RESUMO
PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the risk of secondary oral cancer following hematopoietic cell transplantation (HCT). METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets to generate a short manual about the best standard of care. RESULTS: Studies described a 7-16-fold higher risk of secondary oral cancer (mainly squamous cell carcinoma) in allogeneic HCT (alloHCT) recipients, particularly in those who developed chronic graft versus host disease (cGVHD). Risk increases over time and is influenced by several risk factors. In autologous HCT, oral cancer risk seemed only slightly elevated. CONCLUSION: Clinicians should be aware of the higher oral cancer risk in alloHCT survivors, and emphasize the importance of lifelong oral cancer surveillance (at least every 6-12 months) and avoiding cancer promoting lifestyle factors in an empathic way, particularly of those with (a history of) cGVHD. Post-HCT for Fanconi anemia or dyskeratosis congenita, education and rigorous follow-up is even more crucial. In case of suspected oral lesions in the presence of oral mucosal cGVHD, a GVHD intervention may facilitate diagnosis. Suspected lesions should be biopsied. More research is needed on the role of HPV in oral cancer post-HCT.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias Bucais , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Neoplasias Bucais/etiologia , Doença Enxerto-Hospedeiro/etiologia , Fatores de Risco , Carcinoma de Células Escamosas/etiologia , Segunda Neoplasia Primária/etiologiaRESUMO
Therapy-related myeloid neoplasms (t-MN) are characterized by aggressive features and a dismal prognosis. Recent evidence suggests a higher incidence of t-MN in individuals harboring clonal hematopoiesis of indeterminate potential (CHIP). In order to gain insight into CHIP-driven malignant progression, we gathered data from ten published reports with available detailed patient characteristics at the time of primary malignancy and t-MN development. Detailed clinical and molecular information on primary malignancy and t-MN were available for 109 patients: 43% harbored at least one somatic mutation at the time of the primary malignancy. TET2 and TP53 mutations showed an increasing variant allele frequency from CHIP to t-MN. ASXL1-associated CHIP significantly correlated with the emergence of TET2 and CEBPA mutations at t-MN, as well as U2AF1-driven CHIP with EZH2 mutation and both IDH2 and SRSF2-driven CHIP with FLT3 mutation. DNMT3A-driven CHIP correlated with a lower incidence of TP53 mutation at t-MN. In contrast, TP53-driven CHIP correlated with a complex karyotype and a lower tendency to acquire new mutations at t-MN. Patients with multiple myeloma as their first malignancy presented a significantly higher rate of TP53 mutations at t-MN. The progression from CHIP to t-MN shows different scenarios depending on the genes involved. A deeper knowledge of CHIP progression mechanisms will allow a more reliable definition of t-MN risk.
Assuntos
Mutação , Segunda Neoplasia Primária , Humanos , Masculino , Feminino , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/etiologia , Idoso , Pessoa de Meia-Idade , Progressão da Doença , Hematopoiese Clonal/genética , Adulto , Transtornos Mieloproliferativos/genética , Idoso de 80 Anos ou maisRESUMO
PURPOSE: In evaluating second primary cancers (SPCs) following External Beam Radiotherapy (EBRT), the role of lifestyle factors is frequently not considered due to data limitations. We investigated the association between smoking, comorbidities, and SPC risks within EBRT-treated patients for localized prostate cancer (PCa). PATIENTS & METHODS: The study included 1,883 PCa survivors aged 50-79, treated between 2006 and 2013, with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT). Clinical data were combined with SPC and survival data from the Netherlands Cancer Registry with a 12-month latency period. Standardized Incidence Ratios (SIRs) were calculated comparing the EBRT cohort with the general Dutch population. To explore the effect of patient and treatment characteristics on SPCs we conducted a Cox regression analysis. Lastly, we estimated cumulative incidences of developing solid SPC, pelvis SPC, and non-pelvis SPC using a competing risk analysis. RESULTS: Significantly increased SIRs were observed for all SPC (SIR = 1.21, 95% confidence interval [CI]: 1.08-1.34), pelvis SPC (SIR = 1.46, 95% CI: 1.18-1.78), and non-pelvis SPC (SIR = 1.18, 95% CI [1.04-1.34]). Smoking status was significantly associated with pelvic and non-pelvic SPCs. Charlson comorbidity index (CCI) ≥ 1 (Hazard Ratio [HR] = 1.45, 95% CI: 1.10-1.91), cardiovascular disease (HR = 1.41, 95% CI: 1.05-1.88), and chronic obstructive pulmonary disease (COPD) (HR = 1.91, 95% CI: 1.30-2.79) were significantly associated with non-pelvis SPC. The proportion of active smoking numbers in the cohort was similar to the general population. INTERPRETATION: We conclude that the presence of comorbidities in the EBRT population might be a relevant factor in observed excess non-pelvis SPC risk, but not for excess pelvis SPC risk.
