Image-guided moderately hypofractionated radiotherapy for localized prostate cancer: a multicentric retrospective study (IPOPROMISE).

BACKGROUND: Moderate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series. MATERIALS AND METHODS: We retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan-Meier survival curves and fitted univariate and multivariable Cox's proportional hazards regression models to study the association between the clinical variables and each survival type. RESULTS: At the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3-99.6%) and 85.5% (95%CI 81.9-89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4-6%) and 6% (95%CI 4-8%), respectively. CONCLUSION: Real-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.

Early results of PRO-EPI: PROspective multicenter observational study on elective pelvic nodes irradiation in patients with intermediate/high/very high-risk non-metastatic prostate cancer submitted to radical, adjuvant, or salvage radiotherapy with or without concomitant androgen deprivation therapy.

Simple Summary: Although radiotherapy plays a fundamental role in the management of intermediate/high/very high-risk non-metastatic prostatic cancer (IHR-nmPca), there is still no consensus on the optimal treatment strategy in this setting. Remarkably, the role of elective nodal irradiation (ENI) is still highly controversial. The PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) was designed to provide "real life" data regarding the patterns of care for IHR-nmPca. Forty-three Italian Radiation Oncology centers participated in the PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) project, with 1029 patients enrolled. In this preliminary analysis, we longitudinally evaluated the impact of Elective Nodal Irradiation (ENI) and radiotherapy features on toxicity and quality of life (QoL). Six months follow-up data were available for 913 patients and 12 months data for 762 patients. Elective Nodal Irradiation was given to 506 patients (48.9%). Volumetric Intensity-Modulated Radiation Therapy (IMRT) was adopted in more than 77% of patients and Image-Guided Radiation Therapy (IGRT) in 84.4%. Androgen deprivation therapy (ADT) was administered to the majority of patients (68.3%), and it was associated to ENI in 408 cases (81.1%). Toxicity was mostly mild and reversible and IGRT resulted in a significant reduction of rectal toxicity, although a non-significant trend toward increased urinary toxicity was observed. No statistically significant differences in QoL and toxicity were seen in patients treated with or without ENI. The adoption of IGRT is widespread and increasing and could reduce treatment toxicity. ENI is not yet the standard treatment, but it is performed in a growing fraction of cases and not resulting into an increase in toxicity or in a deterioration of QoL. Further analyses are needed to clarify the long-term toxicity profile and the impact of ENI on survival.

Combining Abiraterone and Radiotherapy in Prostate Cancer Patients Who Progressed During Abiraterone Therapy.

BACKGROUND/AIM: This multicenter, retrospective, 'field-practice' study investigated treatment outcomes of ongoing abiraterone therapy with the addition of radiotherapy (RT) - initiated for oligoprogression or with a palliative intent. PATIENTS AND METHODS: Consecutive patients affected by metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate were considered if they had received RT after the initiation of abiraterone treatment. RESULTS: A total of 32 patients were enrolled in the study. Median duration of abiraterone treatment was 13.0 months (range=3.8-40.9 months). Median duration of abiraterone treatment before RT was 5.9 months (range=0.4-40.0 months), and 7.2 months after RT (range=0.1-29.7 months). Median progression-free survival (PFS) was 12.6 months (95%CI=10.5-14.7) from the initiation of abiraterone treatment. From RT administration, PFS was 9.6 months (95%CI=6.4-12.9). Median overall survival (OS) since abiraterone initiation was 18.9 months (95%CI=4.7-33.0). CONCLUSION: RT prolongs abiraterone treatment in mCRPC patients leading to better clinical outcomes with this molecule.

Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions.

OBJECTIVE: Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. METHODS: Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. RESULTS: Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. CONCLUSION: This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. ADVANCES IN KNOWLEDGE: Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.

Survival and breast relapse in 3834 patients with T1-T2 breast cancer after conserving surgery and adjuvant treatment.

