Long-Term Results of Bladder Preservation with Twice-Daily Radiation plus 5-Flourouracil/Cisplatin or Daily Radiation plus Gemcitabine for MIBC - Updated Report of NRG/RTOG 0712: A Randomized Phase 2 Trial.

PURPOSE: 5-FU/cisplatin and twice-daily radiation (FCT) or gemcitabine and once daily radiation (GD) are effective chemoradiation (CRT) regimens for bladder sparing treatment of muscle-invasive bladder cancer (MIBC). This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer term results are reported here. METHODS AND MATERIALS: Patients with cT2-4a MIBC were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder intact distant metastasis free survival (BI-DMFS) were also assessed. RESULTS: From 12/2008 to 4/2014, 70 patients were enrolled; 66 eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. BI-DMFS was 58% (95% CI: 41 - 76) and 68% (95% CI: 51-84), respectively. The post-hoc hazard ratio of 0.75 (95% CI: 0.37-1.55) showed no difference between treatments (p=0.44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%) and 0 grade 3, 4 and 5 late toxicities reported. In the GD arm, there were 7 (23%), 0 and 0. CONCLUSIONS: Both regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder sparing therapies.

Corrigendum to "Androgen Deprivation and Radiotherapy with or Without Docetaxel for Localized High-risk Prostat Cancer: Long-term Follow-up from the Randomized NRG Oncology RTOG 0521 Trial" [Eur. Eurol. 84(2) (2023) 156-163].

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer. OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT. DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival (OS). Analyses with Cox proportional hazards were performed as prespecified in the protocol; however, there was evidence of nonproportional hazards. Thus, a post hoc analysis was performed using the restricted mean survival time (RMST). The secondary endpoints included biochemical failure, distant metastasis (DM) as detected by conventional imaging, and disease-free survival (DFS). RESULTS AND LIMITATIONS: After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 0.70-1.14; one-sided log-rank p = 0.22). Survival at 10 yr was 64% for ADT + EBRT and 69% for ADT + EBRT + docetaxel. The RMST at 12 yr was 0.45 yr and not statistically significant (one-sided p = 0.053). No differences were detected in the incidence of DFS (HR = 0.92, 95% CI 0.73-1.14), DM (HR = 0.84, 95% CI 0.73-1.14), or prostate-specific antigen recurrence risk (HR = 0.97, 95% CI 0.74-1.29). Two patients had grade 5 toxicity in the chemotherapy arm and zero patients in the control arm. CONCLUSIONS: After a median follow-up of 10.4 yr among surviving patients, no significant differences are observed in clinical outcomes between the experimental and control arms. These data suggest that docetaxel should not be used for high-risk localized prostate cancer. Additional research may be warranted using novel predictive biomarkers. PATIENT SUMMARY: No significant differences in survival were noted after long-term follow-up for high-risk localized prostate cancer patients in a large prospective trial where patients were treated with androgen deprivation therapy + radiation to the prostate ± docetaxel.

Prognostic Significance of Immune Cell Infiltration in Muscle-invasive Bladder Cancer Treated with Definitive Chemoradiation: A Secondary Analysis of RTOG 0524 and RTOG 0712.

