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1.
Lancet Haematol ; 8(4): e278-e288, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33770483

RESUMO

BACKGROUND: To improve the long-term tumour control in early, unfavourable Hodgkin Lymphoma, the German Hodgkin Study Group (GHSG) HD14 trial compared four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with an intensified chemotherapy regimen consisting of two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escalated BEACOPP) plus two cycles of ABVD. The final analysis of the trial showed a significant advantage in terms of freedom from treatment failure (difference 7·2% [95% CI 3·8-10·5] at 5 years) for patients who received two cycles of escalated BEACOPP and two cycles of ABVD. However, there was no difference in overall survival between the two groups. To evaluate long-term efficacy and toxicity of this strategy, we did a follow-up analysis. METHODS: Patients aged 18-60 years with performance status of 2 or less and primary diagnosis of early, unfavourable Hodgkin lymphoma (all histologies) were included in an international, randomised, open-label, phase 3 trial. Patients were randomly assigned to receive four cycles of ABVD (ABVD group) or two cycles of escalated BEACOPP and two cycles of ABVD (2 + 2 group), both groups also received 30 Gy involved field radiotherapy. The ABVD dosing regimen was doxorubicin 25 mg/m2 (days 1 and 15), bleomycin 10 mg/m2 (days 1 and 15), vinblastine 6 mg/m2 (days 1 and 15), and dacarbazine 375 mg/m2 (days 1 and 15), repeated on day 29. The escalated BEACOPP dosing regimen was cyclophosphamide 1250 mg/m2 (day 1), doxorubicin 35 mg/m2 (day 1), etoposide 200 mg/m2 (days 1-3), procarbazine 100 mg/m2 (days 1-7), prednisone 40 mg/m2 (days 1-14), vincristine 1·4 mg/m2 (day 8; maximum 2 mg), and bleomycin 10 mg/m2 (day 8), repeated on day 22. After closure of the ABVD group according to prespecified rules, patients were assigned to receive two cycles of escalated BEACOPP and two cycles of ABVD (non-randomised 2 + 2 group), which continued until the end of the predefined 5-year recruitment period. In this prespecified long-term follow-up analysis, we aimed to evaluate the secondary endpoints progression-free survival, overall survival, and long-term toxicity. To this end, we did a descriptive intention-to-treat analysis of all qualified HD14 patients and on the predefined subsets of randomised qualified HD14 patients and patients in the non-randomised 2 + 2 group. The trial was registered on the International Standard Randomised Controlled Trial database, 04761296. FINDINGS: Between Jan 28, 2003, and Dec 29, 2009, 1686 patients were randomly assigned to the ABVD group (847 [50·2%] patients) and the 2 + 2 group (839 [49·8%] patients). 370 additional patients were recruited to the non-randomised 2 + 2 group. 1550 (92%) randomly assigned patients (median observation time 112 months [IQR 80-132]) and 339 (92%) patients in the non-randomised 2 + 2 group (median observation time 74 months [58-100]) were included in the qualified analysis set. 10-year overall survival in the randomly assigned patients was 94·1% (95% CI 92·0-95·7) for the ABVD group and 94·1% (91·8-95·7) for the 2 + 2 group (HR 1·0 [95% CI 0·6-1·5]; p=0·88). 8-year overall survival in the non-randomised 2 + 2 group was 95·1% (95% CI 91·6-97·2). 10-year progression-free survival in the randomly assigned patients was 85·6% (95% CI 82·6-88·1) for the ABVD group and 91·2% (88·4-93·3) for the 2 + 2 group (HR 0·5% [95% CI 0·4-0·7]; p=0·0001), accounting for a significant difference of 5·6% (95% CI 1·9-9·2) favouring the 2 + 2 group (p=0·0001). In the non-randomised 2 + 2 group, 8-year progression-free survival was 94·5% (95% CI 91·1-96·6). Standardised incidence ratios of second primary malignancies were similar between the ABVD group (2·3 [95% CI 1·6-3·1]) and the 2 + 2 group (2·5 [1·8-3·4]; Gray's p=0·80). Standardised incidence ratio of second primary malignancies was 3·1 (95% CI 1·7-5·0) in the non-randomised 2 + 2 group. INTERPRETATION: This long-term analysis confirms superior tumour control in the 2 + 2 group compared with the ABVD group without translating into an overall survival difference. At longer follow-up, there is no difference regarding second primary malignancies between groups. In conclusion, the 2 + 2 regimen spares a significant number of patients from the burden of relapse and additional treatment without increased long-term toxicity. FUNDING: Deutsche Krebshilfe eV and Swiss Federal Government.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adulto , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Alemanha/epidemiologia , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Segunda Neoplasia Primária/epidemiologia , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Procarbazina/administração & dosagem , Procarbazina/uso terapêutico , Intervalo Livre de Progressão , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Vincristina/administração & dosagem , Vincristina/uso terapêutico
2.
Magy Onkol ; 65(1): 39-45, 2021 Mar 17.
Artigo em Húngaro | MEDLINE | ID: mdl-33730115

