Randomized clinical trial of tissue equivalent bolus prescription in postmastectomy radiotherapy stratified by skin involvement status.

Purpose: To assess the impact and optimize the prescription of tissue-equivalent bolus in postmastectomy radiotherapy (PMRT), we compared the use of different bolus regimens tailored by skin involvement status. Methods: Patients with breast cancer who required PMRT were recruited (NCT01925651) and classified into two groups: standard-risk (SR, without skin involvement) and high-risk (HR, with skin involvement). SR was randomized between no bolus or 5 mm-bolus on alternate days and HR between 5 mm-bolus on alternate days or daily. Conventional fractionation (50.4 Gy; 1.8 Gy/daily) was used. Acute skin toxicity was evaluated blindly and the radiodermatitis-specific toxicity index [rads-TI] calculated. Subsequently, patients were followed up to assess oncologic outcomes, focusing on chest wall (CW) local control. Results: Fifty-eight patients were enrolled (34 SR and 24 HR). Baseline characteristics were similar between arms within the same risk group. Overall, maximal radiodermatitis rates were 29.4 % (G2) and 15.7 % (G3). In the SR group, no difference existed in G2 radiodermatitis incidence between the subgroups (p = 0.70) and no G3 events occurred. In the HR group, incidences of G2 (100 % vs 44.5 %, p = 0.01) and G3 radiodermatitis (70 % vs 11.1 %, p = 0.02) were higher with daily bolus. After adjusting for confounders, the daily bolus had a higher incidence of G2 (p = 0.03), G3 radiodermatitis (p = 0.04), and worse rads-TI (p < 0.01). After a median follow-up of 6.2 years, the 5-year local control was 95.8 % (95 %CI: 88.2 %-100 %) in the SR and 91.7 % (95 %CI: 77.3 %-100 %) in the HR groups. Per risk group, there was no difference in local control between the SR (p = 0.90) or the HR bolus regimens (p = 0.70). Conclusion: Daily 5 mm bolus prescription significantly increased the overall toxicity burden. In this preliminary study, within the same risk group, no detriment in CW local control was detected with less intense bolus regimens (SR: no bolus; HR: alternate-days bolus). Additionally, the rads-TI was able to distinguish overall radiodermatitis burden.

Local control after radiosurgery for brain metastases: predictive factors and implications for clinical decision.

BACKGROUND: To evaluate the local control of brain metastases (BM) in patients treated with stereotactic radiosurgery (SRS), correlate the outcome with treatment parameters and lesion characteristics, and define its implications for clinical decisions. METHODS: Between 2007 and 2012, 305 BM in 141 consecutive patients were treated with SRS. After exclusions, 216 BM in 100 patients were analyzed. Doses were grouped as follows: ≤15 Gy, 16-20 Gy, and ≥21 Gy. Sizes were classified as ≤10 mm and >10 mm. Local control (LC) and overall survival (OS) were estimated using the Kaplan-Meier method. Log-rank statistics were used to identify the prognostic factors affecting LC and OS. For multivariate analyses, a Cox proportional model was applied including all potentially significant variables reached on univariate analyses. RESULTS: Median age was 54 years (18-80). Median radiological follow-up of the lesions was 7 months (1-66). Median LC and the LC at 1 year were 22.3 months and 69.7%, respectively. On univariate analysis, tumor size, SRS dose, and previous whole brain irradiation (WBRT) were significant factors for LC. Patients with lesions >10 and ≤10 mm had an LC at 1 year of 58.6% and 79.1%, respectively (p = 0.008). In lesions receiving ≤15 Gy, 16-20 Gy, and ≥21 Gy, the 1-year LC rates were 39.6%, 71.7%, and 92.3%, respectively (p < 0.001). When WBRT was done previously, LC at 1 year was 57.9% compared with 78.4% for those who did not undergo WBRT (p = 0.004). On multivariate analysis, dose remained the single most powerful prognostic factor for LC. Median OS for all patients was 17 months, with no difference among the groups. CONCLUSIONS: Dose is the most important predictive factor for LC of BM. Doses below 16 Gy correlated with poor LC. The SRS dose as salvage treatment after previous WBRT should not be reduced unless there is a pressing reason to do so.

Prognostic value of nuclear factor κ B expression in patients with advanced cervical cancer undergoing radiation therapy followed by hysterectomy.

