Fatores Preditores de Complicações após Radioterapia Conformacional 3D em Pacientes com Adenocarcinoma de Próstata / Predictors of Complications following 3D Conformational Radiotherapy in Patients with Prostate Adenocarcinoma / Factores Predictores de Complicaciones después de la Radioterapia Conformacional 3D en Pacientes con Adenocarcinoma de Próstata

Introdução: O câncer de próstata é considerado a neoplasia maligna mais comum que acomete homens em todas as Regiões do país, à exceção do câncer de pele não melanoma. Se diagnosticado e tratado precocemente, o câncer de próstata tem alta taxa de cura; contudo, terapêuticas como a radioterapia podem gerar complicações agudas que podem impactar as atividades cotidianas. Apesar das complicações no pós-tratamento, a radioterapia tem sido um método bastante praticado e que apresenta resultados positivos, ocasionando melhoria da sobrevida livre de doença. Objetivo: Avaliar os principais fatores preditores de complicações agudas que acometem pacientes em tratamento radioterápico para câncer de próstata. Método: Para identificação de fatores preditores de complicações agudas pós-radioterapia, avaliaram-se, consecutiva e prospectivamente, 208 pacientes diagnosticados com adenocarcinoma de próstata tratados com radioterapia conformacional 3D em um centro referência vinculado ao SUS entre os anos 2016 e 2017. Realizou-se ainda avaliação retrospectiva de prontuários para coleta de dados adicionais. A análise estatística foi realizada por meio dos testes qui-quadrado, exato de Fisher, Anova e regressão logística ordinal. Resultados: Após análise da amostra, evidenciou-se que, entre as complicações agudas, as de maior incidência foram radiodermite, cistite e enterite/retite, de forma que tais complicações tiveram como fatores associados volume irradiado, tratamento prévio e sintomas prévios ao tratamento. Conclusão: O estudo sugere que, apesar da existência de complicações ao final do tratamento, a grande maioria é de baixa complexidade e que pacientes submetidos a procedimentos cirúrgicos prévios podem evoluir com presença de complicações mais graves.

Introduction: Prostate cancer is considered the most common malignancy that affects men in all regions of the country, except for non-melanoma skin cancer. If diagnosed and treated early, prostate cancer has a high cure rate; however, therapies such as radiotherapy can generate acute complications that can impact daily activities. Despite post-treatment complications, radiotherapy has been a widely practiced method and has shown positive results, leading to improved disease-free survival. Objective: To evaluate the main predictive factors for acute complications that affect patients undergoing radiotherapy for prostate cancer. Method: To identify predictive factors for acute post-radiotherapy complications, 208 patients diagnosed with prostate adenocarcinoma treated with 3D conformational radiotherapy were consecutively and prospectively evaluated at a referral center linked to SUS between the years 2016 and 2017. It was carried out retrospective evaluation of medical records to collect additional data. Statistical analysis was performed using the chi-square test, Fisher's exact, Anova and ordinal logistic regression. Results: After analyzing the sample, it was evidenced that among the acute complications, those with the highest incidence were radiodermatitis, cystitis, enteritis/rectitis, so that these complications had associated predictive factors as irradiated volume, previous treatment and symptoms. Conclusion: The study suggests that despite the existence of complications at the end of the treatment, the vast majority are of low complexity and that the patients submitted to previous surgical procedures can evolve with the presence of more severe complications.

