and randomly assigned to receive either afatinib (30 mg) plus bevacizumab (AfaBev group) or afatinib (40 mg) monotherapy (Afa group). The primary endpoint was PFS. The power was >50% under the assumptions of a median PFS of 12 months for the Afa group and hazard ratio (HR) of 0.6 for the AfaBev group. RESULTS: Between August 2017 and September 2019, 100 patients were enrolled. There was no significant difference in PFS between the groups. The median PFS was 16.3 and 16.1 months for the AfaBev and Afa groups, respectively, with an HR of 0.865 (95% confidence interval [CI], 0.539 to 1.388; p = 0.55). In terms of overall survival, there was no significant difference between the groups (HR, 0.84; 95% CI, 0.39 to 1.83; p = 0.67). The overall response rate was 82.6% and 76.6% in the AfaBev and Afa groups, respectively (p = 0.61). Grade ≥ 3 diarrhea, hypertension, acneiform rash, paronychia, and stomatitis were frequently observed in the AfaBev group. CONCLUSIONS: This study failed to show efficacy of AfaBev over Afa for improving PFS in untreated patients with EGFR-mutated NSCLC.

FDG PET texture indices as imaging biomarkers for epidermal growth factor receptor mutation status in lung adenocarcinoma.

Identifying the epidermal growth factor receptor (EGFR) mutation status is important for the optimal treatment of patients with EGFR mutations. We investigated the relationship between 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) texture indices and EGFR mutation status in patients with newly diagnosed lung adenocarcinoma. We retrospectively analyzed data of patients with newly diagnosed lung adenocarcinoma who underwent pretreatment FDG PET/computed tomography and EGFR mutation testing between August 2014 and November 2020. Patients were divided into mutated EGFR and wild-type EGFR groups. The maximum standardized uptake value (SUVmax) and 31 texture indices for the primary tumor were calculated from PET images and compared between the two groups. Of the 66 patients included, 22 had mutated EGFR and 44 had wild-type EGFR. The SUVmax did not significantly differ between the two groups. Among the 31 evaluated texture indices, the following five showed a statistically significant difference between the groups: correlation (P = 0.003), gray-level nonuniformity for run (P = 0.042), run length nonuniformity (P = 0.02), coarseness (P = 0.006), and gray-level nonuniformity for zone (P = 0.04). Based on the preliminary results of this study in a small patient population, FDG PET texture indices may be potential imaging biomarkers for the EGFR mutation status in patients with newly diagnosed lung adenocarcinoma.

Association of longer telomere length in cancer cells and cancer-associated fibroblasts with worse prognosis.

BACKGROUND: Telomere dysfunction has been reported to be directly involved in carcinogenesis owing to chromosomal instability and immortalization; however, the clinicopathological significance of telomeres remains controversial. We have shown that telomere shortening occurs in normal-appearing duct cells at initiation and then continues during the progression of pancreatic cancer. In this study, we determined the clinicopathological and prognostic value of telomere length (TL) in cancer progression. METHODS: TL in both cancer cells and cancer-associated fibroblasts (CAFs) was analyzed by high-throughput quantitative fluorescence in situ hybridization using a previously reported cohort comprising 1434 cases of adenocarcinoma (ADC), squamous cell carcinoma (SCC), adenosquamous carcinoma, hepatocellular carcinoma, and renal cell carcinoma (RCC), which are known cancers with a statistically significantly low incidence of alternative lengthening of telomeres. Cases were divided into 2 groups as follows: longer and shorter telomeres, according to the median TL of cancer cells and CAFs. The statistical significance of TL in cancer cells and CAFs on clinicopathological characteristics and prognosis was analyzed. RESULTS: There was a close association between TL in cancer cells and CAFs. Longer telomeres in cancer cells and CAFs were associated with aggressive features such as advanced stage, high mitosis score and nuclear score, poorly differentiated cancer, and desmoplastic stroma in ADC. Furthermore, a longer TL was an independent prognostic factor for ADC, SCC, and RCC. CONCLUSIONS: Longer telomeres are associated with worse prognosis in ADC, SCC, and RCC. Thus, TL is a novel biomarker for the diagnosis of aggressive cancers with poor prognoses.

