Background:The prognosis of stage IV non-small cell lung cancer(NSCLC)with pleural metastasis is poor,with a 5-year survival rate of only 2%to 4%for patients,with the median survival was 9.5-11.5 months.According to ...Background:The prognosis of stage IV non-small cell lung cancer(NSCLC)with pleural metastasis is poor,with a 5-year survival rate of only 2%to 4%for patients,with the median survival was 9.5-11.5 months.According to the“NCCN Lung Cancer Guidelines,”stage IV NSCLC lung cancer is a contraindication for surgery.It is recommended to adopt a standard treatment plan mainly based on chemotherapy or targeted therapy with EGFR-TKIs.However,Neoadjuvant therapy with alectinib for non-small cell lung cancer with pleural metastasis is rarely reported.Case presentation:A 41-year-old Asian male patient presented with a persistent cough for one month.A chest computed tomography(CT)scan conducted two years prior revealed that a nodular radiative anomalous concentrated shadow was observed in the inferior tongue segment of the upper lobe of the left lung,approximately 2.2×1.6×1.2 cm in size,with a SUVmax of about 5.5.Two small nodular shadows were seen beside the disease in the inferior lingual segment of the upper lobe of the left lung,with the larger one having a diameter of approximately 0.6 cm.Multiple lymph node metastases in the left hilum and mediastinum;Multiple metastases of the left pleura and a small amount of pleural effusion on the left side.The patient began to receive 2 courses of chemotherapy and targeted therapy(pemetrexed+carboplatin+crizotinib)and 1 course of chemotherapy and other targeted therapy(pemetrexed+carboplatin+alectinib).The result of re-examination of CT demonstrated that peripheral lung cancer in the lower lingual segment of the left upper lung is approximately 0.8×0.9 cm in size,slightly smaller than before.A thoracoscopic lobectomy was performed,and the pulmonary bulla was removed concurrently.Pathological examination confirmed non-small cell lung carcinoma(NSCLC)in the mass.Patient discharged on the 7th day after the operation and received 2 courses of chemotherapy(pemetrexed+carboplatin)and had been receiving alectinib targeted drug treatment all along for over 5 years.However,the patient stopped taking the medicine on his own for half a year.Though in the recent CT examination,the result demonstrated no recurrence and metastasis and the patient has been clinically cured.Unfortunately,the results of brain magnetic resonance imaging suggested that multiple brain metastases of lung cancer occurred,and the patient began taking the third-generation ALK-targeted drug lorlatinib.Conclusions:The patient with stage IV non-small cell lung cancer(NSCLC)presenting with pleural metastasis received neoadjuvant alectinib therapy and underwent thoracoscopic lobectomy,which resulted in significant therapeutic effects and fulfilled the criteria for clinical cure.This case highlights the potential for improved preventative strategies and treatment approaches in similar patients.展开更多
The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South Univers...The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South University has treated 2 NSCLC patients with 2 distinct novel ALK gene fusions.Case 1 was a 55-year-old male with a solid nodule located in the right hilar lobe on enhanced CT scan.Case 2 was a 47-year-old female with enhanced CT showing involvement of the left upper lobe of lung.Histopathological examination of tumor tissues confirmed lung adenocarcinoma in both cases.Immunohistochemical(IHC)staining demonstrated positivity for thyroid transcription factor 1(TTF-1)and ALK-D5F3 in tumor cells,while negativity for P40.The next-generation sequencing(NGS)tests identified a PNPT1-ALK(Exon22:Exon20)fusion variant in case 1 and a TCEAL2-ALK(Exon3:Exon19)fusion variant in case 2.The TCEAL2-ALK fusion was further confirmed by amplification refractory mutation system(ARMS)-PCR at the mRNA level.Both patients were treated with oral alectinib at a dosage of 600 mg twice daily.The tumors in both patients were significantly decreased after alectinib treatment,achieving partial response.At the time of submission,there was an absence of disease progression and the progression-free survival(PFS)had surpassed 1 year.It offered compelling evidences that the individuals with NSCLC and harboring either a PNPT1-ALK(Exon22:Exon20)fusion or a TCEAL2-ALK(Exon3:Exon19)fusion,experience favorable therapeutic outcomes through the administration of alectinib.This study expands the known ALK fusion variants database and supports the precision treatment of NSCLC using ALK tyrosine kinase inhibitors(TKIs).展开更多
