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The differential diagnosis of myelopathy in patients with malignancies may be challenging, as a spinal biopsy is not always applicable. A 66-year-old woman who had shown transient double vision and nausea developed spasticity and impaired deep sensation in both feet. Magnetic resonance imaging showed abnormal gadolinium enhancement of the brainstem, spinal meninges, and nerve root. Cerebrospinal fluid (CSF) revealed mild pleocytosis and elevated protein and decreased glucose levels, although CSF cytology was normal. Lung carcinoma was simultaneously detected, and noncaseating granuloma was detected from the hilar and axillary lymph nodes, so she was diagnosed with sarcoid-associated myelopathy. Her symptoms were kept stable by intravenous methylprednisolone, oral prednisolone, and methotrexate. This is the first case of sarcoid-associated myelopathy accompanied by lung cancer, suggesting the importance of clinical course, repetitive CSF cytology, and a biopsy of the lymph nodes to distinguish sarcoid-associated myelopathy from meningeal metastasis in patients with malignancies.

Purpose: Real-time tracking systems of moving respiratory targets such as CyberKnife, Radixact, or Vero4DRT are an advanced robotic radiotherapy device used to deliver stereotactic body radiotherapy (SBRT). The internal target volume (ITV) of lung tumors is assessed through a fiducial marker fusion using four-dimensional computed tomography (CT). It is important to minimize the ITV to protect normal lung tissue from exposure to radiation and the associated side effects post SBRT. However, the ITV may alter if there is a change in the position of the fiducial marker with respect to the tumor. This study investigated the relationship between fiducial marker position and the ITV in order to prevent radiation exposure of normal lung tissue, and correct target coverage., Materials and Methods: This study retrospectively reviewed 230 lung cancer patients who received a fiducial marker for SBRT between April 2015 and September 2021. The distance of the fiducial marker to the gross tumor volume (GTV) in the expiratory (d ex ) and inspiratory (d in ) CT, and the ratio of the ITV/V(GTV ex ), were investigated., Results: Upon comparing each lobe, although there was no significant difference in the d diff and the ITV/V(GTV ex ) between all lobes for d ex  < 10 mm, there was significant difference in the d diff and the ITV/V(GTV ex ) between the lower and upper lobes for d ex ≥ 10 mm (p < 0.05). Moreover, there was significant difference in the d diff and the ITV/V(GTV ex ) between d ex ≥10 mm and d ex  < 10 mm in all lung regions (p < 0.05)., Conclusion: The ITV that had no margin from GTVs increased when d ex was ≥10 mm for all lung regions (p < 0.05). Furthermore, the increase in ITV tended to be greater in the lower lung lobe. These findings can help decrease the possibility of adverse events post SBRT, and correct target coverage., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

We retrospectively reviewed the effect of stereotactic body radiation therapy (SBRT) in patients with stage I lung cancer whose lung tumor showed a nodular appearance of ground glass opacity, so-called ground glass nodule (GGN). A total of 84 patients (42 men, 42 women; mean age, 75 years) with stage I lung cancer with GGN accompanying a solid component <50% in diameter of the tumor and no metastases were studied. Concerning histology, 32 tumors were adenocarcinoma, 1 was squamous cell carcinoma, 2 were unclassified carcinoma and 49 cases were histology-unproven but increased in size or had a positive finding in 18F-FDG positron emission tomography (PET) examination. The median tumor size was 20 mm (range, 10-41 mm). All of the patients were treated with SBRT, and the total prescribed dose at the isocenter ranged between 48 Gy in four fractions and 84 Gy in ten fractions. Median follow-up duration was 33 months. No patient had local failure nor regional lymph node failure. The 3-year rate of distant failure was 2.6%. Two patients who experienced distant metastases had a past surgical history of initial lung cancer before SBRT. The rates of cause-specific and overall survival at 3 years were 98.2 and 94.6%, respectively. Treatment-related adverse events of ≥grade 4 were not reported. Although more cases and longer follow-ups are mandatory, SBRT may be one of the radical treatment options for patients with GGN., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