First and repeat rebiopsy for detecting EGFR T790M mutation in non-small-cell lung cancer: CS-Lung-003 prospective observational registry study.

PURPOSE: Osimertinib is still essential for the treatment of epidermal growth factor receptor (EGFR)-T790M-positive non-small-cell lung cancer (NSCLC) even in a relapsed setting, which suggests the importance of rebiopsy. The clinical value of repeat rebiopsy in patients with NSCLC who are T790M-negative on a first rebiopsy remains unclear. In this study, we examined the status of the first rebiopsy and evaluated the frequency of repeat rebiopsy of T790M-negative tumors detected by the first rebiopsy. METHODS: We reviewed 144 patients with NSCLC with major EGFR mutations, but not T790M, who received first- or second-generation EGFR tyrosine kinase inhibitors (TKIs), registered in the prospective, umbrella-type lung cancer patient registry (CS-Lung-003). RESULTS: Overall, 63 patients (44%) underwent the first rebiopsy. In the first rebiopsy, 51 (81%) and 12 (19%) of 63 underwent histological/cytological rebiopsy and liquid biopsy with the blood sampling, respectively. In the repeat rebiopsy, 23 (85%) and 4 (15%) of 27 underwent histological/cytological rebiopsy and liquid biopsy, respectively. The most frequently rebiopsied site was a pulmonary lesion (n = 24, 38.7%). Overall, 29 (46.0%) of 63 patients harbored the T790M mutation. Interestingly, a high detection rate of cancer cells did not necessarily indicate a high detection rate of the T790M mutation (p < 0.01). Among 34 patients with T790M-negative tumors confirmed on the first rebiopsy, 20 (58.8%) underwent repeat rebiopsies following interval therapy, revealing that seven (36.8%) had T790M-positive tumors. Osimertinib yielded median progression-free survival of 11.8 and 16.2 months in patients with the 790M mutation detected by the first rebiopsy and repeat rebiopsy, respectively. CONCLUSION: In our prospective cohort, the T790M mutation was detected in 46% of patients who underwent the first rebiopsy. Repeat rebiopsy may increase the ability to detect the T790M mutation positivity rate.

Phosphorylation of hTERT at threonine 249 is a novel tumor biomarker of aggressive cancer with poor prognosis in multiple organs.

Recent evidence indicates that RNA-dependent RNA polymerase (RdRP) activity of human telomerase reverse transcriptase (hTERT) regulates expression of target genes and is directly involved in tumor formation in a telomere-independent manner. Non-canonical function of hTERT has been considered as a therapeutic target for cancer therapy. We have previously shown that hTERT phosphorylation at threonine 249 (p-hTERT), which promotes RdRP activity, is an indicator of an aggressive phenotype and poor prognosis in liver and pancreatic cancers, using two cohorts with small sample sizes with polyclonal p-hTERT antibody. To clarify the clinical relevance of p-hTERT, we developed a specific monoclonal antibody and determined the diagnostic and prognostic value of p-hTERT in cancer specimens using a large cohort. A monoclonal antibody for phosphorylated hTERT (p-hTERT) at threonine 249 was developed and validated. The antibody was used for the immunohistochemical staining of formalin-fixed, paraffin-embedded specimens from 1523 cases of lung, colon, stomach, pancreatic, liver, breast, and kidney cancers. We detected elevated p-hTERT expression levels in cases with a high mitotic activity, high pathological grade, and high nuclear pleomorphism. Elevated p-hTERT expression was an independent prognostic factor for lung, pancreatic, and liver cancers. Furthermore, p-hTERT expression was associated with immature and aggressive features, such as adenosquamous carcinoma (lung and pancreas), invasive type of cancer (lung), high serum alpha-fetoprotein level (liver), and triple-negative status (breast). In conclusion, RdRP activity indicated by p-hTERT expression predicts aggressive cancer phenotypes in various types of cancer. Thus, p-hTERT is a novel biomarker for the diagnosis of aggressive cancers with a poor prognosis. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Correlation of epidermal growth factor receptor mutation status and PD-L1 expression with [18F]FDG PET using volume-based parameters in non-small cell lung cancer.

