Neoadjuvant radiochemotherapy in the treatment of fixed and semi-fixed rectal tumors. Analysis of results and prognostic factors.

PURPOSE: To report the retrospective analysis of patients with locally advanced rectal cancer treated with neodjuvant radiochemotherapy. METHODS AND MATERIALS: From January 1994 to December 2003, 101 patients with fixed (25%) or semi-fixed (75%) rectal adenocarcinoma were treated by preoperative radiotherapy with a dose of 45 Gy at the whole pelvis and 50.4 Gy at primary tumor, concomitant to four weekly chemotherapies with 5-Fluorouracil (425 mg/m2) and Leucovorin (20 mg/m2). In 71 patients (70.3%) the primary tumor was located up to 6 cm from the anal verge and in 30 (29.7%) from 6.5 cm to 10 cm. Age, gender, tumor fixation, tumor distance from the anal verge, clinical response, surgical technique, and postoperative TNM stage were the prognostic factors analyzed for overall survival (OS), disease-free survival (DFS), and local control (LC) at five years. RESULTS: Median follow-up time was 38 months (range, 2-141). Complete response was observed in eight patients (7.9%), partial in 54 (53.4%) and absence in 39 (38.7%). OS, DFS and LC were 52.6%, 53.8%, and 75.9%, respectively. Distant metastasis occurred in 40 (39.6%) patients, local recurrence in 20 (19.8%) and both in 16 (15.8%). Patients with fixed tumors had lower OS (17% Vs 65.6%; p < 0.001), DFS (31.2% Vs 60.9%; p = 0.005), and LC (58% Vs 82%; p = 0.004). Patients with tumors more than 6 cm above the anal verge had better LC (93% Vs 69%; p = 0.04). The postoperative TNM stage was a significant factor for DFS (I:64.1%, II:69.6%, III:35.2%, IV:11.1%; p < 0.001) and for LC (I:75.7%, II: 92.9%, III:54.1%, IV:100%; p = 0.005). Patients with positive lymph nodes had worse OS (37.9% Vs 70.4%, p = 0.006), DFS (32% Vs 72.7%, p < 0.001) and LC (56.2% Vs 93.4%; p < 0.001). CONCLUSION: This study suggests that the neoadjuvant treatment employed was effective for local control. Fixation of the lesion and lymph nodes metastasis were the main adverse prognostic factors. Distant failures were frequent, supporting the need of new drugs for adjuvant chemotherapy.

Biochemical Relapse for Prostate Cancer Following Radical Prostatectomy: Salvage Radiotherapy Without HormonalTherapy

Objectives: This paper aims to study biochemical control, hormonal therapy-free survival, and prognostic factors related tosalvage radiation for prostate cancer patients submitted to radical prostatectomy (RP) without hormonal therapy (HT) before orduring radiation. Materials and Methods: from August 2002 to July 2004, 39 prostate cancer patients submitted to RPpresented biochemical failure after achieving PSA nadir (<0.2ng/ml). All patients were submitted to three-dimensional conformalexternal beam radiation therapy (3DC-EBRT) and no patients had received HT. Median age was 62 years, median preoperativePSA was 9.4ng/ml, median Gleason Score was 7. We defined PSA rise above 0.2 as biochemical failure after surgery. Median3DC-EBRT dose was 70Gy, and biochemical failure after EBRT was defined as three consecutive rises in PSA or a single risesufficient to trigger HT. Results: Biochemical non-evidence of disease (BNED) in 3 years was 72%. PSA doubling time (PSADT)lower than 4 months (p=0.04), and delay to salvage EBRT (p=0.05) were associated to worse chance of successful salvagetherapy. Late morbidity was acceptable. Conclusion: Expressive PSA control (72% BNED / 3years) could be achieved withsalvage radiotherapy in well-selected patients. The importance of PSADT was confirmed, and radiotherapy should be started asearly as possible. Follow-up is somewhat short, but it is possible to conclude that it is possible to achieve a long interval freefrom hormonal therapy with low rate of toxicity, avoiding or at least delaying morbidity related to hormonal treatment.radiotherapy

Comparison of low and high dose rate brachytherapy in the treatment of uterine cervix cancer. Retrospective analysis of two sequential series.

