RESUMO
A rapid increase in the incidence of anal squamous cell carcinoma (SCC) was reported in several countries over the past decades. This study assessed trends in epidemiology and primary treatment over a 32-year period (1990-2021) using the Netherlands Cancer Registry. The study population included 4273 patients, 44.2% male and 55.8% female (median age 63 years). The age-standardised incidence rate (European Standardised Rate, ESR) increased from 0.5 to 1.6 per 100,000, which entailed an average annual percentage change (AAPC) of 5.0% (95% confidence interval [CI]: 4.5%-5.8%). While incidence among females increased continuously over the total period (AAPC 4.9%; 95%CI: 4.4%-5.6%), to 1.8 per 100,000 ESR in 2021, incidence among males increased until 2016 (annual percentage change [APC] of 6.3%; 95%CI: 5.6%-10.7%), after which it seemed to stabilise (APC -2.1%; 95%CI: -16.8%-4.5%). Significant trends were also observed in distribution of age, tumour stage and primary treatment modalities. Five-year relative survival (RS) was estimated using the Pohar-Perme estimator, and this improved from 56.1% in 1990-1997 (95%CI: 49.3%-62.4%) to 67.9% in 2014-2021 (95%CI: 64.7%-70.9%), but remained poor for stage IV disease. Evaluation through a multivariable Poisson regression model demonstrated diagnosis in the most recent period to be independently associated with better RS, in addition to female sex, younger age, early disease stage and any treatment. In conclusion, the rising incidence of anal SCC seems to decline in males, but not in females, and advances in diagnostics and therapeutic management have likely contributed to improved prognosis.
Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/terapia , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/terapia , Neoplasias do Ânus/patologia , Incidência , Prognóstico , Sistema de RegistrosRESUMO
Background: To date, anal cancer patients are treated with radiotherapy to similar volumes despite a marked difference in risk profile based on tumor location and stage. A more individualized approach to delineation of the elective clinical target volume (CTVe) could potentially provide better oncological outcomes as well as improved quality of life. The aim of the present work was to establish Nordic Anal Cancer (NOAC) group guidelines for delineation of the CTVe in anal cancer.Methods: First, 12 radiation oncologists reviewed the literature in one of the following four areas: (1) previous delineation guidelines; (2) patterns of recurrence; (3) anatomical studies; (4) common iliac and para-aortic recurrences and delineation guidelines. Second, areas of controversy were identified and discussed with the aim of reaching consensus.Results: We present consensus-based recommendations for CTVe delineation in anal cancer regarding (a) which regions to include, and (b) how the regions should be delineated. Some of our recommendations deviate from current international guidelines. For instance, the posterolateral part of the inguinal region is excluded, decreasing the volume of irradiated normal tissue. For the external iliac region and the cranial border of the CTVe, we agreed on specifying two different recommendations, both considered acceptable. One of these recommendations is novel and risk-adapted; the external iliac region is omitted for low-risk patients, and several different cranial borders are used depending on the individual level of risk.Conclusion: We present NOAC consensus guidelines for delineation of the CTVe in anal cancer, including a risk-adapted strategy.
Assuntos
Neoplasias do Ânus , Radioterapia de Intensidade Modulada , Humanos , Anticoagulantes , Qualidade de Vida , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/radioterapia , Neoplasias do Ânus/patologia , Planejamento da Radioterapia Assistida por ComputadorRESUMO
Methylation silencing of certain cellular genes is a sign of carcinogenesis progression and therefore tests that detect methylation could be used in the diagnosis or staging of malignant diseases. In the diagnosis of squamous cell carcinomas of the cervix which are almost 100% caused by long-term infection with highrisk human papillomavirus (HR-HPV), methylation silencing of certain cellular genes is a highly specific marker of advanced dysplastic lesions and appears to result from aberrant activation of the methyltransferase DNMT1 by viral oncoproteins E6 and E7. A methylation test performed on a cervicovaginal cytology specimen allows to increase the diagnostic value of this non-invasive test and to select patients with severe squamous cell lesions for follow-up. Other less frequent anogenital malignancies that are induced by HR-HPV to a lesser extent can also be detected by cytological examination - glandular lesions of various origins, most commonly cervical and endometrial adenocarcinomas and anal carcinoma. The aim of our pilot study was to evaluate the utility of a methylation test for the diagnosis of these malignancies in a cohort of 50 liquid-based cervicovaginal cytologies with glandular lesion and 74 liquid-based anal cytologies from HIV-positive men having sex with men who are at high risk for anal cancer development.
Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Masculino , Feminino , Humanos , Metilação , Projetos Piloto , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Proteínas Oncogênicas Virais/genética , Citodiagnóstico , Papillomaviridae/genéticaRESUMO
BACKGROUND: This study investigates the patterns of PET-positive lymph nodes (LNs) in anal cancer. The aim was to provide information that could inform future anal cancer radiotherapy contouring guidelines. METHODS: The baseline [18F]-FDG PET-CTs of 190 consecutive anal cancer patients were retrospectively assessed. LNs with a Deauville score (DS) of ≥3 were defined as PET-positive. Each PET-positive LN was allocated to a LN region and a LN sub-region; they were then mapped on a standard anatomy reference CT. The association between primary tumor localization and PET-positive LNs in different regions were analyzed. RESULTS: PET-positive LNs (n = 412) were identified in 103 of 190 patients (54%). Compared to anal canal tumors with extension into the rectum, anal canal tumors with perianal extension more often had inguinal (P < 0.001) and less often perirectal (P < 0.001) and internal iliac (P < 0.001) PET-positive LNs. Forty-two patients had PET-positive LNs confined to a solitary region, corresponding to first echelon nodes. The most common solitary LN region was inguinal (25 of 42; 60%) followed by perirectal (26%), internal iliac (10%), and external iliac (2%). No PET-positive LNs were identified in the ischiorectal fossa or in the inguinal area located posterolateral to deep vessels. Skip metastases above the bottom of the sacroiliac joint were quite rare. Most external iliac PET-positive LNs were located posterior to the external iliac vein; only one was located in the lateral external iliac sub-region. CONCLUSIONS: The results support some specific modifications to the elective clinical target volume (CTV) in anal cancer. These changes would lead to reduced volumes of normal tissue being irradiated, which could contribute to a reduction in radiation side-effects.
Assuntos
Neoplasias do Ânus/diagnóstico , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Neoplasias do Ânus/radioterapia , Fluordesoxiglucose F18 , Humanos , Imageamento Tridimensional , Metástase Linfática , Estadiamento de Neoplasias , Pelve/diagnóstico por imagem , Pelve/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
BACKGROUND: The incidence of anal squamous cell carcinoma has been increasing, particularly in people living with HIV (PLWH). There is concern that radiosensitizing drugs, such as protease inhibitors, commonly used in the management of HIV, may increase toxicities in patients undergoing chemoradiation. This study examines treatment outcomes and toxicities in PLWH managed with and without protease inhibitors who are receiving chemoradiation for anal cancer. METHODS: Patient demographic, HIV management, and cancer treatment information were extracted from multiple Veterans Affairs databases. Patients were also manually chart reviewed. Among PLWH undergoing chemoradiation for anal carcinoma, therapy outcomes and toxicities were compared between those treated with and without protease inhibitors at time of cancer treatment. Statistical analysis was performed using chi-square, Cox regression analysis, and logistic regression. RESULTS: A total of 219 PLWH taking anti-retroviral therapy undergoing chemoradiation for anal cancer were identified and included in the final analysis. The use of protease inhibitors was not associated with any survival outcome including colostomy-free survival, progression-free survival, or overall survival (all adjusted hazard ratio p-values> 0.05). Regarding toxicity, protease inhibitor use was not associated with an increased odds of hospitalizations or non-hematologic toxicities; however, protease inhibitor use was associated with increased hospitalizations for hematologic toxicities, including febrile neutropenia (p < 0.01). CONCLUSION: The use of protease inhibitors during chemoradiation for anal carcinoma was not associated with any clinical outcome or increase in non-hematologic toxicity. Their use was associated with increased hospitalizations for hematologic toxicities. Further prospective research is needed to evaluate the safety and efficacy of protease inhibitors for patients undergoing chemoradiation.