OBJECTIVE: We investigated the relationship between 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET using volume-based parameters and epidermal growth factor receptor (EGFR) mutation status, programmed death-ligand-1 (PD-L1) expression level, and their combination, in pretreated non-small cell lung cancer (NSCLC). METHODS: FDG PET findings and EGFR mutation status and PD-L1 expression level were investigated retrospectively in 93 patients with newly diagnosed NSCLC (77 adenocarcinomas, 16 squamous cell carcinomas). Tumors were divided into six groups: EGFR mutant/negative PD-L1, EGFR mutant/low PD-L1, EGFR mutant/high PD-L1, EGFR wild/negative PD-L1, EGFR wild/low PD-L1, and EGFR wild/high PD-L1. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumor were measured from PET images. The EGFR mutation status and PD-L1 expression level were estimated in tumor tissue specimens and compared with the PET parameters. RESULTS: None of the PET parameters differed significantly between EGFR-mutated and wild-type EGFR. According to the PD-L1 level, significant differences were detected in SUVmax (P = 0.001) and TLG (P = 0.016), but not MTV. Comparing all six groups, significant difference was detected in only SUVmax (P = 0.011). CONCLUSION: Based on the preliminary results of this study, FDG PET may help in the prediction of PD-L1 expression level, but not EGFR mutation status, in patients with newly diagnosed NSCLC. The SUVmax rather than MTV or TLG, may be of value in predicting the six groups according to the combination of EGFR mutation status and PD-L1 expression level.

Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B).

BACKGROUND: Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown. METHODS: Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2-4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety. RESULTS: Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3-5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations. CONCLUSION: Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.

A phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small-cell lung cancer in Japan (SAMURAI study).

BACKGROUND: Based on the results of the PACIFIC study, chemoradiotherapy followed by 1-year consolidation therapy with durvalumab was established as the standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC). However, some topics not foreseen in that design can be explored, including progression-free survival (PFS) and overall survival (OS) after the start of chemoradiotherapy, the proportion of patients who proceeded to consolidation therapy with durvalumab, and the optimal chemotherapeutic regimens. In Japan, the combination regimen of S-1 + cisplatin (SP), for which the results of multiple clinical studies have suggested a good balance of efficacy and tolerability, is frequently selected in clinical settings. However, the efficacy and safety of consolidation therapy with durvalumab following this SP regimen have not been evaluated. We therefore planned a multicenter, prospective, single-arm, phase II study. METHODS: In treatment-naïve LA-NSCLC, two cycles of combination chemotherapy with S-1 (80-120 mg/body, Days 1-14) + cisplatin (60 mg/m2, Day 1) will be administered at an interval of 4 weeks, with concurrent thoracic radiotherapy (60 Gy). Responders will then receive durvalumab every 2 weeks for up to 1 year. The primary endpoint is 1-year PFS rate. DISCUSSION: Compared with the conventional standard regimen in Japan, the SP regimen is expected to be associated with lower incidences of pneumonitis, esophagitis, and febrile neutropenia, which complicate the initiation of consolidation therapy with durvalumab, and have higher antitumor efficacy during chemoradiotherapy. Therefore, SP-based chemoradiotherapy is expected to be successfully followed by consolidation therapy with durvalumab in more patients, resulting in prolonged PFS and OS. Toxicity and efficacy results of the SP regimen in this study will also provide information important to the future establishment of the concurrent combination of chemoradiotherapy and durvalumab. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.

Phase I trial of nedaplatin and S-1 in patients with advanced squamous cell lung cancer.