PURPOSE: This retrospective analysis aims to report on the comparative outcome of cervical cancer patients treated with low dose rate (LDR) and high dose rate (HDR) brachytherapy. METHODS AND MATERIALS: From 1989 to 1995, 190 patients were treated with low dose rate (LDR) brachytherapy (LDR group) and from 1994 to 2001, 118 patients were treated with high dose rate (HDR) brachytherapy (HDR group). FIGO stage distribution for the LDR group was Stage I: 6.3%; Stage II: 57.4%; and Stage III: 36.3% and for the HDR group Stage I: 9.3%; Stage II: 43.2%; and Stage III: 47.4%. All patients were treated with telecobalt external-beam radiotherapy (EBR). Median doses of LDR brachytherapy at Point A were 40 Gy and 50 Gy for patients treated with 1 and 2 implants, respectively. All patients from the HDR group were treated with 24 Gy in 4 fractions of 6 Gy to Point A. Survival, disease-free survival, local control, and late complications at 5 years, were endpoints compared for both groups. RESULTS: Median follow-up time for LDR and HDR groups was 70 months (range, 8-127 months) and 33 months (range, 4-117 months), respectively. For all stages combined, overall survival, disease-free survival, and local control at 5 years were better in the LDR group (69% vs. 55%, p = 0.007; 73% vs. 56%, p = 0.002; and 74% vs. 65%; p = 0.04, respectively). For clinical Stages I and II, no differences was seen in overall survival, disease-free survival, and local control at 5 years between the two groups. For clinical Stage III, overall survival and disease-free survival at 5 years were better in the LDR group than in the HDR group (46% vs. 36%, p = 0.04 and 49% vs. 37%, p = 0.03, respectively), and local control was marginally higher in the LDR group than in the HDR group (58% vs. 50%, p = 0.19). The 5-year probability of rectal complications was higher in the LDR group than in the HDR group (16% vs. 8%, p = 0.03) and 5-year probability of small bowel and urinary complications was not statistically different between the the LDR group and the HDR group (4.6% vs. 8.9%, p = 0.17 and 6% vs. 3%, p = 0.13, respectively). CONCLUSIONS: This comparative series suggests similar outcome for Stages I and II patients treated with either HDR or LDR brachytherapy. Lower overall and disease-free survival and marginally lower local control were observed for Stage III patients treated with HDR brachytherapy. Less late rectal complications were observed in the HDR group patients. These findings were probably the result of the relatively low HDR brachytherapy dose delivered at Point A.

High-dose-rate brachytherapy as part of a multidisciplinary treatment of nasopharyngeal lymphoepithelioma in childhood.

BACKGROUND: Nasopharyngeal carcinoma in childhood is rare. Radiochemotherapy is considered the standard treatment and yields increased survival and local control rates. In this article, the authors report on the results from the multidisciplinary treatment of pediatric patients who had nasopharyngeal lymphoepithelioma with radiochemotherapy, including high-dose-rate brachytherapy of the primary tumor site. METHODS: Between May 1992 and May 2000, 16 children with nasopharyngeal lymphoepithelioma received neoadjuvant chemotherapy, conventional external beam radiotherapy, high-dose-rate brachytherapy, and adjuvant chemotherapy. Patients ranged in age from 7 years to 18 years, and 9 patients were male. Patient distribution according to clinical disease stage was as follows: Stage III, 1 patient; Stage IVA, 5 patients; Stage IVB, 9 patients; and Stage IVC, 1 patient. Three cycles of neoadjuvant and adjuvant chemotherapy in 3-week intervals were administered with cyclophosphamide, vincristine, doxorubicin, and cisplatin. The median doses of external beam radiotherapy to the primary tumor, positive lymph nodes, and subclinical areas of disease were 55 grays (Gy), 55 Gy, and 45 Gy, respectively. Children received 2 insertions of high-dose-rate brachytherapy at 5 Gy per insertion: These were performed with metallic applicators inserted through the transnasal access under local anesthesia. RESULTS: The median of follow-up was 54 months. At the time of last follow-up, 13 patients were alive without disease, 2 patients had died of disease, and 1 patient had died of treatment-related cardiac failure. Local control was achieved in 15 of 16 patients. Chemotherapy-related and radiotherapy-related acute toxicity was relevant but tolerable. CONCLUSIONS: In the current study, it was shown that the treatment was effective in the control of both local and distant disease, although there was relevant acute and late toxicity. High-dose-rate brachytherapy was deliverable on an outpatient basis with local anesthesia. Close follow-up of these patients was necessary to evaluate the significance of treatment-related late effects and their impact on quality of life.