KDM5 family members (A, B, C and D) that demethylate H3K4me3 have been shown to be involved in human cancers. Here we performed screening for KDM5A inhibitors from chemical libraries using the AlphaScreen method and identified a battery of screening hits that inhibited recombinant KDM5A. These compounds were further subjected to cell-based screening using a reporter gene that responded to KDM5A inhibition and 6 compounds were obtained as candidate inhibitors. When further confirmation of their inhibition activity on cellular KDM5A was made by immunostaining H3K4me3 in KDM5A-overexpressing cells, ryuvidine clearly repressed H3K4me3 demethylation. Ryuvidine prevented generation of gefitinib-tolerant human small-cell lung cancer PC9 cells and also inhibited the growth of the drug-tolerant cells at concentrations that did not affect the growth of parental PC9 cells. Ryuvidine inhibited not only KDM5A but also recombinant KDM5B and C; KDM5B was the most sensitive to the inhibitor. These results warrant that ryuvidine may serve as a lead compound for KDM5 targeted therapeutics.

Background: The adaptation criteria for administration of stereotactic body radiotherapy (SBRT) to patients with lung cancer who previously underwent surgery and subsequently developed a second primary lung cancer (SPLC) or intra-parenchymal lung metastasis (IPLM) are controversial, unlike the criteria for repeat surgery. We aimed to evaluate the feasibility of SBRT for these patients. Factors associated with decreased respiratory function were also evaluated., Material and Methods: Sixty-nine patients with 89 lesions who underwent SBRT between 2008 and 2017 were analyzed. Of these, 29 were diagnosed with SPLC while the remaining 40 had IPLM. The distribution of histological types was as follows: squamous cell carcinoma (n = 13 lesions); adenocarcinoma (n = 25); non-small cell carcinoma (n = 1); unknown histological type (n = 49). The prescribed doses to the planning target volume (PTV) were 50 Gy in five fractions for 85 lesions and 60 Gy in 10 fractions for four lesions at PTV mean., Results: Over a median follow-up period of 55 months, the 4-year overall survival and local control rates were 50.3% and 87.6%, respectively. Six patients experienced grade 2 radiation pneumonitis and one experienced grade 3. Two patients experienced grade 5 pulmonary fibrosis. Decreased respiratory function was observed in 10 patients (15.1%). On multivariate analysis, the presence of pulmonary disease before SBRT was the only statistically significant factor associated with decreased respiratory function., Conclusions: SBRT is safe and feasible in patients with SPLC or IPLM previously treated surgically. Pre-existing pulmonary disease was a predictive factor for decreased respiratory function.

Lung metastasis constitutes the leading cause of the death in patients with osteosarcoma. We have previously reported that plasminogen activator inhibitor-1 (PAI-1) regulates the invasion and lung metastasis of osteosarcoma cells in a mouse model and as well as in clinical samples. In the present study, we examined the anti-metastatic effect of SK-216, a small compound PAI-1 inhibitor, in human 143B osteosarcoma cells. An in vitro study showed that SK-216 treatment suppressed invasion activity by inhibiting PAI-1 expression in 143B cells, but had no influence on their proliferation or migration. 143B cells treated with SK-216 exhibited reduced matrix metalloproteinase-13 (MMP-13) secretion in a dose-dependent manner. Moreover, intraperitoneal injection of SK-216 into mouse models resulted in downregulation of PAI-1 expression levels in the primary tumors and showed suppression of lung metastases without influencing the proliferative activity of the tumor cells in the primary lesions. These results indicate that SK-216, a PAI-1 inhibitor, may serve as a novel drug to prevent lung metastasis in human osteosarcoma., Competing Interests: The authors declare no conflict of interest.

