Preoperative Concurrent Chemoradiotherapy for Locally Advanced Rectal Cancer: Treatment Outcomes and Analysis of Prognostic Factors

공문규,홍성언,최우석,김시영,최진현 대한암학회 2012 Cancer Research and Treatment Vol.44 No.2

Purpose This study was designed to investigate the long-term oncologic outcomes for locally advanced rectal cancer patients after treatment with preoperative concurrent chemoradiotherapy followed by total mesorectal excision, and to identify prognostic factors that affect survival and pathologic response. Materials and Methods From June 1996 to June 2009, 135 patients with locally advanced rectal cancer were treated with preoperative concurrent chemoradiotherapy followed by total mesorectal excision at Kyung Hee University Hospital. Patient data was retrospectively collected and analyzed in order to determine the treatment outcomes and identify prognostic factors for survival. Results The median follow-up time was 50 months (range, 4.5 to 157.8 months). After preoperative chemoradiotherapy, sphincter preservation surgery was accomplished in 67.4% of whole patients. A complete pathologic response was achieved in 16% of patients. The estimated 5- and 8-year overall survival, loco-regional recurrence-free survival, and distant metastasis-free survival rate for all patients was 82.7% and 75.7%, 76.8% and 71.9%, 67.9% and 63.3%, respectively. The estimated 5- and 8-year overall survival, loco-regional recurrence-free survival, and distant metastasis-free survival rate for pathologic complete responders was 100% and 100%, 100% and 88.9%,95.5% and 95.5%, respectively. In the multivariate analysis, pathologic complete response was significantly associated with overall survival. The predictive factor for pathologic complete response was pretreatment clinical stage. Conclusion Preoperative chemoradiotherapy for locally advanced rectal cancer resulted in a high rate of overall survival, sphincter preservation, down-staging, and pathologic complete response. The patients achieving pathologic complete response had very favorable outcomes. Pathologic complete response was a significant prognostic factor for overall survival and the significant predictive factor for a pathologic complete response was pretreatment clinical stage.

Response Assessment with MRI after Chemoradiotherapy in Rectal Cancer: Current Evidences

서니은,김한솔,Min Soo Cho,임준석 대한영상의학회 2019 Korean Journal of Radiology Vol.20 No.7

Baseline magnetic resonance imaging (MRI) has become the primary staging modality for surgical plans and stratification of patient populations for more efficient neoadjuvant treatment. Patients who exhibit a complete response to chemoradiotherapy (CRT) may achieve excellent local tumor control and better quality of life with organ-preserving treatments such as local excision or even watch-and-wait management. Therefore, the evaluation of tumor response is a key factor for determining the appropriate treatment following CRT. Although post-CRT MRI is generally accepted as the first-choice method for evaluating treatment response after CRT, its application in the clinical decision process is not fully validated. In this review, we will discuss various oncologic treatment options from radical surgical technique to organ-preservation strategies for achieving better cancer control and improved quality of life following CRT. In addition, the current status of post-CRT MRI in restaging rectal cancer as well as the main imaging features that should be evaluated for treatment planning will also be described for the tailored treatment.

Impact of Immunohistochemistry-Based Molecular Subtype on Chemosensitivity and Survival in Patients with Breast Cancer Following Neoadjuvant Chemotherapy

유창훈,안진희,정경해,김성배,김학희,신희정,안세현,손병호,공경엽 한국유방암학회 2012 Journal of breast cancer Vol.15 No.2

Purpose: Pathologic complete response (pCR) has been suggested as a surrogate prognostic indicator in breast cancer patients treated with neoadjuvant chemotherapy. We assessed whether the likelihood of pCR and survival is associated with the immunohistochemistry-based molecular subtypes. Methods: We retrospectively analyzed the records of 276 patients with breast cancer who received neoadjuvant chemotherapy between January 2000 and January 2010. Patients were classified into four molecular subtypes based on the immunohistochemistry profiles of estrogen receptor, progesterone receptor, and HER2/neu. Logistic regression was used to analyze variables associated with pCR. Results: The pCR was achieved in 45 patients (16.3%). The triple negative subtype was an independent predictive factor for pCR (odds ratio, 3.21; 95% confidence interval, 1.20-8.56;p=0.020), and the ERBB-2 subtype showed a trend for higher pCR rates (odds ratio, 3.03; 95% confidence interval, 0.93-9.89; p=0.067) compared with the luminal A subtype. In 99 patients with HER2/neu-positive breast cancer, pCR rates were higher in those who received trastuzumab (31.7%) than those treated with conventional chemotherapy regimens (17.2%, p=0.023). The pCR was significantly associated with prolonged progressionfree survival (p=0.008). The triple negative subgroup had shorter progression-free survival (p=0.001) and overall survival (p=0.001) than the other subgroups. Conclusion: We demonstrated that the triple negative and ERBB-2 subtypes are more likely to obtain pCR when neoadjuvant chemotherapy is given, compared to the luminal A subtype. Despite the high pCR rate, the triple negative subtype showed worse survival outcomes, paradoxically, primarily due to patients who had residual disease.

