Purpose We aimed to evaluate the effectiveness of prophylactic cranial irradiation (PCI) for “early brain metastasis”, which occurs before extracranial recurrence (ECR), and “late brain metastasis”, which occurs after ECR, in limited-stage small cell lung cancer (LS-SCLC).
Materials and Methods We retrospectively analyzed 271 LS-SCLC patients who underwent definitive chemoradiation. All patients were initially staged with brain magnetic resonance imaging and positron emission tomography. Intracranial recurrence (ICR), ECR, progression-free rate (PFR), and overall survival (OS) were analyzed as clinical endpoints. The competing risk of the first recurrence with ICR (ICRfirst) was evaluated. Significantly associated variables in multivariate analysis of ECR were considered as ECR risk factors. Patients were stratified according to the number of ECR risk factors.
Results The application of PCI was associated with higher PFR (p=0.008) and OS (p=0.045). However, PCI was not associated with any of the clinical endpoints in multivariate analysis. The competing risk of ICRfirst was significantly decreased with the application of PCI (hazard ratio, 0.476; 95% confidence interval, 0.243 to 0.931; p=0.030). Stage III disease, sequential, and stable disease after thoracic radiation were selected as ECR risk factors. For patients without these risk factors, the application of PCI was significantly associated with increased OS (p=0.048) and a decreased risk of ICRfirst (p=0.026).
Conclusion PCI may play a role in preventing early brain metastasis rather than late brain metastasis after ECR, suggesting that only patients with a low risk of ECR may currently benefit from PCI.
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Purpose The role of epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) in the management of persistent subsolid nodules (SSNs) is unclear. This study aimed to investigate the impact of EGFR-TKIs on concurrent SSNs in patients with stage IV non–small cell lung cancer (NSCLC).
Materials and Methods Patients who received an EGFR-TKI for at least 1 month for stage IV NSCLC and had concurrent SSN(s) that had existed for at least 3 months on chest computed tomography were included in this retrospective study. Size change of each nodule before and after EGFR-TKI therapies were evaluated using a cutoff value of 2 mm; increase (≥ 2 mm), decrease (≤ –2 mm), and no change (–2 mm < size change < +2 mm).
Results A total of 77 SSNs, 51 pure ground-glass (66.2%) and 26 part-solid nodules (33.8%), were identified in 59 patients who received gefitinib (n=45) and erlotinib (n=14). Among 58 EGFR mutation analysis performed for primary lung cancer, 45 (77.6%) were EGFR mutant. The proportions of decrease group were 19.5% (15/77) on per-nodule basis and 25.4% (15/59) on per-patient basis. Four SSNs (5.2%) disappeared completely. On per-patient based multivariable analysis, EGFR exon 19 deletion positivity for primary lung cancer was associated with a decrease after initial EGFR-TKI therapy (adjusted odds ratio, 4.29; 95% confidence interval, 1.21 to 15.29; p=0.025).
Conclusion Approximately 20% of the concurrent SSNs decreased after the initial EGFR-TKI therapy. EGFR exon 19 deletion positivity for primary lung cancer was significantly associated with the size change of concurrent SSNs.
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Kwai Han Yoo, Su Jin Lee, Jinhyun Cho, Ki Hyeong Lee, Keon Uk Park, Ki Hwan Kim, Eun Kyung Cho, Yoon Hee Choi, Hye Ryun Kim, Hoon-Gu Kim, Heui June Ahn, Ha Yeon Lee, Hwan Jung Yun, Jin-Hyoung Kang, Jaeheon Jeong, Moon Young Choi, Sin-Ho Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(2):718-726. Published online September 3, 2018
Purpose
The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).
Materials and Methods
We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles.
Results
A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms.
Conclusion
The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.
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Erdheim-Chester disease is a rare non-Langerhans–cell histiocytosis with bone and organ involvement. A 76-year-old man presented with low back pain and a history of visits for exertional dyspnea. We diagnosed him with anemia of chronic disease, cytopenia related to chronic illness, chronic renal failure due to hypertension, and hypothyroidism. However, we could not determine a definite cause or explanation for the cytopenia. Multiple osteosclerotic axial skeleton lesions and axillary lymph node enlargement were detected by computed tomography. Bone marrow biopsy revealed histiocytic infiltration, which was CD68-positive and CD1a-negative. This report describes an unusual presentation of Erdheim-Chester disease involving the bone marrow, axial skeleton, and lymph nodes.
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Purpose Platinum-based doublet chemotherapy is the treatment of choice for patients with non-small cell lung cancer (NSCLC); however, the role of a platinum-based doublet as second-line therapy after failure of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for NSCLC patients has not yet been elucidated. The purpose of this study was to compare the clinical efficacy of pemetrexed versus a platinum-based doublet as second-line therapy after failure of EGFR TKI used as first-line therapy for NSCLC patients with EGFR mutations. Materials and Methods We designed a multicenter retrospective cohort study of 314 NSCLC patients with EGFR mutations who received an EGFR TKI as first-line palliative chemotherapy. Our analysis included 83 patients who failed EGFR TKI therapy and received second-line cytotoxic chemotherapy.