Chemoradiation therapy (CRT) is a treatment for muscle-invasive bladder cancer (MIBC). Using a novel transcriptomic profiling panel, we validated prognostic immune biomarkers to CRT using 70 pretreatment tumor samples from prospective trials of MIBC (NRG/RTOG 0524 and 0712). Disease-free survival (DFS) and overall survival (OS) were estimated via the Kaplan-Meier method and stratified by genes correlated with immune cell activation. Cox proportional-hazards models were used to assess group differences. Clustering of gene expression profiles revealed that the cluster with high immune cell content was associated with longer DFS (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.26-1.10; p = 0.071) and OS (HR 0.48, 95% CI 0.24-0.97; p = 0.040) than the cluster with low immune cell content. Higher expression of T-cell infiltration genes (CD8A and ICOS) was associated with longer DFS (HR 0.40, 95% CI 0.21-0.75; p = 0.005) and OS (HR 0.49, 95% CI 0.25-0.94; p = 0.033). Higher IDO1 expression (IFNγ signature) was also associated with longer DFS (HR 0.44, 95% CI 0.24-0.88; p = 0.021) and OS (HR 0.49, 95% CI 0.24-0.99; p = 0.048). These findings should be validated in prospective CRT trials that include biomarkers, particularly for trials incorporating immunotherapy for MIBC. PATIENT SUMMARY: We analyzed patient samples from two clinical trials (NRG/RTOG 0524 and 0712) of chemoradiation for muscle-invasive bladder cancer using a novel method to assess immune cells in the tumor microenvironment. Higher expression of genes associated with immune activation and high overall immune-cell content were associated with better disease-free survival and overall survival for patients treated with chemoradiation.

Testosterone recovery after androgen deprivation therapy in localised prostate cancer: Long-term data from two randomised trials.

BACKGROUND AND PURPOSE: To determine the rate and time of testosterone (T) recovery in patients (pts) with localised prostate cancer treated with radiotherapy plus 0-, 6-, 18- or 36-month of androgen deprivation therapy (ADT). MATERIALS AND METHODS: In 1230 pts with prostate cancer randomised into two phase III trials, serum T was measured at baseline, then regularly. T recovery rate was compared between normal vs. abnormal baseline T and with ADT duration with Chi-square test or Fisher's exact test. A multivariable logistic regression model to predict the probability of recovering normal T was performed. RESULTS: Overall, 87.4 % (167/191), 75.9 % (293/386), 54.8 % (181/330) and 43.2 % (80/185) of pts, recovered normal T on the 0-, 6-, 18- or 36-month schedule, respectively (p < 0.001). In patients recovering normal T, the median time to T recovery increased with ADT duration ranging from 0.31, 1.64, 3.06 to 5.0 years for the 0-, 6-, 18- or 36-month schedules, respectively (p < 0.001) and was significantly faster for those with a normal T at baseline (p < 0.001). On multivariable analysis, older age and longer ADT duration are associated with a lower T recovery. CONCLUSIONS: Testosterone recovery rate after ADT depends on several factors including hormonal duration, normal baseline T, age and medical comorbidities. A longer ADT duration is the most important variable affecting T recovery. The data from this report might be a valuable tool to help physicians and patients in evaluating risks and benefits of ADT.

Cardiovascular Mortality and Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-term Update of NRG/RTOG 9202.

BACKGROUND: Androgen deprivation therapy (ADT) has been associated with coronary heart disease and myocardial infarction (MI) in prostate cancer patients, but controversy persists regarding its effects on cardiovascular mortality (CVM). OBJECTIVE: We assessed the long-term relationship between ADT and CVM in a prostate cancer randomized trial (NRG Oncology/Radiation Therapy Oncology Group 9202). DESIGN, SETTING, AND PARTICIPANTS: From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-T4, prostate-specific antigen <150 ng/ml) received radiotherapy with 4 mo (short-term [STADT]) versus 28 mo (longer-term [LTADT]) of ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using the Fine-Gray and Cox regression models, the relationship between ADT and mortality was evaluated. RESULTS AND LIMITATIONS: With a median follow-up of 19.6 yr, LTADT was associated with improved overall survival (OS) versus STADT (adjusted hazard ratio [HR] 0.88; p = 0.03) and prostate cancer survival (subdistribution HR [sHR] 0.70, p = 0.003). Comparing LTADT with STADT, prostate cancer mortality improved by 6.0% (15.6% [95% confidence interval 13.0-18.3%] vs 21.6% [18.6-24.7%]) at 15 yr, while CVM increased by 2.2% (14.9% [12.4-17.6%] vs 12.7% [10.4-15.3%]). In multivariable analyses, LTADT was not associated with increased CVM versus STADT (sHR 1.22 [0.93-1.59]; p = 0.15). An association between LTADT and MI death was detected (sHR 1.58 [1.00-2.50]; p = 0.05), particularly in patients with prevalent cardiovascular disease (CVD; sHR 2.54 [1.16-5.58]; p = 0.02). CONCLUSIONS: With 19.6 yr of follow-up, LTADT was not significantly associated with increased CVM in men with locally advanced prostate cancer. Patients may have increased MI mortality with LTADT, particularly those with baseline CVD. Overall, there remained a prostate cancer mortality benefit and no OS detriment with LTADT. PATIENT SUMMARY: In a long-term analysis of a large randomized prostate cancer trial, radiation with 28 mo of hormone therapy did not increase the risk of cardiovascular death significantly versus 4 mo of hormone therapy. Future studies are needed for patients with pre-existing heart disease, who may have an increased risk of myocardial infarction death with longer hormone use.

