As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer of...As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer often developing after esophageal cancer due to potential“field cancerization”effects.Despite this observation,the genetic heterogeneity underlying MPCs remains understudied.However,the recent emergence of genetic testing has expanded the scope of investigations into MPCs to investigate signatures underlying cancer predisposition.This report reveals 3 unprecedented TP53 fusion mutations in a Chinese patient afflicted by MPCs,namely,AP1M2–TP53(A1;T11)fusion,TP53–ILF3(T10;I13)fusion,and SLC44A2–TP53(S5;T11)fusion.This patient exhibited an extended period of survival after diagnosis of extensive-stage small cell lung cancer,which occurred 6 years after the diagnosis of esophageal squamous cell cancer.This unique reportmay provide supplementary data that enhance our understanding of the genetic landscape ofMPCs.展开更多
The advent of targeted molecular therapy against the EML4-ALK fusion gene is the latest therapeutic intervention for a subset of patients with non-small cell lung cancer (NSCLC). Crizotinib (Xalkori) is an orally avai...The advent of targeted molecular therapy against the EML4-ALK fusion gene is the latest therapeutic intervention for a subset of patients with non-small cell lung cancer (NSCLC). Crizotinib (Xalkori) is an orally available small molecule tyrosine kinase inhibitor proven in clinical trials to significantly impact progression free survival and overall response rate. We present a case of a 56-year-old male with NSCLC whose lack of a positive treatment response to this therapy led to the clinical suspicion and identification of the underdiagnosed entity known as synchronous multiple primary lung cancer (SMPLC).展开更多
Objective:To analyze the feasibility of simultaneous bilateral thoracoscopic lung resection in the treatment of multiple primary lung cancers in the early stage.Methods:The study time range is between March 2019 and M...Objective:To analyze the feasibility of simultaneous bilateral thoracoscopic lung resection in the treatment of multiple primary lung cancers in the early stage.Methods:The study time range is between March 2019 and March 2021.A sample of 30 patients with early multiple primary lung cancer admitted to this hospital were included,and they were divided into a study group,a control group,and samples within the group using a random number table scheme n=15,patients in the control group underwent staged bilateral thoracoscopic pneumonectomy,and patients in the study group underwent bilateral thoracoscopic pneumonectomy at the same time.The indicators of the two groups were compared and analyzed.Results:There was no significant difference in the operation time and intraoperative blood loss between the two groups(P>0.05).There were significant differences in the VAS score,total length of hospital stay,and total surgical costs on the first day after surgery(P<0.05);there was no significant difference in the two groups'postoperative recovery indicators and the incidence of complications(P>0.05).Conclusion:It is safe and feasible to treat patients with multiple primary lung cancer in both lungs at the same time with simultaneous bilateral thoracoscopic surgery,and is suitable for promotion.展开更多
Multiple primary cancers refer to the condition where more than two cancers occur independently in an individual. The incidence of lung cancer in cases of colorectal cancer is rare and synchronous rectal cancer and lu...Multiple primary cancers refer to the condition where more than two cancers occur independently in an individual. The incidence of lung cancer in cases of colorectal cancer is rare and synchronous rectal cancer and lung cancer is even rare. A 61-year-old man was referred to our hospital with a 2-month history of blood in his stool, tenesmus, and mucous discharge in July 2010. Colonoscopy showed an irregular ulcerated rectal mass and histological examination of biopsy material showed a poorly differentiated adenocarcinoma. Computed tomography （CT） scan of the chest and abdomen showed a mass in the posterior segment of the right upper lobe of the lung and a mass in the right rectal wall of upper rectum. The rectal tumor was diagnosed as primary cancer based on the findings of immunohistochemical stain. An anterior resection （AR） and video assisted thoracoscopic （VAT） wedge resection were performed and histological findings of resected rectal and lung tumor specimen showed synchronous primary rectal cancer and lung cancer. A combination chemotherapy regimen with docetaxel and Iobaplatin was used and the patient was successfully discharged from hospital in August 2010. Although the incidence of synchronous multiple primary cancers is very low, we need to remain suspicious, when faced with two or even multiple organ lesions, and employ the necessary examination methods to confirm the diagnosis. For synchronous multiple primary cancers, if conditions allow, surgical resection for all the cancers can be performed in a single operation.展开更多