Results Forty-six patients were treated using a platinum-based doublet and 37 patients were treated using singlet pemetrexed. The overall response rates of patients receiving a platinum-based doublet and patients receiving pemetrexed were17.4% and 32.4%, respectively (p=0.111). The median progression-free survival (PFS) of patients receiving pemetrexed was significantly longer than that of patients receiving a platinum-based doublet (4.2 months vs. 2.7 months, respectively; p=0.008). The hazard ratio was 0.54 (95% confidence interval, 0.34 to 0.86; p=0.009). Conclusion Our retrospective analysis found that second-line pemetrexed singlet therapy provided significantly prolonged PFS compared to second-line platinum-based doublet chemotherapy for NSCLC patients with EGFRmutations who failed first-line EGFR TKI. Conduct of prospective studies for confirmation of our results is warranted.
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PURPOSE The dosimetric advantages of multiple non-coplanar stationary fields for stereotactic radiotherapy or adiosurgery (SRT/S) are well known. However, this technique is not widely used due to the logistical problems associated with producing and testing customized collimators. We report our experience of SRT/S using multiple non-coplanar stationary fields (conformal SRT/ S). MATERIALS AND METHODS: Between August 1997 and February 2002, we performed frameless SRT/S in 63 patients. We chose conformal SRT/S when the tumor was of a very irregular shape or larger than 4 cm. We obtained three pieces of information: 1) the couch translations required to bring the target point to the isocenter, 2) the distance between the stereotaxic markers in the CT study, and the distance between the markers determined from orthogonal beam films, taken in the anterior- posterior and lateral directions, and 3) the rotational movement of the head position between the CT study and actual treatment position. We evaluated two kinds of data: 1) the precision of the isocenter setup, and 2) the reproducibility of the head position in the a) translational and b) rotational components. RESULTS: Twenty-six of the 63 patients receiving stereotactic treatment received conformal SRT/S. The precision of the isocenter setup for the conformal SRT/S was x=-0.03+/-0.26 mm, y=0.19+/-0.25 mm and z=-0.20+/-0.27 mm. The reproducibilities of the head position with the conformal SRT/S were 0.5 mm and less than 1degrees C, for the translational and rotational components, in any plane. CONCLUSION: We were able to apply conformal stereotactic irradiation, which has a dosimetric advantage, to irregularly shaped intracranial tumors, with precision and reproducibility of head position for the isocenter setup nearly equivalent to that of frame-based SRS or multiple-arc SRT/S.
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Clinical results of stereotactic body frame based fractionated radiation therapy for primary or metastatic thoracic tumors Sang Min Yoon, Eun Kyung Choi, Sang-Wook Lee, Byong Yong Yi, Seung Do Ahn, Seong Soo Shin, Heon Joo Park, Su Ssan Kim, Jin-Hong Park, Si Yeol Song, Charn Il Park, Jong Hoon Kim Acta Oncologica.2006; 45(8): 1108. CrossRef
PURPOSE To evaluate the clinical impact of the altered expression of cell cycle regulators in stage I and II breast cancers. MATERIALS AND METHODS The interaction between cyclin D1/E and p27Kip1 expressions were analyzed using tissue microarray (TMA) technology in 133 breast cancers. Data from the immunohistochemical assays of 3 molecules were merged, and analyzed, with a Ki67 labeling index of the same tumors. RESULTS Cyclin D1 was expressed in 72 breast carcinomas (54.1%) and cyclin E in 60 (45.1%) out of the 133 breast carcinomas. Expressions of cyclin D1 and cyclin E were inversely related to each other, and significantly associated with the estrogen receptor (ER) expression and differentiation of the breast carcinoma. The expression of cyclin E was significantly decreased in tumors expressing cyclin D1 (p=0.022). There was a trend for cyclin D1 expression to increase in tumors expressing p27Kip1 (p=0.053), but the expression of cyclin E did not correlate with p27Kip1 expression. The Ki67 labeling index was markedly increased in tumors expressing cyclin E, whereas it was significantly decreased in the cyclin D1 or p27Kip1 expressing-tumors. From survival analysis, cyclin E expression was the only significant variable for the prediction of poor survival. CONCLUSION The abnormal expressions of cell cycle regulatory molecules are prevalent, and interrelated with each other in breast cancer. Integration of TMA technology allowed a high-throughput analysis for correlating molecular the in situ findings, with the clinico-pathologic information. Among the three molecules studied, the cyclin E had a prognostic implication for stage I and II breast cancer.