Assuntos
Segunda Neoplasia Primária , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Idoso , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fatores de Risco , Incidência , Radioterapia de Intensidade Modulada/efeitos adversos , Comorbidade , Fumar/epidemiologia , Fumar/efeitos adversos , Radioterapia Conformacional/efeitos adversos , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Sistema de Registros/estatística & dados numéricosRESUMO
The clinical impact of therapy-related acute leukemias is increasing with the extension of cancer-related survival; however, the origins remain largely unknown. Acute erythroleukemia (AEL), a rare unfavorable type of myeloid neoplasia, may also develop secondary to cytotoxic therapy. The disorder is featured by specific genetic alterations, most importantly multi-allelic mutations of the TP53 gene. While AEL might appear as a part of the therapy-related MDS/AML, spectrum information regarding the genetic complexity and progression is largely missing. We present two AEL cases arising after cytotoxic therapy and melphalan-based myeloablation/autologous peripheral stem cell transplantation due to multiple myeloma (MM). As stated, multiple pathogenic TP53 variants were present unrelated to preexisting MM, in parallel with uninvolved/wild-type hemopoiesis. Potential mechanisms of leukemic transformation are discussed, which include (1) preexisting preneoplastic hemopoietic stem cells (HSC) serving as the common origin for both MM and AEL, (2) the generation and intramedullary survival of p53-deficient post-chemotherapy HSCs, (3) reinoculation of mobilized autologous TP53 mutated HSCs, and (4) melphalan treatment-related late-onset myelodysplasia/leukemia with newly acquired TP53 mutations.
Assuntos
Leucemia Eritroblástica Aguda , Mieloma Múltiplo , Transplante Autólogo , Mieloma Múltiplo/terapia , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Humanos , Pessoa de Meia-Idade , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/patologia , Leucemia Eritroblástica Aguda/terapia , Masculino , Proteína Supressora de Tumor p53/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Transformação Celular Neoplásica/genética , Mutação , Feminino , Melfalan/uso terapêutico , Melfalan/administração & dosagem , Idoso , Quimiorradioterapia/métodos , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/terapia , Segunda Neoplasia Primária/genéticaRESUMO
BACKGROUND: The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern. METHODS: We reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR T cells, and the normal hematopoietic cells in the patient. RESULTS: A total of 724 patients who had received T-cell therapies at our center were included in the study. A lethal T-cell lymphoma was identified in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma, and both lymphomas were deeply profiled. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein-Barr virus and were associated with DNMT3A and TET2 mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques. CONCLUSIONS: Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.).
Assuntos
Antineoplásicos Imunológicos , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Linfoma de Células T , Segunda Neoplasia Primária , Receptores de Antígenos Quiméricos , Feminino , Humanos , Pessoa de Meia-Idade , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Hematopoiese Clonal , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/genética , Imunoterapia Adotiva/efeitos adversos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma de Células T/etiologia , Linfoma de Células T/genética , Linfoma de Células T/imunologia , Linfoma de Células T/terapia , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/etiologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Integração ViralRESUMO
Renal cancer, although still rare among individuals under 45 years of age, is on the rise in the general population. The risk and timing of subsequent renal cancer in survivors of childhood cancer is not well established. Using the SEER registry, we reported the incidence of subsequent malignant renal neoplasms after treatment for primary malignancy diagnosed under 20 years of age. We evaluated clinical characteristics, standardized incidence ratio (SIR), and Kaplan-Meier survival estimates. Fifty-three survivors developed subsequent renal cancer (54 total cases). Of these, 54.7% were female, 88.7% were white, and 13.2% were Hispanic. Mean ages at primary malignancy and subsequent renal cancer were 10.1 and 31.1 years, respectively. Forty-seven cases were second cancers, 6 were third, and 1 was fourth. For survivors of childhood cancer, the overall SIR for renal cancer was 4.52 (95% CI: 3.39-5.89). The 5-year overall survival rate after development of subsequent renal cancer was 73% (95% CI: 58%-83%). Renal cancer occurs 4.5 times more frequently in childhood cancer survivors than in the general population, necessitating long-term care considerations.