Assuntos
Neoplasias do Ânus/induzido quimicamente , Carcinoma de Células Escamosas/complicações , Quimiorradioterapia/efeitos adversos , Infecções por HIV/complicações , Inibidores de Proteases/efeitos adversos , Adulto , Carcinoma de Células Escamosas/tratamento farmacológico , Quimiorradioterapia/métodos , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , VeteranosRESUMO
PURPOSE: Radiochemotherapy is the standard treatment for anal carcinoma (ACa). Intensity-modulated radiotherapy (IMRT) has been introduced, allowing focused irradiation of the tumor area. Whether physical benefits of IMRT translate to clinical benefits has not been sufficiently demonstrated. METHODS: We retrospectively reviewed data from 82 patients with newly diagnosed ACa. Patients treated with IMRT were compared with previous patients treated with conventional three-dimensional computational radiotherapy (3D-CRT). The influence of IMRT on complete remission and acute and chronic side effects was analyzed in univariate and multivariate analyses. RESULTS: 39/40 patients treated with IMRT were in complete remission after 1 year compared to 31/39 patients treated with 3D-CRT (pâ¯= 0.014). Multivariate analysis confirmed tumor T stage as well as lack of IMRT treatment as risk factors for persistent tumor at 6 months. No significant benefits of IMRT were apparent at later timepoints (median follow up 52 months, IQR: 31.5-71.8 months). Patients treated with IMRT had a significantly lower degree of skin toxicity (median 2 vs. 3 in a scale ranging from 0 to 3, pâ¯= 0.00092). Rates of hematological toxicity/proctitis were not reduced and rates of acute diarrhea increased (pâ¯= 0.034). Median length of hospitalization tended to be shorter in patients treated with IMRT (n.â¯s.). CONCLUSION: We present a real-world experience of shifting radiation technique from conventional 3D-CRT to IMRT. IMRT patients had better tumor control at 1 year and lower degrees of skin toxicity. Our data indicate that IMRT can enable therapies with lower side effects with equal or better oncological results for patients with ACa.
Assuntos
Neoplasias do Ânus/radioterapia , Radiodermite/prevenção & controle , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/patologia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Fluoruracila/uso terapêutico , Humanos , Infusões Intravenosas , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Lesões por Radiação/etiologia , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) regimen has become a new standard for the treatment of metastatic or unresectable locally advanced recurrent squamous cell carcinoma of the anus (SCCA) after demonstrating improved efficacy (12-month PFS of 47%) in the Epitopes-HPV02 trial. Antibodies targeting the checkpoint inhibitor (CKI) programmed cell death protein-1 (PD1) have demonstrated the efficacy as monotherapies in second-line treatment of SCCA. The aim of this study is to evaluate the combination of atezolizumab and mDCF as first-line chemotherapy in a non-comparative multicentre randomized phase II study of advanced SCCA patients. METHODS: Patients with chemo-naive advanced histologically proven SCCA, metastatic or unresectable locally advanced recurrence, and Eastern Cooperative Oncology Group-performance status (ECOG-PS) < 2 will be eligible. The primary endpoint is a 12-month PFS rate. Using one-arm non-parametric survival with unilateral alpha type I error of 5% and a statistical power of 80%, the upper critical value for the 12-month PFS rate is 47% to reject H0. Assuming 5% lost to follow-up, 99 patients will be randomized on a 2:1 basis, 66 to the experimental arm (arm A, mDCF plus atezolizumab) and 33 to the standard arm (arm B, mDCF). In both arms, 8 cycles of mDCF will be administered. In arm A, patients receive mDCF with a fixed dose of atezolizumab (800 mg every 2 weeks) and are followed up to 1 year. Secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and an extensive biomarker programme and its correlation with the treatment efficacy. DISCUSSION: Although the Epitopes-HPV02 trial has changed long-lasting prognosis of patients with SCCA in advanced stage disease, more than 50% of patients will progress at 12 months. The purpose of the SCARCE trial to establish the addition of atezolizumab to mDCF as a new standard in this rare disease. Associated biomarker studies and the control arm could contribute to better understanding of the potential synergic and tumour resistance mechanisms in SCCA. TRIAL REGISTRATION: NCT03519295.