RESUMO

Head and neck cancer patients are at high risk for secondary primary cancer (SPC) development. Mutagen hypersensitivity may be associated with elevated risk of SPC. A survey was made of SPC among 124 young (≤50 years) patients with squamous cell carcinoma of the head and neck who were enrolled in a pretreatment mutagen sensitivity investigation during 1996-2006. Mutagen sensitivity was assessed by exposing lymphocytes to bleomycin in vitro and quantitating the bleomycin-induced chromatid breaks per cell (b/c). Patients were classified as hypersensitive (>1 b/c) or not hypersensitive (≤1 b/c). The mean follow-up time was 64 months (range: 5-244 months). Eighteen patients (15%) developed a SPC. The 10-year estimated rate of SPC for hypersensitive (n=65) or not hypersensitive (n=59) patients were 17% and 30%, respectively (p=0.4272). Thirty-nine percent of SPC was developed after 10-year follow-up. The 5-year cancer-specific survival was 17% following the development of SPC. According to our findings, mutagen hypersensitivity does not increase the risk of developing SPC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Segunda Neoplasia Primária , Bleomicina/efeitos adversos , Carcinoma de Células Escamosas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Mutagênicos , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia
3.
J Surg Oncol ; 123(2): 622-629, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33616972

RESUMO

BACKGROUND: A subset of metachronous colon cancer recurrence manifests as peritoneal metastases (PM). Risk factors for metachronous PM recurrence are not well-defined in patients with stage II or III colon cancers after curative resection and standard adjuvant treatments. METHODS: Population data from the California Cancer Registry for patients with Stage II or III colon cancer were collected between 2004 and 2012. Multivariate analysis was used to identify factors associated with metachronous PM. RESULTS: Of the 2077 patients with stage II or III colon cancer, female patients (odds ratio [OR] = 1.84, p = 0.02), T4 primary tumor (OR = 2.36, p = 0.02), mucinous (OR = 3.97, p < 0.01) or signet-ring histology (OR = 6.01, p = 0.01), and right-sided cancer (OR = 2.2, p < 0.01) were found with increased risk of metachronous isolated PM recurrence after curative resection. Median survival after diagnosis for patients without PM recurrence was 22 months, compared with 12 months for PM recurrence (p < 0.001). CONCLUSION: PM recurrence groups have a worse overall survival than patients with recurrent disease in other sites. A better understanding of the tumor biology and molecular characteristics of colon cancers likely to recur as PM is needed to explain behavior and identify potential targeted therapy.


Assuntos
Colectomia/efeitos adversos , Neoplasias do Colo/cirurgia , Recidiva Local de Neoplasia/patologia , Segunda Neoplasia Primária/secundário , Neoplasias Peritoneais/secundário , Idoso , Neoplasias do Colo/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Segunda Neoplasia Primária/epidemiologia , Neoplasias Peritoneais/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
4.
JAMA Netw Open ; 4(1): e2031661, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33416884

RESUMO

Importance: Radiotherapy is a common treatment for rectal cancer, yet the risk of second gynecological malignant neoplasms (SGMNs) in patients with rectal cancer undergoing radiotherapy have not been adequately studied. Objective: To investigate the association between radiotherapy and the risk of individual types of SGMN in patients with rectal cancer and assess survival outcomes. Design, Setting, and Participants: A large population-based cohort study was designed to identify the risk of SGMNs in patients with rectal cancer diagnosed from January 1973 to December 2015. The statistical analysis was conducted from September 2019 to April 2020. The study was based on the 9 cancer registries of Surveillance, Epidemiology, and End Results database. A total of 20 142 female patients with rectal cancer in localized and regional stage were included. Exposure: Receipt of neoadjuvant radiotherapy for rectal cancer. Main Outcomes and Measures: The development of an SGMN defined as any type of GMN occurring more than 5 years after the diagnosis of rectal cancer. The cumulative incidence of SGMNs was estimated by Fine-Gray competing risk regression. Poisson regression was used to evaluate the radiotherapy-associated risk for SGMNs in patients undergoing radiotherapy vs patients not undergoing radiotherapy. The Kaplan-Meier method was used to assess the survival outcomes of patients with SGMNs. Results: Of 20 142 patients, 16 802 patients (83.4%) were White and the median age was 65 years (interquartile range, 54-74 years). A total of 5310 (34.3%) patients were treated with surgery and radiotherapy, and 14 832 (65.7%) patients were treated with surgery alone. The cumulative incidence of SGMNs during 30 years of follow-up was 4.53% among patients who received radiotherapy and 1.53% among patients who did not. In competing risk regression analysis, undergoing radiotherapy was associated with a higher risk of developing cancer of the uterine corpus (adjusted hazard ratio, 3.06; 95% CI, 2.14-4.37; P < .001) and ovarian cancer (adjusted hazard ratio, 2.08; 95% CI, 1.22-3.56; P = .007) compared with those who did not receive radiotherapy. The dynamic radiotherapy-associated risks (RR) for cancer of the uterine corpus significantly increased with increasing age at rectal cancer diagnosis (aged 20-49 years: adjusted RR, 0.79; 95% CI, 0.35-1.79; P = .57; aged 50-69 years: adjusted RR, 3.74; 95% CI, 2.63-5.32; P < .001; aged ≥70 years: adjusted RR, 5.13; 95% CI, 2.64-9.97; P < .001) and decreased with increasing latency since rectal cancer diagnosis (60-119 months: adjusted RR, 3.22; 95% CI, 2.12-4.87; P < .001; 120-239 months: adjusted RR, 2.72; 95% CI, 1.75-4.24; P < .001; 240-360 months: adjusted RR, 1.95; 95% CI, 0.67-5.66; P = .22), but the dynamic RR for ovarian cancer increased with increasing latency since rectal cancer diagnosis (60-119 months: adjusted RR, 0.70; 95% CI, 0.26-1.89; P = .48; 120-239 months: adjusted RR, 2.26; 95% CI, 1.09-4.70; P = .03; 240-360 months: adjusted RR, 11.84; 95% CI, 2.18-64.33; P = .004). The 10-year overall survival among patients with radiotherapy-associated cancer of the uterine corpus was significantly lower than that among matched patients with primary cancer of the uterine corpus (21.5% vs 33.6%; P = .01). Conclusions and Relevance: Radiotherapy for rectal cancer was associated with an increased risk of cancer of the uterine corpus and ovarian cancer. Special attention should be paid to reduce radiotherapy-associated SGMNs and improve their prognosis.