Purpose: The CyberKnife Xsight Lung Tracking (XLT) and 1-View tracking systems can synchronize beam targeting to a visible lung tumor with respiratory motion during irradiation without requiring internal fiducial markers. The systems use a correlation model that relates external marker positions to tumor positions as well as a prediction model that predicts the target's future position. In this study, the correlation and prediction model uncertainties related to the CyberKnife fiducial-free tumor tracking system were evaluated using clinical log data., Methods and Materials: Data from 211 fractions in 42 patients with lung tumors were analyzed. Log files produced by the CyberKnife Synchrony system were acquired after each treatment; the mean correlation and prediction errors for each patient were calculated. Additionally, we examined the tracking tumor-related parameters and analyzed the relationships between the model errors and tracking tumor-related parameters., Results: The overall means ± standard deviations (SDs) of the correlation errors were 0.70 ± 0.43 mm, 0.36 ± 0.16 mm, 0.44 ± 0.22 mm, and 0.95 ± 0.43 mm for the superoinferior (SI), left-right (LR), anteroposterior (AP), and radial directions, respectively. The overall means ± SDs of the prediction errors were 0.13 ± 0.11 mm, 0.03 ± 0.02 mm, 0.03 ± 0.02 mm, and 0.14 ± 0.11 mm for the SI, LR, AP, and radial directions, respectively. There were no significant differences in these errors between the XLT and 1-View tracking methods. The tumor motion amplitude was moderately associated with the correlation error and strongly related to the prediction error in the SI and radial directions., Conclusions: Clinical log data analysis can be used to determine the necessary margin sizes in treatment plans to compensate for correlation and prediction errors in the CyberKnife fiducial-free lung tumor tracking system. The tumor motion amplitude may facilitate margin determination., (Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Objective: The aims of this study were to investigate the frequency of symptomatic radiation pneumonitis (RP) after CyberKnife lung stereotactic body radiotherapy (SBRT) and to evaluate predictive factors of symptomatic RP., Methods: 56 patients with peripheral non-small-cell lung cancer were treated using the CyberKnife ® VSI ™ System (Accuracy Inc., Sunnyvale, CA) between May 2013 and September 2015. Total radiation doses ranged from 48 to 56 Gy, as delivered in four equal fractions. Symptomatic RP was defined as a grade of ≥2. Predictive factors for symptomatic RP were evaluated using univariate and multivariate analyses., Results: With a median follow-up duration of 12.5 months (range, 3-27 months), symptomatic RP was observed in 6 (10.7%) of the 56 patients. In the univariate analysis, percent vital capacity (p < 0.05), maximum tumour diameter (p < 0.05), gross tumour volume (p < 0.05), planning target volume (p < 0.01), mean lung dose (p < 0.01) and a normal lung volume receiving 5-50 Gy of radiation (V 5-50 ) (p < 0.01) were identified as significant predictive factors for symptomatic RP. In the multivariate analysis, only a V 25 >3.4% (p = 0.011) was identified as a significant predictive factor of symptomatic RP., Conclusion: The incidence of symptomatic RP after CyberKnife SBRT was almost identical to the incidences reported in the linear accelerator-based SBRT. A significant association was observed between a V 25 >3.4% and the risk of developing symptomatic RP. Advances in knowledge: This is the first report that has investigated prognostic factors for symptomatic RP after CyberKnife SBRT for lung cancer. The newly developed scoring system may help to predict symptomatic RP.

Aim: To evaluate the efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) for brain metastases (BMs) from lung cancer, and to explore prognostic factors associated with local control (LC) and indication., Patients and Methods: We evaluated patients who were treated with linac-based HSRT for BMs from lung cancer. Lesions treated with stereotactic radiosurgery (SRS) in the same patients during the same periods were analysed and compared with HSRT in terms of LC or toxicity. There were 53 patients with 214 lesions selected for this analysis (HSRT: 76 lesions, SRS: 138 lesions). For HSRT, the median prescribed dose was 35 Gy in 5 fractions., Results: The 1‑year LC rate was 83.6 % in HSRT; on multivariate analysis, a planning target volume (PTV) of <4 cm(3), biologically effective dose (BED10) of ≥51 Gy, and adenocarcinoma were significantly associated with better LC. Moreover, in PTVs ≥ 4 cm(3), there was a significant difference in LC between BED10 < 51 Gy and ≥ 51 Gy (p = 0.024). On the other hand, in PTVs < 4 cm(3), both HSRT and SRS had good LC with no significant difference (p = 0.195). Radiation necrosis emerged in 5 of 76 lesions (6.6 %) treated with HSRT and 21 of 138 (15.2 %) lesions treated with SRS (p = 0.064)., Conclusion: Linac-based HSRT was safe and effective for BMs from lung cancer, and hence might be particularly useful in or near an eloquent area. PTV, BED10, and pathological type were significant prognostic factors. Furthermore, in BMs ≥ 4 cm(3), a dose of BED ≥ 51 Gy should be considered.