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/secundário , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: In clinical oncology, only a few applications have been developed using HPV as a personalized tumor marker, a lack most probably related to the limited information obtained by the classical Polymerase Chain Reaction (PCR) approach. To overcome this limitation, we have recently developed the capture-based Next-Generation Sequencing (NGS) "CaptHPV" assay, designed to provide an extensive and comprehensive molecular characterization of HPV DNA sequences associated with neoplasias, ie the sequence of the viral genome (245 genotypes), its physical state, viral load, integration site and genomic alterations at integration locus. These data correspond to highly specific tumor markers that can be used to improve diagnosis and patient's follow-up. CASE PRESENTATION: We report here a case that is a straightforward and practical illustration of the power of the CaptHPV method. A patient developed successively a carcinoma of the anal canal and of the tongue. The two tumors were squamous cell carcinoma, found associated with HPV16 using PCR. In order to document a possible metastasis to the tongue from the anal cancer, we performed CaptHPV analysis on the two tumors. The analysis of the anal carcinoma found 55 viral/human hybrid reads allowing the identification of the HPV16 DNA integration in the 4q25 chromosomal band locus with a 178,808 bp deletion in the cell genome. Molecular analysis of the tongue tumor disclosed 6110 reads of HPV16, with a viral pattern strictly identical to that of the anal tumor. A total of 131 hybrid reads between HPV16 and the cell genome were found, corresponding exactly to the same locus of integration of viral DNA at the 4q25 site. The 178,808 bp genomic deletion was also found in the lingual tumor. The exact identity of HPV insertional signatures in the two tumors, demonstrates unambiguously that the tongue tumor derived from the anal cancer whereas neither histological immunophenotyping nor classical viral analysis using PCR could allow a definitive diagnosis. CONCLUSION: Our observation indicates that the establishment of a detailed cartography of HPV DNA sequences in a tumor specimen provides crucial information for the design of specific biomarkers that can be used for diagnostic, prognostic or predictive purposes.
Assuntos
Neoplasias do Ânus/virologia , Carcinoma de Células Escamosas/virologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Papillomavirus Humano 16/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias da Língua/secundário , Biomarcadores Tumorais/genética , Cromossomos Humanos Par 4/genética , Cromossomos Humanos Par 4/virologia , DNA Viral/genética , Papillomavirus Humano 16/genética , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Análise de Sequência de DNA , Deleção de Sequência , Neoplasias da Língua/virologia , Integração ViralRESUMO
PURPOSE: To investigate the correlation between inflammatory-related parameters and overall survival (OS) and disease-free survival (DFS) in anal canal cancer population. METHODS AND MATERIALS: Patients diagnosed with anal canal carcinoma and treated with curative intent chemoradiotherapy (CRT) were included. Data about pre-treatment complete blood count were collected. Neutrophil to lymphocyte ratio (NLR), fibrinogen (F), and a combination of these (F-NLR score) were correlated with OS. RESULTS: A total of 58 patients were enrolled. In multivariate analysis, the strongest OS prognostic factor was NLR, with a hazard ratio (HR) for low NLR compared to high NLR of 1.30 (95% confidence interval 1.01-14.12). Kaplan-Meier survival analysis showed that patients with high NLR, F, and F-NLR had significantly shorter OS and DFS. CONCLUSION: To our knowledge, this is the first study providing evidence that elevated pre-treatment NLR, F, and F-NLR score significantly correlate with worse survival outcomes in patients with anal canal carcinoma. In view of our findings, future clinical trials in anal canal cancer patients are warranted to verify our results.