Assuntos
Neoplasias dos Genitais Femininos/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias Retais/epidemiologia , Neoplasias Retais/radioterapia , Idoso , Estudos de Coortes , Feminino , Seguimentos , Neoplasias dos Genitais Femininos/etiologia , Humanos , Incidência , Pessoa de Meia-Idade , Terapia Neoadjuvante/estatística & dados numéricos , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/patologia , Neoplasias Retais/patologia , Programa de SEER , Estados Unidos/epidemiologia
5.
Cancer Radiother ; 25(2): 114-118, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33487559

RESUMO

PURPOSE: The breast sarcoma induced by radiation therapy is rare but increasing, given the increased long-term survival of patients receiving radiation therapy. Fibrosarcoma, histiocytofibroma and angiosarcoma are the most common breast sarcoma. Angiosarcoma is the most common after breast cancer treated by radiation therapy, often diagnosed too late, with a severe prognosis and a high rate of recurrence. However, because of the low incidence of angiosarcoma associated with radiation therapy (AAR), the benefit of radiation therapy in breast cancer treatment outweighs the risk to develop angiosarcoma. The aim of this study is to evaluate these rare cases of AAR diagnosed in eastern Belgium in comparison to the data from the literature. PATIENTS AND METHODS: Nine cases of AAR after radiation for breast ductal carcinoma were included in this retrospective study. AAR was diagnosed according to Cahan criteria between January 2007 and December 2016. Latency, incidence, management and prognosis are comparable to the literature. RESULTS, CONCLUSION: The median latency was 10 (4-24) years, the incidence of AAR in the East Belgian area was 0.09% of the patients irradiated on the same period. Patients were treated by surgery with wide local excision with or without reconstructive surgery, without radiotherapy and chemotherapy treatment. Kaplan-Meier analysis showed median overall survival of 61.8 months, patient survival of 55.6% at one year and 29.6% at five years. With the constant progress of medicine and its technologies, it would be possible to limit the occurrence of AAR or to diagnose it at an earlier stage.


Assuntos
Neoplasias da Mama/etiologia , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Hemangiossarcoma/etiologia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/mortalidade , Feminino , Hemangiossarcoma/epidemiologia , Hemangiossarcoma/mortalidade , Hemangiossarcoma/cirurgia , Humanos , Incidência , Estimativa de Kaplan-Meier , Mastectomia , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/mortalidade , Neoplasias Induzidas por Radiação/cirurgia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/cirurgia , Doenças Raras/epidemiologia , Doenças Raras/etiologia , Doenças Raras/mortalidade , Doenças Raras/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Neoplasias Unilaterais da Mama/epidemiologia , Neoplasias Unilaterais da Mama/etiologia , Neoplasias Unilaterais da Mama/mortalidade
6.
Crit Rev Oncol Hematol ; 157: 103175, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33321295

RESUMO

Second breast cancer (SBC) is the most common solid cancer among Hodgkin Lymphoma (HL) female survivors. We reviewed the related modifying risk factors, radiation-induced carcinogenesis, tumors characteristics, management specificities, prevention and surveillance modalities based on current evidence. The risk of developing SBC may be influenced essentially by the age at HL treatment, follow-up latency, dose of irradiation received and the extent of irradiated field. SBCs generally develop at younger age, they are often bilateral, and exhibit more aggressive biological features and worse prognosis. No firm answer about the benefits of breast surveillance is provided by literature, but compelling evidence tends toward a clinical benefit in early detection. Increasing awareness among health providers' care and current survivors as well as the implementation of screening measures is crucial. Great efforts are ongoing in individualizing treatment strategies for future HL patients and response-adapted approaches are holding promise in prevention of these second malignancies.