Background: The purpose of the present study was to present the treatment outcomes of particle therapy for indeterminate pulmonary nodules (IPNs) diagnosed as stage I non-small cell lung cancer, including a comparative analysis involving pathologically proven lung cancer (PPLC)., Material and Methods: A total of 54 patients (57 lesions) who underwent particle therapy for IPNs were enrolled in this study. Median patient age was 76 (range 52-87) years. T-classification was: T1a, 30; T1b, 16; and T2a, 11. Particle therapy using protons or carbon ions was delivered at total doses of 52.8-80 Gy equivalent in 4-26 fractions. The PPLC cohort included 111 patients., Results: The median follow-up time was 41 (range 7-90) months. For all IPN patients, the three-year overall survival, progression-free survival, local control and distant progression-free survival rates were 90%, 72%, 94% and 79%, respectively. Grade 2 toxicities were radiation pneumonitis (19%), dermatitis (9%), rib fracture (2%), chest wall pain (2%) and neuropathy (2%). No ≥grade 3 toxicities were observed. In univariate analysis, the IPN group showed significantly better survival relative to the PPLC group. However, after adjustment for baseline imbalances between these two groups in multivariate analysis, pathological confirmation did not correlate with survival., Conclusions: Particle therapy for IPNs provided favorable outcomes with minimal toxicities, which may be comparable to those for PPLC patients. Further studies are needed to clarify the optimal management of IPN patients.

Background: A study was undertaken to analyze the efficacy and feasibility of particle beam radiation therapy (PBRT) using carbon ions and protons for the treatment of patients with oligometastatic lung tumors., Methods: A total of 47 patients with 59 lesions who underwent PBRT for oligometastatic lung tumors between 2003 and 2011 were included in this study. Patient median age was 66 (range, 39-84) years. The primary tumor site was the colorectum in 11 patients (23.4%), lung in 10 patients (21.3%) and a variety of other sites in 26 patients (55.3%). Thirty-one patients (66%) received chemotherapy prior to PBRT. Thirty-three lesions were treated with 320-MeV carbon ions and 26 were treated with 150- or 210-Mev protons in 1-4 portals. A median total dose of 60 (range, 52.8-70.2) GyE was delivered at the isocenter in 8 (range, 4-26) fractions., Results: The median follow-up time was 17 months. The local control, overall survival and progression-free survival rates at 2 years were 79%, 54 and 27% respectively. PBRT-related toxicities were observed; six patients (13%) had grade 2 toxicity (including grade 2 radiation pneumonitis in 2) and six patients (13%) had grade 3 toxicity. Univariate analysis indicated that patients treated with a biologically equivalent dose of 10 (BED10) <110 GyE10, had a significantly higher local recurrence rate. Local control rates were relatively lower in the subsets of patients with the colorectum as the primary tumor site. No local progression was observed in metastases from colorectal cancer irradiated with a BED10 ≥ 110 GyE10. There was no difference in treatment results between proton and carbon ion therapy., Conclusions: PRBT is well tolerated and effective in the treatment of oligometastatic lung tumors. To further improve local control, high-dose PBRT with a BED10 ≥ 110 GyE10 may be promising. Further investigation of PBRT for lung oligometastases is warranted.

