Cancer Research and Treatment

Original Articles

EGFR Mutation Is Associated with Short Progression-Free Survival in Patients with Stage III Non-squamous Cell Lung Cancer Treated with Concurrent Chemoradiotherapy: Song Ee Park, Jae Myoung Noh, You Jin Kim, Han Sang Lee, Jang Ho Cho, Sung Won Lim, Yong Chan Ahn, Hongryull Pyo, Yoon-La Choi, Joungho Han, Jong-Mu Sun, Se Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2019;51(2):493-501. Published online June 18, 2018; DOI: https://doi.org/10.4143/crt.2018.125

Purpose
This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT).
Materials and Methods
From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status.
Results
Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression.
Conclusion
EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.

Citations

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S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial: Choong-kun Lee, Minkyu Jung, Hyo Song Kim, Inkyung Jung, Dong Bok Shin, Seok Yun Kang, Dae Young Zang, Ki Hyang Kim, Moon Hee Lee, Bong-Seog Kim, Kyung Hee Lee, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2019;51(1):1-11. Published online February 5, 2018; DOI: https://doi.org/10.4143/crt.2018.028

Abstract PDF Supplementary Material PubReader ePub

Purpose
We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients.
Materials and Methods
Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m² /day on days 1-14 plus docetaxel 35 mg/m² on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m² /day on days 1-14 plus cisplatin 60 mg/m² on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate.
Results
Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment.
Conclusion
Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

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Definitive Bimodality Concurrent Chemoradiotherapy in Patients with Inoperable N2-positive Stage IIIA Non-small Cell Lung Cancer: Jae Myoung Noh, Yong Chan Ahn, Hyebin Lee, Hongryull Pyo, BoKyong Kim, Dongryul Oh, Hyojung Park, Eonju Lee, Keunchil Park, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun; Cancer Res Treat. 2015;47(4):645-652. Published online February 12, 2015; DOI: https://doi.org/10.4143/crt.2014.144

Abstract PDF PubReader ePub

Purpose
This study was conducted to evaluate the treatment outcomes following definitive bimodality concurrent chemoradiotherapy (CCRT) in patients with inoperable N2-positive stage IIIA (N2- IIIA) non-small cell lung cancer (NSCLC). Materials and Methods From May 1997 to December 2012, 65 out of 633 patients with N2-IIIA NSCLC received bimodality therapy. The treatment modality was selected during/after neoadjuvant CCRT in 21 patients or primarily at diagnosis in 44 through a multidisciplinary consensus meeting. The median age was 65 years (range, 36 to 76 years). Sixty patients (92.3%) had clinically evident N2 disease, while 22 (33.8%) had multi-station N2 involvement. The median radiation therapy dose was 66 Gy in 33 fractions, while the dose was elevated to 72 Gy in 13 patients who had a treatment break due to delayed decision regarding resectability. The most frequent chemotherapy regimen was weekly paclitaxel or docetaxel plus cisplatin or carboplatin (54, 83.1%).
Results
During the median follow-up of 18.8 months (range, 1.6 to 173.1 months), 34 patients (52.3%) experienced disease progression, with distant metastasis being the most common first treatment failure pattern (23, 34.8%). The median and 2-year rates of progression-free survival were 18.8 months and 45.9%, respectively. The median and 2-year rates of overall survival were 28.6 months and 50.1%, respectively. Conclusion Definitive bimodality therapy in patients with N2-IIIA NSCLC demonstrated favorable outcomes, while trimodality therapy could be considered for candidates for less than pneumonectomy.

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Effect of Radiation Therapy Techniques on Outcome in N3-positive IIIB Non-small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy: Jae Myoung Noh, Jin Man Kim, Yong Chan Ahn, Hongryull Pyo, BoKyong Kim, Dongryul Oh, Sang Gyu Ju, Jin Sung Kim, Jung Suk Shin, Chae-Seon Hong, Hyojung Park, Eonju Lee; Cancer Res Treat. 2016;48(1):106-114. Published online February 12, 2015; DOI: https://doi.org/10.4143/crt.2014.131

