Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death p...Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.展开更多
Background:Immune checkpoint inhibitors(ICIs)as the neoadjuvant therapy for resectable locally advanced esophageal carcinoma(rlaEC)remains challenging given the poor reports of efficacy and safety.This study aimed to ...Background:Immune checkpoint inhibitors(ICIs)as the neoadjuvant therapy for resectable locally advanced esophageal carcinoma(rlaEC)remains challenging given the poor reports of efficacy and safety.This study aimed to summarize reliable evidence for the preoperative neoadjuvant immunotherapy of rlaEc by analyzing all the published clinical trials on the ICIs as the neoadjuvant therapy for rlaEC.Methods:PubMed,Cochrane Library,Embase and ClinicalTrials.gov were searched from inception until June 1st,2023,for available reports to perform a meta-analysis.The primary endpoints were RO resection,objective response rate(ORR),pathological complete response(pCR)and major pathological response(MPR),as well as treatment-related adverse events(AEs)and postoperative complications.The Stata 14.0 software was employed to estimate pooled effect size.Results:A total of 18 single-arm clinical trials involving 625 patients met the inclusion criteria.Meta-analysis showed that,among these patients with rlaEC,the pooled R0 resection rate was 97.0%(95%CI:94.0%-99.0%),the p0oled ORR was 70.0%(95%CI:64.0%-76.0%),the p0oled pCR and MPR rate were 34.0%(95%CI:29.0%-39.0%)and 56.0%(95%CI:47.0%-65.0%)respectively.The incidence of main treatment-related AEs and postoperative complications was about 6%-45% and 8%-19% respectively.Conclusions:Patients with rlaEC were tolerated to neoadjuvant immunotherapy and it might be beneficial to improve efficacy.But this meta-analysis had limitations and the conclusions still needed to be validated by more rigorous phase II randomized controlled clinical trials.展开更多
AIM:To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma(NPC).METHODS:We reviewed data of 40 patients with locally advanced NPC treated with ind...AIM:To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma(NPC).METHODS:We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy(CCRT)(22/40 patients)or CCRT alone(18/40)from March 2006 to March 2012.Patients underwent fiberoscopy with biopsy of the primitive tumor,and computed tomography scan of head,neck,chest and abdomen with and without contrast.Cisplatin was used both as induction and as concomitant chemotherapy,while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions(total dose,70 Gy).The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly.This retrospective analysis was approved by the review boards of the participating institutions.Patients gave their consent to treatment and to anonymous analysis of clinical data.RESULTS:Thirty-three patients were males and 7 were females.Median follow-up time was 58 mo(range,1-92 mo).In the sub-group of twenty patients with a follow-up time longer than 36 mo,the 3-year survival and disease free survival rates were 85%and 75%,respectively.Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%.Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients.Grade 2 mucositis was seen in 29 patients,while grade 2 xerostomia was seen in 30 patients.Overall toxicity was manageable and it did not cause any significant treatment delay.In the whole sample population,long term toxicity included grade 2 xerostomia in 22 patients,grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients.CONCLUSION:Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC.The role of adjuvant chemotherapy remains to be defined.展开更多
Background: The prognosis of patients with Epidermal Growth Factor Receptor (EGFR) overexpression in inoperable Locally Advanced Squamous Cell Carcinoma of Head and Neck (LASCCHN) remains poor. Nimotuzumab is an Anti ...Background: The prognosis of patients with Epidermal Growth Factor Receptor (EGFR) overexpression in inoperable Locally Advanced Squamous Cell Carcinoma of Head and Neck (LASCCHN) remains poor. Nimotuzumab is an Anti EGFR humanized monoclonal antibody approved for treatment of LASCCHN, with concurrent chemoradiation. Objective: To assess the efficacy and safety of nimotuzumab with concurrent chemoradiation in inoperable LASCCHN patients. Methodology: This is a single-centre, single arm, retrospective study evaluating 35 patients with histologically confirmed inoperable LASCCHN (stages III-IV). The patients were administered IV cisplatin 50 mg/m2 and IV nimotuzumab 200 mg for 6 - 7 weeks, along with radiotherapy of 6600 - 7000 cGy over 35 fractions. Patients were evaluated over response evaluation criteria in solid tumors (RECIST) criteria 12 weeks after the last cycle of chemotherapy. They were also followed up for overall survival and relapse free survival. Results: The median duration of follow-up was 20 months. The most common site of cancer was oropharynx (68.6%). One patient was lost to follow up. Objective Response Rate (ORR) was observed in 97% of the patients with 17 patients (48.6%) achieving complete response (CR) and 17 patients (48.6%) achieving partial response (PR). The median overall survival was 22.7 months (95% CI: 21.30, 34.27). The median relapse free survival was 16.7 months (95% CI: 9.80, 24.50). Nimotuzumab was safe and well tolerated with few mild, self-limiting adverse events. Conclusion: Nimotuzumab with chemoradiation is a safe and efficacious option in patients with LASCCHN. Larger studies are needed to verify the same.展开更多
