Preliminary results of a vaginal constraint for reducing G2 late vaginal complications after postoperative brachytherapy in endometrial cancer: a prospective analysis

PurposeTo evaluate the preliminary results of the use of 68 Gy EQD2(α/β=3 Gy) as a dose limit to the lowest dose in the most exposed 2 cm3 of the vagina in order to reduce G2 late vaginal problems in postoperative endometrial carcinoma (EC).MethodsFrom November 2016 to October 2019, 69 postoperative EC patients receiving vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) were prospectively analyzed. The median EBRT dose was 45 Gy (range: 44–50.4 Gy), 1.8−2 Gy/day, 5 fractions(Fr)/week. VBT was administered with the following schedule: 1Fr of 7 Gy after EBRT and 2 daily Fr × 7.5 Gy in exclusive VBT. The dose was prescribed at 0.5 cm from the applicator surface with an active length of 2.5 cm; 56 patients were treated with vaginal cylinders (49–3.5 cm, 6–3 cm, and 1–2.5 cm) and 13 with the colpostat technique. The overall VBT dose was adjusted to meet the vaginal restriction of < 68 Gy EQD2(α/β=3 Gy) at 2 cm3. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum, and the objective LENT-SOMA criteria for vagina.ResultsWith a median follow-up of 31.0 months, no vaginal-cuff recurrences were found. Late toxicity: only 1G1(1.4%) rectal toxicity; 21G1(30.4%) and 3G2(4.3%) vaginal complications. Only one (1.4%) of 3 G2 manifested as vaginal shortening.ConclusionsIn postoperative EC patients treated with VBT, only one developed G2 vaginal stenosis with the use of 68 Gy EQD2(α/β=3 Gy) as a dose constraint. These preliminary results seem to indicate the value of this dose limit for reducing G2 vaginal stenosis. Nonetheless, these findings should be confirmed in a larger number of patients with longer follow-up.

Are endometrial cancer radiotherapy results age related?

Objective: To analyze the impact of age on radiotherapy results based on cancer-specific survival (CSS), vaginal-cuff relapses (VCR) and complications analysis in 438 patients with endometrial carcinoma (EC) receiving postoperative radiotherapy (PRT) divided into three age groups for analysis. Materials and methods: From 2003 to 2015, 438 patients with EC were treated with PRT and divided into three age groups: Group-1: 202 patients < 65 years; Group-2: 210 patients ≥ 65 and < 80 years; Group-3: 26 patients ≥ 80 years. Vaginal toxicity was assessed using the objective LENT-SOMA criteria and RTOG scores were recorded for the rectum, bladder, and small bowel. Statistics: Chi square and Student’s t tests, Kaplan-Meier survival study for analysis of CSS. Results: The mean follow-up was 5.6 years in Group-1, 5.6 years in Group-2 and 6.3 years in Group-3 (p = 0.38). No differences were found among the groups in distribution of stage, grade, myometrial invasion, Type 1 vs. 2 EC and VLSI (p = 0.97, p = 0.52, p = 0.35, p = 0.48, p = 0.76, respectively). There were no differences in rectal, bladder and vagina late toxicity (p = 0.46, p = 0.17, p = 0.75, respectively). A better CSS at 5 years was found in Group-1 (p = 0.006), and significant differences were found in late severe small bowel toxicity in Group-3 (p = 0.005). VCR was increased in Group-3 (p = 0.017). Conclusions: Patients ≥ 65 years had a worse outcome in comparison to younger patients. Late vaginal, rectal and bladder toxicities were similar in the three groups, although an increase of severe late small bowel toxicity led to IMRT in patients ≥ 80 years. Further larger studies are needed including quality of life analysis in patients ≥ 80 years

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Vacuna nonavalente frente al virus del papiloma humano. Actualización 2017 / Human papillomavirus nonavalent vaccine. Update 2017