Introducción: El cáncer de próstata se considera la neoplasia maligna más común que afecta a los hombres en todas las regiones del país, con la excepción del cáncer de piel no melanoma. Si se diagnostica y trata temprano, el cáncer de próstata tiene una alta tasa de curación; sin embargo, las terapias como la radioterapia pueden generar complicaciones agudas que pueden afectar las actividades diarias. A pesar de las complicaciones posteriores al tratamiento, la radioterapia ha sido un método ampliamente practicado y ha mostrado resultados positivos, lo que lleva a una mejor supervivencia libre de enfermedad. Objetivo: Evaluar los principales predictores de complicaciones agudas que afectan a los pacientes sometidos a radioterapia para el cáncer de próstata. Método: Para identificar los factores predictivos de complicaciones agudas posteriores a la radioterapia, 208 pacientes diagnosticados con adenocarcinoma de próstata tratados con radioterapia conformacional 3D fueron evaluados consecutiva y prospectivamente en un centro de referencia vinculado al SUS entre los años 2016 y 2017. Se realizó evaluación retrospectiva de registros médicos para recopilar datos adicionales. El análisis estadístico se realizó utilizando la prueba de chi-cuadrado, exacta de Fisher, de Anova y la regresión logística ordinal. Resultados: Después de analizar la muestra, se evidenció que, entre las complicaciones agudas, las de mayor incidencia fueron radiodermatitis, cistitis, enteritis/retitis y síntomas obstructivos, por lo que estas complicaciones tenían factores predictivos asociados, como el volumen irradiado, el tratamiento previo y los síntomas. Conclusión: El estudio sugiere que a pesar de la existencia de complicaciones al final del tratamiento, la gran mayoría son de baja complejidad. Como factores predictivos encontrados, se puede mencionar el volumen irradiado, la existencia de tratamiento previo y los síntomas en la consulta inicial.

Intensity modulated radiotherapy (IMRT) or conformational radiotherapy (3D-CRT) with conventional fractionation for prostate cancer: Is there any clinical difference?

ABSTRACT Purpose: To compare the treatment outcomes of a cohort of prostate cancer patients treated with conventional schedule using IMRT or 3DRT technique. Materials and Methods: Between 2010-2017, 485 men with localized prostate cancer were treated with conventional radiotherapy schedule with a total dose ≥74Gy using IMRT (231) or 3DCRT (254). Late gastrointestinal (GI) and genitourinary (GU) toxicity were retrospectively evaluated according to modified RTOG criteria. The biochemical control was defined by the Phoenix criteria (nadir + 2ng/mL). The comparison between the groups included biochemical recurrence free survival (bRFS), overall survival (OS) and late toxicity. Results: With a median follow-up of 51 months (IMRT=49 and 3DRT=51 months), the maximal late GU for >=grade- 2 during the entire period of follow-up was 13.1% in the IMRT and 15.4% in the 3DRT (p=0.85). The maximal late GI ≥ grade- 2 in the IMRT was 10% and in the 3DRT 24% (p=0.0001). The 5-year bRFS for all risk groups with IMRT and 3D-CRT was 87.5% vs. 87.2% (p=0.415). Considering the risk-groups no significant difference for low-, intermediate- and high-risk groups between IMRT (low-95.3%, intermediate-86.2% and high-73%) and 3D-CRT (low-96.4%, intermediate-88.2% and high-76.6%, p=0.448) was observed. No significant differences for OS and DMFS were observed comparing treatment groups. Conclusion: IMRT reduces significantly the risk of late GI severe complication compared with 3D-CRT using conventional fractionation with a total dose ≥74Gy without any differences for bRFS and OS.

A Comparison of Gastrointestinal Toxicities between Intensity-Modulated Radiotherapy and Three-Dimensional Conformal Radiotherapy for Pancreatic Cancer

BACKGROUND/AIMS: Concurrent chemoradiotherapy (CCRT) is considered the treatment option for locally advanced pancreatic cancer, but accompanying gastrointestinal toxicities are the most common complication. With the introduction of three-dimensional conformal radiotherapy (3-D CRT) and intensity-modulated radiotherapy (IMRT), CCRT-related adverse events are expected to diminish. Here, we evaluated the benefits of radiation modalities by comparing gastrointestinal toxicities between 3-D CRT and IMRT. METHODS: Patients who received CCRT between July 2010 and June 2012 in Severance Hospital, Yonsei University College of Medicine, were enrolled prospectively. The patients underwent upper endoscopy before and 1 month after CCRT. RESULTS: A total of 84 patients were enrolled during the study period. The radiotherapy modalities delivered included 3D-CRT (n=40) and IMRT (n=44). The median follow-up period from the start of CCRT was 10.6 months (range, 3.8 to 29.9 months). The symptoms of dyspepsia, nausea/vomiting, and diarrhea did not differ between the groups. Upper endoscopy revealed significantly more gastroduodenal ulcers in the 3-D CRT group (p=0.003). The modality of radiotherapy (3D-CRT; odds ratio [OR], 11.67; p=0.011) and tumor location (body of pancreas; OR, 11.06; p=0.009) were risk factors for gastrointestinal toxicities. CONCLUSIONS: IMRT is associated with significantly fewer gastroduodenal injuries among patients treated with CCRT for pancreatic cancer.