Background: Head and neck cancers (HNCs) constitute 5% of all cancers globally and are the most common cancers in India. Chemotherapy and radiotherapy have not been proved to be effective in advanced cases and the pro...Background: Head and neck cancers (HNCs) constitute 5% of all cancers globally and are the most common cancers in India. Chemotherapy and radiotherapy have not been proved to be effective in advanced cases and the prognosis remains dismal. This underscores the need for newer treatment options in these cases. Nimotuzumab, an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, was safer when combined with chemo- or radio-therapy. Aim: To evaluate the safety and efficacy of concurrently administered nimotuzumab with chemo-radiotherapy in patients with advanced inoperable squamous cell carcinomas of head and neck (LASCCHN). Methods:?This was an open-label, single arm study evaluating 57 patients with histologically confirmed inoperable LASCCHN (stages III and IV) and eastern co-operative oncology group (ECOG) performance status < 2. Informed consent was obtained from all patients. The patients were administered IV cisplatin 30 mg/m2?and IV nimotuzumab 200 mg weekly for 6 weeks, along with radiotherapy of 6600 cGy over 33 fractions. Patients were evaluated over response evaluation criteria in solid tumors (RECIST) criteria 24 weeks after the last cycle of chemotherapy. Results: Mean age of patient was 50 years old (29 - 79 years old). The most common site of cancer was oral cavity (56.1%). Forty six patients (80.7%) completed 6 cycles of therapy. Objective response rate (ORR) was 80.7%, with 34 patients (59.6%) achieving complete response (CR), and 12 (21%) achieving partial response (PR). Stable disease (SD) was noted in 8 (14%) patients and progressive disease in 3 (5.2%) patients. Conclusion: Addition of nimotuzumab is a safe and efficacious option in patients with inoperable LASCCHN. Our observations confirm the available Phase II data. The long term survival benefits based on this encouraging response rate need to be further evaluated in this subset of cancer patients.展开更多
AIM: To assess whether radiation dose and duration of treatment influence local control and survival of patients with locally advanced anal cancer treated with definitive chemoradiation. METHODS: Twenty-eight consecut...AIM: To assess whether radiation dose and duration of treatment influence local control and survival of patients with locally advanced anal cancer treated with definitive chemoradiation. METHODS: Twenty-eight consecutive patients who were treated with definitive radiation therapy for bulky anal cancers (> 5 cm in size) were reviewed. Nineteen patients had T3 lesions, 8 patients had T4 lesions, and 15 patients had lymph node involvement. The median tumor size was 7.5 cm. All but one patient received concurrent chemoradiation. The median radiation dose was 54 Gy. The median duration of treatment was 58 d. RESULTS: With a median follow-up of 2.5 years in all patients and 7.8 years in living patients, the 2-year local recurrence-free probability was 57% and overall survival rate was 67%. Neither radiation dose nor duration of treatment alone was predictive of either time to local failure or overall survival. However, longer treatment breaks can potentially mask an advantage over higher radiation doses. Therefore, we examined those patients who received ≥ 54 Gy within 60 d, comparing them to the rest of the patients. Of patients who received ≥ 54 Gy within 60 d, local progression-free probability was 89% versus 42% for the rest of the group (P = 0.01). CONCLUSION: Local failure is a significant problem in locally advanced carcinomas of the anal canal. Higher radiation doses with limited treatment breaks may offer an increase in local control and survival.展开更多
Background: Tailoring therapy is the target in the management of any cancer;if factors which can predict response to treatment are identified, we can individualize treatment. Locally advanced rectal cancer studies rep...Background: Tailoring therapy is the target in the management of any cancer;if factors which can predict response to treatment are identified, we can individualize treatment. Locally advanced rectal cancer studies reported that tumor microenvironment and host immune response played roles in sensitivity to chemoradiotherapy (CRT) by proving that both peripheral circulating lymphocytes and tumor infiltrating lymphocytes (TILs) strongly correlated with the response rate to CRT and it impacted disease outcome. Aim of the work: We aimed to assess the predictive value of peripheral blood lymphocytes and tumor infiltrating lymphocytes by correlation with regression rate post chemo-radiotherapy in patients with rectal cancer, and to find correlation between peripheral and tissue lymphocytes. Method: Before neoadjuvant, CRT venous blood samples were obtained from 40 patients with rectal cancer, and prior to surgery. Blood cell counts in the samples were analyzed using an automated hematology analyzer and