PURPOSE: The aim of the present analysis is to determine the long-term results in terms of breast relapse and specific survival in patients treated with conserving surgery and adjuvant treatment for early breast cancer. METHODS: From January 1980 to December 2001, 3834 patients with pT1-T2 breast cancer were treated consecutively at the University of Florence. The median age of the patient population was 55 years (range 30-80). All patients were followed for a median of 7.4 years (range 0.6 year to 22.5 years). The crude probability of survival (or local recurrence) was estimated by using Kaplan-Meier method, and survival (or local recurrence) comparisons were carried out using Cox proportional hazard regression models. RESULTS: The Cox regression model by stepwise selection showed some parameters, such as chemotherapy (HR 1.53; CI 1.19-1.95), pT status (HR 1.62, CI 1.31-2.01), positive axillary lymph nodes (HR 1.92, CI 1.66-2.22), and local recurrence (HR 4.58; CI 3.66-5.73), as independent prognostic factors for breast cancer death. Moreover, we found lower rate survival among patients treated before 1991 in comparison to women treated after 1991 (p=0.0001) probably due to inadequate treatment. For local disease free survival, age at presentation (HR 0.47; CI 0.35-0.63), use of tamoxifen (HR 0.42; CI 0.25-0.71), surgical margins (HR 2.00; CI 1.21-3.30), and chemotherapy (HR 0.53; CI 0.31-0.91) emerged by multivariate analyses as significant breast relapse predictors. CONCLUSION: In our experience breast conserving surgery followed by adjuvant radiotherapy treatment gives high rates of local control in women with early breast cancer. The use of routinely adjuvant chemotherapy and hormone therapy lowered the local recurrence and probably the modification of therapeutic approach in the last decades also improved the specific survival.

Alternating intravenous and oral vinorelbine plus epirubicin with pegfilgrastim as neoadjuvant treatment of locally advanced breast cancer.

In order to downstage locally advanced breast cancer, neoadjuvant chemotherapy consisting of intravenous vinorelbine 25 mg/m plus epirubicin 75 mg/m given on day 1 and oral vinorelbine 60 mg/m on day 8 was administered every 3 weeks for four courses. On day 2, all patients received a single subcutaneous injection of pegfilgrastim (6 mg). From March 2004 to June 2005, 22 patients were enrolled. Patients characteristics were: median age, 53 years (range: 39-70 years); postmenopausal, 7/22; clinical TNM stage, T2 (n=14), T3 (n=8), N0 (n=17) and N1 (n=5). The median number of courses was four (range: two to six courses) with full dose intensity. National Cancer Institute grade 3 haematological toxicities observed were neutropenia in 9% of patients, anaemia in 13% of patients and thrombocytopenia in 9% of patients; no toxicity grade 4 occurred. Two patients (9%) registered grade 2 polyneuropathy; no cardiac failure was observed. Conservative surgery was performed in 14 patients (63%). All patients were evaluable for response: complete pathological response was documented in three patients (13.6%); three patients (13.6%) obtained more than 75% of tumour size reduction; 11 other patients (50%) had 50% of tumour size reduction; stable disease was observed in five patients (22.7%). The present findings indicate that vinorelbine in combination with epirubicin is an effective and safe treatment in locally advanced breast cancer: this regimen obtained more than 50% of tumour size reduction in 77% of patients; the use of pegfilgrastim allowed full dose intensity. Oral vinorelbine on day 8 offers greater convenience to the patient by reducing the need for intravenous injection and the time spent in hospital.

Loco regional failure pattern after lumpectomy and breast irradiation in 4,185 patients with T1 and T2 breast cancer. Implications for nodal irradiation.

The aim of this study is to determinate incidence and risk factors for loco regional failure (LRR) (breast, supraclavicular, axillary and internal mammary nodes) and indications for nodal irradiation. From January 1980 to December 2001, 4,185 patients with T1-T2 breast cancer were treated with conservative surgery and whole breast radiotherapy without nodal irradiation at the University of Florence. The median age was 55 years (range 19-86). All patients were followed for a median of eight years (range 3 months to 20 years). Multivariate analysis showed as independent prognostic factors for isolated nodal relapse (NR) the presence of more than three positive lymph nodes (PAN) (p = 0.001), angiolymphatic invasion (p = 0.002) and pT2 (p = 0.02). However, only 4.8% of patients with more than three PAN developed NR as the only site of recurrence. Having one to three PAN was not associated with an increased risk of NR. We believe that it is not necessary to prescribe nodal irradiation to patients with negative or one to three PAN. Regarding patients with more than three PAN, the number of isolated NR is also small to routinely justify a node irradiation.