Ultrasound guided conformal brachytherapy of cervix cancer: survival, patterns of failure, and late complications / 부인종양

OBJECTIVE: The aim of this study was to report on the long-term results of transabdominal ultrasound guided conformal brachytherapy in patients with cervical cancer with respect to patterns of failures, treatment related toxicities and survival. METHODS: Three hundred and nine patients with cervical cancer who presented to Institute between January 1999 and December 2008 were staged with magnetic resonance imaging and positron emission tomography and treated with external beam radiotherapy and high dose rate conformal image guided brachytherapy with curative intent. Follow-up data relating to sites of failure and toxicity was recorded prospectively. RESULTS: Two hundred and ninety-two patients were available for analyses. The median (interquantile range) follow-up time was 4.1 years (range, 2.4 to 6.1 years). Five-year failure free survival and overall survival (OS) were 66% and 65%, respectively. Primary, pelvic, para-aortic, and distant failure were observed in 12.5%, 16.4%, 22%, and 23% of patients, respectively. In multivariate analysis, tumor volume and nodal disease related to survival, whereas local disease control and point A dose did not. CONCLUSION: Ultrasound guided conformal brachytherapy of cervix cancer has led to optimal local control and OS. The Melbourne protocol compares favorably to the more technically elaborate and expensive GEC-ESTRO recommendations. The Melbourne protocol's technical simplicity with real-time imaging and treatment planning makes this a method of choice for treating patients with cervical cancer.

Evaluation of Acute Toxicity and Symptoms Palliation in a Hypofractionated Weekly Schedule of External Radiotherapy for Elderly Patients with Muscular Invasive Bladder Cancer

Aim To evaluate acute toxicity and symptoms palliation of a weekly hypofractionated 3DCRT schedule as radical treatment in elderly patients with organ confined bladder cancer cT1-2N0. Materials and Methods Between February 2005 and June 2011, 58 prospectively selected patients diagnosed with organ confined bladder cancer were treated with external 3DCRT (4-field arrangement). All candidates were medically inoperable, with poor performance status, and with age ranged from 75 to 88 years (median 78). A dose of 36 Gy in 6 weekly fractions was prescribed. The primary study endpoints were the evaluation of haematuria, dysuria, frequency and pain palliation as well as the acute toxicity according to the RTOG/EORTC scale: an assessment was performed at baseline, during and 3 months after radiotherapy, while the maximum reported score was taken into account. Results The gastrointestinal acute toxicities were 13/58 (22.4%) and 5/58 (5.6%), for grade I and II respectively. The genitourinary acute toxicities were 19/58 (32.7%) and 10/58 (17.2%), for grade I and II respectively. In terms of clinical outcome, 55/58 patients (94.8%) reported palliation of haematuria, while 19 out of 58 reported no change in frequency and dysuria. All patients reported significant improvement (P < 0.01) for pain, concerning the visual analogue score before and after radiotherapy. The median progression free survival was 14 months. CONCLUSIONS The incidence of patient-reported acute toxicity following weekly hypofractionated external 3DCRT is low while the symptom palliation compares very favorably with other reported outcomes. .

From two-dimensional to three-dimensional conformal radiotherapy in prostate cancer: An Indian experience.

Background: Sparse data from India are available regarding the outcome of prostate cancer treatment. We report our experience in treating prostate cancer with radiotherapy (RT). Materials and Methods: This study included 159 men with locally advanced cancer treated with RT with or without hormone therapy between 1984 and 2004. The median RT dose was 70 Gy over 35 fractions. Eighty-five patients received whole pelvic RT and prostate boost, and 74 patients were treated with 3-dimensional conformal radiotherapy (3DCRT) to prostate and seminal vesicles alone. Results: The median follow-up was 25 months and the freedom from biochemical failure for all the patients at 5 years was 76%, disease-free survival (DFS) 59.1%, and overall survival (OAS) was 70.1%. The risk stratification (91% vs 52%, P < 0.03) and RT dose (72.8% for dose > 66 Gy vs 43.5% for dose < 66 Gy; P = 0.01) affected the DFS. DFS at 5 years was better in the group receiving 3DCRT to prostate and seminal vesicles (78% vs 51.5%; P = 0.001) and was reflected in OAS as well (P = 0.01). Conclusion: CRT technique with dose escalation results in significant benefit in DFS and OAS in locally advanced prostate cancer.