Assuntos
Neoplasias da Mama , Doença de Hodgkin , Segunda Neoplasia Primária , Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/terapia , Humanos , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Sobreviventes
7.
JAMA ; 324(24): 2521-2535, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33351041

RESUMO

Importance: The number of cancer survivors who develop new cancers is projected to increase, but comprehensive data on the risk of subsequent primary cancers (SPCs) among survivors of adult-onset cancers are limited. Objective: To quantify the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types and sex. Design, Setting, and Participants: A retrospective cohort study from 12 Surveillance, Epidemiology, and End Results registries in the United States, that included 1 537 101 persons aged 20 to 84 years diagnosed with FPCs from 1992-2011 (followed up until December 31, 2017) and who survived at least 5 years. Exposures: First primary cancer. Main Outcomes and Measures: Incidence and mortality of SPCs per 10 000 person-years; standardized incidence ratio (SIR) and standardized mortality ratio (SMR) compared with those expected in the general population. Results: Among 1 537 101 survivors (mean age, 60.4 years; 48.8% women), 156 442 SPC cases and 88 818 SPC deaths occurred during 11 197 890 person-years of follow-up (mean, 7.3 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 18 of the 30 FPC types, and risk of dying from any SPCs was statistically significantly higher for 27 of 30 FPC types as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 21 of the 31 FPC types, and risk of dying from any SPCs was statistically significantly higher for 28 of 31 FPC types as compared with risks in the general population. The highest overall SIR and SMR were estimated among survivors of laryngeal cancer (SIR, 1.75 [95% CI, 1.68-1.83]; incidence, 373 per 10 000 person-years) and gallbladder cancer (SMR, 3.82 [95% CI, 3.31-4.39]; mortality, 341 per 10 000 person-years) among men, and among survivors of laryngeal cancer (SIR, 2.48 [95% CI, 2.27-2.72]; incidence, 336 per 10 000 person-years; SMR, 4.56 [95% CI, 4.11-5.06]; mortality, 268 per 10 000 person-years) among women. Substantial variation existed in the associations of specific types of FPCs with specific types of SPC risk; however, only a few smoking- or obesity-associated SPCs, such as lung, urinary bladder, oral cavity/pharynx, colorectal, pancreatic, uterine corpus, and liver cancers constituted considerable proportions of the total incidence and mortality, with lung cancer alone accounting for 31% to 33% of mortality from all SPCs. Conclusions and Relevance: Among survivors of adult-onset cancers in the United States, several types of primary cancer were significantly associated with greater risk of developing and dying from an SPC, compared with the general population. Cancers associated with smoking or obesity comprised substantial proportions of overall SPC incidence and mortality among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors.


Assuntos
Sobreviventes de Câncer , Segunda Neoplasia Primária/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/mortalidade , Obesidade/complicações , Estudos Retrospectivos , Risco , Programa de SEER , Fumar/efeitos adversos , Estados Unidos/epidemiologia
8.
Medicine (Baltimore) ; 99(30): e21328, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791729

RESUMO

The purpose of this study was to report the clinicopathological characteristics and treatment outcomes of 45 rectal cancer patients who have a history of cervical cancer with or without remote radiotherapy. Twenty-nine patients (64.4%) with a history of cervical cancer treated with pelvic radiotherapy were classified as group A, 16 (35.6%) patients with a history of cervical cancer not treated with radiotherapy were classified as group B. The median duration between radiotherapy for cervical cancer and rectal adenocarcinoma diagnosis was 18 years. At the time of rectal cancer diagnosis, 5 (17.2%) patients presented stage I disease, 15 (51.7%) had stage II, 1 (3.4%) had stage III, and 8 (27.6%) had stage IV. The patients in group A had older age, higher rates of gross ulcerative lesions, low hemoglobin levels, and a lower rate of lymph node metastases. The patients with secondary rectal cancer developed after radiotherapy for cervical cancer usually presented with abnormal abdominal symptoms, such as proctitis, cystitis, or rectal fistula. Higher colostomy rate was found in this group of patients due to severe pelvic fibrosis or proctitis.


Assuntos
Segunda Neoplasia Primária/patologia , Radioterapia/efeitos adversos , Neoplasias Retais/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Colostomia/estatística & dados numéricos , Cistite/epidemiologia , Cistite/etiologia , Feminino , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Induzidas por Radiação/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Proctite/epidemiologia , Proctite/etiologia , Prognóstico , Fístula Retal/epidemiologia , Fístula Retal/etiologia , Neoplasias Retais/mortalidade , Estudos Retrospectivos , Taiwan/epidemiologia , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/radioterapia
9.
Eur J Endocrinol ; 183(4): 471-480, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32738133

RESUMO

Context: Growth hormone (GH) deficiency is a common late effect of cranial irradiation. However, concerns have been raised that GH treatment might lead to an increased risk of a second neoplasm (SN). Objective: To study the impact of GH treatment on the risk of SN in a French cohort of survivors of childhood cancer (CCS) treated before 1986. Design and setting: Cohort study and nested case-control study. Participants: Of the 2852 survivors, with a median follow-up of 26 years, 196 had received GH therapy (median delay from cancer diagnosis: 5.5 years). Main outcome measures: Occurrence of SN. Results: In total, 374 survivors developed a SN, including 40 who had received GH therapy. In a multivariate analysis, GH treatment did not increase the risk of secondary non-meningioma brain tumors (RR: 0.6, 95% CI: 0.2-1.5, P = 0.3), secondary non-brain cancer (RR: 0.7, 95% CI: 0.4-1.2, P = 0.2), or meningioma (RR: 1.9, 95% CI: 0.9-4, P = 0.09). Nevertheless, we observed a slight non-significant increase in the risk of meningioma with GH duration: 1.6-fold (95% CI: 1.2-3.0) after an exposure of less than 4 years vs 2.3-fold (95% CI: 0.9-5.6) after a longer exposure (P for trend = 0.07) confirmed by the results of a case-control study. Conclusion: This study confirms the overall safety of GH use in survivors of childhood cancer, which does not increase the risk of a SN. The slight excess in the risk of meningioma in patients with long-term GH treatment is non-significant and could be due to difficulties in adjustment on cranial radiation volume/dose and/or undiagnosed meningioma predisposing conditions.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Hormônio do Crescimento Humano/uso terapêutico , Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/induzido quimicamente , Neoplasias Encefálicas/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Irradiação Craniana/efeitos adversos , Feminino , Seguimentos , França/epidemiologia , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias Meníngeas/induzido quimicamente , Neoplasias Meníngeas/epidemiologia , Meningioma/induzido quimicamente , Meningioma/epidemiologia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/induzido quimicamente , Estudos Retrospectivos , Adulto Jovem
10.
Cancer Causes Control ; 31(11): 1011-1019, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32839916