Assuntos
Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/cirurgia , Inflamação/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Fibrinogênio/metabolismo , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Prognóstico , Análise de SobrevidaRESUMO
BACKGROUND: The eighth edition of the tumor-node-metastasis classification of malignant tumors updates cancer staging according to the evidence accumulated in the last 8 years since the release of the tumor-node-metastasis seventh edition. This review focuses on the new staging system. METHODS: The eight edition was compared with the seventh edition as well as the Japanese Classification of Colorcetal, Appendiceal, and Anal carcinoma ninth edition. RESULTS: Of colon and rectum, the tumor-node-metastasis eighth edition expands the M category. Specifically, colorectal cancer with peritoneal metastasis is newly categorized as M1c, distinguishing it from M1a (metastasis to one organ) and M1b (metastasis to more than one organ). In the ninth edition of Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma, M1c is further subdivided into M1c1 (metastasis to the peritoneum without other organ involvement) and M1c2 (metastasis to the peritoneum with other organ involvement). In the T category, the tumor-node-metastasis eighth edition excludes high-grade dysplasia (intraepithelial carcinoma) from Tis; this differs from both the tumor-node-metastasis seventh edition and the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma ninth edition. In the N category, the tumor-node-metastasis eighth edition does not add the number of tumor deposits to the number of positive regional lymph nodes, whereas this number is added in the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma ninth edition. The definition of anal cancer is also modified considerably in the tumor-node-metastasis eighth edition; specifically, tumors of perianal skin defined as within 5 cm of the anal margin are also classified as anal canal carcinoma, external iliac lymph nodes become regional lymph nodes, and both N2 and N3 are abolished in the N category. With regard to appendix, Tis (low-grade appendiceal mucinous neoplasma) and tumor deposit(s) are newly introduced. Finally, the tumor-node-metastasis eighth edition offers a new structure, labeled a 'prognostic factors grid', which consists of prognostic factors for survival in both colorectal and anal cancer. CONCLUSIONS: Staging classification is updated regularly, which clinicians should always catch up with.
Assuntos
Neoplasias do Ânus/patologia , Neoplasias do Apêndice/patologia , Metástase Linfática/patologia , Estadiamento de Neoplasias/métodos , Neoplasias do Ânus/classificação , Neoplasias do Apêndice/classificação , Feminino , Humanos , Estadiamento de Neoplasias/normas , PrognósticoRESUMO
Canal anal carcinoma. Anal carcinomas are rare, but their incidence has increased in recent years. They are induced by the Human papillomas virus (mostly genotype 16). The prevalence is high among HIV-infected men who have sex with men (MSM) and primary prevention by vaccination against HPV is a source of hope in this population. Screening is based on the detection and treatment of precancerous lesions, called anal intra-epithelial neoplasia, which can be of low grade or high grade. It concerns a category of HIV-infected patients: MSM, history of condyloma or precancerous/cancerous lesions of the cervix. Treatment, based on a combination of simultaneous chemotherapy and radiation therapy, allows a complete response rate of 80%. In case of persistence or tumor recurrence, abdominoperineal resection remains the treatment of choice. Advanced diseases can benefit from highly effective chemotherapy combinations or even in the future, combination of chemotherapy and immunotherapy.
Carcinomes du canal anal. Les carcinomes anaux sont des tumeurs rares, dont l'incidence a augmenté durant les dernières années. Ils sont viro-induits par le human papillomavirus [HPV) [génotype 16 essentiellement]. La prévalence est élevée chez les hommes homosexuels infectés par le virus de l'immunodéficience humaine (VIH), dont la prévention primaire par vaccination anti-HPV constitue une source d'espoir. Le dépistage repose sur la détection et le traitement des lésions précancéreuses : néoplasies intraépithéliales anales qui peuvent être de bas grade ou de haut grade, chez une certaine catégorie de patients séropositifs pour le VIH : homme ayant des relations sexuelles avec les hommes, antécédents de condylome ou de lésion tumorale cervicale utérine. Le traitement, fondé sur une association de chimio- et de radiothérapie concomitantes permet une rémission complète dans 80 % des cas. En cas de persistance ou de récidive tumorale, l'amputation abdomino-pelvienne reste le traitement de choix. Les maladies avancées peuvent bénéficier de combinaisons de chimiothérapies très efficaces, voire dans le futur de combinaisons de chimiothérapie et d'immunothérapie.
Assuntos
Neoplasias do Ânus/virologia , Infecções por HIV , Homossexualidade Masculina , Infecções por Papillomavirus , Canal Anal , Neoplasias do Ânus/epidemiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/imunologia , Humanos , Masculino , Recidiva Local de Neoplasia , Prevalência , Minorias Sexuais e de GêneroRESUMO
AIM: To report the long-term results after definitive chemoradiotherapy (CRT) for anal carcinoma, using consistent time-to-event endpoints. METHODS AND MATERIALS: Anal carcinoma patient charts were reviewed. All patients received definitive CRT. Overall survival (OS), local failure-free survival (LFFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and anal dysfunction-free survival (ADFS) were estimated. RESULTS: In total, 65 patients were included. CRT was well tolerated, with only 24.6% grade ≥3 acute toxicity. Overall, the 5-year OS, LFFS, LRFFS, and DMFS were 75.3, 60.2, 74.2, and 66.2%, respectively. Early complete clinical response and tumor stage at diagnosis were the strongest predictors of OS (p = 0.04) and local failure (p = 0.03), respectively. CONCLUSIONS: In the treatment of anal cancers, excellent ADFS and OS, and valid LFFS, LRFFS, and DMFS can be achieved with definitive CRT. Adequacy of time-to-event endpoints is paramount.