El virus del papiloma humano (VPH) es el agente causal del 5% de los casos de cáncer en humanos, siendo causa necesaria para el desarrollo del cáncer cervical y responsable de un porcentaje variable de casos de cáncer de ano, vulva, vagina, pene y orofaringe. Desde 2007, en España se comercializan 2 vacunas frente al VPH: bivalente (tipos VPH 16/18) y tetravalente (tipos VPH 6/11/16/18). Con el fin de ampliar la protección conferida por las vacunas frente al VPH, en el año 2006 se inició el programa clínico de la nueva vacuna nonavalente, que incluye 9 tipos de VPH (6/11/16/18/31/33/45/52/58). Estos tipos son responsables del 90% de cánceres cervicales, del 82% de lesiones precancerosas anogenitales de alto grado y del 90% de verrugas genitales. El objetivo de esta publicación es poner a disposición del profesional sanitario los datos científicos que avalan la nueva vacuna, así como el valor clínico que ofrece en nuestro medio (AU)

Human papillomavirus (HPV) is the causative agent of 5% of human cancers. HPV infection is necessary for the development of cervical cancer and is responsible of a variable percentage of cancers of anus, vulva, vagina, penis, and oropharynx. Since 2007, 2 vaccines against HPV have been commercially available in Spain: bivalent (HPV types 16/18), and tetravalent (HPV types 6/11/16/18). In order to extend the protection afforded by HPV vaccines, a clinical program was launched in 2006 for the new nonavalent vaccine, including 9 HPV types (6/11/16/18/31/33/45/52/58). These types are responsible for 90% of cervical cancers, 82% of high-grade ano-genital pre-cancerous lesions, and 90% of genital warts. The purpose of this publication is to provide healthcare professionals with the scientific evidence that supports the new vaccine, as well as the clinical value that it offers in our environment (AU)

18F-FDG PET/CT and sentinel lymph node biopsy in the staging of patients with cervical and endometrial cancer. Role of dual-time-point imaging / PET/TC con 18F-FDG y biopsia del ganglio centinela en la estadificación de pacientes con cáncer de cérvix y endometrio. Utilidad de la imagen dual-time-point

Objective. Definitive staging for cervical (CC) and endometrial cancer (EC) takes place once surgery is performed. The aim of this study was to evaluate the role of PET/CT in detecting lymphatic metastasis in patients with CC and EC using dual-time-point imaging (DPI), taking the histopathological results of sentinel lymph node (SLN) and lymphadenectomy as the reference. Material and methods. A prospective study was conducted on 17 patients with early CC, and 13 patients with high-risk EC. The patients had a pre-operative PET/CT, MRI, SLN detection, and lymphadenectomy, when indicated. PET/CT findings were compared with histopathological results. Results. In the pathology study, 4 patients with CC and 4 patients with EC had lymphatic metastasis. PET/CT showed hypermetabolic nodes in 1 patient with CC, and 5 with EC. Four of these had metastasis, one detected in the SLN biopsy. Four patients who had negative PET/CT had micrometastasis in the SLN biopsy, 1 patient with additional lymph nodes involvement. The overall patient-based sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT to detect lymphatic metastasis was 20.0%, 100.0%, 100.0%, 87.9%, and 88.2%, respectively, in CC, and 57.1%, 88.9%, 66.7%, 84.2% and 80.0%, respectively, in EC. DPI showed higher retention index in malignant than in inflammatory nodes, although no statistically significant differences were found. Conclusions. PET/CT has low sensitivity in lymph node staging of CC and EC, owing to the lack of detection of micrometastasis. Thus, PET/CT cannot replace SLN biopsy. Although no statistically significant differences were found, DPI may help to differentiate between inflammatory and malignant nodes (AU)