External Validation of a Digital Pathology-based Multimodal Artificial Intelligence Architecture in the NRG/RTOG 9902 Phase 3 Trial.

BACKGROUND: Accurate risk stratification is critical to guide management decisions in localized prostate cancer (PCa). Previously, we had developed and validated a multimodal artificial intelligence (MMAI) model generated from digital histopathology and clinical features. Here, we externally validate this model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial. OBJECTIVE: To externally validate the MMAI model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial. DESIGN, SETTING, AND PARTICIPANTS: Our validation cohort included 318 localized high-risk PCa patients from NRG/RTOG 9902 with available histopathology (337 [85%] of the 397 patients enrolled into the trial had available slides, of which 19 [5.6%] failed due to poor image quality). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Two previously locked prognostic MMAI models were validated for their intended endpoint: distant metastasis (DM) and PCa-specific mortality (PCSM). Individual clinical factors and the number of National Comprehensive Cancer Network (NCCN) high-risk features served as comparators. Subdistribution hazard ratio (sHR) was reported per standard deviation increase of the score with corresponding 95% confidence interval (CI) using Fine-Gray or Cox proportional hazards models. RESULTS AND LIMITATIONS: The DM and PCSM MMAI algorithms were significantly and independently associated with the risk of DM (sHR [95% CI] = 2.33 [1.60-3.38], p < 0.001) and PCSM, respectively (sHR [95% CI] = 3.54 [2.38-5.28], p < 0.001) when compared against other prognostic clinical factors and NCCN high-risk features. The lower 75% of patients by DM MMAI had estimated 5- and 10-yr DM rates of 4% and 7%, and the highest quartile had average 5- and 10-yr DM rates of 19% and 32%, respectively (p < 0.001). Similar results were observed for the PCSM MMAI algorithm. CONCLUSIONS: We externally validated the prognostic ability of MMAI models previously developed among men with localized high-risk disease. MMAI prognostic models further risk stratify beyond the clinical and pathological variables for DM and PCSM in a population of men already at a high risk for disease progression. This study provides evidence for consistent validation of our deep learning MMAI models to improve prognostication and enable more informed decision-making for patient care. PATIENT SUMMARY: This paper presents a novel approach using images from pathology slides along with clinical variables to validate artificial intelligence (computer-generated) prognostic models. When implemented, clinicians can offer a more personalized and tailored prognostic discussion for men with localized prostate cancer.

Prostate-Specific Antigen Response to Androgen Deprivation Therapy in the Neoadjuvant Setting for High-Risk Prostate Adenocarcinoma (PIRANHA): Pooled Analysis of Two Randomized Clinical Trials.