Assuntos
Sobreviventes de Câncer , Neoplasias Renais , Segunda Neoplasia Primária , Programa de SEER , Humanos , Feminino , Masculino , Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias Renais/epidemiologia , Neoplasias Renais/mortalidade , Criança , Adolescente , Pré-Escolar , Adulto , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/mortalidade , Incidência , Adulto Jovem , Lactente , Taxa de Sobrevida , Neoplasias/epidemiologia , Neoplasias/mortalidade , Estados Unidos/epidemiologiaRESUMO
PURPOSE: The increased risk of second cancer after prostate radiotherapy is a debated clinical concern. The objective of the study was to assess the risk of occurrence of second cancers after prostate radiation therapy based on the analysis the literature, and to identify potential factors explaining the discrepancies in results between studies. MATERIALS AND METHODS: A review of the literature was carried out, comparing the occurrence of second cancers in patients all presenting with prostate cancer, treated or not by radiation. RESULTS: This review included 30 studies reporting the occurrence of second cancers in 2,112,000 patients treated or monitored for localized prostate cancer, including 1,111,000 by external radiation therapy and 103,000 by brachytherapy. Regarding external radiation therapy, the average follow-up was 7.3years. The majority of studies (80%) involving external radiation therapy, compared to no external radiation therapy, showed an increased risk of second cancers with a hazard ratio ranging from 1.13 to 4.9, depending on the duration of the follow-up. The median time to the occurrence of these second cancers after external radiotherapy ranged from 4 to 6years. An increased risk of second rectal and bladder cancer was observed in 52% and 85% of the studies, respectively. Considering a censoring period of more than 10 years after irradiation, 57% and 100% of the studies found an increased risk of rectal and bladder cancer, without any impact in overall survival. Studies of brachytherapy did not show an increased risk of second cancer. However, these comparative studies, most often old and retrospective, had many methodological biases. CONCLUSION: Despite numerous methodological biases, prostate external radiation therapy appears associated with a moderate increase in the risk of second pelvic cancer, in particular bladder cancer, without impacting survival. Brachytherapy does not increase the risk of a second cancer.
Assuntos
Braquiterapia , Neoplasias Induzidas por Radiação , Segunda Neoplasia Primária , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/epidemiologia , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/etiologia , Neoplasias Retais/radioterapia , Neoplasias Retais/etiologiaRESUMO
Thyroid cancer is the ninth most common cancer worldwide. While differentiated thyroid cancer (DTC) has a high survival rate, concerns arise regarding optimal treatment strategies and potential long-term risks, including second primary malignancies (SPMs), associated with therapies such as radioiodine (RAI). The aim of the present study was to investigate the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia in Germany. This retrospective cohort study used the IQVIA TM Disease Analyzer database and included adults with a first documented diagnosis of thyroid cancer between January 2005 and December 2021 as well as propensity score matched individuals without thyroid cancer in 1284 general practices. Univariate Cox regression models were performed to examine the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia. A total of 4232 thyroid cancer patients (mean age: 54.2 years; 73.6% female) and 21 160 controls (mean age: 54.2 years; 72.6% female) were available for analyses. Thyroid cancer was significantly associated with a higher lymphoma incidence (HR: 3.35, 95% CI: 2.04-5.52), especially in men (HR: 5.37) and those aged 61-70 years. Leukemia incidence was not significantly associated with thyroid cancer (HR: 1.79, 95% CI: 0.91-3.53), although associations were notable in younger age groups. Thyroid cancer is positively associated with a risk of subsequent lymphoma, highlighting the need for vigilant surveillance and tailored treatment strategies. While the association with leukemia is less pronounced, close surveillance remains critical, especially in younger patients.
