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Purpose: The optimal management of locally recurrent prostate cancer after definitive irradiation is still unclear but local salvage treatments are gaining interest. A retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity after salvage I-125 low-dose-rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer was conducted in a Comprehensive Cancer Center. Patients and methods: A total of 94 patients treated with salvage LDR-BT between 2006 and 2021 were included. The target volume was either the whole-gland +/- a boost on the GTV, the hemigland, or only the GTV. The prescribed dose ranged from 90 to 145 Gy. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Median follow-up was 34 months. Initial radiotherapy was external beam radiotherapy in 73 patients (78 %) with a median dose of 76 Gy and I-125 BT in 21 patients (22 %) with a prescribed dose of 145 Gy. Median PSA at salvage was 3.75 ng/ml with a median interval between first and salvage irradiation of 9.4 years. Salvage brachytherapy was associated with androgen deprivation therapy for 32 % of the patients. Only 4 % of the patients were castrate-resistant. Failure free survival was 82 % at 2 years and 66 % at 3 years. The only factors associated with failure-free survival on multivariate analysis were hormonosensitivity at relapse and European Association of Urology (EAU) prognostic group. Late grade 3 urinary and rectal toxicities occurred in 12 % and 1 % of the patients respectively.No significant difference in toxicity or efficacy was observed between the three implant volume groups. Conclusion: The efficacy and toxicity results are consistent with those in the LDR group of the MASTER meta-analysis. Salvage BT confirms to be an effective and safe option for locally recurrent prostate cancer. A focal approach could be interesting to reduce late severe toxicities, especially urinary.
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PURPOSE: The increased risk of second cancer after prostate radiotherapy is a debated clinical concern. The objective of the study was to assess the risk of occurrence of second cancers after prostate radiation therapy based on the analysis the literature, and to identify potential factors explaining the discrepancies in results between studies. MATERIALS AND METHODS: A review of the literature was carried out, comparing the occurrence of second cancers in patients all presenting with prostate cancer, treated or not by radiation. RESULTS: This review included 30 studies reporting the occurrence of second cancers in 2,112,000 patients treated or monitored for localized prostate cancer, including 1,111,000 by external radiation therapy and 103,000 by brachytherapy. Regarding external radiation therapy, the average follow-up was 7.3years. The majority of studies (80%) involving external radiation therapy, compared to no external radiation therapy, showed an increased risk of second cancers with a hazard ratio ranging from 1.13 to 4.9, depending on the duration of the follow-up. The median time to the occurrence of these second cancers after external radiotherapy ranged from 4 to 6years. An increased risk of second rectal and bladder cancer was observed in 52% and 85% of the studies, respectively. Considering a censoring period of more than 10 years after irradiation, 57% and 100% of the studies found an increased risk of rectal and bladder cancer, without any impact in overall survival. Studies of brachytherapy did not show an increased risk of second cancer. However, these comparative studies, most often old and retrospective, had many methodological biases. CONCLUSION: Despite numerous methodological biases, prostate external radiation therapy appears associated with a moderate increase in the risk of second pelvic cancer, in particular bladder cancer, without impacting survival. Brachytherapy does not increase the risk of a second cancer.
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Braquiterapia , Neoplasias Induzidas por Radiação , Segunda Neoplasia Primária , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/epidemiologia , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/etiologia , Neoplasias Retais/radioterapia , Neoplasias Retais/etiologiaRESUMO
Prostate brachytherapy techniques are described, concerning both permanent seed implant and high dose rate brachytherapy. The following guidelines are presented: brachytherapy indications, implant procedure for permanent low dose rate implants and high dose rate with source projector, as well as dose and dose-constraints objectives, immediate postoperative management, post-treatment evaluation, and long-term follow-up.
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Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Antineoplásicos Hormonais , Braquiterapia/efeitos adversos , Terapia Combinada , Contraindicações de Procedimentos , Fracionamento da Dose de Radiação , França , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Radioterapia (Especialidade) , Dosagem Radioterapêutica , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Terapia de Salvação/métodosRESUMO
The issue of radiation-induced cancers must be taken into consideration during therapeutic irradiations. Risk factors for radiation-induced cancer include: the age of the patients, the volumes irradiated, the presence of risk cofactors and the exposure of critical organs. Those should be part of the therapeutic decision, in terms of indication, as well as choice of the radiotherapy technique (including repositioning systems). We present the update of the recommendations of the French society for radiation oncology on the modalities for preventing radiation-induced cancers.