Multiple primary lung cancer(MPLC)is an increasingly prevalent subtype of lung cancer.According to recent genomic studies,the different lesions of a single MPLC patient exhibit functional similarities that may reflect...Multiple primary lung cancer(MPLC)is an increasingly prevalent subtype of lung cancer.According to recent genomic studies,the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence.We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found.Using our own and other relevant public data,evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk,indicating evolutionary contingency rather than adaptive convergence.Additionally,tumors from the same MPLC patient are as genetically diverse as those from different patients,while within-tumor genetic heterogeneity is significantly lower.Furthermore,the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor,but not with samples from other tumors or other patients.Overall,there is no evidence of adaptive convergence during the evolution of MPLC.Most importantly,the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient.To fully exploit the strategic value of precision medicine,targeted therapies should be designed and delivered on a per-lesion basis.展开更多
Background:Distinguishing multiple primary lung cancer(MPLC)from intrapulmonary metastasis(IPM)is critical for their disparate treatment strategy and prognosis.This study aimed to establish a non-invasive model to mak...Background:Distinguishing multiple primary lung cancer(MPLC)from intrapulmonary metastasis(IPM)is critical for their disparate treatment strategy and prognosis.This study aimed to establish a non-invasive model to make the differentiation pre-operatively.Methods:We retrospectively studied 168 patients with multiple lung cancers(307 pairs of lesions)including 118 cases for modeling and internal validation,and 50 cases for independent external validation.Radiomic features on computed tomography(CT)were extracted to calculate the absolute deviation of paired lesions.Features were then selected by correlation coefficients and random forest classifier 5-fold cross-validation,based on which the lesion pair relation estimation(PRE)model was developed.A major voting strategy was used to decide diagnosis for cases with multiple pairs of lesions.Cases from another institute were included as the external validation set for the PRE model to compete with two experienced clinicians.Results:Seven radiomic features were selected for the PRE model construction.With major voting strategy,the mean area under receiver operating characteristic curve(AUC),accuracy,sensitivity,and specificity of the training versus internal validation versus external validation cohort to distinguish MPLC were 0.983 versus 0.844 versus 0.793,0.942 versus 0.846 versus 0.760,0.905 versus 0.728 versus 0.727,and 0.962 versus 0.910 versus 0.769,respectively.AUCs of the two clinicians were 0.619 and 0.580.Conclusions:The CT radiomic feature-based lesion PRE model is potentially an accurate diagnostic tool for the differentiation of MPLC and IPM,which could help with clinical decision making.展开更多
Background:Although examinations and therapies for bronchial lung cancer,also called lung cancer(LC),have become more effective and precise,the morbidity and mortality of LC remain high worldwide.Describing the changi...Background:Although examinations and therapies for bronchial lung cancer,also called lung cancer(LC),have become more effective and precise,the morbidity and mortality of LC remain high worldwide.Describing the changing profile of LC characteristics over time is indispensable.This study aimed to understand the changes in real-world settings of LC and its characteristics in China.Methods:In this study,119,785 patients were enrolled from 2012 to 2020 in the Shanghai Pulmonary Hospital.The patients’medical records were extracted from the hospital’s database.Demographic characteristics,general clinicopathological information,and blood coagulation indices at the initial diagnoses were analyzed using the Kruskal-Wallis,Nemenyi,chi-squared,and Bonferroni tests.Changes in demographic characteristics during the 8-year study period,namely dynamic changes among different stages and different pathological types,were evaluated.Results:The percentages of female(from 38.50%[323/839]in 2012 to 48.29%[5112/10,585]in 2020)and non-smoking LC(from 69.34%[475/685]to 80.48%[8055/10,009])patients increased significantly during the study period,with a trend toward a younger age at diagnosis(from 3.58%[30/839]to 8.99%[952/10,585]).Over the study period,the proportion and absolute number of lung adenocarcinoma cases increased(from 67.97%[433/637]to 76.31%[6606/8657])while the proportion of lung squamous cell carcinoma decreased(from 21.19%[135/637]to 12.08%[1046/8657]).Comprehensive driver gene mutation examination became more common,and epidermal growth factor receptor(EGFR)mutation occurred more frequently in female vs.male(62.03%[12793/20625]vs.29.90%[8207/27,447])and non-smoking vs.smoking(53.54%[17,203/32,134]vs.23.73%[3322/13,997])patients(both P<0.001).The distribution of the common driver genes differed among different stages of LC.EGFR mutation was detected most frequently at each stage,and other driver gene alterations were more common in advanced stages(P<0.001).The combination of chemotherapy,targeted ther-apy,and immunotherapy,as a comprehensive management regimen,gradually became predominant over the study period(P<0.001).A hypercoagulable state was shown in advanced-stage LC patients and patients with the anaplastic lymphoma kinase fusion,indicated by significantly elevated levels of d-dimer,fibrinogen,and fibrinogen degradation products.Conclusions:This study comprehensively depicted the changing characteristics of Chinese LC patients over an 8-year period to provide preliminary insights into LC treatment.Trial registration:ClinicalTrials.gov,NCT05423236.展开更多
基金supported by the National Natural Science Foun-dation of China(grant numbers 81974483 and 82072589)the ChineseSocietyofClinicalOncology-HengruiCancerResearch Fund(Y-HR2020QN-0946).