Assuntos
Leucemia , Linfoma , Neoplasias da Glândula Tireoide , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Alemanha/epidemiologia , Estudos Retrospectivos , Idoso , Linfoma/epidemiologia , Leucemia/epidemiologia , Leucemia/complicações , Adulto , Incidência , Fatores de Risco , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologiaRESUMO
INTRODUCTION: Medulloblastoma is a central nerves tumor that often occurs in pediatrics. The main radiotherapy technique for this tumor type is craniospinal irradiation (CSI), through which the whole brain and spinal cord are exposed to radiation. Due to the immaturity of healthy organs in pediatrics, radiogenic side effects such as second cancer are more severe. Accordingly, the current study aimed to evaluate the risk of secondary cancer development in healthy organs following CSI. MATERIALS AND METHODS: Seven organs at risk (OARs) including skin, eye lens, thyroid, lung, liver, stomach, bladder, colon, and gonads were considered and the dose received by each OAR during CSI was measured inside an anthropomorphic RANDO phantom by TLDs. Then, the mean obtained dose for each organ was used to estimate the probability of secondary malignancy development according to the recommended cancer risk coefficients for specific organs. RESULTS: The results demonstrated that the stomach and colon are at high risk of secondary malignancy occurrence, while the skin has the lowest probability of secondary cancer development. The total received dose after the treatment course by all considered organs was lower than the corresponding tolerable dose levels. CONCLUSIONS: From the results, it can be concluded that some OARs during CSI are highly at risk of secondary cancer development. This issue may be of concern due to organ immaturity in pediatrics which can intensify the radiogenic effects of radiation exposure. Accordingly, strict shielding the OARs during craniospinal radiotherapy and/or sparing them from the radiation field through modern techniques such as hadron therapy is highly recommended.
Assuntos
Radiação Cranioespinal , Meduloblastoma , Neoplasias Induzidas por Radiação , Órgãos em Risco , Humanos , Radiação Cranioespinal/efeitos adversos , Órgãos em Risco/efeitos da radiação , Medição de Risco , Neoplasias Induzidas por Radiação/etiologia , Meduloblastoma/radioterapia , Criança , Segunda Neoplasia Primária/etiologia , Masculino , Dosagem Radioterapêutica , Feminino , Neoplasias Cerebelares/radioterapiaRESUMO
SUMMARY: Given the rarity of cancer in childhood, it should be even more uncommon for pediatric cancer survivors to develop a second, independent malignancy, yet they incur a greatly elevated risk after initial remission. In this issue of Cancer Discovery, Sánchez-Guixé and colleagues unpick the origins of second tumours in four children, and the potential role platinum-based chemotherapy may play in subsequent tumorigenesis. See related article by Sánchez-Guixé et al., p. 953 (8).
Assuntos
Segunda Neoplasia Primária , Humanos , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/epidemiologia , Criança , Sobreviventes de Câncer , Neoplasias/tratamento farmacológicoRESUMO
Type II diabetes is associated with cancer risk in the general population but has not been well studied as a risk factor for subsequent malignancies among cancer survivors. We investigated the association between diabetes and subsequent cancer risk among older (66-84 years), 1-year breast cancer survivors within the linked Surveillance Epidemiology and End Results (SEER)-Medicare database using Cox regression analyses to quantify hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Among 133â324 women, 29.3% were diagnosed with diabetes before or concurrent with their breast cancer diagnosis, and 10â452 women developed subsequent malignancies over a median follow-up of 4.3 years. Diabetes was statistically significantly associated with liver (HR = 2.35, 95% CI = 1.48 to 3.74), brain (HR = 1.94, 95% CI = 1.26 to 2.96), and thyroid cancer risks (HR = 1.38, 95% CI = 1.01 to 1.89). Future studies are needed to better understand the spectrum of subsequent cancers associated with diabetes and the role of diabetes medications in modifying subsequent cancer risk, alone or in combination with cancer treatments.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Diabetes Mellitus Tipo 2 , Modelos de Riscos Proporcionais , Programa de SEER , Humanos , Feminino , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Idoso de 80 Anos ou mais , Sobreviventes de Câncer/estatística & dados numéricos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Estados Unidos/epidemiologia , Fatores de Risco , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/etiologia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/etiologia , Medicare/estatística & dados numéricos , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologiaRESUMO
Acute promyelocytic leukaemia (APL) is a form of acute myelogenous leukaemia. APL is characterised by anaemia due to suppression of normal haematopoiesis and infection. Haematopoietic stem cell transplantation (HSCT) is current option for the treatment of haematopoietic malignancies and is proving to be successful. Although HSCT has been effective for the treatment of haematopoietic malignant tumours, chronic graft-versushost disease (GVHD) but secondary cancers can occur, which is a serious complication and frequently involves the oral cavity and skin. Here, we report the case of tongue cancer occurring 17 years after transplantation in a patient who developed GVHD after haematopoietic stem cell transplantation and APL remission. To the best of our knowledge, this is the first report of secondary oral cancer after HSCT with APL as the primary disease.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Promielocítica Aguda , Neoplasias da Língua , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Promielocítica Aguda/terapia , Neoplasias da Língua/cirurgia , Neoplasias da Língua/terapia , Masculino , Doença Enxerto-Hospedeiro/etiologia , Pessoa de Meia-Idade , Adulto , Segunda Neoplasia Primária/etiologiaRESUMO