Alectinib is a selective Anaplastic Lymphoma Kinase (ALK) tyrosine kinase inhibitor used as standard therapy for ALK-rearranged lung adenocarcinoma. Hemolytic anemia is considered a rare but significant adverse event ...Alectinib is a selective Anaplastic Lymphoma Kinase (ALK) tyrosine kinase inhibitor used as standard therapy for ALK-rearranged lung adenocarcinoma. Hemolytic anemia is considered a rare but significant adverse event of alectinib. Here, we report the case of a 78-year-old female with advanced ALK rearrangement-positive lung adenocarcinoma who developed grade 4 drug-induced hemolytic anemia after receiving alectinib as first-line therapy. We discontinued alectinib treatment and switched to brigatinib. As a result, anemia improved without recurrence of lung adenocarcinoma over one year.展开更多
BACKGROUND The development of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitors(TKIs)has remarkably improved the prognosis of patients with ALK-positive advanced non-small cell lung cancer(NSCLC).Alectinib,th...BACKGROUND The development of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitors(TKIs)has remarkably improved the prognosis of patients with ALK-positive advanced non-small cell lung cancer(NSCLC).Alectinib,the second-generation ALK-TKI,has been approved as first-line treatment for advanced or metastatic NSCLC patients with ALK rearrangement.Neoadjuvant therapy can achieve tumor downstaging and eradicate occult lesions in patients with potentially resectable disease.Whether neoadjuvant alectinib can be a conversion therapy in ALK-positive advanced NSCLC patients remains unclear.CASE SUMMARY A 41-year-old man was pathologically diagnosed with locally advanced ALKpositive stage IIIB NSCLC.Alectinib was prescribed to induce tumor downstaging and facilitate the subsequent surgical resection.The tumor was successfully downstaged and pathological complete response was achieved.Left upper lobectomy with mediastinal lymphadenectomy was performed after tumor downstaging.The patient has continued to receive alectinib as adjuvant therapy during postoperative follow-up with a recurrence-free survival of 29 mo as of writing this report.CONCLUSION This case sheds light on the feasibility and safety of alectinib as a neoadjuvant treatment for stage IIIB NSCLC patients with ALK rearrangement.Its efficacy needs to be validated in prospective clinical trials.展开更多
BACKGROUND The aberrant expression of the anaplastic lymphoma kinase(ALK)gene in ALKpositive(ALK+)anaplastic large cell lymphoma(ALCL)is usually due to t(2;5)/NPM-ALK.However,rarely,aberrant ALK expression can also re...BACKGROUND The aberrant expression of the anaplastic lymphoma kinase(ALK)gene in ALKpositive(ALK+)anaplastic large cell lymphoma(ALCL)is usually due to t(2;5)/NPM-ALK.However,rarely,aberrant ALK expression can also result from a rearrangement of the ALK gene with various partner genes.Central nervous system(CNS)metastasis is very rare in ALK+ALCL.Patients with CNS involvement show an inferior prognosis.CASE SUMMARY Here,we present the case of an 8-year-old girl diagnosed with ALK+ALCL.She presented with fever,skin nodules,leg swelling,and abdominal pain over the preceding 6 mo.She had extensive involvement and showed an extraordinary rare translocation,t(2;17)/CLTC-ALK,as demonstrated by RNA-seq.She underwent chemotherapy as per ALCL99,followed by vinblastine(VBL)maintenance treatment,and achieved complete remission.However,she developed CNS relapse during VBL monotherapy.The patient achieved a durable second remission with high-dose chemotherapy(including methotrexate 8 g/m2)and continuous treatment with alectinib and VBL.CONCLUSION Alectinib showed significant and durable CNS effects in this patient.However,more cases are needed to prove the efficacy and safety of alectinib for pediatric ALK+ALCL patients.展开更多
Alectinib is a first-line treatment for patients withadvanced non-small cell lung cancer(NSCLC)harbor-ing anaplastic lymphoma kinase-positive(ALK+)driveraberrations with a median progression-free survival of 35months ...Alectinib is a first-line treatment for patients withadvanced non-small cell lung cancer(NSCLC)harbor-ing anaplastic lymphoma kinase-positive(ALK+)driveraberrations with a median progression-free survival of 35months and a 5-year overall survival of 63%[1].Currently,alectinib also shows improvement as an adjuvant treat-ment in resected stage IA-IIIB ALK+NSCLC[2].Alectinibhas a mild safety profile,but a notable underreported side-effect is weight gain[3].Studies show sarcopenic obesityrates doubling from 24%to 47%in the first year of treatment[3],with persisting weight gain appearing early[4].Givenpatients’extended survival,this poses risks for metabolic,cardiovascular,and psychological health.展开更多