Evaluation of Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Experience in a Single Institution over a 10-Year Period

최미선,조은윤,박연희,안진석,임영혁,남석진,조수연 대한병리학회 2017 Journal of Pathology and Translational Medicine Vol.51 No.1

Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with favorable clinical outcome in breast cancer patients. However, the possibility that the prognostic significance of pCR differs among various definitions has not been established. Methods: We retrospectively evaluated the pathologic response after NAC in 353 breast cancer patients and compared the prognoses after applying the following different definitions of pCR: ypT0/is, ypT0, ypT0/is ypN0, and ypT0 ypN0. Results: pCR was significantly associated with improved distant disease-free survival (DDFS) regardless of the definition (ypT0/is, p = .002; ypT0, p = .008; ypT0/is ypN0, p < .001; ypT0 ypN0, p = .003). Presence of tumor deposits of any size in the lymph nodes (LNs; ypN ≥ 0(i+)) was associated with worse DDFS (ypT0 ypN0 vs ypT0 ypN ≥ 0(i+), p = .036 and ypT0/is ypN0 vs ypT0/is ypN ≥ 0(i+), p = .015), and presence of isolated tumor cells was associated with decreased overall survival (OS; ypT0/is ypN0 vs ypT0/is ypN0(i+), p = .013). Residual ductal carcinoma in situ regardless of LN status showed no significant difference in DDFS or OS (DDFS: ypT0 vs ypTis, p = .373 and ypT0 ypN0 vs ypTis ypN0, p = .462; OS: ypT0 vs ypTis, p = .441 and ypT0 ypN0 vs ypTis ypN0, p = .758). In subsequent analysis using ypT0/is ypN0, pCR was associated with improved DDFS and OS in triple-negative tumors (p < .001 and p = .003, respectively). Conclusions: Based on our study results, the prognosis and rate of pCR differ according to the definition of pCR and ypT0/is ypN0 might be considered a more preferable definition of pCR.

Oncologic Outcomes in Patients Who Undergo Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision for Locally Advanced Rectal Cancer: A 14-Year Experience in a Single Institution

김민정,정승용,박지원,유승범,조상식,이기영,박규주 대한대장항문학회 2019 Annals of Coloproctolgy Vol.35 No.2

Purpose: This study evaluated the oncologic outcomes of locally advanced rectal cancer patients who underwent preoperative neoadjuvant chemoradiotherapy (CRT) followed by surgery and determined the prognostic significance of pathologic complete response (pCR). Methods: Between January 2002 and December 2015, 580 patients with rectal cancer who underwent surgery after neoadjuvant CRT were identified. Survival according to tumor response to CRT and pathologic stage was analyzed using the Kaplan-Meier method, and the Cox proportional hazard model was used to identify factors associated with survival outcomes. Results: A total of 111 patients (23.7%) achieved pCR while the other 469 patients showed residual disease. Patients with pCR had a lower pretreatment carcinoembryonic antigen level and earlier cT classification than those with residual disease. With a median follow-up of 78 months, disease-free survival (DFS) and overall survival (OS) were significantly better in the pCR group than in the residual disease group. The 5-year DFS and 5-year OS for patients with ypStage 0, I, II, or III were 92.5%, 85.1%, 72.2%, 54.3% (P < 0.001) and 94.5%, 91.0%, 83.1%, 69.3%, respectively (P < 0.001). Pathologic AJCC stage after CRT was the most statistically significant independent predictor of OS (HR, 6.97 [95% confidence interval, 3.16–15.39] for stage III vs. stage 0) and DFS (HR, 7.30 [95% confidence interval, 3.63–14.67] for stage III vs. stage 0). Conclusion: Rectal cancer patients who achieved pCR showed improved survival compared to those with residual disease after preoperative CRT. Moreover, pCR was an independent indicator of OS and DFS, and pathologic AJCC stage was correlated with survival after preoperative CRT.

Androgen Receptor as a Predictive Marker for Pathologic Complete Response in Hormone Receptor‒Positive and HER-2‒Negative Breast Cancer with Neoadjuvant Chemotherapy

이은경,이동은,김현희,한재홍,이시연,강한성,이은숙,채희정,심성훈,이근석,권영미,정소연 대한암학회 2023 Cancer Research and Treatment Vol.55 No.2

Purpose This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors. Materials and Methods We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR. Results Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR–) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2–) subtype. The rate of pCR was 31.4% (196/624). AR– patients had a significantly higher rate of pCR than AR+ patients (AR– 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR– tumor showed higher pCR rate in HR+/HER2– subtype (AR– 28.6% vs. AR+ 7.3%, p=0.022). Conclusion AR expression is predominant in the HR+/HER2– subtype. AR– is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2– subtype. When determining neoadjuvant chemotherapy for the HR+/HER2– subtype, AR expression can be considered as a pCR predictive marker.