PURPOSE: A suboptimal prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) among men who go on to receive definitive radiation therapy for prostate cancer might suggest the existence of castration-resistant disease or altered androgen receptor signaling. This in turn may portend worse long-term clinical outcomes, especially in men with high-risk disease. We set out to evaluate the prognostic impact of poor PSA response to neoadjuvant ADT in men with high-risk prostate cancer. METHODS AND MATERIALS: This was a post hoc analysis of the multicenter TROG 03.04 RADAR and PCS IV randomized clinical trials. Inclusion criteria for this analysis were patients with high-risk prostate cancer (defined as Gleason score ≥8, initial PSA ≥20 ng/mL, or cT3a disease or higher) who received definitive radiation therapy, at least 18 months of ADT, and had a preradiation therapy PSA level drawn after at least 3 months of neoadjuvant ADT. Poor PSA response was defined as PSA >0.5 ng/mL. Cox regression and Fine-Gray models were used to test whether poor PSA response was associated with metastasis-free survival, biochemical recurrence, prostate-cancer specific mortality, and overall survival. RESULTS: Nine hundred thirty men met inclusion criteria for this analysis. Median follow-up was 130 months (interquartile range [IQR], 89-154 months). After a median of 3 months (IQR, 3-4.2 months) of neoadjuvant ADT, the median PSA was 0.60 ng/mL (IQR, 0.29-1.59). Overall, 535 men (57%) had a PSA >0.5 ng/mL. Poor PSA response was associated with significantly worse metastasis-free survival (hazard ratio [HR], 3.93; P = .02), worse biochemical recurrence (subdistribution HR, 2.39; P = .003), worse prostate-cancer specific mortality (subdistribution HR, 1.50; P = .005), and worse overall survival (HR, 4.51; P = .05). CONCLUSIONS: Patients with PSA >0.5 mg/mL after at least 3 months of neoadjuvant ADT had worse long-term clinical outcomes and should be considered for treatment intensification.

Radiation therapy and androgen deprivation in the management of high risk prostate cancer

The combined use of radiation therapy (RT) and androgen deprivation for patients with localized high-risk prostate cancer is commonly accepted as the standard treatment among uro-oncologists. Preclinical studies have provided rationale for the use of this combination. Additionally, results of phase 3 studies using conventional doses of RT have supported the combined approach. Other phase 3 studies have also shown a benefit for using higher doses of RT; however, the role of androgen deprivation in this context is not clear. The optimal duration of the androgen deprivation, in both the neoadjuvant and adjuvant setting, is still under investigation. This article critically reviews the data on the use of RT combined with androgen deprivation for the treatment of high-risk prostate cancer with emphasis on the results of phase 3 trials.

O uso de FDG-PET/TC scan no planejamento da radioterapia em câncer do pulmão não de pequenas células / Use of FDG-PET/CT scan in the planning of radiation therapy for non-small cell lung cancer

Radioterapia é uma importante alternativa de tratamento curativo em pacientes com câncer do pulmão não de pequenas células. Entretanto, pulmões são muito sensíveis à radiação e isto aumenta a importância em se delimitar o volume a ser irradiado com precisão. Ultimamente, a tomografia por emissão de pósitron (PET) e a tomografia computadorizada (TC) são feitas de forma combinada, e a literatura sugere que seu impacto no planejamento da radioterapia é significativo. Ao se utilizar exames de PET/TC no planejamento da radioterapia é importante reconhecer e adaptar-se às diferenças entre os equipamentos de diagnóstico e de tratamento. Este texto discute alguns dos problemas técnicos que devem ser resolvidos quando se incorpora PET no planejamento radioterápico.

Radiation therapy represents an important alternative for curative treatment of patients with nonsmall cell lung cancer. However, an accurate definition of the volume to be irradiated becomes even more important, considering that lungs are highly sensitive to radiation. Most recently, combined FDG-PET/CT scan has been utilized, and the literature reports its significant role in the planning of radiation therapy, since it seems to influence the target-volume delineation in cases of lung cancer. Differences between diagnostic and treatment equipments must be taken into consideration when FDG-PET/CT scan is utilized in the planning of radiation therapy. The present study discusses some of the many technical problems that must be solved when PET is incorporated into the planning of radiation therapy for non-small cell lung cancer.