Abstract PDF PubReader ePub

Purpose
This study was conducted to evaluate clinical outcomes following definitive concurrent chemoradiotherapy (CCRT) for patients with N3-positive stage IIIB (N3-IIIB) non-small cell lung cancer (NSCLC), with a focus on radiation therapy (RT) techniques. Materials and Methods From May 2010 to November 2012, 77 patients with N3-IIIB NSCLC received definitive CCRT (median, 66 Gy). RT techniques were selected individually based on estimated lung toxicity, with 3-dimensional conformal RT (3D-CRT) and intensity-modulated RT (IMRT) delivered to 48 (62.3%) and 29 (37.7%) patients, respectively. Weekly docetaxel/paclitaxel plus cisplatin (67, 87.0%) was the most common concurrent chemotherapy regimen.
Results
The median age and clinical target volume (CTV) were 60 years and 288.0 cm3, respectively. Patients receiving IMRT had greater disease extent in terms of supraclavicular lymph node (SCN) involvement and CTV ≥ 300 cm3. The median follow-up time was 21.7 months. Fortyfive patients (58.4%) experienced disease progression, most frequently distant metastasis (39, 50.6%). In-field locoregional control, progression-free survival (PFS), and overall survival (OS) rates at 2 years were 87.9%, 38.7%, and 75.2%, respectively. Although locoregional control was similar between RT techniques, patients receiving IMRT had worse PFS and OS, and SCN metastases from the lower lobe primary tumor and CTV ≥ 300 cm3were associated with worse OS. The incidence and severity of toxicities did not differ significantly between RT techniques. Conclusion IMRT could lead to similar locoregional control and toxicity, while encompassing a greater disease extent than 3D-CRT. The decision to apply IMRT should be made carefully after considering oncologic outcomes associated with greater disease extent and cost.

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Results of Radio-thermotherapy in Stage IIIb Uterine Cervical Cancer Local response, survival rate and analysis of prognostic factor: Chang Woo Moon; J Korean Cancer Assoc. 2000;32(4):714-723.

Abstract PDF: PURPOSE
This retrospective study was conducted to obtain local response and survival rates, and to analyze prognostic factors affecting survival of patients treated with radio-thermotherapy for stage IIIb uterine cervical cancer.
MATERIALS AND METHODS
From May 1992 to Dec. 1996, 24 patients treated with radio-thermo therapy for stage IIIb uterine cervical cancer at department of Radiation Oncology in Kosin Medical College, Kosin University were enrolled. Radiotherapy used 6~10 MV linear accelerator was performed in whole pelvis with 4 portals box technique by conventional (180~200 cGy/ fraction, 5 fraction/week) method in 5 patients (20.8%) or hyperfractionated (120~135 cGy/fr., 2 fr./day, 10 fr./wk) in 19 patients (79.2%). Total dose of A-point was 67~112 Gy (median: 77.27 Gy). Hyperthermia used 8 MHz radiofrequency capacitive heating device was applied in pelvic area with 2~3 sessions per wk. Each course started within 15 to 20 minutes after radio therapy and took 40 to 60 minutes. Local progression free (LPFS), disease free (DFS) and overall (OS) rates were calculated in survival analysis. Statistics was calculated by Kaplan-Meier Method in survival and Log-rank test in statistical significance. Multivariate analysis for prognostic factor was applied to Cox Regression model. Follow-up duration was 6~82 months (median: 25 months).
RESULTS
Overall local response rate was 95.8% (45.8% in CR/50.0% in PR). Five year LPFS, DFS, OS were 48.6%, 31.7%, 67.1%, respectively. In univariate analysis, an age was the signi ficant prognostic factor in terms of OS (p=0.03), but was insignificant in LPFS and DFS. In multivariate analysis, none of evaluated factors are important in LPFS, DFS or OS.
CONCLUSION
Radio-thermotherapy for stage IIIb uterine cervical cancer did not increase 5 year LPFS, DFS and OS in spite of higher local response rate. Age was the only significant factor for OS in univariate analysis.

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Concomitant Boost Radiotherapy for Stage 3 Non - Small Cell Lung Cancer: Kyung Hwan Shin, Charn Il Park, Young Soo Shim, Yung Jue Bang, Sung Koo Han; J Korean Cancer Assoc. 1998;30(6):1110-1118.