Assuntos
Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: We aimed to assess the prognostic value of CYFRA 21-1 in a series of patients with anal canal squamous cell carcinoma treated by radiation-based therapy. METHODS: All patients with anal cancer referred between September 2005 and July 2013 were considered. Patients with diagnosis of anal squamous cell carcinoma and in whom pre- and post-treatment serum CYFRA 21-1 levels were available were included. Serum CYFRA 21-1 levels at initial workup and after therapy were collected. Survival rates were estimated using the Kaplan-Meier method. Cox regression analysis was used to evaluate prognostic variables for prediction of outcomes. RESULTS: Eighty-two patients were included. Median follow-up was 60 months (range: 8-128). Pre-treatment serum CYFRA 21-1 levels were significantly correlated with tumour stage (p < 0.001). Normal post-treatment serum CYFRA 21-1 level was significantly correlated with tumour complete response (p = 0.004). Elevated post-treatment serum CYFRA 21-1 level was significantly associated with poorer progression-free survival (p = 0.02) and overall survival (p = 0.003). T stage and post-treatment serum CYFRA 21-1 were independent prognostic factors for overall survival (p = 0.04 and 0.03, respectively). CONCLUSIONS: Serum CYFRA 21-1 appears to be a useful marker for the monitoring of anal squamous cell carcinoma patients. Elevated post-treatment value appears to be correlated with treatment failure.
Assuntos
Antígenos de Neoplasias/sangue , Neoplasias do Ânus/sangue , Neoplasias do Ânus/mortalidade , Biomarcadores Tumorais , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/mortalidade , Queratina-19/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/patologia , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Resultado do TratamentoRESUMO
Background: Safety and efficacy of pembrolizumab, a humanized programmed death 1 monoclonal antibody, was assessed in KEYNOTE-028, a multicohort, phase Ib trial for patients with programmed death ligand 1 (PD-L1)-positive advanced solid tumors. We report results for the cohort of patients with advanced anal carcinoma. Patients and methods: Patients with PD-L1-positive tumors (≥1%) received intravenous pembrolizumab 10 mg/kg once every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter per Response Evaluation Criteria In Solid Tumors, version 1.1. Primary endpoints were safety and overall response rate per investigator review. Secondary endpoints included progression-free survival, overall survival, and response duration. Data cutoff date was 1 July 2015. Results: Of the 43 patients with advanced anal carcinoma evaluable for PD-L1 expression, 32 (74%) had PD-L1-positive tumors as assessed with the 22C3 prototype assay, of whom 25 were enrolled between April and September 2014. Sixteen patients (64%) experienced treatment-related adverse events; the most common ones were diarrhea and fatigue in four patients (16%) each and nausea in three patients (12%). There were no treatment-related deaths or discontinuations as of the data cutoff date. Among the 24 patients with squamous cell carcinoma histology, four had confirmed partial response, for an overall response rate of 17% [95% confidence interval (CI), 5%-37%) and 10 (42%) had confirmed stable disease, for a disease control rate of 58%. One additional patient with non-squamous histology had confirmed stable disease. Conclusion: In this population of patients with PD-L1-positive advanced squamous cell anal carcinoma, pembrolizumab demonstrated a manageable safety profile and encouraging antitumor activity. These data support further study of pembrolizumab for this patient population. ClinicalTrials.gov: NCT02054806.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Canal Anal/patologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias do Ânus/mortalidade , Carcinoma de Células Escamosas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND: The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months. We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses. Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients. METHODS: This multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) <2, and being eligible for DCF. Patients receive either 6 cycles of standard DCF or 8 cycles of modified DCF depending on age (> vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon's optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy. DISCUSSION: Since the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA. TRIAL REGISTRATION: NCT02402842 , EudraCT: 2014-001789-81.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/uso terapêutico , Fluoruracila/uso terapêutico , Recidiva Local de Neoplasia , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Docetaxel , França , Humanos , Pessoa de Meia-Idade , Prognóstico , Projetos de Pesquisa , Adulto JovemRESUMO