Tratamento do câncer de pequenas células de pulmão: doenca limitada: resultados de uma única instituicão / Treatment of limited stage small-cell lung cancer: results from a single center

OBJETIVO: Relatar os resultados de tratamento de pacientes com câncer de pulmão de pequenas células com doenca limitada (CPPC-DL), num período de dez anos, numa única instituicão, para controle de qualidade e comparacão com dados de literatura. MATERIAIS E MÉTODOS: Entre janeiro de 1992 e dezembro de 2002, 101 pacientes portadores de CPPC-DL completaram tratamento em nossa instituicão. Seus resultados foram revistos e incluíram quimioterapia, radioterapia, a seqüência dos dois tratamentos e o uso de irradiacão profilática cerebral (PCI). A radiacão foi administrada com dose mediana de 45 Gy em 1,8 a 2 Gy por fracão. A dose mediana de PCI foi de 25 Gy em dez fracões. RESULTADOS: O seguimento mediano foi de 50,6 meses e a idade mediana dos pacientes foi de 63 anos. Houve 85 mortes confirmadas, 5 pacientes foram perdidos de seguimento e 11 estavam vivos. O tempo de sobrevida mediano foi de 11 meses, a sobrevida global em dois e cinco anos foi de 25,5 por cento e 10 por cento, respectivamente. Não houve diferenca significante na sobrevida global em dois ou cinco anos segundo a idade e sexo dos pacientes. Também não houve diferenca significante na sobrevida global entre os pacientes que realizaram PCI ou não, ou foram tratados em dois períodos diferentes (1997-2002 vs. 1992-1996). CONCLUSAO: Os resultados de tratamento dos pacientes portadores de CPPC-DL na nossa instituicão refletem as constantes mudancas no manuseio do CPPC. Nossa sobrevida global em dois anos de 25,5 por cento é semelhante a outros resultados uni-institucionais publicados, mas menor que os resultados de 47 por cento a 54 por cento recentemente publicados por grupos cooperativos.

Hipofracionamento no câncer de próstata / Hypofractionated radiotherapy in the management of prostatic cancer

A radioterapia é uma opção terapêutica padrão para o tratamento radical do câncer de próstata localizado. Umamelhora nos índices terapêuticos, através da elevação da dose total do tratamento pelas irradiações, tem sidoexaustivamente pesquisada nos últimos anos, com o auxílio de modernos e mais precisos sistemas de planejamentoe de tratamento. Recentemente, um interesse renovado sobre o uso do hipofracionamento para o tratamento docâncer de próstata pela radioterapia está sendo observado. Tal mudança de estratégia está relacionada ao novoconceito radiobiológico de que os tumores prostáticos possuem um índice α/β muito mais baixo do que previamenteestimado. O hipofracionamento, portanto, parece ser uma opção terapêutica interessante para este tumor, tendoem vista a possibilidade de melhora do índice terapêutico com uma alteração na dose diária de radioterapia. Estetrabalho avalia criticamente o valor do hipofracionamento nos tumores prostáticos malignos.

Biochemical failure as single abnormality in patients with prostate cancer following radical treatment with external radiotherapy: follow-up without immediate treatment