The platinum doublet is considered to be the standard cytotoxic chemotherapy for advanced lung cancer. It has been previously reported that nedaplatin and S-1 have clinical efficacy against squamous cell lung cancer. As the combination of nedaplatin and S-1 has never been studied for advanced squamous cell lung cancer, a phase I trial of this combination in the first-line setting was conducted. Patients who had not received chemotherapy previously, aged ≤75 years and with advanced squamous cell lung cancer were recruited. Nedaplatin was administered intravenously (day 1), and S-1 was orally administered (days 1-14) at a fixed dose based on the body surface area (BSA) <1.25 m2, 80 mg/day; BSA=1.25-1.5 m2, 100 mg/day; and BSA ≥1.5 m2, 120 mg/day. A total of 9 patients were enrolled. The maximum tolerated dose was 80 mg/m2 for nedaplatin. At this dosage, dose-limiting toxicity was observed in 2 of the 6 patients. A total of one patient experienced grade 3 thrombocytopenia, and the other patient experienced grade 3 anorexia and grade 3 nausea. The recommended dose for phase II studies was determined as being 70 mg/m2 for nedaplatin (clinical trial registration no. UMIN-CTR UMIN000036387).

Clinical features of patients with small cell lung cancer and idiopathic pulmonary fibrosis treated with chemotherapy or chemoradiotherapy.

BACKGROUND: The clinical features of patients with small cell lung cancer (SCLC) and idiopathic pulmonary fibrosis (IPF) have not been fully elucidated. PATIENTS AND METHODS: Data on 366 patients with pathologically confirmed SCLC who had been treated with chemotherapy or chemoradiotherapy were retrospectively analyzed to investigate the clinical features of SCLC with IPF. RESULTS: A total of 97 out of the 366 patients were diagnosed with interstitial lung disease (ILD), and 75 of them had IPF. For both the limited disease (LD) and extensive disease (ED) stages, the median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the patients with IPF compared with non-ILD patients. A multivariate analysis showed that poor performance status, ED stage, and the presence of IPF were associated with shorter OS. The response rate to first-line therapy was significantly lower in patients with IPF compared with the non-ILD patients. The rate of patients receiving fewer than three cycles of first-line chemotherapy was higher in patients with IPF, which was a factor of poor survival. In LD-stage patients with IPF, chemoradiotherapy was associated with longer PFS and OS compared with chemotherapy only. CONCLUSION: In patients with SCLC, the presence of IPF was associated with a lower response rate as well as shorter PFS and shorter OS. There are some cases that are suitable for chemoradiotherapy, even among patients with IPF.The reviews of this paper are available via the supplemental material section.

Characteristics of multiple nodules in a patient with pulmonary Langerhans cell histiocytosis: A case report.

BACKGROUND: The common computed tomography findings of pulmonary Langerhans cell histiocytosis (PLCH) are multiple cysts and micronodules predominantly in middle to upper lung lobes. Non-cystic nodules and large nodules are atypical findings of PLCH. CASE SUMMARY: The patient was a 48-year-old Japanese man with a smoking history (20 cigarettes/d, 28 years) and no symptoms. Multiple nodules existed in all lung lobes, predominantly in the right lower lobe. Some nodules seemed to be distributed randomly, and others were adjacent to bronchus. Most nodules were solid; some small ones were cystic. The largest nodule was 22 mm in diameter. Although metastatic lung tumors were suspected, thoracoscopic lung biopsy led to the diagnosis of PLCH. At 6 months after he quit smoking, all nodules had almost disappeared. We investigated the characteristics of nodules at diagnosis in detail. Of 349 nodules in total, 116 were in upper and 199 were in lower lobes. Ninety-six (27.5%) were cystic; the remaining 253 (72.5%) were non-cystic. The prevalence of cystic nodules was higher in upper lobes than in lower lobes (right upper 37.5% vs lower 18.2%, P = 0.0068; left upper 48.1% vs lower 24.4%, P = 0.0078). The average size (dia.) of cystic nodules was smaller than that of non-cystic nodules (5.03 mm vs 7.40 mm, respectively, P < 0.0001). CONCLUSION: Although multiple non-cystic nodules including large nodules (over 20 mm) are atypical, PLCH should be included in differential diagnoses. The presence of small cystic nodules predominantly in upper lobes and asymptomatic situation are also important for differential diagnoses to distinguish from metastatic cancers.