Radiotherapy and radiosurgery for Cushing's disease

Patients with residual or recurrent Cushing's disease receive external beam radiotherapy (RT) with the aim of achieving long-term tumour control and normalization of elevated hormone levels. Treatment is given either as conventional radiotherapy using conformal techniques or as stereotactic radiotherapy, which is either used as fractionated treatment (SCRT) or as single fraction radiosurgery (SRS). We describe the technical aspects of treatment and report a systematic review of the published literature on the efficacy and toxicity of conventional RT, SCRT and SRS. There are no studies directly comparing the different radiation techniques and the reported results are inevitably of selected patients by investigators with interest in the treatment tested. Nevertheless the review of the published literature suggests better hormone and tumour control rates after fractionated irradiation compared to single fraction radiosurgery. Hypopituitarism represents the most commonly reported late complication of radiotherapy seen after all treatments. Although the incidence of other late effects is low, the risk of radiation injury to normal neural structures is higher with single fraction compared to fractionated treatment. Stereotactic techniques offer more localized irradiation compared with conventional radiotherapy, however longer follow-up is necessary to confirm the potential reduction of long-term radiation toxicity of fractionated SCRT compared to conventional RT. On the basis of the available literature, fractionated conventional and stereotactic radiotherapy offer effective treatment for Cushing's disease not controlled with surgery alone. The lower efficacy and higher toxicity of single fraction treatment suggest that SRS is not the appropriate therapy for the majority of patients with Cushing's disease.

Pacientes com doença de Cushing residual ou recorrente recebem radioterapia externa em feixe (RT) com o objetivo de alcançar um controle tumoral prolongado e a normalização dos níveis hormonais elevados. O tratamento é realizado tanto com RT convencional, usando técnicas conformacionais, ou com RT estereotáxica, que é usada tanto como tratamento fracionado (RTF) ou como radiocirurgia em procedimento único (RCU). Descreveremos os aspectos técnicos do tratamento e mostraremos uma revisão sistemática da literatura sobre a eficácia e toxicidade da RT convencional, da RTF e da RCU. Não existem estudos comparando diretamente as diferentes técnicas de radiação, e os resultados reportados são inevitavelmente os de pacientes selecionados pelos investigadores com interesse no tratamento testado. De qualquer maneira, a revisão dos dados publicados sugere que há melhores taxas de controle hormonal e tumoral após RTF em comparação com RCU. O hipopituitarismo representa a complicação tardia mais comumente relatada da RT, vista após todos os tipos de tratamento. Embora a incidência de outros efeitos tardios seja baixa, o risco de a radiação comprometer estruturas neurais normais é mais elevado com RCU do que com RTF. Técnicas estereotáxicas oferecem irradiação mais localizada se comparadas com a RT convencional, embora um acompanhamento prolongado seja necessário para confirmar a possível redução da toxicidade continuada da radiação na RTF em comparação com a RT convencional. Com base na literatura disponível, a RT fracionada convencional e a estereotáxica oferecem tratamento efetivo para a doença de Cushing não controlada isoladamente pela cirurgia. A baixa eficácia e alta toxicidade do tratamento em dose única sugere que a RCU não seja a terapia mais apropriada para a maioria dos pacientes com doença de Cushing.

Prognostic factors for late urinary toxicity grade 2-3 after conformal radiation therapy on patients with prostate cancer