Background and Purpose: This retrospective study aimed to compare the clinical outcomes and late toxicities of proton therapy (PT) with those of carbon ion therapy (CIT) for stage I non-small cell lung cancer (NSCLC)., Material and Methods: A total of 111 patients who underwent particle therapy for stage I NSCLC between April 2003 and December 2009 were enrolled in this study. PT (n=70) and CIT (n=41) were delivered to total doses of 52.8-80 GyE in 4-26 fractions and 52.8-70.2 GyE in 4-26 fractions, respectively. The median follow-up time was 41 months., Results: Differences in outcome between the PT and CIT groups regarding 3-year overall survival (72% and 76%, respectively), progression-free survival (44% and 53%, respectively), and local control (81% and 78%, respectively) were not statistically significant. In multivariate analysis, the type of treatment beam did not correlate with overall survival. The severity of late toxicities was comparable between the two groups., Conclusions: Clinical results in the PT group were comparable to those in the CIT group. However, this study was a retrospective analysis of a highly heterogeneous population. Consequently, more homogeneous prospective data, large multicentric databases and, ideally, randomized trials are warranted., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: : Although many reports have shown the safety and efficacy of stereotactic body radiotherapy (SBRT) for T1N0M0 non-small-cell lung cancer (NSCLC), it is rather difficult to treat T2N0M0 NSCLC, especially T2b (>5 cm) tumor, with SBRT. Our hypothesis was that particle therapy might be superior to SBRT in T2 patients. We evaluated the clinical outcome of particle therapy for T2a/bN0M0 NSCLC staged according to the 7th edition of the International Union Against Cancer (UICC) tumor, node, metastasis classification., Methods: : From April 2003 to December 2009, 70 histologically confirmed patients were treated with proton (n = 43) or carbon-ion (n = 27) therapy according to institutional protocols. Forty-seven patients had a T2a tumor and 23 had a T2b tumor. The total dose and fraction (fr) number were 60 (Gray equivalent) GyE/10 fr in 20 patients, 52.8 GyE/4 fr in 16, 66 GyE/10 fr in 16, 80 GyE/20 fr in 14, and other in four patients, respectively. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, Version 4.0., Results: : The median follow-up period for living patients was 51 months (range, 24-103). For all 70 patients, the 4-year overall survival, local control, and progression-free survival rates were 58% (T2a, 53%; T2b, 67%), 75% (T2a, 70%; T2b, 84%), and 46% (T2a, 43%; T2b, 52%), respectively, with no significant differences between the two groups. The 4-year regional recurrence rate was 17%. Grade 3 pulmonary toxicity was observed in only two patients., Conclusion: : Particle therapy is well tolerated and effective for T2a/bN0M0 NSCLC. To further improve treatment outcome, adjuvant chemotherapy seems a reasonable option, whenever possible.

The purpose of this study is to assess predictive value of the positron emission tomography (PET) with 18F-fluoro-deoxyglucose (FDG) for recurrence and survival after radiotherapy (RT) for non-small cell lung cancer (NSCLC). One hundred forty-nine patients underwent pretreatment PET (n = 67) or PET/computed tomography (CT) (n = 82) and definitive RT for NSCLC. We evaluated the relationship between the maximum-pixel standardized uptake value (SUV(max)) and clinical tumor features. Univariate Cox proportional hazard analysis (UVA) was used to quantify the risk for local-regional recurrence, distant metastases, and death. Multivariate Cox proportional hazard analysis (MVA) was used to assess the potential independent effect of SUV(max). In the PET group, T1 tumors showed significantly lower SUV(max) than T2, T3, and T4 tumors; in the PET/CT group, T1 tumors showed significantly lower SUV(max) than T3 and T4 tumors. A high SUV(max )was a negative factor for local-regional control (LRC) (p < 0.001), distant metastasis-free survival (DMFS) (p = 0.02), and overall survival (OS) (p = 0.001) on UVA in the PET group. However, the significance decreased to 0.05 for LRC, 0.04 for DMFS, and 0.04 for OS by MVA when tumor size was included in the analysis. A high SUV(max) was not a negative factor for LRC, DMFS, or OS on UVA and MVA in the PET/CT group. In conclusion, assessment of predictive value of SUV(max) for NSCLC requires consideration of primary tumor size, and the evidence is not sufficient to suggest that FDG uptake in a primary NSCLC provides prognostic information.

Purpose: To investigate whether the bleomycin sensitivity assay, an in vitro peripheral blood lymphocyte assay, can predict outcome in patients with inoperable stage III non-small-cell lung cancer (NSCLC) treated with definitive radiotherapy and chemotherapy., Experimental Design: We identified 102 patients with inoperable stage III NSCLC cell lung cancer treated with definitive radiotherapy and chemotherapy. The patients' pretreatment peripheral blood lymphocyte cultures were treated with the radiomimetic mutagen bleomycin. An index of bleomycin sensitivity was determined by counting the number of chromatid breaks in 50 metaphases. The correlation between bleomycin sensitivity (expressed as mean breaks per cell) and clinical outcome was analyzed., Results: High bleomycin sensitivity (defined as a mean of >1.02 chromatid breaks/cell, representing the third quartile of bleomycin sensitivity) predicted poor disease-specific survival and overall survival. The 6-year disease-specific survival was 27% in patients with high bleomycin sensitivity compared with 46% in patients without such sensitivity (P = 0.0094). The association remained statistically significant when adjusted for smoking status, age, and radiation dose. The 6-year overall survival was 19% for patients with high bleomycin sensitivity and 29% for those without (P = 0.0193). There was a trend toward worse local regional control and worse disease-free survival among patients with high bleomycin sensitivity. There was no difference between the two groups in distant metastasis-free survival or radiation treatment-related complications., Conclusions: High bleomycin sensitivity correlated with poor overall survival and disease-specific survival in these patients with stage III NSCLC treated with radiotherapy and chemotherapy. Bleomycin sensitivity may function as a biomarker for poor clinical outcome for this group of patients.