AIMS: The nuclear factor κ B (NF-κB) family comprises transcription factors that promote the development and progression of cancer. The NF-κB pathway is induced by radiation therapy and may be related to tumour radioresistance. The aim of this study was to evaluate the expression of NF-κB as a predictor of the response to radiotherapy and its value as a prognostic marker. METHODS: A retrospective analysis was performed in a series of 32 individuals with stage IB2 and IIB cervical cancer who underwent radiotherapy, followed by radical hysterectomy, from January 1992 to June 2001. NF-κB-p65 and NF-κB-p50 expression was examined by immunohistochemistry in biopsies from all patients before radiotherapy and in 12 patients with residual tumours after radiotherapy. RESULTS: 16 (50%) patients had residual disease after radical hysterectomy. The median follow-up time was 73.5 months, and the 5-year overall survival was 66.5%. Before radiotherapy, cytoplasmic expression of NF-κB-p65 and NF-κB-p50 was noted in 91% and 97% of cases, respectively, versus 59% of cases with nuclear expression of these subunits. Cytoplasmic expression of NF-κB-p65 and NF-κB-p50 in the residual tumours after radiotherapy was observed in 50% of cases; 75% of cases with residual tumours had nuclear expression of NF-κB-p50 versus none with NF-κB-p65. NF-κB-p65 and NF-κB-p50 did not correlate with the risk of residual tumours after radiotherapy or recurrence or death. CONCLUSIONS: These data suggest that NF-κB does not predict the response to radiotherapy and does not correlate with poor outcomes in advanced cervical cancer.

Radiotherapy and collagenosis: is it safe? A case report of reirradiation in a patient with scleroderma

Historically, scleroderma and other collagenous diseases have been considered a relative contraindication to radiation. The literature has few studies describing poor outcomes and cosmesis in this situation and there are almost no data concerning about reirradiation and colagenosis. The authors describe a case of a patient with a soft tissue sarcoma in the arm submitted to conservative surgery. They describe the outcome, cosmesis and function of this rare twice-irradiated scleroderma patient.

Impacto da nutrição enteral na toxicidade aguda e na continuidade do tratamento dos pacientes com tumores de cabeça e pescoço submetidos a radioterapia com intensidade modulada / Impact of enteral nutrition on acute toxicity and treatment continuity in head and neck cancer patients submitted to intensity-modulated radiotherapy

OBJETIVO: Analisar o impacto da terapia nutricional enteral na manutenção do peso corpóreo e na necessidade de replanejamento e/ou interrupção da radioterapia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia de intensidade modulada (IMRT). MATERIAIS E MÉTODOS: Foram analisados, retrospectivamente, os pacientes submetidos a IMRT entre janeiro de 2005 e outubro de 2008, com a inclusão de 83 casos. RESULTADOS: A idade mediana foi de 58,6 anos. Em apenas em cinco pacientes (6 por cento) houve interrupção do tratamento, que variou de 4 a 18 dias, e em 19 casos (23 por cento) houve necessidade de replanejamento. A terapia nutricional enteral foi instituída antes do início da radioterapia em 16 pacientes (19 por cento). Perda de peso > 5 por cento ocorreu em 58 casos (70 por cento), sendo mais prevalente no grupo de pacientes em que a terapia nutricional enteral não foi instituída pré-radioterapia. Na comparação entre os grupos não houve diferença significativa na realização de replanejamento (25 por cento versus 21 por cento; p = 0,741) ou na ocorrência e duração da interrupção da radioterapia. CONCLUSÃO: A terapia nutricional enteral tem um claro ganho na manutenção do peso corporal, porém, não houve um benefício na realização da gastrostomia percutânea endoscópica ou da sonda nasoenteral em relação à interrupção e ao replanejamento da radioterapia.

OBJECTIVE: The present study was aimed at analyzing the impact of enteral nutrition on the maintenance of body weight and on the necessity of replanning and/or interruption of treatment of head and neck cancer patients undergoing intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Cases of patients submitted to IMRT in the period from January 2005 to October 2008 were retrospectively reviewed, and 83 of them were included in the study. RESULTS: Median patients' age was 58.6 years. Only five patients (6 percent) had their treatment interrupted for a period ranging from 4 to 18 days, and in 19 cases (23 percent) required replanning. Enteral nutrition was initiated before the radiotherapy in 16 patients (19 percent). Weight loss of > 5 percent was observed in 58 patients (70 percent), with a higher prevalence in the group of patients who had not received pre-radiotherapy enteral nutrition. No significant difference was observed between the groups regarding the necessity of radiotherapy replanning (25 percent versus 21 percent; p = 0.741) and necessity and duration of treatment interruption. CONCLUSION: Enteral nutrition is of a great value in the body weight maintenance, but no benefit was observed with the performance of endoscopic percutaneous gastrostomy as compared with radiotherapy interruption/replanning.