flowcytometry used to analyze lymphocyte subsets. Colonscopic biopsies were obtained before the CRT;the numbers and distributions of T cells (CD4 & CD8) were evaluated by immunostaining. Results: Pre CRT peripheral total lymphocytes, T lymphocytes, T helper, T cytotoxic lymphocytes significantly correlated with tumor regression rate (p = 0.04, 0.05, 0.06, 0.04 respectively). The density of tissue CD4(+) and CD8(+) T cells was highly correlated with tumor regression post CRT (p = 0.01 for both). The high expressions of tissue CD4 & CD 8 were significantly correlated with high number of pretreatment peripheral total lymphocytes, T lymphocytes, T helper, and T cytotoxic lymphocytes with significant p value for all. Conclusion: We concluded that peripheral lymphocytic count and its subsets have significant correlation to tissue CD4, CD8 and both can predict pathological response to CRT;enhancement of lymphocytes mediated immune response can help for outcome improvement.展开更多
Background: There is an underutilization of postoperative radiation therapy (PORT) in renal cell carcinoma (RCC) following radical nephrectomy (RN). The main reason for that is the lack of strong evidence and the cont...Background: There is an underutilization of postoperative radiation therapy (PORT) in renal cell carcinoma (RCC) following radical nephrectomy (RN). The main reason for that is the lack of strong evidence and the contradictory data in the literature regarding its benefit. We aimed to evaluate the efficacy of PORT in locally advanced patients with RCC following complete resection. Materials and Methods: The patients had RN and at least two of the poor prognostic factors like lymph nodes involvement (LN+), renal vein invasion (RVI), inferior vena cava invasion (IVCI) and renal capsule infiltration (RCI) were included in the study. Ninety-four patients were retrospectively evaluated;56 patient received PORT 50Gy/25 fractions/5 weeks and 38 patients who did not receive PORT were compared. The LN+, RVI, IVCI and RCI were documented in 63 (67%), 46 (49%), 30 (32%) and 71 (76%) patients respectively. Results: Eight patients (14%) in PORT arm developed local recurrence (LR) are compared with 10 patients (26%) for non-PORT arm. Five-year overall survival (OS) rates were 78% and 70% for PORT and non-PORT arms respectively (p = 0.3), while 5-year locoregional control (LRC) rates were 88% for PORT arm and 70% for the non-PORT arm (p = 0.05). The IVCI and LN+ affected OS significantly (p values 0.007 and 0.009) respectively. The RCI and LN+ only affected the LRC with p values 0.03, 0.04 respectively. Two out of 56 patients (3.5%) received PORT developed intestinal obstruction which was treated surgically. Conclusion: The PORT decreased the LR rate in high risk locally advanced RCC patients significantly. The high incidence of distant metastasis offsets this improvement at the level of overall survival.展开更多
BACKGROUND The outcomes of patients diagnosed with head and neck squamous cell carcinoma(HNSCC)who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal.A ...BACKGROUND The outcomes of patients diagnosed with head and neck squamous cell carcinoma(HNSCC)who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal.A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors(ICIs).The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field.AIM To evaluate the evidence on the effectiveness of ICIs in HNSCC,based on published phase-3 clinical trials.METHODS We searched PubMed,Cochrane Library,Embase,and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC(R/M HNSCC)and locally advanced head and neck squamous cell carcinoma(LAHNSCC).We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma,recurrent,metastatic,locally advanced,immunotherapy,immune checkpoint inhibitors,monoclonal antibodies,programmed cell death protein-1(PD-1),programmed death-ligand 1(PD-L1),cytotoxic T-lymphocyte associated protein-4(CTLA-4),and phase-3 clinical trial.A sensitive search filter was used to limit our results to randomized controlled trials.RESULTS Five phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far:Four in R/M HNSCC and one in LAHNSCC.In patients with R/M HNSCC,anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care(standard singleagent systemic therapy).While the net gain in overall survival(OS)with nivolumab was 2.4 mo[hazard ratio(HR)=0.69,P=0.01],that with pembrolizumab was 1.5 mo(HR=0.80 nominal P=0.0161).The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T-lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes.In the first-line setting,in R/M HNSCC,pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo(HR=0.77,P=0.0034)in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive(combined positive score>20)population compared to standard of care(EXTREME regime).In patients with PD-L1 positive R/M HNSCC,monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME.In LAHNSCC,immunotherapy using avelumab(an anti-PD-L1 agent)along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy.CONCLUSION Anti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings,with acceptable toxicity profiles compared to standard therapy.There is no proven efficacy in the curative setting to date.展开更多
基金Supported by Natural Science Foundation of Fujian Province,No.2021J011259.