BACKGROUND: Incidence of anal carcinoma (AC) is increasing and timely diagnosis is critical for efficient therapy. However, there is a paucity of recent studies addressing clinical symptoms and physical findings of anal carcinoma. METHODS: We performed a retrospective study reviewing history, symptoms and physical findings from 86 patients with newly diagnosed AC. We analyzed frequency of symptoms and physical findings according to T and TNM stage and their predictive value regarding tumor stage. RESULTS: Most patients presented with T2 (37 %) or T3 (29 %) cancer. 85 of 86 patients were symptomatic with anal bleeding (78 %), anal/perianal pain (63 %), weight loss (31 %) and foreign body sensation (22 %). 95 % of patients had ≥1 finding on physical examination including a visible tumor, palpable resistance and pain/blood during digital rectal examination. Patients with locally advanced disease (T3/T4) presented with more symptoms (p < 0.01) and more physical findings (p = 0.04) than patients with T1/T2 disease. On multivariate regression analysis perianal pain, painful defecation and weight loss were significantly associated with T3/T4 disease. CONCLUSION: Clinical symptoms and physical findings are present in nearly all AC patients. Pain referred to the perianal region, painful defecation and weight loss have predictive value for locally advanced disease.
Assuntos
Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Linfonodos/patologia , Redução de Peso , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/complicações , Neoplasias do Ânus/diagnóstico , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico , Defecação , Exame Retal Digital , Feminino , Hemorragia Gastrointestinal/etiologia , Virilha , Infecções por HIV/complicações , Humanos , Metástase Linfática , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dor/etiologia , Pelve , Exame Físico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Chemoradiotherapy is the standard treatment for squamous cell anal cancer. Salvage abdominoperineal resection (APR) is usually reserved for patients presenting with recurrent or persistent disease. Aim of our study was to review the outcomes of salvage surgery and perineal wound healing with or without a vertical rectus abdominis myocutaneous (VRAM) flap in a single institution over a 6-year period. METHODS: Data of all patients with biopsy-proven squamous cell anal cancer treated with chemoradiation at the University Medical Center Mannheim were recorded prospectively. Medical records of all patients who underwent salvage surgery for anal carcinoma between June 2008 and June 2014 were reviewed with regard to surgical and oncological outcomes. RESULTS: One hundred twenty-four patients received chemoradiation with a 5-year overall survival of 79 %. Seventeen patients required (salvage) APR for recurrent (n = 8), persistent (n = 7), or primary anal carcinoma (n = 2). Median overall survival was 33.4 months. Median duration until completion of perineal wound healing was shorter in the VRAM group (17 vs. 24.5 weeks; p = 0.0541). CONCLUSIONS: Salvage APR has a reasonable chance of long-time survival. Perineal reconstruction with a VRAM flap may reduce the duration until completion of perineal wound healing.
Assuntos
Abdome/cirurgia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/cirurgia , Recidiva Local de Neoplasia/cirurgia , Períneo/patologia , Períneo/cirurgia , Cicatrização , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/etiologia , Terapia de Salvação , Resultado do TratamentoRESUMO
The aim of the present retrospective study was to evaluate the prognostic significance of epidermal growth factor receptor (EGFR) expression in patients treated with radiotherapy or concomitant chemoradiotherapy for squamous cell anal cancer (SCAC)Patients and methods: A total of 17 patients with SCAC (clinical stages I-III) were studies. All patients were treated with radiotherapy (total dose range 40 - 68 Gy), 13 patients received concomitant chemotherapy (7 patients mitomycin/5-fluorouracil, 5 patients cisplatine/5-fluorouracil, 1 patient cisplatine weekly). EGFR expression in the pretreatment biopsieswas assessed with imunohistochemistry.Patients with EGFR expression had significantly shorter progression free survival (PFS) (p=0.0109; HR 9.38, 95% CI 1.75 - 50.35) and overall survival (OS) (p=0.0351; HR 7.11, 95% CI 1.4 - 36.13) than patients without expression EGFR. The 4-year PFS in patients with increased EGFR expression was only 28.57% (95% CI 17.07 - 62.04%) compared to 87.5% (95% CI 64.58 - 100%) in patients without EGFR expression. The 4-year OS in patients with increased EGFR expression was only 50.0% (95% CI 15.35 - 84.65%) compared to 87.5% (95% CI 64.58 - 100.0%) in patients without EGFR expression.Patients with expression EGFR had significantly shorter PFS and OS compared with patients without EGFR expression.