Objetivo. La estadificación definitiva del cáncer de cérvix (CC) y de endometrio (CE) tiene lugar tras la cirugía. Nuestro objetivo fue evaluar la utilidad de la PET/TC para la detección de metástasis ganglionares en el CC y en el CE con imagen dual-time-point (DPI), considerando como gold standard la histopatología del ganglio centinela (GC) y la linfadenectomía. Material y métodos. Diecisiete pacientes con CC inicial y 13 con CE de alto riesgo fueron incluidas prospectivamente. Preoperatoriamente se realizó una PET/TC, RM, detección del GC y linfadenectomía en los casos indicados. Se comparó la PET/TC con la histopatología. Resultados. En el estudio anatomopatológico, 4 pacientes con CC y 4 con CE tuvieron metástasis ganglionares. La PET/TC mostró ganglios hipermetabólicos en una paciente con CC y en 5 con CE. Cuatro de ellas tenían metástasis, una detectada en el GC. Cuatro pacientes con PET/TC negativa presentaron micrometástasis en el GC, una paciente con ganglios adicionales infiltrados. La sensibilidad, especificidad, valor predictivo positivo y negativo y la exactitud diagnóstica de la PET/TC para detectar metástasis ganglionares fueron 20,0; 100,0; 100,0; 87,9 y 88,2% para el CC, y 57,1; 88,9; 66,7; 84,2 y 80,0% para el CE. La DPI mostró un índice de retención superior en ganglios infiltrados respecto a los inflamatorios, sin hallar diferencias estadísticamente significativas. Conclusiones. La PET/TC tiene baja sensibilidad para estadificar el CC y CE por la incapacidad de detectar micrometástasis y, por tanto, no sustituye la detección del GC. Aunque no hubo diferencias estadísticamente significativas, la DPI podría ayudar a diferenciar ganglios inflamatorios de tumorales (AU)

How to deal with prognostic factors and radiotherapy results in uterine neoplasms with a sarcomatous component?

PURPOSE: Uterine tumours with a sarcomatous component are rare neoplasms with a wide pathologic heterogeneity in which the stage is the main prognostic factor. These aspects and their aggressiveness make the analysis of prognostic factors and radiotherapy difficult. The aim of this study was to evaluate the prognostic factors by stages and to assess the impact of prognostic factors and the effect of radiotherapy on the outcome of the disease. METHODS AND MATERIALS: Eighty-one patients diagnosed and treated for uterine tumours with a sarcomatous component at the Hospital Clinic in Barcelona between 1975 and 2003 were retrospectively studied; 76/81 patients underwent surgery (total hysterectomy plus bilateral salpingo-oophorectomy, and in 13/76 of these patients an additional pelvic lymphadenectomy was performed). All 76 patients were staged after pathological evaluation of the surgical specimen by FIGO classification with 54 patients being stages I-II and 27 patients stages III-IVA. Only 5 patients were clinically staged as III-IVA. Radiotherapy was administered in 21 women with early-stage tumours and in 16 with advanced neoplasms. 5/81 patients received complementary chemotherapy to the surgery and 5 patients received chemotherapy as treatment of local and distant relapse (All the patients were treated with a different chemotherapy schedule). The impact of pathologic prognostic factors and radiotherapy on specific overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were analysed by Log Rank test and Cox proportional risk models. The effect of each risk factor was studied by the hazard ratio and 95% confidence interval. RESULTS: An increased frequency of several adverse prognostic factors was observed in tumours with advanced stages compared to early neoplasms in deep myometrial invasion (83% vs. 27%), VLSI (75% vs. 29%), tumour size >8 cm (50% vs. 30%) and multicentricity (36% vs. 10%), and similar values were found for necrosis (79% vs. 78%) and high mitotic index (78% vs. 80%). For pathological type the frequency by advanced vs. early stages was 54% vs. 52% for carcinosarcomas, 33.5% vs. 17.5% for leiomyosarcoma, and 30.5% and 12.5% for adenosarcoma and endometrial stromal sarcoma, respectively. Univariate analysis showed that the stage was the only independent prognostic factor. Stratification by early (I-II) and advanced stages (III, IV) revealed tumour size >8 cm was the only prognostic factor significantly associated with OS, DFS, LRFS and DMFS on univariate analysis for early stages (HR: OS 2.52, DFS 3.10, LRFS 3.10 and DMFS 2.63). For advanced stages, radiotherapy was the only prognostic factor associated with OS, DFS, LRFS and DMFS on multivariate analysis (HR: OS 4.26, DFS 3.14, LRFS 3.25 and DMFS 3.66). CONCLUSIONS: Uterine tumours with a sarcomatous component have a poor outcome in spite of treatment in comparison to endometrial carcinoma, probably due to the higher frequency of adverse prognostic factors. In early stages tumour size was the most determining factor for OS, DFS, LRFS and DMFS. Radiotherapy significantly improved these survivals in advanced cases (AU)