文摘Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.
基金supported by funded by National Nature Science Foundation of China,grant number 82074315.
文摘Background:Immune checkpoint inhibitors(ICIs)as the neoadjuvant therapy for resectable locally advanced esophageal carcinoma(rlaEC)remains challenging given the poor reports of efficacy and safety.This study aimed to summarize reliable evidence for the preoperative neoadjuvant immunotherapy of rlaEc by analyzing all the published clinical trials on the ICIs as the neoadjuvant therapy for rlaEC.Methods:PubMed,Cochrane Library,Embase and ClinicalTrials.gov were searched from inception until June 1st,2023,for available reports to perform a meta-analysis.The primary endpoints were RO resection,objective response rate(ORR),pathological complete response(pCR)and major pathological response(MPR),as well as treatment-related adverse events(AEs)and postoperative complications.The Stata 14.0 software was employed to estimate pooled effect size.Results:A total of 18 single-arm clinical trials involving 625 patients met the inclusion criteria.Meta-analysis showed that,among these patients with rlaEC,the pooled R0 resection rate was 97.0%(95%CI:94.0%-99.0%),the p0oled ORR was 70.0%(95%CI:64.0%-76.0%),the p0oled pCR and MPR rate were 34.0%(95%CI:29.0%-39.0%)and 56.0%(95%CI:47.0%-65.0%)respectively.The incidence of main treatment-related AEs and postoperative complications was about 6%-45% and 8%-19% respectively.Conclusions:Patients with rlaEC were tolerated to neoadjuvant immunotherapy and it might be beneficial to improve efficacy.But this meta-analysis had limitations and the conclusions still needed to be validated by more rigorous phase II randomized controlled clinical trials.
文摘AIM:To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma(NPC).METHODS:We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy(CCRT)(22/40 patients)or CCRT alone(18/40)from March 2006 to March 2012.Patients underwent fiberoscopy with biopsy of the primitive tumor,and computed tomography scan of head,neck,chest and abdomen with and without contrast.Cisplatin was used both as induction and as concomitant chemotherapy,while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions(total dose,70 Gy).The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly.This retrospective analysis was approved by the review boards of the participating institutions.Patients gave their consent to treatment and to anonymous analysis of clinical data.RESULTS:Thirty-three patients were males and 7 were females.Median follow-up time was 58 mo(range,1-92 mo).In the sub-group of twenty patients with a follow-up time longer than 36 mo,the 3-year survival and disease free survival rates were 85%and 75%,respectively.Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%.Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients.Grade 2 mucositis was seen in 29 patients,while grade 2 xerostomia was seen in 30 patients.Overall toxicity was manageable and it did not cause any significant treatment delay.In the whole sample population,long term toxicity included grade 2 xerostomia in 22 patients,grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients.CONCLUSION:Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC.The role of adjuvant chemotherapy remains to be defined.
文摘Background: The prognosis of patients with Epidermal Growth Factor Receptor (EGFR) overexpression in inoperable Locally Advanced Squamous Cell Carcinoma of Head and Neck (LASCCHN) remains poor. Nimotuzumab is an Anti EGFR humanized monoclonal antibody approved for treatment of LASCCHN, with concurrent chemoradiation. Objective: To assess the efficacy and safety of nimotuzumab with concurrent chemoradiation in inoperable LASCCHN patients. Methodology: This is a single-centre, single arm, retrospective study evaluating 35 patients with histologically confirmed inoperable LASCCHN (stages III-IV). The patients were administered IV cisplatin 50 mg/m2 and IV nimotuzumab 200 mg for 6 - 7 weeks, along with radiotherapy of 6600 - 7000 cGy over 35 fractions. Patients were evaluated over response evaluation criteria in solid tumors (RECIST) criteria 12 weeks after the last cycle of chemotherapy. They were also followed up for overall survival and relapse free survival. Results: The median duration of follow-up was 20 months. The most common site of cancer was oropharynx (68.6%). One patient was lost to follow up. Objective Response Rate (ORR) was observed in 97% of the patients with 17 patients (48.6%) achieving complete response (CR) and 17 patients (48.6%) achieving partial response (PR). The median overall survival was 22.7 months (95% CI: 21.30, 34.27). The median relapse free survival was 16.7 months (95% CI: 9.80, 24.50). Nimotuzumab was safe and well tolerated with few mild, self-limiting adverse events. Conclusion: Nimotuzumab with chemoradiation is a safe and efficacious option in patients with LASCCHN. Larger studies are needed to verify the same.