OBJECTIVE: Identify prognostic factors associated to late urinary toxicity in patients with prostate cancer submitted to radical conformal radiotherapy (3DCRT) MATERIALS AND METHODS: From July 1997 to January 2002, 285 patients with localized prostate cancer were consecutively treated with 3DCRT and retrospectively analyzed. Thirty seven (13 percent) patients were submitted to transurethral prostate resection previously to 3DCRT. The median dose delivered to the prostate was 7920 cGy (7020-8460). Patient and treatment characteristics were analyzed and correlated to late urinary toxicity grade 2-3, especially whether certain radiation doses applied to certain bladder volumes, when visualized through computerized tomography (CT) planning, correlated with the observed actuarial incidences of late urinary complications, using bladder volume as a continuous variable RESULTS: On a median follow-up of 53.6 months (3.6-95.3), the 5-year actuarial free from late urinary toxicity grade 2-3 survival was 91.1 percent. Seven and fifteen patients presented late urinary toxicity grades 2 and 3, respectively. Prior transurethral resection of prostate and radiation dose over 70 Gy on 30 percent of initial bladder volume were independent prognostic factors for late urinary toxicity grade 2-3 CONCLUSIONS: This study suggests that restricting radiation doses to 70 Gy or less on 30 percent of bladder volume, visualized through CT planning, may reduce late urinary complications. It furthermore suggests that patients with prior transurethral resection of prostate may indicate a group of patients with a greater risk for late urinary toxicity grade 2-3 after 3DCRT.

Efficacy of Transarterial Chemolipiodolization with or without 3-Dimensional Conformal Radiotherapy for Huge HCC with Portal Vein Tumor Thrombosis / 대한간학회지

BACKGROUND/AIMS: The treatment efficacy for advanced hepatocellular carcinoma is poor. This study examined the efficacy and toxicity of 3-dimensional conformal radiotherapy (3D-CRT) in combination with transarterial chemolipiodolization (TACL) for a huge hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). METHODS: From March 2001 to November 2004, 49 patients with advanced HCC with PVTT (size>8 cm, modified UICC stage IVa) were enrolled in this retrospective study. Twenty two patients underwent more than 2 cycles of TACL (adriamycin 50 mg/m2, cisplatin 60 mg/m2, 5-fluorouracil 200 mg/m2 every 4-6 weeks) without 3D-CRT, while 27 patients underwent consecutive TACL with 3D-CRT (40-45 Gy for 4-5 weeks) that was started one week after the 1st TACL. The response was assessed by a computed tomography (CT) and the serum alpha-fetoprotein (AFP) level at 1-2 month intervals. RESULTS: The objective response rates in the TACL group and TACL with 3D-CRT group were 18% and 48% at 3 months (P=0.051), and 10.5% and 42% at 6 months (P=0.024) respectively. The median survival time was 13 months and 13.5 months in TACL and TACL with 3D-CRT groups, respectively (P=0.502). The treatment response was better in the TACL with 3D-CRT group but there was no significant difference in survival between the two groups. Most toxicities in the two groups were mild, not exceeding grade 1 according to the WHO criteria. CONCLUSIONS: For patients with a huge HCC with PVTT, TACL with 3D-CRT achieved some meaningful clinical benefit. Prospective controlled trials will be needed to confirm the real benefit of TACL combined with 3D-CRT.

Salvage conformal radiotherapy for biochemical recurrent prostate cancer after radical prostatectomy

OBJECTIVE: Assess the results of salvage conformal radiotherapy in patients with biochemical failure after radical prostatectomy and identify prognostic factors for biochemical recurrence and toxicity of the treatment. MATERIALS AND METHODS: From June 1998 to November 2001, 35 patients were submitted to conformal radiotherapy for PSA > 0.2 ng/mL in progression after radical prostatectomy and were retrospectively analyzed. The mean dose of radiation in prostatic bed was of 77.4 Gy (68-81). Variables related to the treatment and to tumor were assessed to identify prognostic factors for biochemical recurrence after salvage radiotherapy. RESULTS: The median follow-up was of 55 months (17-83). The actuarial survival rates free of biochemical recurrence and free of metastasis at a distance of 5 years were 79.7 percent e 84.7 percent, respectively. The actuarial global survival rate in 5 years was 96.1 percent.The actuarial survival rate free of biochemical recurrence in 5 years was 83.3 percent with PSA pre-radiotherapy < 1, 100 percent when > 1 and < 2, and 57.1 percent when > 2 (p = 0.023). Dose > 70 Gy in 30 percent of the bladder volume implied in more acute urinary toxicity (p = 0.035). The mean time for the development of late urinary toxicity was 21 months (12-51). Dose > 55 Gy in 50 percent bladder volume implied in more late urinary toxicity (p = 0.018). A patient presented late rectal toxicity of 2nd grade. CONCLUSIONS: Conformal radiotherapy showed to be effective for the control of biochemical recurrence after radical prostatectomy. Patients with pre-therapy PSA < 2 ng/mL have more biochemical control.