RESUMO

PURPOSE: Previous studies have shown an overall decreased risk of second cancers among prostate cancer survivors, but this has not been comprehensively examined by race/ethnicity. We conducted a retrospective cohort study of 716,319 one-year survivors of prostate cancer diagnosed at ages 35-84 during 2000-2015 as reported to 17 US Surveillance, Epidemiology and End Results (SEER) registries. METHODS: We estimated standardized incidence ratios (SIRs) for second primary non-prostate malignancies by race/ethnicity (non-Latino white, Black, Asian/Pacific Islander [API] and Latino), by Gleason, and by time since prostate cancer diagnosis. Poisson regression models were used to test heterogeneity between groups with the expected number as the offset. RESULTS: 60,707 second primary malignancies were observed. SIRs for all second cancers combined varied significantly by race/ethnicity: SIRwhite: 0.88 (95% confidence interval: 0.87-0.89), SIRLatino: 0.92 (0.89-0.95), SIRBlack: 0.97 (0.95-0.99), and SIRAPI: 1.05 (1.01-1.09) (p-heterogeneity < 0.001). SIRs for all cancers combined were higher among survivors of higher vs. lower Gleason prostate cancers irrespective of race/ethnicity. We observed significant heterogeneity by race/ethnicity in SIRs for 9 of 14 second cancer types investigated including lung, bladder, kidney, and liver. CONCLUSIONS: Our results confirm that most prostate cancer survivors have lower risks of second cancers than expected, but the magnitude varied by race/ethnicity. Exceptionally, API men had small but significantly increased risk. Further research to understand drivers of the observed race/ethnicity heterogeneity is warranted.


Assuntos
Sobreviventes de Câncer , Segunda Neoplasia Primária/epidemiologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupos Étnicos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Risco , Programa de SEER , Estados Unidos
11.
Gac. sanit. (Barc., Ed. impr.) ; 34(4): 393-398, jul.-ago. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-198711

RESUMO

OBJECTIVE: To compare the incidence rates of gastric cancer among cancer survivors with those in the general population, and estimate the probability of a gastric second primary cancer being diagnosed 10 years after any other first primary cancer. METHOD: A cohort of first primary cancers (other than gastric) diagnosed in Northern Portugal between 2000 and 2006 (n=64,648) was followed until 31/12/2012 for gastric second primary cancers. Incidence rates, standardized incidence ratios and the cumulative incidence of gastric second primary cancers were calculated. RESULTS: Overall, 330 patients developed gastric second primary cancers (21.2% within two months). The incidence rate of gastric second primary cancers was higher within two months of the first primary cancer (standardized incidence ratios: 5.20 in males and 7.89 in females), particularly among survivors of cancers of the oesophagus, colon and rectum, than in the remaining period (standardized incidence ratios: 0.64 in males and 0.74 in females). The 10-year risk of a gastric second primary cancer was 0.6% (males: 0.7%; females: 0.4%). CONCLUSION: The incidence rate of gastric second primary cancers among cancer survivors was higher than in the general population only soon after the first primary cancer, and lower thereafter. Despite the high mortality, the probability of a gastric second primary cancer within 10-years of the first primary cancer was 0.6%


OBJETIVO: Comparar las tasas de incidencia de cáncer gástrico entre los sobrevivientes de cáncer con las de la población general y estimar la probabilidad de que se diagnostique un segundo cáncer primario gástrico 10 años después de cualquier otro primer cáncer primario. MÉTODO: Se siguió una cohorte de pacientes con un primer cáncer primario (excluyendo los gástricos) en el norte de Portugal entre 2000 y 2006 (n=64.648) hasta el 31/12/2012 para identificar un segundo cáncer primario gástrico. Se calcularon las tasas de incidencia, las razones de incidencia estandarizadas (RIE) y la incidencia acumulada de segundos cánceres primarios gástricos. RESULTADOS: En total, 330 pacientes desarrollaron un segundo cáncer primario gástrico (21,2% en 2 meses). La tasa de incidencia de los segundos cánceres primarios gástricos fue mayor dentro de los 2 meses posteriores al primero (RIE: 5,20 en hombres y 7,89 en mujeres), en particular entre los sobrevivientes de cáncer de esófago, colon y recto, que en el período restante (RIE: 0,64 en hombres y 0,74 en mujeres). El riesgo a 10 años de un segundo cáncer primario gástrico fue del 0,6% (hombres: 0,7%; mujeres: 0,4%). CONCLUSIONES: La tasa de incidencia de segundos cánceres primarios gástricos entre los sobrevivientes de cáncer fue más alta que en la población general solo poco después del primer cáncer, y más baja a partir de entonces. A pesar de la alta mortalidad, la probabilidad de un segundo cáncer primario gástrico a 10 años del primero fue del 0,6%