Tumor fibroso solitário na pele: relato de caso / Solitary fibrous tumor of the skin: case report

O tumor fibroso solitário (TFS) é uma neoplasia benigna muito rara, derivada de células mesenquimais. Há relatos de casos deste tumor em diversos sítios pleurais ou extrapleurais, sendo a região cutânea e subcutânea localizações ainda mais incomuns. O prognóstico, na maioria dos casos, é bom, mas o comportamento pode ser agressivo. O diagnóstico clínico diferencial é importante na prática diária do cirurgião plástico, pois não raramente aparecem lesões tumorais dos componentes do revestimento cutâneo, com características semelhantes ao TFS - consistência fibro elástica e não aderência a planos profundos - que devem ser bem conhecidas e diferenciadas de neoplasias malignas, para que o tratamento adequado seja instituído.

Solitary fibrous tumor (TFS) is a very rare benign tumor, derived from mesenchymal cells. There are reports of cases of this tumor in different pleural or extra-pleural’s sites, and the skin is even a more unusual spot. The prognosis in most cases is good, but the behavior in few cases can be aggressive. The differential diagnosis is important in the daily practice of plastic surgeons. There are several lesions well known with similar characteristics to TFS in skin layers: fibro elastic consistency, not adhered to deep planes. Those lesions should be differentiated from malignant neoplasms, so that proper treatment is instituted.

Impacto da adição da temozolamida à radioterapia no tratamento de crianças portadoras de tumor de tronco cerebral / Impact of the addition of temozolomide to radiotherapy in the treatment of children with brain stem tumors

OBJETIVO: Analisar o impacto da adição da temozolamida à radioterapia em tumores de tronco cerebral em crianças. MATERIAL E MÉTODO: Entre 2000 e 2005 foram analisadas, retrospectivamente, 64 crianças com tumor do tronco cerebral. Dessas crianças, 32 receberam temozolamida(grupo 1) e 32 não a receberam (grupo 2). RESULTADOS: A idade mediana no grupo 1 foi de 8,2 anos e no grupo 2 foi de 7,5 anos. A localização tumoral era predominantemente difusa (53%) emambos os grupos. Todos os pacientes receberam radioterapia com doses superiores a 50 Gy. No grupo1 foram ministrados nove ciclos, em média, de quimioterapia (3û14 ciclos). O tempo de progressão de doença foi de 7,9 meses no grupo 2 versus 13,8 meses no grupo 1. A sobrevida global foi de 8,8 meses (0,3û30,9 meses) no grupo 1 e de 14,6 meses (4,3û33 meses) no grupo 2. CONCLUSÃO: A utilização da temozolamida após a radioterapia proporcionou aumento da sobrevida, deseis meses em média, nos pacientes pediátricos com tumor do tronco cerebral.

OBJECTIVE: To analyze the impact of adding temozolomide to radiotherapyin pediatric brain stem tumors. MATERIAL AND METHOD: Between 2000 and 2005, 64 children with brain stem tumor were analyzed: 32 received temozolomide (group 1) and 32 did not(group 2). RESULTS: The median age of patients in group 1 was 8.2 year-old and in group 2 was 7.5 year-old. The predominant tumoral localization was diffuse (53%) in both groups. All of the patients were submitted to radiotherapy. In group 1, the median number of temozolomide cycles was 9 (3û14 cycles). Time of disease progression was 7.9 months in group 2 versus 13.8 months in group 1. Overall survival was 8.8 months (0.3û30.9 months) in group 1 and 14.6 months (4.3û33 months) in group 2. CONCLUSION: In our institution,adding temozolomide to radiotherapy increased the overall survival in approximately six months in brain stem pediatric tumors.