Breast cancer in the elderly: treatment of 1500 patients.

There is a significant difference in the extent of treatment offered to the elderly with breast cancer; in the United States, while 98% of patients less than 65 years of age receive standard treatment, 81% of those older than 65 years were treated according to protocol. This study's goal was to evaluate disease-specific survival and local-regional recurrence in breast cancer patients more than 65 years of age at diagnosis. A total of 1500 patients with invasive breast carcinoma were treated consecutively from May 1971 to July 2002 at the University of Florence, Florence, Italy. All patients were more than 65 years of age. The median age was 70.6 years (range 65.1-87.3 years). The median follow-up was 8.7 years (range 1-30 years). The crude probability of survival (or relapse occurrence) was estimated using the Kaplan-Meier method and survival (or relapse occurrence) comparisons were carried out using Cox proportional hazard regression models. The Cox regression model by stepwise selection showed as independent prognostic factors for disease-specific survival (DSS), the occurrence of a local relapse (p < 0.0001), pN status (p < 0.0001), the type of surgery (p < 0.0001), and the use of radiotherapy (p < 0.0006) and chemotherapy (p = 0.01). For local disease-free survival (LDFS), the Cox regression model by stepwise selection showed that mastectomy (p < 0.0001), histotype (p < 0.0001), pN status (p < 0.0001), and pT status (p = 0.001) were the only independent prognostic factors. Age was not a prognostic factor for DSS nor LDFS. We suggest treating patients with appropriate treatment for their prognostic factors.

Pé torto congênito / Congenital club foot

Definição: Atitude viciosa permanente condicionando apoio anormal. Vamos estudar apenas o pé eqüinovaro. Etiologia: Alterações primitivas no esboço cartilaginoso do talo e do calcâneo, de origem genética, como possível gene dominante de baixa penetrância ou poligênica com efeito "threshold"; influência de fatores ambientais. Anatomia patológica: 1) adução-supinação do antepé na articulação mediotársica; 2) varo do calcâneo, na articulação subtalar. A associação de 1) e 2) dá a inversão do pé; 3) eqüinismo do pé -na articulação tibiotársica (um pouco na subtalar); 4) cavismo -na articulação mediotársica; 5) alterações esqueléticas: diminuição do ângulo entre corpo e colo do talo que tem direção medial e plantar; aberturado seio do tarso, diminuição de tamanho do navicular; 6) alterações de partes moles: (secundárias) - retração dos elementos posteriores, mediais, subtalares e plantares; distensão dos laterais e atrofia da panturrilha. Pé, perna e coxa menores. Fisiopatologia: Subtalar e mediotársica são solidárias à tibiotársica: na flexão plantar, o antepé supina e o calcâneo variza; na flexão dorsal, o antepé prona e o calcâneo valgiza. Quadro clínico: Tipos rígido e flexível, conforme a gravidade das deformidades e a redutibilidade. Períodos evolutivos: Redutibilidade nos primeiros meses; redutibilidade relativa na segunda infância; irredutibilidade em tomo dos cinco anos. Radiologia: Útil na avaliação do grau de desvios e critério de redução. Em ântero-posterior (AP) o ângulo de abertura da subtalar é menor que 20° e os eixos do calcâneo e talo são quase paralelos. Em perfil o ângulo talocalcaneano é maior que 35°. No pé em "mata-borrão" a linha do solo cruza a calcâneo-cubóide e na torção lateral a superfície sup. do talo aparece plana. Tratamento: Iniciar o mais precocemente possível. Incruento: Manipulação, só nos primeiros dias; bandagens adesivas, menos usadas; aparelhos ortopédicos, só para manter redução; aparelhos gessados (cunhas de Kite), começa pela adução e varismo e depois o eqüino, para evitar "mata-borrão". Em vez de cunha pode-se trocar o gesso. Aparelho de Denis-Browne para manutenção. Cruento: Em casos difíceis ou recidivas. Alongamento do Aquiles e capsulotomia aos 12 meses: operação de Codivilla de um a quatro anos e operação de Evans de quatro a oito anos. Complicações: Imediatas - distúrbios vasculares; tardias - deiscência de suturas, necrose de pele...