Mean Platelet Volume as an Independent Predictive Marker for Pathologic Complete Response after Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer

Mutlu, Hasan,Eryilmaz, Melek Karakurt,Musri, Fatma Yalccn,Gunduz, Seyda,Salim, Derya Kivrak,Coskun, Hasan Senol Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

Background: The impact of mean platelet volume (MPV) on prognosis, diagnosis and response to therapy in cancer patients has been widely investigated. In the present study, we evaluated whether MPV at diagnosis has predictive value for pathologic complete response (pCR) after neoadjuvant chemotherapy in patients with locally advanced breast cancer (LABC). Materials and Methods: A total of 109 patients with LABC from Akdeniz University and Antalya Research and Training Hospital were evaluated retrospectively. Results: ROC curve analysis suggested that the optimum MPV cut-off point for LABC patients with pCR (+) was 8.15 (AUC:0.378, 95%CI [0.256-0.499], p=0.077). The patients with MPV <8.15 had higher pCR rates (29.2% vs. 13.1%, p=0.038). After binary logistic regression analysis, MPV and estrogen receptor absence were independent predictors for pCR. Conclusions: MPV has an independent predictive value for pCR after neoadjuvant chemotherapy in patients with LABC.

The Neutrophil to Lymphocyte Ratio has a High Negative Predictive Value for Pathologic Complete Response in Locally Advanced Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

Eryilmaz, Melek Karakurt,Mutlu, Hasan,Salim, Derya Kivrak,Musri, Fatma Yalcin,Tural, Deniz,Coskun, Hasan Senol Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.18

Background: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with pancreatic, colorectal, lung, gastric cancer and renal cell carcinoma. The aim of this study was to determine the relationship between pathological complete response (pCR) and pretreatment NLR values in locally advanced breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT). Materials and Methods: Datawere collected retrospectively from the Akdeniz University School of Medicine Database for locally advanced BC patients treated with NACT between January 2000-December 2013. Results: A total of 78 patients were analyzed. Sixteen (20%) patients achieved pCR. Estrogen receptor (ER) positivity was lower in pCR+ than pCR-cases (p=0.011). The median NLR values were similar in both arms. The optimum NLR cut-off point for BC patients with PCR+ was 2.33 (AUC:0.544, 95%CI [0.401-0.688], p=0.586) with sensitivity, specificity, positive predictive value and negative predictive value (NPV) of 50%, 51,6%, 21,1%, and 80%, respectively. Conclusions: This study showed no relationship between the pCR and pretreatment NLR values. Because of a considerable high NPV, in the patients with higher NLR who had luminal type BC in which pCR is lower after NACT, such treatment may not be recommended.

A Phase II Study of Preoperative Chemoradiotherapy with Capecitabine Plus Simvastatin in Patients with Locally Advanced Rectal Cancer

조현지,김승태,이지연,박세훈,박준오,박영석,임호영,유정일,박희철,최두호,박윤아,조용범,허정욱,윤성현,김희철,이우용,강원기 대한암학회 2023 Cancer Research and Treatment Vol.55 No.1

Purpose The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC).Materials and Methods Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity.Results Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin.Conclusion The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.

PIK3CA H1047R Mutation Associated with a Lower Pathological Complete Response Rate in Triple-Negative Breast Cancer Patients Treated with Anthracycline-Taxane–Based Neoadjuvant Chemotherapy

Sanxing Guo,Sibylle Loibl,Gunter von Minckwitz,Silvia Darb-Esfahani,Bianca Lederer,Carsten Denkert 대한암학회 2020 Cancer Research and Treatment Vol.52 No.3

Purpose PIK3CA, encoding for subunit p110a of phosphatidylinositol 3 kinase, is frequently mutated in breast cancer. PIK3CAmutation was predictive for pathological complete response (pCR) in human epidermal growth factor 2 positive breast cancer. This study explores the association of PIK3CA mutation and pCR in triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy. Materials and Methods A total of 92 patients with TNBC derived from a prospectively randomized phase II trial GeparSixto study (NCT01426880). Exon 9 and exon 20 of PIK3CA mutations were evaluated by using classical Sanger method with formalin-fixed paraffin-embedded tumor tissues. Results Seven of 90 tumors (7.8%) were detectable with a PIK3CA H1047R mutation. Overall, PIK3CA H1047R mutation was significantly associated with a lower pCR rate (14.3% vs. 56.6%; odds ratio, 0.128; 95% confidence interval [CI], 0.015 to 1.108; p=0.047). In carboplatin- containing treatment patients, H1047R mutation trended to predict a lower pCR rate (20% vs. 62.5%; p=0.146). In a multivariable analysis, H1047R mutation trended to predict a lower pCR rate (hazard ratio, 0.1; 95% CI, 0.01 to 1; p=0.056). Conclusion TNBC with a PIK3CA H1047R mutation was less likely to achieve pCR after anthracyclinebased neoadjuvant chemotherapy. Development of H1047R mutant selective inhibitors might be helpful to conquer this subtype of breast cancer.