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

Radioterapia adjuvante no tratamento do câncer de endométrio: experiência com a associação de radio-terapia externa e braquiterapia de alta taxa de dose / Adjuvant radiation therapy for the treatment of endometrial cancer: experience with combination of external radiation therapy and high-dose rate brachytherapy

OBJETIVO: Analisar, retrospectivamente, os resultados da radioterapia externa (RT) combinada a braquiterapia de alta taxa de dose (BATD), adjuvantes à cirurgia para o carcinoma de endométrio. MATERIAIS E MÉTODOS: Avaliamos 141 pacientes tratados com RT e BATD adjuvantes à cirurgia, no período de janeiro de 1993 a janeiro de 2001. RT pélvica foi realizada com dose mediana de 45 Gy, e BATD realizada na dose mediana de 24 Gy, em quatro inserções semanais de 6 Gy. A idade mediana das pacientes foi de 63 anos e a distribuição por estádio clínico (EC) foi: EC I (FIGO), 52,4 por cento; EC II, 13,5 por cento; EC III, 29,8 por cento; EC IV, 4,3 por cento. RESULTADOS: Com seguimento mediano de 53,7 meses, a sobrevida livre de doença (SLD) em cinco anos foi: EC I, 88,0 por cento; EC II, 70,8 por cento; EC III, 55,1 por cento; EC IV, 50,0 por cento (p = 0,0003). A sobrevida global em cinco anos foi: EC I, 79,6 por cento; EC II, 74,0 por cento; EC III, 53,6 por cento; EC IV, 100,0 por cento (p = 0,0062). Fatores que influíram na SLD foram grau histológico e histologia seropapilífera. Dos 33 casos que apresentaram recidiva da doença, em 13 (9,2 por cento) esta ocorreu na pelve, vagina ou cúpula vaginal. RT + BATD do fundo vaginal permitiram o controle da doença em 90,8 por cento dos casos. CONCLUSÃO: A RT exerce papel fundamental no controle loco-regional do câncer de endométrio e permite excelentes taxas de cura nos estádios iniciais. Para os estádios mais avançados, a falha terapêutica tende a ser a distância, sugerindo a necessidade de complementação terapêutica sistêmica, com introdução de novas modalidades de tratamento, em particular a quimioterapia.

Conventional External Beam Radiation Therapy and High Dose Rate Afterloading Brachytherapy as a Boost for Patients Olderthan 70 years

The treatment options for patients with non metastatic prostate cancer range from observation, radical prostatectomy, radiationtherapy, hormonal therapy to various combination of some to all of them. Objective: We evaluated the impact on biochemicalcontrol of disease (bNED), acute and late intestinal (GI) and urological (GU) morbidity for a group of patients older than 70years presenting initial or locally advanced prostate cancer treated with fractionated high dose rate brachytherapy (HDRB) asa boost to conventional external beam radiation therapy (RT) at the Department of Radiation Oncology from Hospital do CâncerA. C. Camargo, São Paulo, Brazil. Methods: A total of 56 patients older than 70 were treated from March, 1997 to June,2002. All patients had prior to HDRB a course of RT to a median dose of 45 Gy. HDRB doses ranged from 16 Gy to 20 Gy, givenin 4 fractions. Results: The median age of the patients was 74.4 years (range 70-83) and the median follow-up 33 months(range 24 to 60). The 5-year actuarial bNED rate was 77%. Acute GU and GI morbidity G1-2 were seen in 17.8% and 7.1% ofpatients, respectively. Late G1 or G2 GU morbidity was seen in 10.7% of the patients, while late G3 morbidity was observedin 7.1% of the patients, represented by urethral strictures. Conclusion: this group of patients had similar bNED rates whencompared to literature, with acceptable morbidity rates.

Cytogenetic damage in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients undergoing radiotherapy.

This study evaluated cytogenetic damage by measuring the frequency of micronucleated cells (MNC) in peripheral blood and buccal mucosa of head-and-neck cancer patients undergoing radiotherapy. MNC frequencies were assessed in 31 patients before, during, and after radiotherapy, and in 17 healthy controls matched for gender, age, and smoking habits. Results showed no statistically significant difference between patients and controls prior to radiotherapy in cytokinesis-blocked lymphocytes or buccal mucosa cells. During treatment, increased MNC frequencies were observed in both cell types. Micronucleated lymphocyte levels remained high in samples collected 30 to 140 days after the end of treatment, while MNC frequency in buccal mucosa decreased to values statistically similar to baseline values. There is controversy over the effects of age, smoking habit, tumor stage, and/or metastasis on MNC frequency. However, increased frequency of micronucleated buccal mucosa cells was seen in patients under 60 years old and in those with tumors >4 cm. In conclusion, the data show that radiotherapy has a potent clastogenic effect in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients, and that the baseline MNC frequency in these two tissues is not a sensitive marker for head-and neck neoplasm.

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.