After publication of the PACIFIC trial results,immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer(NSCLC).The PACIFIC trial demonstrat...After publication of the PACIFIC trial results,immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer(NSCLC).The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III NSCLC.This is the first treatment in decades to successfully improve survival in this clinical setting,with manageable toxicity and without deterioration in quality of life.The integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary,coordinated decision-making among lung cancer specialists,bringing new challenges and controversies as well as important changes in clinical work routines.The aim of the present article is to review—from a practical,multidisciplinary perspective—the findings and implications of the PACIFIC trial.We evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 determination.In addition,we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical practice.Finally,we discuss unresolved questions and future challenges.In short,the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.展开更多
BACKGROUND Neoadjuvant treatment(NT)with chemotherapy(Ch)is a standard option for resectable stage III(N2)NSCLC.Several studies have suggested benefits with the addition of radiotherapy(RT)to NT Ch.The International A...BACKGROUND Neoadjuvant treatment(NT)with chemotherapy(Ch)is a standard option for resectable stage III(N2)NSCLC.Several studies have suggested benefits with the addition of radiotherapy(RT)to NT Ch.The International Association for the Study of Lung Cancer(IASLC)published recommendations for the pathological response(PHR)of NSCLC resection specimens after NT.AIM To contribute to the IASLC recommendations showing our results of PHR to NT Ch vs NT chemoradiotherapy(ChRT).METHODS We analyzed 67 consecutive patients with resectable stage III NSCLC with positive mediastinal nodes treated with surgery after NT Ch or NT ChRT between 2013 and 2020.After NT,all patients were evaluated for radiological response(RR)according to Response Evaluation Criteria in Solid Tumours criteria and evaluated for surgery by a specialized group of thoracic surgeons.All histological samples were examined by the same two pathologists.PHR was evaluated by the percentage of viable cells in the tumor and the resected lymph nodes.RESULTS Forty patients underwent NT ChRT and 27 NT Ch.Fifty-six(83.6%)patients underwent surgery(35 ChRT and 21 Ch).The median time from ChRT to surgery was 6 wk(3-19)and 8 wk(3-21)for Ch patients.We observed significant differences in RR,with disease progression in 2.5%and 14.8%of patients with ChRT and Ch,respectively,and partial response in 62.5%ChRT vs 29.6%Ch(P=0.025).In PHR we observed≤10%viable cells in the tumor in 19(54.4%)and 2 cases(9.5%),and in the resected lymph nodes(RLN)30(85.7%)and 7(33.3%)in ChRT and Ch,respectively(P=0.001).Downstaging was greater in the ChRT compared to the Ch group(80%vs 33.3%;P=0.002).In the univariate analysis,NT ChRT had a significant impact on partial RR[odds ratio(OR)12.5;95%confidence interval(CI):1.21-128.61;P=0.034],a decreased risk of persistence of cancer cells in the tumor and RLN and an 87.5%increased probability for achieving downstaging(OR 8;95%CI:2.34-27.32;P=0.001).CONCLUSION We found significant benefits in RR and PHR by adding RT to Ch as NT.A longer follow-up is necessary to assess the impact on clinical outcomes.展开更多
Background:?Ovarian cancer (OC) is the most lethal gynecologic malignancy. About 70% of ovarian cancer patients have advanced disease and often not totally resectable. Previous studies of neoadjuvant chemotherapy (NAC...Background:?Ovarian cancer (OC) is the most lethal gynecologic malignancy. About 70% of ovarian cancer patients have advanced disease and often not totally resectable. Previous studies of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) versus primary debulking surgery (PDS) give inconsistent results. The aim of this retrospective study is to evaluate the outcome of the neoadjuvant chemotherapy followed by IDS versus PDS followed by adjuvant chemotherapy for the International Federation of Gynecology and Obstetrics (FIGO) stage III epithelial ovarian cancer.?Methods:?This study was performed on eligible patients with ovarian cancer admitted in Surgical Oncology and Medical Oncology departments at South Egypt Cancer Institute-Assiut University in the period from January 2010 to December 2015. Patients were divided into two groups, the first group included those who have NACT and underwent IDS plus adjuvant chemotherapy, and the second group included those who underwent PDS followed by adjuvant chemotherapy.?Results:?This study included 380 cases. One hundred and fifty-four patients (40.53%) had IDS. The remaining two hundred and twenty-six patients (59.47%) underwent PDS. In this study, treatment modality was significant for both disease-free survival (DFS) and overall survival (OS). DFS was significantly reduced after IDS when compared to PDS (median DFS: 33.00 months vs. 45.00 months, respectively;p??0.001). Also, OS was significantly reduced after IDS when compared to PDS. (Median OS: 43 months vs. 46 months, respectively;p = 0.047). Moreover, this drop of the survivals mainly occurred in specific subgroups such as the elderly patients, patients with bad performance status, suboptimal cytoreduction, as well as high-grade tumors. Conclusion:?This study showed that PDS resulted in a better disease-free survival and overall survival than IDS. Moreover, OS and DFS have significantly dropped in specific patients’ subgroups. Therefore, patients selection should be considered.展开更多