文摘Background: Head and neck cancers (HNCs) constitute 5% of all cancers globally and are the most common cancers in India. Chemotherapy and radiotherapy have not been proved to be effective in advanced cases and the prognosis remains dismal. This underscores the need for newer treatment options in these cases. Nimotuzumab, an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, was safer when combined with chemo- or radio-therapy. Aim: To evaluate the safety and efficacy of concurrently administered nimotuzumab with chemo-radiotherapy in patients with advanced inoperable squamous cell carcinomas of head and neck (LASCCHN). Methods:?This was an open-label, single arm study evaluating 57 patients with histologically confirmed inoperable LASCCHN (stages III and IV) and eastern co-operative oncology group (ECOG) performance status < 2. Informed consent was obtained from all patients. The patients were administered IV cisplatin 30 mg/m2?and IV nimotuzumab 200 mg weekly for 6 weeks, along with radiotherapy of 6600 cGy over 33 fractions. Patients were evaluated over response evaluation criteria in solid tumors (RECIST) criteria 24 weeks after the last cycle of chemotherapy. Results: Mean age of patient was 50 years old (29 - 79 years old). The most common site of cancer was oral cavity (56.1%). Forty six patients (80.7%) completed 6 cycles of therapy. Objective response rate (ORR) was 80.7%, with 34 patients (59.6%) achieving complete response (CR), and 12 (21%) achieving partial response (PR). Stable disease (SD) was noted in 8 (14%) patients and progressive disease in 3 (5.2%) patients. Conclusion: Addition of nimotuzumab is a safe and efficacious option in patients with inoperable LASCCHN. Our observations confirm the available Phase II data. The long term survival benefits based on this encouraging response rate need to be further evaluated in this subset of cancer patients.
文摘AIM: To assess whether radiation dose and duration of treatment influence local control and survival of patients with locally advanced anal cancer treated with definitive chemoradiation. METHODS: Twenty-eight consecutive patients who were treated with definitive radiation therapy for bulky anal cancers (> 5 cm in size) were reviewed. Nineteen patients had T3 lesions, 8 patients had T4 lesions, and 15 patients had lymph node involvement. The median tumor size was 7.5 cm. All but one patient received concurrent chemoradiation. The median radiation dose was 54 Gy. The median duration of treatment was 58 d. RESULTS: With a median follow-up of 2.5 years in all patients and 7.8 years in living patients, the 2-year local recurrence-free probability was 57% and overall survival rate was 67%. Neither radiation dose nor duration of treatment alone was predictive of either time to local failure or overall survival. However, longer treatment breaks can potentially mask an advantage over higher radiation doses. Therefore, we examined those patients who received ≥ 54 Gy within 60 d, comparing them to the rest of the patients. Of patients who received ≥ 54 Gy within 60 d, local progression-free probability was 89% versus 42% for the rest of the group (P = 0.01). CONCLUSION: Local failure is a significant problem in locally advanced carcinomas of the anal canal. Higher radiation doses with limited treatment breaks may offer an increase in local control and survival.