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Neoplasias Induzidas por Radiação/prevenção & controle , Fatores Etários , Humanos , Órgãos em Risco/efeitos da radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Fatores de RiscoRESUMO
The French society of oncological radiotherapy (Société française de radiothérapie oncologique, SFRO) was created in 1990. On the occasion of its thirtieth annual congress, in October 2019, a session was devoted to it, with the objective of exposing its functioning, its actions and its productions during these three decades during which radiotherapy and oncology have undergone unprecedented transformations. We propose in this article to outline the content of this session.
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Aniversários e Eventos Especiais , Radioterapia (Especialidade) , Sociedades Médicas/história , Congressos como Assunto/história , França , História do Século XX , História do Século XXI , Humanos , Guias de Prática Clínica como AssuntoRESUMO
The irradiation of non-malignant diseases, essentially for anti-inflammatory purpose, have been largely proposed and performed worldwide until the 1970-80s. At that time, the better assessment of the radio-induced malignancies, essentially in children and young patients, as well as the efficacy of the new anti-inflammatory drugs (steroids and non-steroids), led to the almost disappearance of those techniques, at least in France. In contrast, our German colleagues are still going on treating about 50,000 patients per year for non-malignant (more or less severe) diseases. After a short historical overview, the present article suggests that we were possibly going too far in the rejection of those low-dose irradiations for benign lesions. The recent emergence of new preclinical data, the better understanding of the risk of radio-induced secondary tumours (almost nil in the elderly), and the severity of some situations, such as the cytokine storm of the COVID-19, should probably lead us to reconsider those low - and sometimes very low (less than 1Gy) - irradiations for well-selected indications in the elderly.
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Radioterapia/tendências , Medicina Baseada em Evidências , Humanos , Neoplasias Induzidas por Radiação , Dosagem RadioterapêuticaAssuntos
Betacoronavirus , Infecções por Coronavirus/radioterapia , Síndrome da Liberação de Citocina/radioterapia , Pulmão/efeitos da radiação , Pneumonia Viral/radioterapia , COVID-19 , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/etiologia , Humanos , Hospedeiro Imunocomprometido , Terapia de Imunossupressão , Pneumopatias/radioterapia , Depleção Linfocítica , Pandemias , Pneumonia Viral/complicações , Dosagem Radioterapêutica , SARS-CoV-2RESUMO
The decision to reirradiate a volume which had been previously irradiated remains in 2019 one of the most difficult challenge for a radiation oncologist. Such a decision has to be based on a number of clinical and technological criteria, and the radiation oncologist will have to answer three main questions: i) can the patient clinically tolerate a second irradiation in the same previously irradiated area? While waiting for fully reliable individual tests of radiosensitivity, one has to take into account the tolerance of the first irradiation, as well as the comorbidities and/or habits which could impact the patient intrinsic radiosensitivity; ii) do the technical data of the first radiotherapy allow a re-irradiation? Unfortunately, and essentially when the discussion of re-irradiating the patient occurs many years (or even decades) after the first treatment, those precise technical data can be missing; iii) which technique should be used for the re-irradiation? In such a specific situation, the patient should be offered the more precise modern technology: stereotactic radiotherapy, protons, brachytherapy (low-, high-, or pulsed-dose rate). The indisputable improvement of the ballistic precision linked to our new technologies should lead to refine and to develop the indications of re-irradiation in the next future.