BACKGROUND: The most common form of therapy for nonsmall cell lung cancer (NSCLC) in early stage is surgery-based combination therapy, including radiotherapy and immunotherapy. However, postoperative radiotherapy (PORT) of cancer is correlated with increasing risk of second primary malignancy (SPM), especially young-onset cancer cases. The authors aimed to quantify the risks of SPM associated with PORT treatment for youngonset NSCLC in early stage. METHODS: The authors screened for SPM that developed over 5 years since the diagnosis of NSCLC. Using the data from the Surveillance, Epidemiology, and End Results database, PORT-correlated risks were estimated with multivariate Logistic regression analysis. Moreover, Fine-Gray's competing risk regression analysis was used to calculate the cumulative incidence of SPMs. RESULTS: Among the 30 308 young-onset NSCLC patients in early stage undergoing surgery, a total of 3728 patients have received PORT. Logistic regression analyses showed that PORT showed substantial correlation with elevated risks of second solid malignancies [relative risks (RR)=1.31; 95% CI: 1.17-1.46], lung cancer (RR=1.23; 95% CI: 1.07-1.42), breast cancer (RR=1.74; 95% CI: 1.16-2.74), and colon and rectum cancers (RR=1.37; 95% CI: 1.07-2.06) as well as a negligible risk of second hematologic malignancies (RR=1.15; 95% CI: 0.82-1.67). The cumulative incidence of SPMs revealed similar findings. Higher RR was obtained in NSCLC patients aged 60-69 years (RR=1.33), in white race (RR=1.36), diagnosed in 1975-2000 (RR=1.23) and 2001-2015 (RR=1.40), or diagnosed with lung adenocarcinoma (RR=1.55). CONCLUSION: PORT for young-onset NSCLC in early stage was correlated with elevated risks of SPMs (lung cancer, breast cancer, as well as colon and rectum cancers), supporting the need for long-term surveillance of these patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Segunda Neoplasia Primária , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Feminino , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto , Programa de SEER , Fatores de Risco , Idoso , Incidência , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/estatística & dados numéricosRESUMO
The introduction of chimeric antigen receptor (CAR) T-cell therapy represents a landmark advancement in treating resistant forms of cancer such as leukemia, lymphoma, and myeloma. However, concerns about long-term safety have emerged following an FDA investigation into reports of second primary malignancies (SPM) after CAR-T cell treatment. This review offers a thorough examination of how genetically modified T cells might transform into CAR+ SPM. It explores genetic and molecular pathways leading to T-cell lymphomagenesis, the balance between CAR T-cell persistence, stemness, and oncogenic risk, and the trade-off of T-cell exhaustion, which may limit therapy efficacy but potentially reduce lymphomagenesis risk. Significance: An FDA probe into 22 cases of second primary T-cell malignancies following CAR T-cell therapy stresses the need to investigate their origins. Few may arise from preexisting genetic and epigenetic alterations and those introduced during therapeutic engineering. Technological advances, regulatory oversight, and patient monitoring are essential to mitigate potential risks.
Assuntos
Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/terapia , Segunda Neoplasia Primária/imunologia , Linfoma de Células T/terapia , Linfoma de Células T/imunologiaRESUMO
OBJECTIVE: Radiation therapy (RT) may increase the risk of second cancer. This study aimed to determine the association between exposure to radiotherapy for the treatment of thoracic cancer (TC) and subsequent secondary lung cancer (SLC). MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for TC. Univariate Cox regression analyses and multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SLC. Subgroup analyses of patients stratified by latency time since TC diagnosis, age at TC diagnosis, and calendar year of TC diagnosis stage were also performed. Overall survival and SLC-related death were compared among the RT and no radiation therapy (NRT) groups by using Kaplan-Meier analysis and competitive risk analysis. RESULTS: In a total of 329 129 observations, 147 847 of whom had been treated with RT. And 6799 patients developed SLC. Receiving radiotherapy was related to a higher risk of developing SLC for TC patients (adjusted HR, 1.25; 95% CI, 1.19-1.32; P < 0.001). The cumulative incidence of developing SLC in TC patients with RT (3.8%) was higher than the cumulative incidence (2.9%) in TC patients with NRT(P). The incidence risk of SLC in TC patients who received radiotherapy was significantly higher than the US general population (SIR, 1.19; 95% CI, 1.14-1.23; P < 0.050). CONCLUSIONS: Radiotherapy for TC was associated with higher risks of developing SLC compared with patients unexposed to radiotherapy.