Background: We retrospectively identified prognostic factors in patients with Stage III colon cancer and considered the effectiveness of postoperative adjuvant chemotherapy based on these prognostic factors. Methods: ...Background: We retrospectively identified prognostic factors in patients with Stage III colon cancer and considered the effectiveness of postoperative adjuvant chemotherapy based on these prognostic factors. Methods: Two hundred and thirty four patients with lymph node metastases who underwent curative surgery for colon cancer between 1999 and 2005 were enrolled in the present study. Firstly, clinicopathological factors and survival data, were analyzed to determine prognostic factors related to cancer-specific survival. Secondly, we examined the effectiveness of postoperative adjuvant chemotherapy based upon these prognostic factors. Results: The multivariate analysis revealed that differentiation (P = 0.03, Hazard ratio = 2.50), lymphatic invasion (P = 0.02, Hazard ratio = 3.23) and the TNM classification, 7th?edition (P = 0.04, Hazard ratio = 1.94) were found to be significant independent prognostic factors. Among the patients classified as TNM IIIA, the recurrence-free survival rates were extremely good. Among the patients classified as IIIB and IIIC, there was no significant difference between the patients with and without postoperative adjuvant chemotherapy. Conclusion: The present study suggests that the patients with Stage IIIA colon cancer may not require postoperative adjuvant chemotherapy. The addition of oxaliplatin to 5-FU should be considered for the patients with Stage IIIB and IIIC colon cancer, for whom the prognoses are far from satisfactory.展开更多
文摘After publication of the PACIFIC trial results,immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer(NSCLC).The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III NSCLC.This is the first treatment in decades to successfully improve survival in this clinical setting,with manageable toxicity and without deterioration in quality of life.The integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary,coordinated decision-making among lung cancer specialists,bringing new challenges and controversies as well as important changes in clinical work routines.The aim of the present article is to review—from a practical,multidisciplinary perspective—the findings and implications of the PACIFIC trial.We evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 determination.In addition,we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical practice.Finally,we discuss unresolved questions and future challenges.In short,the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.
文摘BACKGROUND Neoadjuvant treatment(NT)with chemotherapy(Ch)is a standard option for resectable stage III(N2)NSCLC.Several studies have suggested benefits with the addition of radiotherapy(RT)to NT Ch.The International Association for the Study of Lung Cancer(IASLC)published recommendations for the pathological response(PHR)of NSCLC resection specimens after NT.AIM To contribute to the IASLC recommendations showing our results of PHR to NT Ch vs NT chemoradiotherapy(ChRT).METHODS We analyzed 67 consecutive patients with resectable stage III NSCLC with positive mediastinal nodes treated with surgery after NT Ch or NT ChRT between 2013 and 2020.After NT,all patients were evaluated for radiological response(RR)according to Response Evaluation Criteria in Solid Tumours criteria and evaluated for surgery by a specialized group of thoracic surgeons.All histological samples were examined by the same two pathologists.PHR was evaluated by the percentage of viable cells in the tumor and the resected lymph nodes.RESULTS Forty patients underwent NT ChRT and 27 NT Ch.Fifty-six(83.6%)patients underwent surgery(35 ChRT and 21 Ch).The median time from ChRT to surgery was 6 wk(3-19)and 8 wk(3-21)for Ch patients.We observed significant differences in RR,with disease progression in 2.5%and 14.8%of patients with ChRT and Ch,respectively,and partial response in 62.5%ChRT vs 29.6%Ch(P=0.025).In PHR we observed≤10%viable cells in the tumor in 19(54.4%)and 2 cases(9.5%),and in the resected lymph nodes(RLN)30(85.7%)and 7(33.3%)in ChRT and Ch,respectively(P=0.001).Downstaging was greater in the ChRT compared to the Ch group(80%vs 33.3%;P=0.002).In the univariate analysis,NT ChRT had a significant impact on partial RR[odds ratio(OR)12.5;95%confidence interval(CI):1.21-128.61;P=0.034],a decreased risk of persistence of cancer cells in the tumor and RLN and an 87.5%increased probability for achieving downstaging(OR 8;95%CI:2.34-27.32;P=0.001).CONCLUSION We found significant benefits in RR and PHR by adding RT to Ch as NT.A longer follow-up is necessary to assess the impact on clinical outcomes.