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Tomada de Decisão Clínica , Tolerância a Radiação , Reirradiação/métodos , Braquiterapia/métodos , Humanos , Terapia com Prótons , Radioterapia , Dosagem Radioterapêutica , Fatores de TempoRESUMO
In 1999, Brenner and Hall reported for prostate cancer a very low alpha/beta ratio (1.5Gy). In the following years, this value has been confirmed by a large series of papers, so that this very low alpha/beta ratio became a "dogma", on which a large number of hypofractionated schemes were being built. This was logical, since this very low value strongly suggested a beneficial advantage of hypofractionation for prostate cancer. However, more recently, several questions arose; first, a number of authors reported, from the analysis of their own data, values of alpha/beta ratio which were higher than the "dogma". Secondly, the three modern "superiority trials", aiming at demonstrating the advantages of hypofractionated schemes, actually failed to show such a superiority, in spite of high equivalent doses (calculated with an alpha/beta of 1.5Gy), reaching up to 84 - 90Gy. In 2018, three review papers/metanalyses shed a new light on what could be the value of the alpha/beta ratio for prostate cancer. In particular, those studies took into account a "time factor" (for repopulation), a parameter which had been either forgotten or underestimated before. In those three studies, the alpha/beta ratio was ranging from 2.7Gy to 4.9Gy. Those data do confirm the sensitivity to the fraction dose variation of prostate cancer, but this sensitivity could be lower than suggested by an alpha/beta ratio of 1.5Gy.
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Fracionamento da Dose de Radiação , Neoplasias da Próstata/radioterapia , Humanos , MasculinoRESUMO
For more than a decade, the majority of radiation oncology centres have been delivering intensity-modulated radiotherapy (then volumetric-modulated arctherapy) with 6 MV photons as their standard of care. This « dogma ¼ had been supported by the usual absence of dosimetric advantages with high-energy photons (15 to 18 MV or more), at least for the planning target volume and the dose received by the adjacent organs at risk, and by the neutron component as soon as the photon energy exceeds 10 MV. Recent data could question such a dogma. First, in 2019, one cannot avoid taking into account the integral dose, delivered outside the treated volume. Actually, most available data show that integral dose is higher with low energy photons (as 6 MV) than with higher energies. Moreover, recent studies have shown that the neutron component at high energies may have been overestimated in the past; in fact, the neutron dose appears to be lower, and sometimes much lower, than the dose we accept for imaging. Finally, a few cohort studies did not show any increase in second cancers incidence after high-energy photon radiotherapy. In such a context, the American Association of Physicists in Medicine (AAPM) TG 158 document, released a few months ago, clearly states that there is a trade-off between high- and low-energy treatments. High-energy therapy is associated with neutron production, while low-energy therapy results in higher stray photon dose. According to the AAPM, « the optimal energy is likely an intermediate such as 10 MV ¼.
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Fótons , Radioterapia de Intensidade Modulada/métodos , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
Salvage brachytherapy after a first prostate radiation therapy is an emerging technique, which has to be considered in the therapeutic armamentarium in the clinically challenging context of patients with isolated local failure from prostate cancer who may still be considered for cure. These occult failures are more and more frequently diagnosed at an early stage, thanks to targeted biopsies and advances in imaging modalities, such as multiparametric MRI and PET-CT. Salvage brachytherapy benefits from the implantation accuracy of brachytherapy procedures using 3D dosimetry and has resulted in more than 50% tumour control rates with long-term. Incontinence rates are always below those of other salvage treatments such as radical prostatectomy, HIFU or cryotherapy. Today, a consensus has been reached to better define good candidates for salvage brachytherapy with respect to disease characteristics at baseline and at failure. No consensus has been clearly defined yet regarding the choice of the technique (low or high dose rate), the total dose to be delivered, or the volume to be implanted (whole gland or focal). While we await robust data from recently completed phase II studies and given the heterogeneous results in the literature, this technique (although already included in the last 2016 NCCN guidelines) remains to be precisely evaluated, optimally within the frame of controlled trials.
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Braquiterapia , Neoplasias da Próstata/radioterapia , Humanos , Masculino , Terapia de Salvação , Falha de TratamentoRESUMO
OBJECTIVE: To perform a state of the art about methods of evaluation and present results in ablative therapies for localized prostate cancer. METHODS: A review of the scientific literature was performed in Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of keywords. Publications obtained were selected based on methodology, language and relevance. After selection, 102 articles were analysed. RESULTS: Analyse the results of ablative therapies is presently difficult considering the heterogeneity of indications, techniques and follow-up. However, results from the most recent and homogeneous studies are encouraging. Oncologically, postoperative biopsies (the most important criteria) are negative (without any tumor cells in the treated area) in 75 to 95%. Functionally, urinary and sexual pre-operative status is spared (or recovered early) in more than 90% of the patients treated. More and more studies underline also the correlation between the results and the technique used considering the volume of the gland and, moreover, the "index lesion" localization. CONCLUSION: The post-treatment pathological evaluation by biopsies (targeted with MRI or, perhaps in a near future, with innovative ultrasonography) is the corner stone of oncological evaluation of ablative therapies. Ongoing trials will allow to standardize the follow-up and determine the best indication and the best techniques in order to optimize oncological and functional results for each patient treated.