External Beam Radiotherapy Boosted With High Dose Rate Brachytherapy in Completely Resected Uterine Sarcomas. Is This a Treatment Option?

Uterine sarcoma (US) is a relative rare tumor, whichaccounts for only about 3-5% of all uterine cancers.Aggressive cytoreductive surgery at the time of the initialdiagnosis with maximum tumor debulking may lead toa prolonged survival or cure. OBJECTIVE: to identifyand review the role of adjuvante external beam radiationtherapy (EBRT) associated with high dose ratebrachytherapy (HDRB) in the management of patientspresenting US with complete resection. MATERIAL ANDMETHODS: this study is a retrospective analysis of 23patients with US treated from 10/92 to 03/03, withsurgery, external beam radiation therapy (EBRT) andhigh dose rate brachytherapy (HDRB). The inclusioncriteria for study participation included: histologicallyproven and graded US, completely resection of tumor,Karnofsky status 60–100, absence of significant infection,and recovery from recent surgery. RESULTS: The medianage of patients was 62 years (range 39-84); ten-yearactuarial disease-free and overall survivals were 42.2%and 63.4%, respectively. On univariate analysis,predictive factors for disease-free survival (DFS) wereage at initial presentation (p=0.0268), parity (p= 0.0441),tumor grade (p= 0.0095), cervical or vaginal invasion(p=0.0014) and node dissection at time of surgery (p=0.0471). On multivariate analysis, the only predictivefactor was cervical or vaginal invasion (p= 0.048), hazardratio of 4.7. CONCLUSION: it is quite likely that neitherradiotherapy nor chemotherapy alone will appreciablyimprove survival in US. If radiation therapy providesbetter locoregional tumor control, hematogenousmetastases will assume an even greater proportion oftreatment failures. Unfortunately, our small andheterogeneous group analyzed precludes any definitiveconclusions about the impact of HDRB associated to EBRTradiation therapy on recurrence or survival.

Tratamento conservador ocular dos melanomas de coróide com braquiterapia utilizando placas de iodo-125 / Conservative treatment of choroidal melanomas using iodine brachytherapy

OBJETIVO: Avaliar, retrospectivamente, o resultado do tratamento conservador do melanoma de coróide, por meio de braquiterapia, usando placas episclerais de iodo-125 (modelo 6711, Amershan). MATERIAIS E MÉTODOS: Foram avaliados 49 pacientes portadores de melanoma de coróide tratados no Hospital do Câncer, São Paulo, SP, de março de 2001 a janeiro de 2003. Os seguintes parâmetros foram analisados e correlacionados ao controle local e sobrevida: sexo, idade, dimensões da lesão, tempo de tratamento e doses no ápice e base das lesões. RESULTADOS: Com diâmetro máximo da base do tumor de 17 mm e altura máxima de 12 mm, observamos que as doses na base do tumor variaram de 213 a 463 Gy (mediana de 347 Gy) e no ápice, de 51 a 250 Gy (mediana de 91 Gy). As taxas de preservação ocular, sobrevida livre de doença e conservação ocular, atuariais em dois anos, foram de 96 por cento, 93,5 por cento e 96,3 por cento, respectivamente. Através de análise univariada, o único fator prognóstico para controle local nesta análise foi a altura do tumor menor que 6 mm (p = 0,0348). CONCLUSÃO: A braquiterapia levou a uma taxa bastante satisfatória de controle local, confirmando que a altura do tumor é um dos fatores prognósticos importantes desse parâmetro.