INTRODUCTION: Biochemical failure has been defined as 3 consecutive increases in PSA following curative treatment of prostate cancer. The appropriate management in such cases is controversial. The most usual treatment has been early introduction of hormones. Such patients will live for many years and hormone therapy causes important secondary effects and increases costs. The guideline in our Department of Radiotherapy has been to follow up, with no initial therapy, cases with low PSA and short PSA doubling time. The present study reports this experience. MATERIALS AND METHODS: 528 patients with localized prostate cancer were treated by radical approach between 1992 and 1999, with external radiotherapy, with or without adjuvant hormone therapy. After a median follow-up of 77 months, there were 207 (39 percent) cases with biochemical failure, 78 of which were followed without therapy after the identification of biochemical failure. All of them were asymptomatic patients and had negative radiographic examinations or did not have imaging exams requested since they presented a favorable outcome. The follow-up included at least 2 annual visits with physical examination and PSA. RESULTS: Of the 78 patients with biochemical failure followed without initial therapy, 7 died from other causes than prostate cancer and the remaining 71 cases were alive and asymptomatic in the last follow-up. Prognostic factors previous to radiotherapy such as stage and Gleason score were not considered when deciding for follow-up without initial therapy in these cases. The most significant aspects considered for this decision were low PSA value (median PSA on the last visit for the 78 cases was only 3.9 ng/mL) and a slow PSA doubling time (in the present experience the median PSA doubling time was 22.5 months). CONCLUSION: There seems to be space for expectant management, without initial hormone therapy, in patients with prostate cancer who present biochemical failure and are asymptomatic after radical external radiotherapy. This decision is important, since early introduction of hormones brings late effects and is expensive. Prospective and randomized studies are required to define this issue.

Metástase cerebral: tratamento paliativo com radiocirurgia / Brain metastasis: palliative treatment with radiosurgery

O artigo faz avaliaçäo de 52 pacientes com metástase cerebral tratados com radiocirurgia estereotática na Universidade McGill, em Montreal. A radiocirurgia foi realizada com a técnica dinâmica em que, ao mesmo tempo, giram a mesa e a cabeça do acelerador linear de 10 MV. Todos os pacientes (56 tratamentos ao todo) foram tratados com um único isocentro e uma dose única mediana de 1800cGy na periferia da metástase. Em 88 por cento dos casos a radiocirurgia foi usada após falha de tratamento radioterápico fracionado em todo cérebro. Todos os 52 casos tiveram avaliaçäo com CT pós radiocirurgia. O seguimento mediano foi de 6 meses (variou entre 1 e 37 meses e a taxa de resposta, parcial ou completa foi de 64 por cento. Apenas 4 pacientes (7 por cento) tiveram algum tipo de complicaçäo tardia relacionada ao tratamento. Estes achados väo de encontro com dados da literatura. A radiocirurgia é tratamento pouco agrassivo, bem tolerado e com alta taxa de resposta para lesöes locais e pode ser útil para pacientes selecionaods. O seu valor definitivo, como tratamento único ou combinado com radioterapia em todo cérebro, está sendo avaliado de forma prospectiva e randomizada

Radiocirurgia estereotática no tratamento paliativo das metástases cerebrais / Stereotactic radiosurgery in the paliative treatment of brain metastases

Entre outubro de 1988 e novembro de 1993, 57 pacientes com metástase cerebral foram tratados com radiocirurgia estereotática na Universidade McGill, Canadá. Quatro pacientes foram excluídos dessa análise, deixando, portanto, um total de 53 pacientes (com 57 lesões) avaliáveis. A radiocirurgia foi realizada com a técnica da rotação dinâmica, que utiliza acelerador linear isocêntrico de 10 MV. Dose mediana de 1.800 cGy foi dada numa única fração. Em 89 por cento dos casos a radiocirurgia foi utilizada após falha do tratamento radioterápico convencional. Com seguimento mediano de seis meses, a taxa de resposta foi de 65 por cento. O tratamento foi bem tolerado e apenas quatro pacientes (7 por cento) desenvolveram complicações tardias relacionadas ao tratamento, sendo que uma paciente necessitou de craniotomia para remoção de uma área de radionecrose. Em geral, a radiocirurgia estereotática parece ser tratamento efetivo e seguro para selecionados pacientes com doença metastática cerebral recidivada pós-tratamento convencional. O seu valor como forma única de terapis na metástate cerebral isolada está sendo agora avaliada em estudos prospectivos.