Association of specific metastatic organs with the prognosis and chemotherapeutic response in patients with advanced lung cancer.

BACKGROUND: This study was performed to investigate the influence of specific metastatic organs on the prognosis and therapeutic effect in patients with advanced lung cancer. METHODS: We retrospectively analyzed 400 patients with pathologically diagnosed advanced lung cancer to determine the association of the patients' metastatic status with their prognoses and responses to first-line therapy. Metastases within the chest cavity (pulmonary metastasis, pleural effusion, and pericardial effusion) were counted as one organ. RESULTS: The numbers of metastatic organs in the patients were as follows: one (n=199 patients), two (n=99), three (n=61), and four or more (n=41). A multivariate analysis showed that liver and muscle metastases were independently associated with shorter overall survival (median of 207 and 120 days, respectively) and shorter progression-free survival (median of 125 and 53 days, respectively). Chest cavity, bone, brain, and lymph node metastases were not associated with survival. The presence of either muscle or skin metastasis was associated with a lower response rate to first-line therapy than was the absence of each metastasis (14.3% vs. 49.4% and 11.1% vs. 48.9% in patients with vs. without muscle or skin metastasis, respectively). CONCLUSIONS: Muscle and liver metastases were associated with poor outcomes. Muscle and skin metastases were associated with a lower response rate to treatment. For patients with advanced lung cancer, oncologists should select treatment strategies considering the patients' metastatic statuses as well as other clinical characteristics.

Pulmonary Multiloculated 'Lotus Torus-like' Sarcoidosis Mimicking Lung Adenocarcinoma.

A 34-year-old Japanese woman exhibited a 35×25-mm solitary multiloculated mass shadow in the left lower lobe mimicking lung adenocarcinoma. On computed tomography, the mass resembled a lotus torus. A transbronchial lung biopsy and mediastinal lymph node biopsy led to the diagnosis of sarcoidosis. This lotus torus-like mass regressed spontaneously. This is the second reported case of pulmonary cavitary sarcoidosis with a 'lotus torus-like' appearance. We propose several findings regarding the lotus torus-like appearance by comparing the findings to those of lung adenocarcinoma. Knowledge of this unique sign may be helpful for the differential diagnosis of pulmonary sarcoidosis from lung adenocarcinoma.

Serum CYFRA 21-1 but not Vimentin is Associated with Poor Prognosis in Advanced Lung Cancer Patients.

BACKGROUND: Cytokeratins and Vimentin are intermediate filament proteins. Vimentin expression in tissue samples has been reported to be associated with a poor prognosis in non-small cell lung cancer patients who underwent surgery. CYFRA 21-1 (Cytokeratin 19 Fragment) is a well known tumor marker. OBJECTIVE: This study aimed to investigate the usefulness of serum vimentin as a tumor marker and significance of CYFRA 21-1 and vimentin expression on prognosis of advanced lung cancer patients. METHODS: One hundred and four advanced lung cancer patients and 19 non-lung cancer patients were included. A total of 157 clinical samples obtained from 113 patients was used for immunostaining of vimentin and measurements of CYFRA 21-1 and vimentin concentrations. RESULTS: Compared to low concentration, high concentration of serum CYFRA 21-1 was associated with shorter overall survival in lung cancer patients. However, there was no difference in the serum vimentin concentration between the patients with lung cancer and those with non-lung cancer. No difference in vimentin concentration was observed between the malignant and non-malignant pleural effusions. Immunostaining revealed that of the 43 tumor samples, 21 were positive and 22 were negative for vimentin. No significant difference was found in overall survival between patients with positive and negative for vimentin. CONCLUSION: An elevated serum CYFRA 21-1 concentration was associated with shorter overall survival in advanced lung cancer patients. However, serum vimentin was not as useful as a tumor marker of lung cancer. The vimentin positivity in tumor samples might not predict patients' prognosis in patients with advanced lung cancer.