OBJECTIVE: To retrospectively evaluate the results of conservative therapy using episcleral iodine-125 (model 6711, Amershan) plaque for brachytherapy of choroidal melanoma. MATERIALS AND METHODS: We evaluated 49 patients with choroidal melanoma treated at "Hospital do Câncer", São Paulo, Brazil, from March 2001 to January 2003. The following clinical parameters were analyzed and correlated with local control and survival rate: gender, age, lesion dimension, treatment duration, as well as doses in apex and base of the tumors. RESULTS: The maximum diameter and height of the base of the tumors treated were 17 mm and 12 mm, respectively. Doses at those points ranged from 213 to 463 Gy (median: 347 Gy) and 51 to 250 Gy (median: 91 Gy), respectively. The actuarial rates of ocular preservation, disease free survival and ocular preservation in 2-years were 96%, 93.5% and 96.3%, respectively. A tumor height < 6 mm was the only predictive factor for local control (p = 0.0348) in the univariate analysis. CONCLUSION: Brachytherapy achieved a very satisfactory rate of tumor local control, confirming that tumor height is one of the most important predictive factors for local control.

Avaliação da resposta bioquímica no câncer inicial de próstata: experiência uninstitucional comparando teleterapia exclusiva ou associada à braquiterapia de alta taxa de dose / Evaluation of biochemical response on early prostate cancer: comparison between treatment with external beam radiation alone and in combination with high-dose rate conformal brachytherapy boost

OBJETIVO: Análise comparativa da resposta bioquímica em pacientes submetidos à teleterapia exclusiva ou associada à braquiterapia de alta taxa de dose para tumores localizados da próstata. MATERIAIS E MÉTODOS: De novembro de 1997 a janeiro de 2000, 74 pacientes foram submetidos à teleterapia com 45 Gy e reforço com braquiterapia de alta taxa de dose com irídio-192 e dose de 16 Gy em quatro inserções (BT). Estes foram comparados a 29 pacientes submetidos à teleterapia com 45 Gy e reforço com arcoterapia e dose mediana de 24 Gy (RT) entre outubro de 1996 e fevereiro de 2000. Nos dois grupos houve associação ocasional de hormonioterapia neoadjuvante. Sobrevida atuarial livre de doença em três anos (SB3) e fatores prognósticos pré-tratamento da resposta bioquímica, como o antígeno prostático-específico inicial (PSAi), escore de Gleason da biópsia de próstata (EG) e estádio clínico (EC), foram analisados. RESULTADOS: O seguimento mediano foi de 25 meses para o grupo RT e 37 meses para o BT. Na análise atuarial, a SB3 foi de 51 por cento e 73 por cento (p = 0,032) para RT e BT, respectivamente. Na análise estratificada pelo PSAi, a SB3 para RT e BT foi de 85,7 por cento e 79,1 por cento (p = 0,76) para PSAi < 10 ng/mL e de 38 por cento e 68 por cento (p = 0,023) para PSAi > 10 ng/mL, respectivamente. Quando estratificado pelo EG, a SB3 para RT e BT foi de 37 por cento e 80 por cento (p = 0,001) para EG < 6 e 78 por cento e 55 por cento para EG > 6 (p = 0,58); estratificando-se pelo EC, a SB3 para RT e BT foi de 36 por cento e 74 por cento (p = 0,018) para EC < T2a e 73 por cento e 69 por cento para EC > T2a (p = 0,692), respectivamente. O risco relativo bruto de recidiva bioquímica foi de 2,3 (95 por cento IC: 1,0-5,1) para os pacientes tratados com RT, em relação à BT; quando ajustado pelo PSAi e EG, o risco relativo de recidiva bioquímica foi de 2,4 (95 por cento IC: 1,0-5,7)...