The development of inhibitors for the tyrosine anaplastic lymphoma kinase (ALK) has advanced rapidly, driven by biology and medicinal chemistry. The first generation ALK inhibitor crizotinib was granted US FDA approva...The development of inhibitors for the tyrosine anaplastic lymphoma kinase (ALK) has advanced rapidly, driven by biology and medicinal chemistry. The first generation ALK inhibitor crizotinib was granted US FDA approval with only four years of preclinical and clinical testing. Although this drug offers significant clinical benefit to the ALK-positive patients, resistance has been developed through a variety of mechanisms. In addition to ceritinib, alectinib is another second-generation ALK inhibitor launched in 2014 in Japan. This drug has a unique chemical structure bearing a 5H-benzo[b] carbazol-11(611)-one structural scaffold with an IC50 value of 1.9 nmol/L, and is highly potent against ALK bearing the gatekeeper mutation L1196M with an IC50 of 1.56 nmoL/L. In the clinic, alectinib is highly efficacious in treatment of ALK-positive non-small cell lung cancer (NSCLC), and retains potency to combat crizotinib-resistant ALK mutations L11.96.M, F1174L, R1275Q and C1156Y. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. All rights reserved.展开更多
基金Guangzhou Municipal Health Commission Project(Project No.:2023C-TS17)。
文摘Background:The prognosis of stage IV non-small cell lung cancer(NSCLC)with pleural metastasis is poor,with a 5-year survival rate of only 2%to 4%for patients,with the median survival was 9.5-11.5 months.According to the“NCCN Lung Cancer Guidelines,”stage IV NSCLC lung cancer is a contraindication for surgery.It is recommended to adopt a standard treatment plan mainly based on chemotherapy or targeted therapy with EGFR-TKIs.However,Neoadjuvant therapy with alectinib for non-small cell lung cancer with pleural metastasis is rarely reported.Case presentation:A 41-year-old Asian male patient presented with a persistent cough for one month.A chest computed tomography(CT)scan conducted two years prior revealed that a nodular radiative anomalous concentrated shadow was observed in the inferior tongue segment of the upper lobe of the left lung,approximately 2.2×1.6×1.2 cm in size,with a SUVmax of about 5.5.Two small nodular shadows were seen beside the disease in the inferior lingual segment of the upper lobe of the left lung,with the larger one having a diameter of approximately 0.6 cm.Multiple lymph node metastases in the left hilum and mediastinum;Multiple metastases of the left pleura and a small amount of pleural effusion on the left side.The patient began to receive 2 courses of chemotherapy and targeted therapy(pemetrexed+carboplatin+crizotinib)and 1 course of chemotherapy and other targeted therapy(pemetrexed+carboplatin+alectinib).The result of re-examination of CT demonstrated that peripheral lung cancer in the lower lingual segment of the left upper lung is approximately 0.8×0.9 cm in size,slightly smaller than before.A thoracoscopic lobectomy was performed,and the pulmonary bulla was removed concurrently.Pathological examination confirmed non-small cell lung carcinoma(NSCLC)in the mass.Patient discharged on the 7th day after the operation and received 2 courses of chemotherapy(pemetrexed+carboplatin)and had been receiving alectinib targeted drug treatment all along for over 5 years.However,the patient stopped taking the medicine on his own for half a year.Though in the recent CT examination,the result demonstrated no recurrence and metastasis and the patient has been clinically cured.Unfortunately,the results of brain magnetic resonance imaging suggested that multiple brain metastases of lung cancer occurred,and the patient began taking the third-generation ALK-targeted drug lorlatinib.Conclusions:The patient with stage IV non-small cell lung cancer(NSCLC)presenting with pleural metastasis received neoadjuvant alectinib therapy and underwent thoracoscopic lobectomy,which resulted in significant therapeutic effects and fulfilled the criteria for clinical cure.This case highlights the potential for improved preventative strategies and treatment approaches in similar patients.