Assuntos
Neoplasias Pulmonares , Segunda Neoplasia Primária , Programa de SEER , Neoplasias Torácicas , Humanos , Masculino , Feminino , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/epidemiologia , Pessoa de Meia-Idade , Idoso , Incidência , Prognóstico , Neoplasias Torácicas/radioterapia , Neoplasias Torácicas/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Radioterapia/efeitos adversos , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Medição de Risco/métodos , AdultoRESUMO
The improved survival rates of childhood cancers raise the long-term risk of second primary malignancy (SPM) in childhood and adolescent cancer survivors. The intensity of the treatment protocol used, the use of some groups of chemotherapeutics, and radiotherapy were found to be risk factors for the development of second primary malignancies (SPMs). Forty-one patients who developed acute myelocytic leukemia or any solid organ cancer within 25 years of follow-up, after completion of pediatric acute lymphoblastic leukemia (ALL) treatment, were included in the study. The mean duration of initial ALL diagnosis to SPM was 9.3 ± 6.1 years. The 3 most common SPMs were acute myelocytic leukemia, glial tumors, and thyroid cancer. Thirteen (81%) of 16 patients exposed to cranial irradiation had cancer related to the radiation field. In total 13/41 (32%) patients died, and the 5-year overall survival rate was 70 ± 8%. Patients older than 5 years old at ALL diagnosis had significantly worse overall survival than cases younger than 5 years old. In conclusion, children and adolescents who survive ALL have an increased risk of developing SPM compared with healthy populations, and physicians following these patients should screen for SPMs at regular intervals.
Assuntos
Sobreviventes de Câncer , Segunda Neoplasia Primária , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/mortalidade , Masculino , Feminino , Adolescente , Pré-Escolar , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Turquia/epidemiologia , Sobreviventes de Câncer/estatística & dados numéricos , Lactente , Taxa de Sobrevida , Fatores de Risco , SeguimentosRESUMO
Introduction: Over the past decade, immune checkpoint inhibitors such as antibodies against cytotoxicity T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have become an important armamentarium against a broad spectrum of malignancies. However, these specific inhibitors can cause adverse autoimmune reactions by impairing self-tolerance. Hematologic side effects of immune checkpoint inhibitors, including autoimmune hemolytic anemia (AIHA), are rare but can be life-threatening. Case report: Herein, we report two patients on immune checkpoint inhibitors for metastatic melanoma who developed AIHA with symptoms of dyspnea and fatigue. In the first patient, symptoms alleviated after discontinuation of combined anti CTLA-4 and anti-PD-1 therapy, initiation of corticosteroids and application of a single red blood cell transfusion. Due to subsequent progress of melanoma, combinational anti-PD-1 and tyrosine kinase inhibitor therapy was initiated based on multidisciplinary tumor board decision. After two months, she again developed the described hematological and clinical signs of AIHA leading to cessation of anti-PD-1 therapy and initiation of corticosteroids, which again resulted in an alleviation of her symptoms. Due to further progression, the patient received dacarbazine for several months before she decided to stop any therapy other than palliative supportive care. In the second patient, discontinuation of anti-PD-1 therapy and initiation of corticosteroids entailed a complete alleviation of his symptoms. After refusing chemotherapy due to subsequent melanoma progression, he received radiotherapy of bone metastases and is currently enrolled in a clinical trial. The patient did not develop AIHA ever since. Conclusion: Hematologic immune-related adverse events due to treatment with immune checkpoint inhibitors are rare but can have life-threatening consequences. If dyspnea and other clinical symptoms are present, AIHA should be considered as a potential cause and treated promptly in a multidisciplinary setting. An expanded comprehension of risk factors and pathogenesis of AIHA is needed to identify high-risk patients beforehand, leading to more effective predictive and reactive treatment approaches.