Purpose: To determine whether the standardized uptake value (SUV) of [(18)F]fluorodeoxyglucose uptake by positron emission tomography could be a prognostic factor for non-small-cell lung cancer (NSCLC)., Patients and Methods: One hundred sixty-two patients with stage I to IIIb NSCLC were analyzed. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional control (LRC) were calculated by the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed by univariate and multivariate analyses., Results: There were 93 patients treated with surgery and 69 patients treated with radiotherapy. A cutoff of 5 for the SUV for the primary tumor showed the best discriminative value. The SUV for the primary tumor was a significant predictor of OS (P = .02) in both groups. Low SUVs ( 5.0; surgery group, P = .02; radiotherapy group, P = .0005). Low SUVs ( 5.0; stage I or II, P = .02; stage IIIa or IIIb, P = .004). However, using the same cutoff point of 5, the SUV for regional lymph nodes was not a significant indicator for DFS (P = .19), LRC (P = .97), or DMFS (P = .17). The multivariate analysis showed that the SUV for the primary tumor was a significant prognostic factor for OS (P = .03) and DFS (P = .001)., Conclusion: The SUV of the primary tumor was the strongest prognostic factor among the patients treated by curative surgery or radiotherapy.

A 50-year-old woman underwent surgical resection of a left adrenocortical carcinoma in April 2000. Bilateral pulmonary metastases and abdominal lymph node metastasis were detected in June 2001. After radiation therapy for the abdominal lymph node metastasis, a pulmonary metastatic lesion was thoracoscopically resected. The specimen was subjected to histoculture drug response assay (HDRA), and results revealed that this tumor was sensitive for cisplatin. We therefore performed concurrent chemoradiotherapy including cisplatin for the residual pulmonary metastatic lesion; a complete response was then obtained. Standard protocols of chemotherapy are often absent for malignant tumors, such as in this case, with low incidences. HDRA seems useful for chemotherapy agent selection in cases of rare malignant tumors.

A 67-year-old woman had undergone lobectomy and mediastinal lymphadenectomy on December 17, 1999, for lung adenocarcinoma. On June 29, 2001, the patient was readmitted because of acute deterioration of diabetic chronic renal failure due to cardiac dysfunction. Serum CEA level was high at 724 ng/ml. Chest X-ray and ultrasound suggested the presence of pericardial effusion, which was managed with pericardial drainage. Cytological examination revealed malignant cells (class V) in the effusion. Therefore, the patient was suffering from carcinomatous pericarditis. After the introduction of hemodialysis, the patient was treated with weekly paclitaxel therapy. Each cycle consisted of 3 weeks of therapy followed by a 1-week treatment break. Weekly paclitaxel therapy (11 infusions) brought about a normalization of the elevated CEA levels and a good control of the pericardial effusion. The patient has developed neither tumor progression nor reelevation of serum CEA levels for 12 month with no further therapy.

Unlabelled: We investigated whether the early postoperative time course of carcinoembryonic antigen (CEA) level after resection of lung cancer could be used to predict patients' prognosis. Fifty-three lung cancer patients were included in this study. Postoperative serum CEA levels were calculated by means of non-linear least-squares fitting to the equation C(t) = (C(0)-C(p))exp(-kt) + C(p), where C(t) is postoperative CEA level, t is days after surgery, C(0) is CEA level at postoperative time 0, C(p) is CEA level at plateau, and k is the rate constant of elimination. Postoperative CEA production (P(p)) was calculated as C(p) multiplied by k. C(p) and P(p) represent the numbers of residual tumor cells after surgery. More residual tumor cells yield higher values of C(p) and P(p), and result in earlier recurrence., Results: Kinetic parameters could be obtained for 30 patients whose preoperative CEA levels were sufficiently elevated. Cutoff levels as predictors for recurrence were 1.1 ng/ml for C(p) and 0.9 ng/ml/day for P(p). The accuracy of prediction of recurrence using these cutoff levels was 79% with C(p) and 89% with P(p). A very poor prognosis was observed for patients with P(p) over 0.9 ng/ml/day., Conclusion: Analysis of the time course of changes in CEA levels after resection of lung cancer appears to be useful for predicting patient prognosis. C(p) and P(p) are very precise predictors of recurrence.