基金supported by the National Natural Science Foundation(81900070)the Natural Science Foundation of Hunan Province(2020JJ5813)China。
文摘The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South University has treated 2 NSCLC patients with 2 distinct novel ALK gene fusions.Case 1 was a 55-year-old male with a solid nodule located in the right hilar lobe on enhanced CT scan.Case 2 was a 47-year-old female with enhanced CT showing involvement of the left upper lobe of lung.Histopathological examination of tumor tissues confirmed lung adenocarcinoma in both cases.Immunohistochemical(IHC)staining demonstrated positivity for thyroid transcription factor 1(TTF-1)and ALK-D5F3 in tumor cells,while negativity for P40.The next-generation sequencing(NGS)tests identified a PNPT1-ALK(Exon22:Exon20)fusion variant in case 1 and a TCEAL2-ALK(Exon3:Exon19)fusion variant in case 2.The TCEAL2-ALK fusion was further confirmed by amplification refractory mutation system(ARMS)-PCR at the mRNA level.Both patients were treated with oral alectinib at a dosage of 600 mg twice daily.The tumors in both patients were significantly decreased after alectinib treatment,achieving partial response.At the time of submission,there was an absence of disease progression and the progression-free survival(PFS)had surpassed 1 year.It offered compelling evidences that the individuals with NSCLC and harboring either a PNPT1-ALK(Exon22:Exon20)fusion or a TCEAL2-ALK(Exon3:Exon19)fusion,experience favorable therapeutic outcomes through the administration of alectinib.This study expands the known ALK fusion variants database and supports the precision treatment of NSCLC using ALK tyrosine kinase inhibitors(TKIs).
文摘Alectinib is a selective Anaplastic Lymphoma Kinase (ALK) tyrosine kinase inhibitor used as standard therapy for ALK-rearranged lung adenocarcinoma. Hemolytic anemia is considered a rare but significant adverse event of alectinib. Here, we report the case of a 78-year-old female with advanced ALK rearrangement-positive lung adenocarcinoma who developed grade 4 drug-induced hemolytic anemia after receiving alectinib as first-line therapy. We discontinued alectinib treatment and switched to brigatinib. As a result, anemia improved without recurrence of lung adenocarcinoma over one year.