文摘Background:?Ovarian cancer (OC) is the most lethal gynecologic malignancy. About 70% of ovarian cancer patients have advanced disease and often not totally resectable. Previous studies of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) versus primary debulking surgery (PDS) give inconsistent results. The aim of this retrospective study is to evaluate the outcome of the neoadjuvant chemotherapy followed by IDS versus PDS followed by adjuvant chemotherapy for the International Federation of Gynecology and Obstetrics (FIGO) stage III epithelial ovarian cancer.?Methods:?This study was performed on eligible patients with ovarian cancer admitted in Surgical Oncology and Medical Oncology departments at South Egypt Cancer Institute-Assiut University in the period from January 2010 to December 2015. Patients were divided into two groups, the first group included those who have NACT and underwent IDS plus adjuvant chemotherapy, and the second group included those who underwent PDS followed by adjuvant chemotherapy.?Results:?This study included 380 cases. One hundred and fifty-four patients (40.53%) had IDS. The remaining two hundred and twenty-six patients (59.47%) underwent PDS. In this study, treatment modality was significant for both disease-free survival (DFS) and overall survival (OS). DFS was significantly reduced after IDS when compared to PDS (median DFS: 33.00 months vs. 45.00 months, respectively;p??0.001). Also, OS was significantly reduced after IDS when compared to PDS. (Median OS: 43 months vs. 46 months, respectively;p = 0.047). Moreover, this drop of the survivals mainly occurred in specific subgroups such as the elderly patients, patients with bad performance status, suboptimal cytoreduction, as well as high-grade tumors. Conclusion:?This study showed that PDS resulted in a better disease-free survival and overall survival than IDS. Moreover, OS and DFS have significantly dropped in specific patients’ subgroups. Therefore, patients selection should be considered.
文摘Background: We retrospectively identified prognostic factors in patients with Stage III colon cancer and considered the effectiveness of postoperative adjuvant chemotherapy based on these prognostic factors. Methods: Two hundred and thirty four patients with lymph node metastases who underwent curative surgery for colon cancer between 1999 and 2005 were enrolled in the present study. Firstly, clinicopathological factors and survival data, were analyzed to determine prognostic factors related to cancer-specific survival. Secondly, we examined the effectiveness of postoperative adjuvant chemotherapy based upon these prognostic factors. Results: The multivariate analysis revealed that differentiation (P = 0.03, Hazard ratio = 2.50), lymphatic invasion (P = 0.02, Hazard ratio = 3.23) and the TNM classification, 7th?edition (P = 0.04, Hazard ratio = 1.94) were found to be significant independent prognostic factors. Among the patients classified as TNM IIIA, the recurrence-free survival rates were extremely good. Among the patients classified as IIIB and IIIC, there was no significant difference between the patients with and without postoperative adjuvant chemotherapy. Conclusion: The present study suggests that the patients with Stage IIIA colon cancer may not require postoperative adjuvant chemotherapy. The addition of oxaliplatin to 5-FU should be considered for the patients with Stage IIIB and IIIC colon cancer, for whom the prognoses are far from satisfactory.