A 70-year-old man who had worked in a stonepit for about fifty years was admitted to our hospital for detailed examination of the signs of pneumoconiosis (3/3, q) and a nodular shadow in the right upper lung field. Under a clinical diagnosis of lung cancer complicated with pneumoconiosis, right upper lobectomy with a right S6 resection was performed. Pathological examination revealed moderately differentiated adenocarcinoma of the right S2, well-differentiated adenocarcinoma of the right S6, and a squamous cell carcinoma of the right S1 which was not detected by chest CT. In addition to the difficulty of diagnosing lung cancer in a patient with severe pneumoconiosis, treatment for lung cancer may be limited by the poor pulmonary function that results from pneumoconiosis. Although the labor administration's decision that lung cancer patients with concomitant pneumoconiosis deserve compensation can be evaluated as a good one, the study of the relationship between pneumoconiosis and lung cancer needs further study through follow-up examination of pneumoconiosis cases.

To improve the response to chemotherapy for non-small cell lung cancer (NSCLC), effective drugs should be selected for each patient. In 1994 we introduced histoculture drug response assay (HDRA) for NSCLC patients. For clinical N2 patients, biopsy of mediastinal lymph node is performed both for histological diagnosis and for HDRA. Induction concurrent chemoradiotherapy is then performed using HDRA positive chemotherapy agents. We have treated three patients with this strategy. HDRA could be performed using mediastinal lymph node biopsy specimens. Tumor reduction rates of these patients were 80.4%, 85.3%, and 57.1%. Their histological responses were Ef.3, Ef.2, and Ef.1b, respectively. Complete resection was done in all patients. This strategy appeared to be useful in NSCLC patients with mediastinal lymph node metastasis.

We reviewed the records of 36 patients with medically inoperable stage I-II non-small cell lung carcinoma who were treated with radiotherapy. The median dose to the target was 60 Gy with conventional fractionation. Fifteen patients were treated without elective irradiation fields, while the remaining 21 were treated with extended fields including elective mediastinal regional lymph nodes. The overall survival rates at three and five years were 32.3% and 18.8%, the cause-specific survival rates were 40.9% and 27.3%, and the local control rates were 31.7% and 23.8%, respectively. In multivariate analysis the radiation dose had a marginally significant influence on the cause-specific survival, while tumor size had a significant influence on the local control rate. Only one patient had relapse in the regional mediastinal lymph nodes as the only site of metastasis. We conclude that the dose used in the present study is inadequate and recommend that further efforts be made to improve local control by dose escalation within a small target volume.

We treated inoperable or recurrent non-small cell lung cancer (NSCLC) patients with weekly outpatient administration of gemcitabine. The aim of this therapy was to improve or to maintain the patients' performance status. From November 1999 to December 2001, 15 NSCLC patients were treated with gemcitabine. The patients were 12 males and 3 females, 14 with adenocarcinoma and 1 with squamous cell carcinoma, aged 57 to 81 years old. A dose of 1,000 mg/m2 of gemcitabine was administered on days 1 and 8 every 3 weeks. Patients were treated for 1 to 17 (median 3) months. Performance status was maintained in 12 of 15 patients during this treatment. Average tumor marker doubling time was 289 days. Median survival time was 8.1 months. Weekly administration of gemcitabine in an outpatient setting is a useful treatment for inoperable or recurrent non-small cell lung cancer.