文摘BACKGROUND The development of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitors(TKIs)has remarkably improved the prognosis of patients with ALK-positive advanced non-small cell lung cancer(NSCLC).Alectinib,the second-generation ALK-TKI,has been approved as first-line treatment for advanced or metastatic NSCLC patients with ALK rearrangement.Neoadjuvant therapy can achieve tumor downstaging and eradicate occult lesions in patients with potentially resectable disease.Whether neoadjuvant alectinib can be a conversion therapy in ALK-positive advanced NSCLC patients remains unclear.CASE SUMMARY A 41-year-old man was pathologically diagnosed with locally advanced ALKpositive stage IIIB NSCLC.Alectinib was prescribed to induce tumor downstaging and facilitate the subsequent surgical resection.The tumor was successfully downstaged and pathological complete response was achieved.Left upper lobectomy with mediastinal lymphadenectomy was performed after tumor downstaging.The patient has continued to receive alectinib as adjuvant therapy during postoperative follow-up with a recurrence-free survival of 29 mo as of writing this report.CONCLUSION This case sheds light on the feasibility and safety of alectinib as a neoadjuvant treatment for stage IIIB NSCLC patients with ALK rearrangement.Its efficacy needs to be validated in prospective clinical trials.
基金Supported by the Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority,No.XTZD20180204。
文摘BACKGROUND The aberrant expression of the anaplastic lymphoma kinase(ALK)gene in ALKpositive(ALK+)anaplastic large cell lymphoma(ALCL)is usually due to t(2;5)/NPM-ALK.However,rarely,aberrant ALK expression can also result from a rearrangement of the ALK gene with various partner genes.Central nervous system(CNS)metastasis is very rare in ALK+ALCL.Patients with CNS involvement show an inferior prognosis.CASE SUMMARY Here,we present the case of an 8-year-old girl diagnosed with ALK+ALCL.She presented with fever,skin nodules,leg swelling,and abdominal pain over the preceding 6 mo.She had extensive involvement and showed an extraordinary rare translocation,t(2;17)/CLTC-ALK,as demonstrated by RNA-seq.She underwent chemotherapy as per ALCL99,followed by vinblastine(VBL)maintenance treatment,and achieved complete remission.However,she developed CNS relapse during VBL monotherapy.The patient achieved a durable second remission with high-dose chemotherapy(including methotrexate 8 g/m2)and continuous treatment with alectinib and VBL.CONCLUSION Alectinib showed significant and durable CNS effects in this patient.However,more cases are needed to prove the efficacy and safety of alectinib for pediatric ALK+ALCL patients.
文摘Alectinib is a first-line treatment for patients withadvanced non-small cell lung cancer(NSCLC)harbor-ing anaplastic lymphoma kinase-positive(ALK+)driveraberrations with a median progression-free survival of 35months and a 5-year overall survival of 63%[1].Currently,alectinib also shows improvement as an adjuvant treat-ment in resected stage IA-IIIB ALK+NSCLC[2].Alectinibhas a mild safety profile,but a notable underreported side-effect is weight gain[3].Studies show sarcopenic obesityrates doubling from 24%to 47%in the first year of treatment[3],with persisting weight gain appearing early[4].Givenpatients’extended survival,this poses risks for metabolic,cardiovascular,and psychological health.
基金Financial support from National Natural Science Foundation of China (Nos. 81430080, 81125021 and 81373277)National Science & Technology Major Project on ‘Key New Drug Creation and Manufacturing Program’, China (No. 2012ZX09103-101-035)
文摘The development of inhibitors for the tyrosine anaplastic lymphoma kinase (ALK) has advanced rapidly, driven by biology and medicinal chemistry. The first generation ALK inhibitor crizotinib was granted US FDA approval with only four years of preclinical and clinical testing. Although this drug offers significant clinical benefit to the ALK-positive patients, resistance has been developed through a variety of mechanisms. In addition to ceritinib, alectinib is another second-generation ALK inhibitor launched in 2014 in Japan. This drug has a unique chemical structure bearing a 5H-benzo[b] carbazol-11(611)-one structural scaffold with an IC50 value of 1.9 nmol/L, and is highly potent against ALK bearing the gatekeeper mutation L1196M with an IC50 of 1.56 nmoL/L. In the clinic, alectinib is highly efficacious in treatment of ALK-positive non-small cell lung cancer (NSCLC), and retains potency to combat crizotinib-resistant ALK mutations L11.96.M, F1174L, R1275Q and C1156Y. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. All rights reserved.