OBJECTIVE: To compare the biochemical response in patients with locally advanced prostate cancer treated with external beam radiation therapy alone or in combination with conformal brachytherapy boost. MATERIALS AND METHODS: From November 1997 to January 2000, 74 patients received 45 Gy of pelvic external irradiation and four were treated with high dose rate iridium-192 conformal boost implants of 4 Gy each (BT). These were compared with 29 other patients treated with 45 Gy of pelvic external irradiation followed by a 24 Gy of bilateral ARC boost (RT) from October 1996 to February 2000. Some patients received neoadjuvant androgen deprivation therapy. Three-year actuarial biochemical control rates (BC3) and pretreatment biochemical response predictors such as prostate-specific antigen pretreatment (PSAi), Gleason score (GS) and clinical stage (CS), were evaluated. RESULTS: Median follow-up was of 25 months for the RT group and 37 months for the BT group. BC3 was 51% versus 73% (p = 0.032) for RT and BT, respectively. Comparisons of biochemical control by treatment group stratified by PSAi showed that BC3 for RT versus BT was 85.7% versus 79.1% (p = 0.76) for PSAi < 10 ng/mL and 38% versus 68% (p = 0.023) for PSAi > 10 ng/mL, respectively. For patients with GS < 6, BC3 was 37% versus 80% (p = 0.001) for RT versus BT and, for patients with GS > 6, BC3 was 78% versus 55% (p = 0.58) for RT versus BT, respectively. For patients with CS < T2a, BC3 was 36% versus 74% (p = 0.018) for RT versus BT and, for patients with CS > T2a, BC3 was 73% versus 69% (p = 0.692) for RT versus BT, respectively. The relative risk of biochemical relapse was 2.3 (95% IC: 1.0–5.1) for patients in RT group compared to the BT group. When adjusted for PSAi and GS, the relative risk of biochemical relapse was 2.4 (95% IC: 1.0–5.7)...

Late urinary morbidity with high dose prostate brachytherapy as a boost to conventional external beam radiation therapy for local and locally advanced prostate cancer.

PURPOSE: Late urinary retention (UR) is a known complication that may occur when using high dose rate brachytherapy (HDR-B) to boost external beam radiation therapy (EBRT) when treating prostate cancer. However, the dosimetric, treatment and clinical factors associated with this complication are not well-known. MATERIALS AND METHODS: From March 1997 to March 2000 a total of 108 patients with local or locally advanced prostate adenocarcinoma were treated with EBRT (45 Gy) and HDR-B as a boost, when 16 to 20 Gy was given in 4 fractions twice daily. Median patient age was 68 years and median followup was 44 months (range 36 to 72). Each implant was performed using 8 to 18 needles with a median active length of 3 cm. Planning ultrasound target volume ranged from 23 to 65 cc. RESULTS: Biological effective doses for the urethral region ranged from 107 to 138 Gy3 (median 113). Crude and 5-year actuarial UR-free survival were 95.4% and 86.2%, respectively. Predictive factors for UR on univariate analysis were age more than 65 years (p = 0.0416), planning ultrasound target volume greater than 35 cc and active length of needles more than 3.5 cm (p = 0.0158). On multivariate analysis by Cox regression age was the only predictive factor (p = 0.027). CONCLUSIONS: HDR-B appears to offer a safe, reproducible and effective method of boosting conventional EBRT in patients with locally advanced prostate cancer. Results with this technology reveal late urinary morbidity rates paralleling those achieved with other forms of treatment, but further long-term followup is still needed to warrant a definitive conclusion.

Radioterapia no melanoma: há lugar? / Radiotherapy on melanoma: is there a place?

Melanoma é considerado tumor radio-resistente e o emprego de radioterapia no tratamento é controverso. Muitas questões sobre o seu uso ainda permanecem sem resposta e o objetivo desta revisão é apresentar as evidências mais recentes que suportam a utilização da radioterapia no tratamento da lesão primária, da metástase linfonodal e da metástase cerebral. Apesar da evidência radiobiológica demonstrar que o melanoma pode ser mais sensível à dose maior por fração, a experiência clínica não evidência superioridade dos regimes hipofracionados. Conclui o autor que, apesar das controvérsias, há situações na prática diária em que a radioterapia deve ser considerada: no paciente idoso, com lesão localizada na face e no couro cabeludo, sem condições para cirurgia. Após linfadenectomia quando o número de gânglios comprometidos for maior que dois, o tamanho exceder 4cm, houver invasão extra-capsular e as margens de ressecção dorem exíguas. Na metástase cerebral isolada ou múltipla, menor de 4cm, em número inferior a três, a radio-cirurgia é benéfica e oferece aumento na sobrevida quando comparada à radioterapia cerebral total. Regimes hipo-fracionados, com frações de 6Gy, duas vezes por semana devem ser preferenciais, pelo valor social baixo e índice de complicações relatado.