文摘As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer often developing after esophageal cancer due to potential“field cancerization”effects.Despite this observation,the genetic heterogeneity underlying MPCs remains understudied.However,the recent emergence of genetic testing has expanded the scope of investigations into MPCs to investigate signatures underlying cancer predisposition.This report reveals 3 unprecedented TP53 fusion mutations in a Chinese patient afflicted by MPCs,namely,AP1M2–TP53(A1;T11)fusion,TP53–ILF3(T10;I13)fusion,and SLC44A2–TP53(S5;T11)fusion.This patient exhibited an extended period of survival after diagnosis of extensive-stage small cell lung cancer,which occurred 6 years after the diagnosis of esophageal squamous cell cancer.This unique reportmay provide supplementary data that enhance our understanding of the genetic landscape ofMPCs.
文摘The advent of targeted molecular therapy against the EML4-ALK fusion gene is the latest therapeutic intervention for a subset of patients with non-small cell lung cancer (NSCLC). Crizotinib (Xalkori) is an orally available small molecule tyrosine kinase inhibitor proven in clinical trials to significantly impact progression free survival and overall response rate. We present a case of a 56-year-old male with NSCLC whose lack of a positive treatment response to this therapy led to the clinical suspicion and identification of the underdiagnosed entity known as synchronous multiple primary lung cancer (SMPLC).
文摘Objective:To analyze the feasibility of simultaneous bilateral thoracoscopic lung resection in the treatment of multiple primary lung cancers in the early stage.Methods:The study time range is between March 2019 and March 2021.A sample of 30 patients with early multiple primary lung cancer admitted to this hospital were included,and they were divided into a study group,a control group,and samples within the group using a random number table scheme n=15,patients in the control group underwent staged bilateral thoracoscopic pneumonectomy,and patients in the study group underwent bilateral thoracoscopic pneumonectomy at the same time.The indicators of the two groups were compared and analyzed.Results:There was no significant difference in the operation time and intraoperative blood loss between the two groups(P>0.05).There were significant differences in the VAS score,total length of hospital stay,and total surgical costs on the first day after surgery(P<0.05);there was no significant difference in the two groups'postoperative recovery indicators and the incidence of complications(P>0.05).Conclusion:It is safe and feasible to treat patients with multiple primary lung cancer in both lungs at the same time with simultaneous bilateral thoracoscopic surgery,and is suitable for promotion.
文摘Multiple primary cancers refer to the condition where more than two cancers occur independently in an individual. The incidence of lung cancer in cases of colorectal cancer is rare and synchronous rectal cancer and lung cancer is even rare. A 61-year-old man was referred to our hospital with a 2-month history of blood in his stool, tenesmus, and mucous discharge in July 2010. Colonoscopy showed an irregular ulcerated rectal mass and histological examination of biopsy material showed a poorly differentiated adenocarcinoma. Computed tomography （CT） scan of the chest and abdomen showed a mass in the posterior segment of the right upper lobe of the lung and a mass in the right rectal wall of upper rectum. The rectal tumor was diagnosed as primary cancer based on the findings of immunohistochemical stain. An anterior resection （AR） and video assisted thoracoscopic （VAT） wedge resection were performed and histological findings of resected rectal and lung tumor specimen showed synchronous primary rectal cancer and lung cancer. A combination chemotherapy regimen with docetaxel and Iobaplatin was used and the patient was successfully discharged from hospital in August 2010. Although the incidence of synchronous multiple primary cancers is very low, we need to remain suspicious, when faced with two or even multiple organ lesions, and employ the necessary examination methods to confirm the diagnosis. For synchronous multiple primary cancers, if conditions allow, surgical resection for all the cancers can be performed in a single operation.
基金supported by the National Key Research and Development Program of China to J.-R. Y.(2021YFF1200904 and2021YFA1302500)the National Natural Science Foundation of China to J.-R. Y.(31871320 and 81830103)+1 种基金by Science and Technology Planning Project of ZhuHai,China to H. C.by Science and Technology Planning Project of Guangdong Province,China to X. Z.(2014A030304053)
文摘Multiple primary lung cancer(MPLC)is an increasingly prevalent subtype of lung cancer.According to recent genomic studies,the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence.We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found.Using our own and other relevant public data,evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk,indicating evolutionary contingency rather than adaptive convergence.Additionally,tumors from the same MPLC patient are as genetically diverse as those from different patients,while within-tumor genetic heterogeneity is significantly lower.Furthermore,the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor,but not with samples from other tumors or other patients.Overall,there is no evidence of adaptive convergence during the evolution of MPLC.Most importantly,the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient.To fully exploit the strategic value of precision medicine,targeted therapies should be designed and delivered on a per-lesion basis.