"Tratar todos os campos por dia?" - Questionando um velho dogma (ou, radioterapia na pelve: especulações sobre fracionamento) / Treating all fields in every radiotherapy session? - Questionig the old dogma

Há mais de vinte anos Wilson e Hall publicavam artigo sugerindo que todos os campos fossem tratados em cada sessão de radioterapia (RT), baseados em cálculos que envolviam o conceito de NSD (ou TDF). O artigo considerava tratamento feitos com cobalto a uma SSD=70cm. Começava mais um tradicional dogma da RT: da necessidade de se irradiar todos os campo todos os dias. no Brasil, a maioria dos serviços trabalha com unidade de cobalto ou aceleradores lineares de baixa energia, em que esta necessidade é mais forte. Entretanto, o grande volume de pacientes e as filas de espera acabaram forçando-nos a não tratar todos os campos por dia. Particularmente, os campos pélvicos têm sido planejados com quatro campos (tijolo), mas apenas dois têm sido irradiados diariamente, em forma de rodízio... No sistema de rodízio mencionado, mesmo o valor de TDF dos tecidos subcutâneo dos campos AP-PA não chega a esse número. Isso talvez explique o fato de não aparecer fibroses, apesar de várias análises sobre esses conceitos e questiona o elho dogma da obrigatoriedade de se irradiar todos os campos por dia.

Radiocirurgia estereotáxica / Estereotactic radiosurgery

A radiocirurgia é uma tecnica de irradiaçäo que nos ultimos anos vem se tornando mais frequentemente utilizada. De inicio realizada apenas em poucos e superespecializados centros, devido à extremamente sofisticada e cara aparelhagem. A introduçäo das tecnicas radiocirurgicas com o acelerador linear fez com que esse procedimento pudesse ser agora realizado na maioria dos grandescentros de radioterapia. Alguns dos requerimentos essenciais para a radiocirurgia incluem a localizaçäo acurada da lesäo a ser tratada, o calculo tridimensional da dose, a precisäo da irradiaçäo no alvo predeterminado e um acentuado gradiente de dose fora do volume-alvo. Nesse trabalho, os princípios, as indicaçöes, uma descriçäo sucinta das principais tecnicas e os resultados terapeuticos iniciais da radiocirurgia, numa variedade de patologias, säo discutidos.

Altas doses de VP-16, ciclofosfamida e irradiaçäo corpórea total hiperfracionada seguida de transplante alogeneico de medula óssea: um regime agressivo e bem tolerado no tratamento de neoplasias hematológicas de mau prognóstico

No período de agosto/86 a fevereiro/87, três pacientes foram tratados com VP-16-1800 mg/m2, em infusäo única em 26 horas no dia -6, seguida por Ciclofosfamida (EDX) 50 mg/Kg/d nos dias -5 -4 e -3. Irradiaçäo corpórea total (ICT) - 1000 cGy em 5 fracçöes de 200cGy nos dias -2, -1 e 0. O transplante de medula óssea (TMO) foi realizado no dia 0 utilizando doadores HLA compatíveis. O estudo incluiu três pacientes: um paciente portador de Leucemia Linfoblástica Aguda (LLA) em 1ª recaída medular; um paciente portador de Leucemia Mielóide Crônica (LMC) em 2ª fase crônica e um paciente portador de LLA em 2ª remissäo. a idade variou entre quatro e 29 anos. A principal toxicidade apresentada por este regime foi mucosite severa que ocorreu nos três pacientes. Todos os três pacientes apresentaram ulceraçöes orais e um deles apresentou diarréia hemorrágica com volume superior a dois litros. Em todos os pacientes o quadro se resolveu nas três semanas que se seguiram ao TMO Um paciente apresentou alteraçöes eletrocardiográficas significativas sem, entretanto, ocorreram manifestaçöes clínicas de cardiotoxicidade. A eficácia do regime pode ser testada no paciente em recaída que permanece em remissäo 210 dias pós-TMO. No paciente portador de LMC houve eliminaçäo do cromossomo Ph1. Concluímos que VP-16/EDX/CT é um regime eficaz e bem tolerado no tratamento de neoplasias hematológicas