Retirada percutânea de enxerto ósseo autólogo / Percutaneous harvesting of autogenous bone graft

A surgical technique developed on cadavers allows for the percutaneous harvesting of cancellous antogenous bone graft from the distal femoral and proximal tibial metaphysis, by means of a specially designed trephine, a guide, and a helical harvester. This technique is quick and effective, poses minimal local damage, and provides readily usable tittle bone fragments.

Lesões das articulação de Lisfranc / Injuries to Lisfranc joint

In the past two decades there has been a great improvement in the knowledge of Lisfranc injuries, but some questions still remain unanswered. X-ray and CT scan are important for diagnosis but clinical examination is still fundamental to determine treatment. The so-called "minor lesions", source of future problems such as pain and limping, have been currently discussed. Open reduction and internal fixation is the best approach to Lisfranc injuries, but many authors affirm that conservative treatment renders the same results. Crush injuries and the resulting soft tissue problems, which may potentially develop into sepsis and avascularity, have to be well managed to achieve a good final outcome. Compartment syndrome is a major problem in Lisfranc injuries, requiring immediate fasciotomy and administration of judicious systemic antibiotics. Late complications such as deformities and arthritis are the goals of the treatment, which also includes pain relief,correction of deformity, and preservation of the function.

Tratamento das fraturas com falha óssea dos ossos da mäo pelo método de Ilizarov: relato de caso / Treatment of hand fractures with bone loss using Ilizarov's method: report of a case

As lesoes músculo-esqueléticas ocasionadas por traumatismos de alta energia têm sido mais e mais frequentes no nosso meio. Essas lesoes possuem como características a extensa perda tecidual. Neste trabalho é apresentado o tratamento com transporte ósseo, por meio do método de Ilizarov, para a perda óssea segmentar da metade distal da falange proximal, da articulaçÝo interfalangiana proximal e da metade proximal da falange média do quinto dedo da mao de um paciente, vítima de acidente do trabalho.

Tratamento cirúrgico das lesöes ligamentares crônicas laterais do tornozelo pela técnica de Brostrom / Surgical treatment of lateral chronic ligament lesions using the Brostrom technique

Os autores relatam a experiência adquirida no tratamento de lesöes crônicas do tornozelo (dos ligamentos fíbulo-talar anterior (FTA) e fíbulo-calcâneo (LFC) utilizando a técnica de Bröstrom. No período entre 1985 e 1995 foram operados nove pés, avaliados num tempo médio de evoluçäo de 34,1 meses. Foram obtidos cinco resultados bons, três regulares e um mau. A técnica cirúrgica proposta é simples, de fácil execuçäo, produz bons resultados, sem alterar a anatomia normal da articulaçäo tibioperoneira-astragalina (ATPA).

Artrodese no retropé nas colizöes tarsais / Arthrodesis in tarsal coalitions

Os autores relatam a experiência adquirida no tratamento das coalizöes sintomáticas talocalcânea e calcaneonavicular com a artrodese da articulaçäo envolvida ou de sua extensäo a outras articulaçöes tarsais. Säo avaliados 24 pacientes, com um total de 28 pés, após um tempo médio de evoluçäo pós-operatória de 37 meses. Baseados nos aspectos clínicos (dor e aparência) e radiográficos (consolidaçäo da artrodese alinhamento do pé), obtiveram bom resultado em 25 pés (89,5 por cento), regular em um (3,5 por cento) e mau em dois (7,0 por cento). Houve quatro complicaçöes precoces (14,2 por cento), que näo influenciaram no resultado final, e três tardias (10,7 por cento).