基金supported by Grants from the National Natural Science Foundation of China(No.82102109)by Grants from Development Center for Medical Science&Technology National Health Commission of China(No.WA2020RW10)by Grants from Shanghai Municipal Commission of Health and Family Planning Program(No.20184Y0037).
文摘Background:Distinguishing multiple primary lung cancer(MPLC)from intrapulmonary metastasis(IPM)is critical for their disparate treatment strategy and prognosis.This study aimed to establish a non-invasive model to make the differentiation pre-operatively.Methods:We retrospectively studied 168 patients with multiple lung cancers(307 pairs of lesions)including 118 cases for modeling and internal validation,and 50 cases for independent external validation.Radiomic features on computed tomography(CT)were extracted to calculate the absolute deviation of paired lesions.Features were then selected by correlation coefficients and random forest classifier 5-fold cross-validation,based on which the lesion pair relation estimation(PRE)model was developed.A major voting strategy was used to decide diagnosis for cases with multiple pairs of lesions.Cases from another institute were included as the external validation set for the PRE model to compete with two experienced clinicians.Results:Seven radiomic features were selected for the PRE model construction.With major voting strategy,the mean area under receiver operating characteristic curve(AUC),accuracy,sensitivity,and specificity of the training versus internal validation versus external validation cohort to distinguish MPLC were 0.983 versus 0.844 versus 0.793,0.942 versus 0.846 versus 0.760,0.905 versus 0.728 versus 0.727,and 0.962 versus 0.910 versus 0.769,respectively.AUCs of the two clinicians were 0.619 and 0.580.Conclusions:The CT radiomic feature-based lesion PRE model is potentially an accurate diagnostic tool for the differentiation of MPLC and IPM,which could help with clinical decision making.
基金This study was supported in part by grants from the National Key Research and Development Program of China(No.2022YFF0705300)National Natural Science Foundation of China(No.52272281)+5 种基金Clinical Research Project of Shanghai Pulmonary Hospital(No.FKLY20010)Young Talents in Shanghai(No.2019 QNBJ)Shang-hai Shuguang Scholars.This study was supported by the Shanghai Mu-nicipal Science and Technology Major Project(No.2021SHZDZX0100)Fundamental Research Funds for the Central Universities(No.22120210562)2021 Science and Technology Think Tank Youth Tal-ent Plan of the China Association for Science and Technology,“Dream Tutor”Outstanding Young Talents Program(No.fkyq1901)the National Key Research and Development Program of China(Nos.2021YFF1201200 and 2021YFF1200900).
文摘Background:Although examinations and therapies for bronchial lung cancer,also called lung cancer(LC),have become more effective and precise,the morbidity and mortality of LC remain high worldwide.Describing the changing profile of LC characteristics over time is indispensable.This study aimed to understand the changes in real-world settings of LC and its characteristics in China.Methods:In this study,119,785 patients were enrolled from 2012 to 2020 in the Shanghai Pulmonary Hospital.The patients’medical records were extracted from the hospital’s database.Demographic characteristics,general clinicopathological information,and blood coagulation indices at the initial diagnoses were analyzed using the Kruskal-Wallis,Nemenyi,chi-squared,and Bonferroni tests.Changes in demographic characteristics during the 8-year study period,namely dynamic changes among different stages and different pathological types,were evaluated.Results:The percentages of female(from 38.50%[323/839]in 2012 to 48.29%[5112/10,585]in 2020)and non-smoking LC(from 69.34%[475/685]to 80.48%[8055/10,009])patients increased significantly during the study period,with a trend toward a younger age at diagnosis(from 3.58%[30/839]to 8.99%[952/10,585]).Over the study period,the proportion and absolute number of lung adenocarcinoma cases increased(from 67.97%[433/637]to 76.31%[6606/8657])while the proportion of lung squamous cell carcinoma decreased(from 21.19%[135/637]to 12.08%[1046/8657]).Comprehensive driver gene mutation examination became more common,and epidermal growth factor receptor(EGFR)mutation occurred more frequently in female vs.male(62.03%[12793/20625]vs.29.90%[8207/27,447])and non-smoking vs.smoking(53.54%[17,203/32,134]vs.23.73%[3322/13,997])patients(both P<0.001).The distribution of the common driver genes differed among different stages of LC.EGFR mutation was detected most frequently at each stage,and other driver gene alterations were more common in advanced stages(P<0.001).The combination of chemotherapy,targeted ther-apy,and immunotherapy,as a comprehensive management regimen,gradually became predominant over the study period(P<0.001).A hypercoagulable state was shown in advanced-stage LC patients and patients with the anaplastic lymphoma kinase fusion,indicated by significantly elevated levels of d-dimer,fibrinogen,and fibrinogen degradation products.Conclusions:This study comprehensively depicted the changing characteristics of Chinese LC patients over an 8-year period to provide preliminary insights into LC treatment.Trial registration:ClinicalTrials.gov,NCT05423236.