Carcinoma do laringe: análise dos resultados de 57 pacientes, estádios III e IV, tratados com cirurgia e radioterapia radicais / Carcinoma of the larynx: analysis of results of 57 patients, staging III and IV treated by radical surgery and radiotherapy

No período de janeiro de 1981 a dezembro de 1983, 57 pacientes matriculados no Instituto Nacional de Câncer com carcinoma avançado do laringe foram tratados com cirurgia e radioterapia radicais. A regiäo supraglótica foi a mais comumente atingida. A taxa de controle local foi de 79% e a sobrevida atuarial em 5 anos foi de 55%. Dez pacientes (17,5%) falharam à distância. O significado prognóstico do estádio T, comprometimento nodal, margens cirúrgicas e tempo decorrido entre a cirurgia e o início da radioterapia foi avaliado. Nenhum desses fatores influiu no controle loco-regional, mas os tumores N2 apresentaram pior sobrevida quando comparados aos N0(36% vs 76%; p = 0,02). Os achados desse estudo sugerem que a abordagem cirúrgica inicial deva ser mais conservadora e que a dissecçäo radical do pescoço näo parece favorecer o controle local nem reduzir a mortalidade

Tratamento combinado nos tumores avançados do rinofaringe / Combined treatment in advanced nasopharyngeal neoplasms

No período entre outubro de 1982 e agosto de 1984, 30 pacientes com carcinoma epidermóide do rinofaringe, estádios III (26,5%) e IV (73,5%), receberam uma combinaçäo de radioterapia (6.500 a 7.000cGy/7 a 7,5 semanas) e quimioterapia com 5-Fluorouracil (750mg/m*2, por infusäo contínua, dias 2 a 4), Mitomicina-C (10mg/m*2, endovenoso, dia 1) e Methotrexate (30mg/m*2, endovenoso, dia 1). A idade mediana foi de 40 anos e 20 pacientes eram do sexo masculino. Lindoepitelioma foi diagnosticado em 66,5% dos casos. O seguimento mínimo foi de 24 meses. As sobrevidas global e livre de doença em 48 meses foram de 49% e 35%, respectivamente. Dos 28 pacientes avaliáveis, 75% obtiveram resposta local completa. O índice de recidiva local foi de 9,5%. Falha à distância foi observada em 31% dos casos. O número de complicaçöes foi alta e inclui mucosite (grave em 52%), xerostomia, infecçäo (dois casos fatais de septicemia). Apesar da alta taxa de respostas completas obtidas, a pouca influência que isso exerceu na curva de sobrevida e o número elevado de complicaçöes nos levam a contra-indicar a terapia combinada como tratamento de rotina nesses tumores. Um estudo randomizado é necessário para estabelecer essa questäo

Fatores prognósticos no carcinoma do colo de útero: estadio III / Prognostic factors in carcinoma of the cervix uteri: stage III

Um total de 148 pacientes com carcinoma do colo de útero, estádio III, encaminhadas ao Serviço de Radioterapia do Instituto Nacional de Câncer, no período de janeiro de 1975 a dezembro de 1979, foram avaliadas numa tentativa de se estabelecer possíveis fatores prognósticos no grupo. A extensäo da invasäo parametrial foi o fator prognóstico mais importante, com a sobrevida das pacientes com invasäo unilateral sendo significativamente superior àquelas com invasäo bilateral (p < 0,005). A presença de anemia também mostrou ser de importância prognóstica e todos os esforços devem ser feitos para manter a hemoglobina acima de 12gm. Apesar de que pacientes com mais de 50 anos de idade tenham tido uma sobrevida melhor, essa diferença näo alcançou significado estatístico. A extensäo da invasäo parametrial parece ser o fator prognóstico mais importante e deve ser sempre levada em consideraçäo quando da elaboraçäo de novos estudos