Cirurgia conservadora, radioterapia externa e reforço de dose com braquiterapia de alta taxa de dose: uma nova perspectiva no tratamento de sarcomas de partes moles do adulto / Limb-sparing surgery, external beam radiotherapy and boost with high-dose rate brachytherapy: a new perspective for the treatment of soft tissue sarcomas in adults

OBJETIVO: Avaliar a influência no controle local de pacientes adultos e portadores de sarcoma de partes moles em extremidades e submetidos a cirurgia conservadora do membro, com braquiterapia de alta taxa de dose (BATD) como reforço para a radioterapia externa (RT). MATERIAL E M+TODOS: Foram avaliados 16 pacientes tratados, de 1993 até 1999. A RT foi utilizada com finalidade pré ou pós-operatória (30-55 Gy) e BATD com dose de 18-36 Gy (fx 3-6 Gy BID). Com base no modelo linear quadrático calculou-se a dose efetiva biológica ("biological effective dose" - BED) para o tumor e comparou-se seu valor a dados da literatura internacional, que utiliza tratamentos com RT e braquiterapia de baixa taxa de dose (BBTD). RESULTADOS: Os valores médios e medianos da BED para os sarcomas de partes moles foram de 78,5 Gy7 e 80 Gy7. A análise univariada mostrou que a BED para o tumor, quando utilizada BATD, era semelhante ao valor de 83 Gy7 quando utilizada BBTD (p = 0,008). As taxas de controle local, sobrevida livre de doença e sobrevida global atuarial em cinco anos foram de 83,2 por cento, 75 por cento e 93,7 por cento, respectivamente. CONCLUSiES: A BATD, quando utilizada como método complementar no reforço de dose da RT no tratamento conservador dos sarcomas de partes moles, apresenta taxas de controle local equiparáveis às da literatura internacional; no entanto, estudos com número maior de pacientes e período maior de seguimento são ainda necessários para determinar o verdadeiro potencial da BATD em substituir a BBTD.

Câncer primário da vagina: Hospital A.C. Camargo (1957 a 1990) / Primary cancer of vagina: Hospital A.C. Camargo (1957 a 1990)

No Hospital A. C. Camargo da Fundagdo Antonio Prudente - Sdo Paulo, Brasil,foram registrados entre 1957 e 1990 36 casos de cdncer primario da vagina. Destes, 32 (94,1%) eram pacientes da raga branca. Afaixa etriria predominante.foi entre 51 e 80 anos de idade, perfazendo 23 (67,4%) casos. O estadio clinico predominantefoi EC II, com l3 (35,2%o) pacientes, seguidas de 7 (24,0%) EC IV. Nas pacientes portadorus de EC I4 a principal invasdo local .foi para a bexiga, somando-se 4 (1 1,7%o) casos. A distribuigdo anatomopatol|gica ntostrou predomindncia do tipo carcinoma espinocelular em 24 (67,6%o) pacientes e apenas 2 (5,8%o) casos de carcinonta in situ. O tipo histoligico adenocarcinoma mostrou 4 (l 1,7%o). O tratamento preferencialmente realizadofoi radioterdpico em l7 (50%") pacientes, seguido de tratamento combinado. O seguimento a 5 anos mostrou 23 (64,7%) das pacientes mortas pelo tumor, 11 (32,3%) vivas e livres de doenga e 5 (14,7%) casos perdidos de vista. A sobrevida geral .foi de 52%. O cdncer da vagina representa um dos maiores desafios relacionados d ginecologia oncologica. Embora exista a oportunidade do diagnostico precoce, muitas pacientes apresentam a doenga avangada no momento do diagn6stico. Na nossa casuistica, assim como aquela apresentada por outros autores, as taxas de cura e de sobrevida ainda sdo muito baixas