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Ganglio centinela en cánceres ginecológicos. Nuestra experiencia / Sentinel node in gynaecological cancers. Our experience

Aunque la identificación del ganglio centinela (GC) presenta en la actualidad una amplia aplicación en el melanoma y el cáncer de mama, no se utiliza rutinariamente en otras neoplasias, como pueden ser las ginecológicas.ObjetivoEvaluar la aplicabilidad y los resultados de la técnica de localización del GC en pacientes con cánceres ginecológicos.MétodoSe estudiaron 155 pacientes con diversas neoplasias ginecológicas (70 vulvares, 50 de cuello uterino y 35 endometriales). Se realizó una linfogammagrafía el día previo a la intervención quirúrgica mediante la inyección de 111 MBq de 99mTc-nanocoloide por diversas vías según el tipo de lesión. La localización intraoperatoria se realizó mediante una sonda detectora y en 100 casos (70 vulvares y 30 de cuello uterino) se administró también un colorante vital pocos minutos antes del inicio de la intervención. Se realizó estudio anatomopatológico del GC. Se practicó linfadenectomía reglada en todas las pacientes con cáncer de cérvix y de endometrio y en las primeras 35 pacientes con cáncer de vulva.ResultadosLa linfogammagrafía prequirúrgica visualizó como mínimo un GC en el 97% de los cánceres de vulva, en el 92% de cérvix y el 64% de tumores de endometrio. Intraoperatoriamente la localización del GC mostró unos porcentajes del 97, del 90 y del 62%, respectivamente. El estudio anatomopatológico demostró metástasis en el 24,2% de las pacientes con lesiones vulvares, el 8,8% en las de cérvix y el 4,5% en las de endometrio. El porcentaje de falsos negativos fue del 5,5% en los cánceres de vulva (1 caso), presentándose 2 casos en el endometrio y ninguno en las pacientes con cáncer de cérvix.ConclusiónLa linfogammagrafía es una técnica útil y sencilla para identificar los GC en este tipo de tumores. La biopsia del GC ofrece resultados fiables en los cánceres de vulva y cuello uterino. Sin embargo, en el cáncer de endometrio nuestros resultados no son óptimos y debe valorarse la adecuación de la técnica(AU)