Assuntos
Humanos , Neoplasias Gástricas/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Fatores de Risco , Sobreviventes de Câncer/estatística & dados numéricos , Portugal/epidemiologia , Seguimentos , Estudos de Coortes
12.
Yonsei Med J ; 61(7): 579-586, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32608201

RESUMO

PURPOSE: The impact of changes in body mass index and waist circumference on the development of metachronous colorectal neoplasia (CRN) after polypectomy has rarely been examined. We evaluated the association between changes in overall/abdominal obesity and metachronous CRN risk. MATERIALS AND METHODS: We studied patients who underwent ≥1 adenoma removal and surveillance colonoscopy. Patients were classified into the following four groups based on the changes in overall obesity from index to follow-up colonoscopy: non-obesity persisted (group 1), obesity to non-obesity (group 2), non-obesity to obesity (group 3), and obesity persisted (group 4). Patients were also divided into another four groups based on similar changes in abdominal obesity (groups 5-8). RESULTS: The number of patients in groups 1, 2, 3, and 4 was 5074, 457, 643, and 3538, respectively, and that in groups 5, 6, 7, and 8 was 4229, 538, 656, and 2189, respectively. Group 4 had a significantly higher risk of metachronous CRN compared to groups 1 and 2. However, metachronous advanced CRN (ACRN) risk was not different among groups 1, 2, 3, and 4. Metachronous CRN risk in group 8 (abdominal obesity persisted) was higher than that in groups 5 (non-abdominal obesity persisted) and 7 (non-abdominal obesity to abdominal obesity), and tended to be higher than that in group 6 (abdominal obesity to non-abdominal obesity). Additionally, group 8 had a significantly higher risk of metachronous ACRN compared to groups 5, 6, and 7. CONCLUSION: Changes in obesity affected the metachronous CRN risk. In particular, changes in abdominal obesity affected the metachronous ACRN risk.


Assuntos
Pólipos do Colo/cirurgia , Colonoscopia/métodos , Neoplasias Colorretais/patologia , Segunda Neoplasia Primária/patologia , Obesidade Abdominal/complicações , Obesidade/complicações , Adulto , Índice de Massa Corporal , Pólipos do Colo/epidemiologia , Pólipos do Colo/patologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/cirurgia , Obesidade/epidemiologia , Obesidade Abdominal/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Circunferência da Cintura/fisiologia
13.
PLoS One ; 15(6): e0232800, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497148

RESUMO

Second primary breast cancer (SPBC) is becoming one of the major obstacles to breast cancer (BC) control. This study was aimed to determine the trend of SPBC incidence over time and the risk of developing SPBC in site-specific primary cancer survivors in the United States. The Surveillance, Epidemiology, and End Results (SEER) 13 registry (1992-2015) was used to identify SPBC patients with previous malignancies. Standardized incidence ratio (SIR) was computed to compare the incidence rates of the observed cases of SPBC in cancer survivors over the expected cases in the general population. Elevated risk of SPBC was observed in women with previous BC (SIR = 1.74) or thyroid cancer (SIR = 1.17). Women with initial skin melanoma in older age (≥50 years) (SIR = 1.11), or White race (SIR = 1.11) presented an elevated incidence of SPBC than the general female population. Besides, Asian/Pacific Islander (API) women with cancer of corpus uteri, ovary, bladder, or kidney were prone to developing SPBC when compared with the general population, with SIRs of 1.61, 1.35, 1.48, and 1.70, respectively. Male BC patients showed profound risk of developing SPBC (SIR = 34.86). Male leukemia patients also presented elevated risk of developing SPBC (SIR = 2.06). Our study suggests significant increase of SPBC in both sexes in the United States. Elevated risk of SPBC exists in survivors with primary BC, female thyroid cancer, male leukemia, and API female cancer patients with primary genitourinary cancer. Our study is helpful in developing strategies for BC control and prevention on specific first primary cancer survivors with an elevated risk of SPBC.


Assuntos
Neoplasias da Mama Masculina/epidemiologia , Neoplasias da Mama/epidemiologia , Sobreviventes de Câncer , Segunda Neoplasia Primária/epidemiologia , Adulto , Fatores Etários , Idoso , Grupos de Populações Continentais/estatística & dados numéricos , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Leucemia/epidemiologia , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/epidemiologia , Especificidade de Órgãos , Programa de SEER , Neoplasias Cutâneas/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Estados Unidos/epidemiologia , Neoplasias Urogenitais/epidemiologia
15.
Crit Rev Oncol Hematol ; 152: 102989, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32485529

RESUMO

This study reviews the relevant epidemiological studies associating cutaneous melanoma and breast carcinomas and provides an overview of the possible genetic, biological and bias factors that underpin this relationship. Standardised incidence ratio (SIR) for primary cutaneous melanoma after breast carcinoma ranged from 1.16 to 5.13 and ranged from 1.03 to 4.10 for primary breast carcinoma after cutaneous melanoma. Epidemiological studies highlight age, gender and use of radiotherapy and chemotherapy as potential risk factors for second primary cancers (SPCs). Mutations in BRCA2, CDKN2A, CDK4 and BAP1 may partly underlie any SPC association. The impact of socio-cultural factors and surveillance bias may be attributed to the findings of SPC partially or entirely. In conclusion, this study has highlighted the association between breast carcinoma and melanoma and identified various factors for further research and the optimised management of patients with both cancers.