Purpose: Local recurrence of lung cancer after previous external beam irradiation poses some problems for subsequent management. We retrospectively reviewed our series of patients with local recurrence of lung cancer to evaluate the efficacy and safety of reirradiation., Patients and Methods: Between 1979 and 2000, 34 patients with local recurrence of lung cancer were retreated with external radiation. There were 29 males and 5 females ranging in age from 38 to 85 years (median: 69 years). At the time of reirradiation, the clinical stage was I or II in 2 patients, IIIa in 5 patients, IIIb in 14 patients, and IV in 13 patients. Reirradiation was performed in 18 patients with the aim of achieving a cure or prolongation of survival (radical treatment), while 16 patients were treated for improvement of their symptoms (symptomatic treatment)., Results: The median interval between the initial radiation therapy and reirradiation was 23 months, with a range of 5 to 87 months. The dose of initial irradiation delivered to the tumor ranged from 30 to 80 Gy (median: 60 Gy) in 1.5--2.0-Gy fractions per day. During reirradiation, it ranged from 10 to 70 Gy (median: 50 Gy) in 1.8--3.0-Gy fractions per day. The cumulative dose delivered to the tumor by treatments of both initial and second irradiation ranged from 56.5 to 150 Gy (median: 110 Gy). A response was observed in 14 out of 18 patients given radical treatment (complete response, 6; partial response, 8). Twelve of the 16 patients (75%) given symptomatic treatment also showed a symptomatic benefit. The overall survival rate after reirradiation was 43% at 1 year and 27% at 2 years, with a median survival time of 8 months. The median survival time after radical treatment was 15 months, with a range of 3 to 58 months, whereas that after symptomatic treatment was 3 months, with a range of 1 to 14 months. Six long-term survivors lived for more than 20 months. Reirradiation-induced toxicity included symptomatic radiation pneumonitis in 19 patients and symptomatic radiation esophagitis in 6 patients. These toxicities were not fatal, and radiation myelopathy was not caused by reirradiation., Conclusion: Based on this study, external beam reirradiation can achieve satisfactory results for local recurrence of lung cancer provided that attention is paid to the possible hazards.

To investigate optimal thoracic irradiation (TI) for stage IV lung cancer, we retrospectively reviewed 150 patients. In all, 101 patients underwent radiotherapy for the primary lesion, and 130 had radiotherapy for metastasized sites. TI fields were basically divided into two groups; whole thoracic lesion irradiation (WTLI) and partial thoracic lesion irradiation (PTLI). Overall survival rates at 6 months, 1 year and 2 years were 58%, 27% and 11%, respectively, and MST was 7.1 months. There was no difference in survival according to histological type. On univariate analysis, the factors of good prognosis included good PS, free of bone metastasis, metastasis limited to a single organ, TI, chemotherapy, age (less than or equal to 75 years), and TN factors (T0-2 and N0-1). Multivariate analysis showed PS was the predominant factor. Among the patients treated with TI, survival rates of patients with PS 0-1 were superior to those of patients with PS 2-4. Radiation pneumonitis was more frequent in WTLI than in PTLI. The rates of thoracic failure death were 31.7% in patients treated with TI and 63.3% without TI. However, the size of the thoracic radiation field did not affect the rates of thoracic failure death. We concluded that TI for stage IV patients could reduce thoracic symptoms and increase the survival rate in the subgroup with good PS. Furthermore, we considered PTLI was worth while in the subgroup with poor PS.

We reviewed patients with intrathoracic recurrence of non-small cell lung cancer after surgery, with reference to the feasibility of radiotherapy. The series consisted of 46 patients (39 males and 7 females) treated by radiotherapy from 1982 to 1995. Histology included squamous cell carcinoma (28 patients), adenocarcinoma (17), and large cell carcinoma (1). Clinical stage by UICC classification (1987) was as follows: stage I(2 patients), stage II(1), stage IIIa(13), stage IIIb(23), and stage IV(7). Recurrences were noted in bronchial stump (18 patients) and surgical scar (4). Metastases occurred in hilar-mediastinal lymphnodes (15), lung fields (7), and pleuropericardium (2). The mean interval from surgery to recurrence was 27 months. Delivered dose ranged from 45 to 80 Gy, and 19 patients received combined chemotherapy. Therapeutic results were as follows: complete response in 16 patients, partial response in 27, no response in 12 and progressive disease in 1, Overall 2- and 5-year survival rates were 17% and 11%, respectively, and 10 months in MST. On univariate analysis, significant prognostic factors were sex, stage at recurrence, recurrence pattern, performance status and initial response to radiotherapy, while multivariate analysis showed sex and initial response. From these data, we are encouraged by effective radiotherapy for postoperative intrathoracic recurrence of non-small cell lung cancer, especially in patients with stump or lymphnode recurrence.