Although sentinel lymph node (SLN) identification is widespread used in melanoma and breast cancer some concerns exist in other malignancies, such gynaecologic cancers, and this staging method has not been adopted in many centers due to lack or large validation studies.AimTo evaluate the applicability and results of SLN technique in gynaecological malignancies referred to our institution.MethodWe studied 155 patients with different malignancies (70 vulvar, 50 cervical and 35 endometrial cancers). The day before surgery a lymphoscintigraphy was performed by injecting 111MBq of 99mTc-nanocolloid in several ways depending on the type of cancer studied. Intraoperative detection of the SLN was always performed by using a hand-held gammaprobe and, in 100 cases with the aid of blue dye injection (70 vulvar and 30 in cervical cancer) few minutes before surgical intervention. Pathological study of SLN was performed in all cases. Lymphadenectomy was done in all cervix and endometrial cancer patients and in the first 35 vulvar cancer patients.ResultsPre-surgical lymphoscintigraphy demonstrated one, at least, SLN in 97% of vulvar cancer patients, 92% in the cervical malignancy and 64% in the endometrial cancer patiuents. During surgery, SLN was harvested in 97%, 90% and 62% of patients, respectively. The pathological study showed metastases in 24.2%, 8.8 and 4.5% of patients with vulvar, cervical and endometrial cancer, respectively. The false negative percentage was 5.5% in vulvar cancer patients, with 2 cases in the endometrial cancer and without any case in the cervical cancer patients.ConclusionLymphoscintigraphy is a relatively simple and useful technique to identify the SLN in this kind of tumours. However, in endometrial cancer more effort has to be made to reach a suitable result. Sentinel lymphm node biopsy seems to be a reliable technique in vulvar and cervical malignancies(AU)

Recurrence and survival in surgically treated endometrioid endometrial cancer

INTRODUCTION: The objective of this study was to evaluate different surgical treatments and radiotherapy on patterns of recurrence and overall survival in patients with endometrioid-type endometrial cancer. MATERIALS AND METHODS: The retrospective records of 162 patients with endometrioid endometrial cancer were collected. Patients were surgically treated from 1997 to 2002. Recurrence and survival were analyzed according to patient age, surgical procedure, lymphadenectomy, externalbeam irradiation, brachytherapy, surgical stage, myometrial invasion, and tumor grade. Standard statistical calculations were used. RESULTS: Median age was 64 years. Median follow-up was 44 months. Overall, ten patients (5.6%) experienced recurrence and 14 (8.6%) died. With univariate analysis, statistical significance for survival was found for age older than 70 years, tumor grade, myometrial invasion, and stage. Multivariate analysis, however, found only age, stage, and grade to be significant. With univariate analysis, statistical significance for recurrence was found for tumor grade, stage, and external-beam radiotherapy as risk factors. Multivariate analysis found only radiotherapy and brachytherapy to be significant, but in an inverted sense, with brachytherapy having a protective effect. CONCLUSION: Our results suggest that brachytherapy protects against recurrence and that neither a surgical approach nor a lymphadenectomy appear to affect recurrence or survival in patients with surgically treated endometrioid endometrial cancer (AU)

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Aspectos clínicos de las lesiones precursoras y del cáncer de cérvix / Clinical features of the precursor lesions and cervical cancer

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Preguntas y respuestas sobre la infección por el virus del papiloma humano / Questions and answers on human papilloma virus infection

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Preguntas y respuestas sobre la vacuna contra el virus del papiloma humano / Questions and answers on human papilloma virus vaccine

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Recurrencia ovárica y paraaórtica de un carcinoma de cuello uterino detectada mediante PET/TC / Ovarian and para-aortic recurrence from cervix cancer detected by PET/CT

Presentamos el caso de una mujer de 34 años de edad con un carcinoma adenoescamoso de cuello uterino en estadio IIB, según la clasificación de la FIGO (International Federation of Gynecology and Obstetrics), tratada mediante quimioterapia, radioterapia externa y braquiterapia con posterior histerectomía, en la que se sospechó recidiva de la enfermedad por un aumento progresivo en los niveles de antígeno carcinoembrionario (CEA). La tomografía por emisión de positrones/tomografía computarizada (PET/TC) mostró depósitos patológicos en ambos ovarios, que habían sido transpuestos mediante cirugía para evitar lesiones rádicas, y en una adenopatía paraaórtica izquierda, confirmándose por biopsia el diagnóstico de recidiva en dichas localizaciones. La PET con FDG (F 18-fluodesoxiglucosa) ha demostrado su utilidad tanto en la estadificación inicial como en el diagnóstico de recurrencia en pacientes con carcinoma de cuello uterino, con valores de sensibilidad y especificidad superiores a la TC y resonancia magnética (RM). La PET/TC mejora la localización anatómica y ayuda a determinar el origen de focos dudosos como en el caso que presentamos en el que los ovarios no estaban en su situación anatómica normal al haber sido transpuestos