Abstract PDF: PURPOSE
This study was undertaken to evaluate the treatment outcome and side effects of accelerated radiotherapy (RT) using concomitant boost for stage III non-small cell lung cancer (NSCLC).
METHODS
Between April 1991 and December 1994, 102 patients with stage III NSCLC who had the favorable prognostic factors by CALGB criteria, were treated with concomitant boost radiotherapy. Patients were treated with standard large fields to 54 Gy in 6 weeks. The boost treatment was administered concomitantly during the last 2 weeks with a dose of 13 Gy in 10 fractions. The interfraction interval was at least 6 hours. The total tumor dose was 66-70 Gy, given over 6 weeks.
RESULTS
With 30 months median follow-up period for survivors, median survival was 15 months with 2 and 3-year overall survival rates of 34% and 19%, respectively. Thirty patients (29%) who had achieved complete remission after RT showed significantly better 2-year survival rates than those without complete remission (58% vs 22%, p 0.001). Local failure and distant metastases as the first or only failure occurred in 40 (44%) and 13 (14%), respectively, and ultimate local and distant failure rates were 45% and 29%, respectively. Although Grade IV esophageal complication of T-E fistula was observed in one patient, most patients with pulmonary complication showed mild, transient radiation pneumonitis.
CONCLUSION
This result suggests that the treatrnent of stage III NSCLC with concomitant boost RT may improve survival rates without enhanced radiation induced toxicity compared with conventional RT. Further investigation of dose escalation by conformal radiotherapy of combining chemotherapy and accelerated RT is warranted.

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Prognostic Value of p53 and Proliferating Cell Nuclear Antigen ( PCNA ) in Stage 3 Gastric Carcinoma: Hyung Tae Oh, Duk Su Lee, Dong Ho Han, Sang Young Kim, Byung Yi Ahn, Min Chul Kim, Myung Jin Joo, Kwang Min Lee, Woo Young Kim, Sung Hye Sin; J Korean Cancer Assoc. 1998;30(1):31-39.

Abstract PDF: PURPOSE
We evaluated the prognostic significance of p53 and proliferating cell nuclear antigen(PCNA) in stage III gastric carcinoma to determine the correlation between the p53 and PCNA expression and various clinicopathological parameters.
MATERIALS AND METHODS
The expression of p53 and PCNA were studied immunohistochemically in 64 cases of stage III gastric carcinomas with paraffin-embedded tissue specimens which were obtained surgically at the department of surgery, Presbyterian Medical Center from 1991 to 1992. Both expression were compared with known factors of prognosis. Survival rate and other clinicopathological parameters were analysed.
RESULTS
Expression rates of p53 and high PCNA group were 40.6% and 26.6%, respectively. There was no significant correlation between the p53 and PCNA expression and various clinicopathological variables such as age, sex, stage, histology, tumor depth, number of metastatic node, tumor size, site and method of operation. To analyse survival, we evaluated overall survival according to the extent of p53 and PCNA expression. No significant correlations between the p53 and PCNA expression and overall survival were found. CONCLUSION: These results suggest that the p53 and PCNA expression seems to be hard to use as a prognostic indicator in stage III gastric carcinoma.

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Prognostic Significance of c-erbB2 , c-fos , p53 , Proliferating Cell Nuclear Antigen ( PCNA ) and Epidermal Growth Factor ( EGF: Seung Do Lee, Sung Uhn Baek, Chung Han Lee, Bang Hur, Man Ha Huh; J Korean Cancer Assoc. 1995;27(4):527-535.

Abstract PDF: To evaluate the prognostic significance of c-erbB2, c-fos, p53, PCNA and EGF in stage III gastric carcinoma, frequency of their expression was examined by immunohistochemical method in 206 cases of stage III gastric carcinomas with paraffin-embedded tissue specimens which were obtained surgically at the department of surgery, Kosin Medical College from 1984 to 1988. Survival rate and other clinicopathological parameters were analysed. Expression rates of c-erbB2, c-fos, p53, PCNA and EGF were 46.1%, 43.7%, 62.1%, 65.0% and 35.9% respectively. Correlation of expression was found betweer. EGF and c-fos, EGF and c- erbB2, and c-erbB2 and c-fos respectively. c-erbB2 expression was more frequently observed in intestinal type, well or moderately differentiated carcinomas than diffuse type, poorly differentiated or mucinous types(p<0.05). Similarly EGF expression rate was high in intestinal type and low in mucinous or signet ring cell types(p<0.05). Five year survival rates of positive cases and negative cases were 27.4% and 23.9% in c-erbB2, 27.7% and 23.9% in c-fos, 24.0% and 27.8% in p53, 25.1% and 26.4% in PCNA and 20.5% and 28.9% in EGF respectively. There were no significant differences between positive cases and negative cases in survival rates. When the above factors and conventiona1 prognostic fectors such es tumor depth(t3, t4), lymph node invasion(n0, nl, n2), number of positive nodes(l-3, 4-6, 7- ), Laurens types, were en- tered simultaneously into the Cox regression model, number of positive nodes, and RGF expression emerged as independent prognostic factors(p=0.0004, p=0.043 respectively).

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