文摘Background: Tailoring therapy is the target in the management of any cancer;if factors which can predict response to treatment are identified, we can individualize treatment. Locally advanced rectal cancer studies reported that tumor microenvironment and host immune response played roles in sensitivity to chemoradiotherapy (CRT) by proving that both peripheral circulating lymphocytes and tumor infiltrating lymphocytes (TILs) strongly correlated with the response rate to CRT and it impacted disease outcome. Aim of the work: We aimed to assess the predictive value of peripheral blood lymphocytes and tumor infiltrating lymphocytes by correlation with regression rate post chemo-radiotherapy in patients with rectal cancer, and to find correlation between peripheral and tissue lymphocytes. Method: Before neoadjuvant, CRT venous blood samples were obtained from 40 patients with rectal cancer, and prior to surgery. Blood cell counts in the samples were analyzed using an automated hematology analyzer and flowcytometry used to analyze lymphocyte subsets. Colonscopic biopsies were obtained before the CRT;the numbers and distributions of T cells (CD4 & CD8) were evaluated by immunostaining. Results: Pre CRT peripheral total lymphocytes, T lymphocytes, T helper, T cytotoxic lymphocytes significantly correlated with tumor regression rate (p = 0.04, 0.05, 0.06, 0.04 respectively). The density of tissue CD4(+) and CD8(+) T cells was highly correlated with tumor regression post CRT (p = 0.01 for both). The high expressions of tissue CD4 & CD 8 were significantly correlated with high number of pretreatment peripheral total lymphocytes, T lymphocytes, T helper, and T cytotoxic lymphocytes with significant p value for all. Conclusion: We concluded that peripheral lymphocytic count and its subsets have significant correlation to tissue CD4, CD8 and both can predict pathological response to CRT;enhancement of lymphocytes mediated immune response can help for outcome improvement.
文摘Background: There is an underutilization of postoperative radiation therapy (PORT) in renal cell carcinoma (RCC) following radical nephrectomy (RN). The main reason for that is the lack of strong evidence and the contradictory data in the literature regarding its benefit. We aimed to evaluate the efficacy of PORT in locally advanced patients with RCC following complete resection. Materials and Methods: The patients had RN and at least two of the poor prognostic factors like lymph nodes involvement (LN+), renal vein invasion (RVI), inferior vena cava invasion (IVCI) and renal capsule infiltration (RCI) were included in the study. Ninety-four patients were retrospectively evaluated;56 patient received PORT 50Gy/25 fractions/5 weeks and 38 patients who did not receive PORT were compared. The LN+, RVI, IVCI and RCI were documented in 63 (67%), 46 (49%), 30 (32%) and 71 (76%) patients respectively. Results: Eight patients (14%) in PORT arm developed local recurrence (LR) are compared with 10 patients (26%) for non-PORT arm. Five-year overall survival (OS) rates were 78% and 70% for PORT and non-PORT arms respectively (p = 0.3), while 5-year locoregional control (LRC) rates were 88% for PORT arm and 70% for the non-PORT arm (p = 0.05). The IVCI and LN+ affected OS significantly (p values 0.007 and 0.009) respectively. The RCI and LN+ only affected the LRC with p values 0.03, 0.04 respectively. Two out of 56 patients (3.5%) received PORT developed intestinal obstruction which was treated surgically. Conclusion: The PORT decreased the LR rate in high risk locally advanced RCC patients significantly. The high incidence of distant metastasis offsets this improvement at the level of overall survival.
文摘BACKGROUND The outcomes of patients diagnosed with head and neck squamous cell carcinoma(HNSCC)who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal.A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors(ICIs).The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field.AIM To evaluate the evidence on the effectiveness of ICIs in HNSCC,based on published phase-3 clinical trials.METHODS We searched PubMed,Cochrane Library,Embase,and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC(R/M HNSCC)and locally advanced head and neck squamous cell carcinoma(LAHNSCC).We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma,recurrent,metastatic,locally advanced,immunotherapy,immune checkpoint inhibitors,monoclonal antibodies,programmed cell death protein-1(PD-1),programmed death-ligand 1(PD-L1),cytotoxic T-lymphocyte associated protein-4(CTLA-4),and phase-3 clinical trial.A sensitive search filter was used to limit our results to randomized controlled trials.RESULTS Five phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far:Four in R/M HNSCC and one in LAHNSCC.In patients with R/M HNSCC,anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care(standard singleagent systemic therapy).While the net gain in overall survival(OS)with nivolumab was 2.4 mo[hazard ratio(HR)=0.69,P=0.01],that with pembrolizumab was 1.5 mo(HR=0.80 nominal P=0.0161).The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T-lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes.In the first-line setting,in R/M HNSCC,pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo(HR=0.77,P=0.0034)in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive(combined positive score>20)population compared to standard of care(EXTREME regime).In patients with PD-L1 positive R/M HNSCC,monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME.In LAHNSCC,immunotherapy using avelumab(an anti-PD-L1 agent)along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy.CONCLUSION Anti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings,with acceptable toxicity profiles compared to standard therapy.There is no proven efficacy in the curative setting to date.