Assuntos
Neoplasias da Mama , Melanoma , Segunda Neoplasia Primária , Neoplasias da Mama/epidemiologia , Humanos , Incidência , Melanoma/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Fatores de Risco , Neoplasias Cutâneas , Proteínas Supressoras de Tumor , Ubiquitina Tiolesterase
16.
J Cancer Res Clin Oncol ; 146(7): 1765-1779, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32356175

RESUMO

PURPOSE: As the number of cancer survivors in the United States increases, quantifying the risks and burden of second primary cancers (SPCs) among cancer survivors will help develop long-term prevention and surveillance strategies. We describe the risk of developing a SPC among survivors of 10 cancer sites with the highest survival rates in the United States. METHODS: Adult patients diagnosed with an index smoking-related (urinary bladder, kidney and renal pelvis, uterine cervix, oral cavity and pharynx, and colon and rectum) and index non-smoking-related (prostate, thyroid, breast, corpus and uterus, and non-Hodgkin lymphoma) cancers were identified from Surveillance, Epidemiology, and End Results (2000-2015). SPC risks were quantified using standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR). RESULTS: A cohort of 2,903,241 patients was identified and 259,685 (8.9%) developed SPC (7.6% of women and 10.3% of men). All index cancer sites (except prostate) were associated with a significant increase in SPC risk for women and men. Patients diagnosed with smoking-related index cancers (SIR range 1.20-2.16 for women and 1.12-1.91 for men) had a higher increased risk of SPC than patients with non-smoking-related index cancers (SIR range 1.08-1.39 for women and 1.23-1.38 for men) relative to the general population. CONCLUSION: We found that 1-in-11 cancer survivors developed a SPC. Given the increasing number of cancer survivors and the importance of SPC as a cause of cancer death, there is a need for increased screening for and prevention of SPC.


Assuntos
Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Neoplasias/epidemiologia , Adulto , Idoso , Suscetibilidade a Doenças , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Medição de Risco , Fatores de Risco , Programa de SEER , Fumar/efeitos adversos
17.
Pediatr Blood Cancer ; 67(7): e28389, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32386119

RESUMO

BACKGROUND: Germline retinoblastoma (Rb) survivors are at lifelong risk for developing subsequent malignancies (SMNs). Optimal surveillance modalities are needed to detect SMN at an early stage in this high-risk cohort. We investigated the use of rapid whole-body magnetic resonance imaging (WB-MRI) as a noninvasive screening modality in this cohort. PROCEDURE: WB-MRI was performed in asymptomatic preadolescent, adolescent, or young adult survivors of germline Rb from February 1, 2008 to December 31, 2018 at a tertiary cancer center. We calculated sensitivity and specificity of WB-MRI and rate of false-positive findings requiring additional evaluation. RESULTS: Overall, 110 WB-MRI were performed in 47 germline Rb survivors (51% female; median age at initial WB-MRI: 15.5 years [range 8-25.3]). Patients received 1-10 annual WB-MRI examinations (median: two). Thirteen patients had an abnormal WB-MRI; three findings were deemed to be likely benign and were not evaluated further. Ten patients required dedicated imaging and three required biopsy; two patients were diagnosed with localized high-grade osteosarcoma, while the other eight had benign findings. One patient was diagnosed with secondary osteosarcoma 3 months after normal WB-MRI. In total, there were 96 true negatives, 11 false positives, two true positives, and one false negative. The sensitivity of WB-MRI in this cohort was 66.7% (95% confidence interval [CI], 14.2-96.0) and the specificity was 89.7% (95% CI, 83.6-93.7). CONCLUSIONS: Based on our 10-year experience, surveillance WB-MRI appears to have limited utility as a surveillance modality for SMN in germline Rb survivors. Alternate screening modalities should be investigated.


Assuntos
Imagem por Ressonância Magnética/métodos , Segunda Neoplasia Primária/diagnóstico , Neoplasias da Retina/terapia , Retinoblastoma/terapia , Imagem Corporal Total/métodos , Adolescente , Adulto , Sobreviventes de Câncer , Criança , Feminino , Seguimentos , Células Germinativas , Humanos , Incidência , Masculino , Segunda Neoplasia Primária/diagnóstico por imagem , Segunda Neoplasia Primária/epidemiologia , New York/epidemiologia , Vigilância da População , Prognóstico , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
18.
Eur J Cancer ; 133: 47-55, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32434110