We present the case of a 34-year-old woman diagnosed of an adenosquamous carcinoma of the uterine cervix, stage IIB of the FIGO classification (International Federation of Gynecology and Obstetrics), treated with quimiotherapy, radiotheraphy and brachytheraphy with posterior hysterectomy. A recurrence of the disease was suspected due to the progressive rise of CEA levels. A PET/CT revealed abnormal focii in both ovaries, that had been transposed to avoid lesions due to radiation, and in a left para-aortic adenopathy. The diagnosis of recurrence in these sites was confirmed by biopsy. PET with FDG (F 18-fluordesoxyglucose) is useful in the staging of primary tumour and in the detection of recurrence in uterine cervical carcinoma, with better sensitivity and especificity than CT and MRI. PET/CT improves anatomic resolution and helps to resolve the origin of unclear focii like in the case presented in which ovaries were not in their normal situation due to transposition

Neoplasia vulvar intraepitelial (vin) / Vulvar intraepithelial neoplasia (ivn)

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Ganglio centinela en el carcinoma de mama. Estudio de 175 casos / Sentinel node in breast carcinoma. Study of 175 cases

Objetivo: Evaluar la eficacia del estudio selectivo del ganglio centinela en el carcinoma de mama. Sujetos: Se incluye en este trabajo a 175 pacientes repartidas en dos grupos. El primero de 105 formado por neoplasias en estadios T1 y T2 y que sirvió para realizar la necesaria curva de aprendizaje en el que realizamos estudio de ganglio centinela y linfadenectomía reglada. Una vez validada la técnica, el grupo de aplicación terapéutica fue formado por 70 pacientes en estadios T1 y T2 de tamaño inferior a 2,5 cm. Resultados: En el grupo de aplicación clínica hemos detectado el ganglio centinela correctamente en el 98,5 per cent de los casos (eficacia), tanto por linfogammagrafía como intraoperatoriamente. Nuestra cifra de falsos negativos es del 0 per cent con un seguimiento clínico de estas pacientes de 8 meses. La sensibilidad del procedimiento y el valor predictivo negativo son del 100 per cent. Conclusiones: El estudio del ganglio centinela en el carcinoma de la mama nos ha permitido disminuir la morbilidad de la cirugía, reducir los ingresos hospitalarios y mejorar la recuperación de las pacientes. (AU)

Colposcopia digital en la neoplasia cervical intraepitelial. Correlación histológica y utilidad clínica / Digital colposcopy in cervical intraepithelial neoplasia. Histological correlation and clinical utility

Objetivo: Determinar, en la neoplasia cervical intraepitelial (CIN), la correlación histológica de la información morfométrica obtenida mediante un sistema original de colposcopia digital, y establecer sus posibles aplicaciones clínicas.Métodos: En 101 pacientes con colposcopia valorable se midió el área de la zona de transformación y de las lesiones colposcópicas. En 62 casos, en los que se practicó exéresis de la lesión con asa, estos datos se correlacionaron con la extensión de las lesiones histológicas.Resultados: A mayor grado histológico las lesiones cervicales incrementan significativamente su tamaño colposcópico (CIN-I, CIN-II, CIN-III: 90 mm2, 134 mm2, 265 mm2, respectivamente) y ocupan una disposición más central en el cérvix. Existe una muy buena correlación, cercana al 85 por ciento, con el tamaño medido mediante morfometría histológica.Conclusiones: El tamaño de la lesión colposcópica de la CIN es un buen indicador del verdadero tamaño lesional. Estos resultados abren una nueva perspectiva en la conducta a seguir en las lesiones de bajo grado, al ofrecer un método objetivo y fiable para controlar su evolución. (AU)