Assuntos
Neoplasias do Ânus/enzimologia , Neoplasias do Ânus/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapia , Quimiorradioterapia , Receptores ErbB/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
As the detection rate of HPV-DNA in anal carcinoma commonly exceeds 90%, a comparison between sole HPV-positive and HPV-negative cancers with respect to treatment response following chemoradiotherapy (CRT) and long-term oncological outcome is challenging. Against this background, we aimed to assess HPV types and HPV DNA load in formalin-fixed paraffin-embedded tissue (FFPE) of 95 patients treated with standard CRT for anal cancer to correlate viral load (≤/> median) with local failure, distant metastases, cancer-specific (CSS) and overall survival (OS) rates. Various clinicopathologic parameters and the immunohistochemical marker p16(INK4a) were evaluated for any correlation with HPV16 DNA load and were included in uni- and multivariate analyses. The overall prevalence of HPV DNA was 95.8% with HPV16 monoinfection being the most commonly encountered HPV type (78.9%), followed by HPV16 and 31, 35, 39, 44, 58, 66 and 81 dual infection in 9 patients (9.5%). HPV16 DNA load was significantly associated with p16(INK4a) expression (p = 0.001). Patients with HPV16 DNA load ≤ median and low p16(INK4a) expression showed significantly worse local control (HPV16 DNA load: univariate p = 0.023, multivariate p = 0.042; p16(INK4a): univariate p = 0.021), and OS (HPV16 DNA load: univariate p = 0.02, multivariate p = 0.03). Moreover, a combined HPV16 DNA load and p16(INK4a) variable revealed a significant correlation to decreased local failure, and increased CSS and OS (p = 0.019, p = 0.04 and p = 0.031). In conclusion, these data indicate that HPV16 DNA load and p16(INK4a) expression are significant prognostic factors for local tumor control and overall survival of patients with anal SCC following CRT.
Assuntos
Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA Viral/análise , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/virologia , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/virologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Estadiamento de Neoplasias , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Prognóstico , Taxa de Sobrevida , Carga ViralRESUMO
BACKGROUND: Primary chemoradiotherapy (CRT) is the standard treatment for locally advanced anal carcinoma. This study compared volumetric intensity-modulated arc therapy (VMAT) to 3-dimensional conformal radiotherapy (3DCRT) in terms of treatment-related side effects and survival. PATIENTS AND METHODS: From 1992-2014, 103 consecutive patients with anal carcinoma UICC stage I-III were treated. Concomitant CRT consisted of whole pelvic irradiation, including the iliac and inguinal lymph nodes, with 50.4 Gy (1.8 Gy per fractions) by VMAT (n = 17) or 3DCRT (n = 86) as well as two cycles of 5-fluorouracil and mitomycin C. Acute organ and hematological toxicity were assessed according to the Common Terminology Criteria (CTC) for Adverse Events version 3.0. Side effects ≥ grade 3 were scored as high-grade toxicity. RESULTS: High-grade acute organ toxicity CTC ≥ 3 (P < 0.05), especially proctitis (P = 0.03), was significantly reduced in VMAT patients. The 2-year locoregional control (LRC) and disease-free survival (DFS) were both 100 % for VMAT patients compared with 80 and 73 % for 3DCRT patients. CONCLUSION: VMAT was shown to be a feasible technique, achieving significantly lower rates of acute organ toxicity and promising results for LRC and DFS. Future investigations will aim at assessing the advantages of VMAT with respect to late toxicity and survival after a prolonged follow-up time.