RESUMO

BACKGROUND: Patients with heritable retinoblastoma are at risk for bilateral retinoblastoma and second primary malignancies (SPMs). The incidence of SPM is significantly raised after radiotherapy. We analysed the impact of the class of constitutional RB1 variant on the incidence of SPM in survivors with and without previous radiotherapy. METHODS: From 1940 to 2008, 655 national patients were treated for heritable retinoblastoma at the German referral centre. Data on SPM, therapy and constitutional RB1 variant were available for 317 patients (48.3%). Heterozygous RB1 variants were classified into variants with regular and incomplete penetrance for retinoblastoma. RESULTS: SPM occurred in 51 of 317 survivors of heritable retinoblastoma. The incidence rate (IR) of SPM per 1000 person years was 8.4 (95% confidence interval (CI): 6.3-11.1) in individuals heterozygous for an oncogenic RB1 variant and 2.1 (95% CI: 0.0-11.4) with RB1 mosaicism. The incidence of SPM was higher in patients with regular penetrance compared with incomplete penetrance RB1 variants (IR 10.3 [95% CI: 7.5-13.8] vs. IR 3.2 [95% CI: 1.0-7.5]; p < 0.05). In the subgroup without previous radiotherapy SPM were only observed in patients with regular penetrance variants (IR 6.3 [95% CI: 3.0-11.5]). Carriers of incomplete penetrance variants developed similar tumour entities as those with regular penetrance. CONCLUSIONS: Patients heterozygous for regular penetrance RB1 variants had a higher risk to develop SPM than patients with incomplete penetrance variants. Increased knowledge on genotype-phenotype relation regarding SPM may influence screening recommendations for SPM in survivors of heritable retinoblastoma.


Assuntos
Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/genética , Neoplasias da Retina/genética , Proteína do Retinoblastoma/genética , Retinoblastoma/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/genética , Neoplasias da Retina/epidemiologia , Neoplasias da Retina/terapia , Retinoblastoma/epidemiologia , Retinoblastoma/terapia , Adulto Jovem
19.
Ann Hematol ; 99(7): 1605-1613, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32451709

RESUMO

Second primary diffuse large B cell lymphoma (spDLBCL) is defined as a metachronous tumor occurring after a first primary cancer. To date, while R-CHOP is the standard first-line treatment for de novo DLBCL, no available data show that R-CHOP is the optimal treatment for spDLBCL. This exploratory study aimed to investigate treatment of spDLBCL. From 2008 to 2015, the Poitou-Charentes general cancer registry recorded 68 cases of spDLBCL ≤ 80 years old, having received a first-line treatment with either R-CHOP (78%) or other regimens (22%). Patients without R-CHOP have worse overall survival in univariate (HR 2.89 [1.33-6.24], P = 0.007) and multivariate (HR 2.98 [1.34-6.67], P = 0.008) analyses. Patients without R-CHOP more frequently had PS > 1 (67% vs. 28%, P = 0.007) and prior chemotherapy (60% vs. 26%, P = 0.02), which suggests that both of these factors influence a clinician's decision to not use R-CHOP. Prior chemotherapy had no prognostic impact in univariate and multivariate analyses; this result could call into question the risk-benefit balance of not using R-CHOP to prevent toxicity. In our study, one DLBCL out of ten occurred after a first primary cancer, and as regards de novo DLBCL, R-CHOP appeared to be the best first-line treatment. Larger series are needed to confirm these results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/classificação , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Terapia Neoadjuvante , Segunda Neoplasia Primária/tratamento farmacológico , Rituximab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , França/epidemiologia , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/epidemiologia , Prednisona/administração & dosagem , Prognóstico , Sistema de Registros , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto Jovem
20.
Breast Cancer Res Treat ; 181(2): 255-268, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32303988

RESUMO

PURPOSE: Women with personal history of breast cancer (PHBC) are currently recommended to receive annual mammography for surveillance of breast cancer recurrence or new primary. However, given issues in accuracy with mammography, there is a need for evolving evidence-based surveillance recommendations with supplemental imaging. In this systematic review, we compiled and compared existing studies that describe the test performance of surveillance breast MRI among women with PHBC. METHODS: We searched PubMed and EMBASE using MeSH terms for studies (2000-2019) that described the diagnostic characteristics of breast MRI in women with PHBC. Search results were reviewed and included based on PICOTS criteria; quality of included articles was assessed using QUADAS-2. Meta-analysis of single proportions was conducted for diagnostic characteristics of breast MRI, including tests of heterogeneity. RESULTS: Our review included 11 articles in which unique cohorts were studied, comprised of a total of 8338 women with PHBC and 12,335 breast MRI done for the purpose of surveillance. We predict intervals (PI) for cancer detection rate per 1000 examinations (PI 9-15; I2 = 10%), recall rate (PI 5-31%; I2 = 97%), sensitivity (PI 58-95%; I2 = 47%), specificity (PI 76-97%; I2 = 97%), and PPV3 (PI 16-40%; I2 = 44%). CONCLUSIONS: Studies addressing performance of breast MRI are variable and limited in population-based studies. The summary of evidence to date is insufficient to recommend for or against use of breast MRI for surveillance among women with PHBC.


Assuntos
Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer/métodos , Imagem por Ressonância Magnética/métodos , Mamografia/métodos , Recidiva Local de Neoplasia/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Vigilância da População , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Recidiva Local de Neoplasia/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Estados Unidos/epidemiologia
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