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PURPOSE To determine the clinical significance of p53, c-erbB-2, chromogranin A (CgA), proliferating cell nuclear antigen (PCNA) expression in ampullary carcinoma, a retrospective study was performed. MATERIALS AND METHODS The cases of 96 patients who underwent curative resection for ampullary carcinoma during the ten-year period (1986-95) were reviewed. And, using paraffin-embedded tumor tissues, immunohistochemical (IHC) staining for p53, c-erbB-2, CgA, and PCNA was performed. RESULTS The overall five-year survival rate (5-YSR) for these 96 patients was 58%. With regard to TNM stage, the 5-YSR was 71% for stage I (n=36), 62% for stage II (n=29), and 39% for stage III (n=31), respectively. IHC expression rate was 17.6% for c-erbB-2, 19.2% for CgA, and 42.9% for p53. The relative proportion of labelling index of PCNA (<25%, 25-50%, >50%) was 30.8%, 25.3%, and 44.0%, respectively. The PCNA labelling index showedsignificant correlation with tumor size (p=0.032). The PCNA labelling index, c-erbB-2, CgA and p53 were not correlated to extent of invasion, lymph node metastasis, stage, or histologic type. CgA and c-erbB-2 expression and the PCNA labelling index thus had no prognostic value. With regard to p53, the 5-YSR of p53 negative cases was 68.6%; that of p53 positive cases was 47%, with significant difference (p=0.038). CONCLUSION This result suggests that p53 expression is related to poor prognosis of ampullary carcinoma, and that c-erbB-2 and CgA expression, and the PCNA labelling index, are not significant prognostic factors.
PURPOSE This study aimed to evaluate the preliminary treatment results of fractionated stereotactic radiotherapy (FSRT) for metastatic brain tumors. MATERIALS AND METHODS Between August 1997 and December 1998, frameless FSRT was performed in 11 patients with metastatic brain tumor (1S lesions).
Primary sites were lung in 7 patients, breast in 2, stomach in 1, and malignant melanoma in 1, All patients received 30-36 Gy/10-20 fx external beam irradiation to whole brain.
Eight patients received FSRT for 1 lesion, one for 2 lesions, and two for 4 lesions.
Fractionation schedule was 25 Gy/5 fx in 11 lesions, 18 Gy(1 fx in 3, 30 Gy/5 fx in 2, 15 Gy/5 fx in 1. Mean tumor volume was 7.0 cc (0.39~55.23 cc). Multiple-arc FSRT was delivered to 16 lesions and conformal FSRT through irregular ports shaped to tumor profile to 2 lesions. RESULTS No patient experienced any acute side reaction from FSRT. Follow-up radiologic evaluation was available in 9 patients. Six of nine patients achieved the complete response, but two showed the partial response and one showed no response on follow-up radiologic studies.
Among six patients with complete response, 5 patients survived from 5 to 15 months and showed no evidence of metastatic brain d#isease clinically and/or radiologically at last follow-up. Among two patients who did not have radiologic evaluation, one showed clinically complete response until death and the other died just after FSRT caused by intercurrent disease. One patient with no response radiologically survived 7 months and showed nearly complete disappearance of clinical symptom with stable status radiologically, CONCLUSION: Initial experience in this study suggests that the external beam irradiation to whole brain with 30 Gy/10 fx followed by FSRT with 20~30 Gy/5~6 fx could be the good treatment option to the patients with metastatic brain tumor. This study suggests that the fractionation schedule for FSRT should be determined in consideration of performance status, number of metastasis, tumor volume, location, presence of extracranial disease, and age.
PURPOSE This study was attempted to evaluate the effect of adjuvant radiotherapy and chemotherapy after curative resection of extrahepatic bile duct cancer. MATERIALS AND METHODS The authors performed a retrospective analysis of 57 patients with extrahepatic bile duct cancer not involving the hepatic duct confluence and curatively resected at Seoul National University Hospital between 1990 and 1995. Resection margins of all cases were confirmed pathologically as free of cancer cells. Among 57 patients, 29 received adjuvant therapy. Total 4000 cGy of external beam radiation was delivered to each. 5-fluorouracil (5-FU) was administered as a radiosensitizer. After 4 weeks of radiation therapy, 5-FU maintenance chemotherapy was started and given every 4 weeks up to 12 cycles or until evidence of relapse. RESULTS The overall median survival of 57 patients was 24 months. I- and 2-year overall survival rate was 73.7 and 52.6%. There was no difference in overall survival rate between adjuvant therapy group (n=29) and operation-only group (n 28). We tried to evaluate the effect on survival of adjuvant therapy according to lymph node status. Patients of Tl stage were excluded from analysis. Adjuvant therapy had no survival benefit in the lymph node positive group. But in the lymph node negative group, 1- and 2-year survival rate of patients who underwent adjuvant therapy were 89.5% and 68.4% whereas 1 and 2-year survival rate of patients in operation-only group were 57.9% and 36.8%, which was statistically significant (p=0.0278, 0.0472). And by multivariate analysis, the survival improvement of 1- and 2-year survival rate in adjuvant therapy group was due to adjuvant therapy itself. CONCLUSION Our trial of external beam radiotherapy combined with 5-FU chemotherapy after curative resection of extrahepatic bile duct cancer did not show improved overall survival. However the 1- and 2-year survival rate of patients with negative lymph node and advanced T stage ( > T 1) were improved in adjuvant therapy group, so adjuvant therapy may give survival benefit to a certain patient group with negative lymph node.