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Técnicas de Ablação , Neoplasias da Próstata/terapia , Biópsia , Humanos , Masculino , Ereção Peniana , Fototerapia , Complicações Pós-Operatórias , Período Pós-Operatório , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Retenção Urinária , MicçãoRESUMO
The question whether a reirradiation is possible, with either curative of palliative intent, is a frequent issue and a true therapeutic challenge, in particular for a critical organ sensitive to cumulative dose, such as the spinal cord. Preclinical experimental data, based on debatable models that are hardly transferable to patients, suggest that there is a possibility of reirradiation, beyond the classical threshold for dose constraints, taking into account the "time-dose factor". Although the underlying biological mechanisms are however uncertain, scarce clinical data seem to confirm that the tolerance of spinal cord to reirradiation does exist, provided that a particular attention to total dose is given. In the context where modern stereotactic irradiation facilities expand therapeutic perspectives, we review the literature on possibilities of reirradiation, through the example of spinal cord reirradiation.
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Dosagem Radioterapêutica , Reirradiação , Medula Espinal/efeitos da radiação , Animais , Humanos , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Tolerância a Radiação , Radiobiologia , Fatores de TempoRESUMO
OBJECTIVE: To perform a state of the art about indications and limits of ablative therapies for localized prostate cancer. METHODS: A review of the scientific literature was performed in Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of keywords. Publications obtained were selected based on methodology, language and relevance. After selection, 107 articles were analysed. RESULTS: The objective to combine reduction of side effects and oncological control has induced recent development of several ablative therapies. Beyond this heterogeneity, some preferential indications appear: unilateral cancer of low risk (but with significant volume, excluding active surveillance) or intermediate risk (excluding majority of grade 4); treatment targeted the index lesion, by quarter or hemi-ablation, based on biopsy and mpMRI. In addition, indications must considered specific limits of each energy, such as gland volume and tumor localization. CONCLUSION: Based on new imaging and biopsy, ablative therapies will probably increased its role in the future in management of localize prostate cancer. The multiple ongoing trials will certainly be helpful to better define their indications and limits.
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Técnicas de Ablação , Neoplasias da Próstata/cirurgia , Tomada de Decisão Clínica , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologiaRESUMO
For prostate cancer, hypofractionation has been based since 1999 on radiobiological data, which calculated a very low alpha/beta ratio (1.2 to 1.5Gy). This suggested that a better local control could be obtained, without any toxicity increase. Consequently, two types of hypofractionated schemes were proposed: "moderate" hypofractionation, with fractions of 2.5 to 4Gy, and "extreme" hypofractionation, utilizing stereotactic techniques, with fractions of 7 to 10Gy. For moderate hypofractionation, the linear-quadratic (LQ) model has been used to calculate the equivalent doses of the new protocols. The available trials have often shown a "non-inferiority", but no advantage, while the equivalent doses calculated for the hypofractionated arms were sometimes very superior to the doses of the conventional arms. This finding could suggest either an alpha/beta ratio lower than previously calculated, or a negative impact of other radiobiological parameters, which had not been taken into account. For "extreme" hypofractionation, the use of the LQ model is discussed for high dose fractions. Moreover, a number of radiobiological questions are still pending. The reduced overall irradiation time could be either a positive point (better local control) or a negative one (reduced reoxygenation). The prolonged duration of the fractions could lead to a decrease of efficacy (because allowing for reparation of sublethal lesions). Finally, the impact of the large fractions on the microenvironment and/or immunity remains discussed. The reported series appear to show encouraging short to mid-term results, but the results of randomized trials are still awaited. Today, it seems reasonable to only propose those extreme hypofractionated schemes to well-selected patients, treating small volumes with high-level stereotactic techniques.
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Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , Ensaios Clínicos como Assunto , Humanos , Masculino , RadiobiologiaRESUMO
PURPOSE: To analyse the rate of secondary malignancies observed in a series of 675 prostate cancer patients who underwent a permanent implant brachytherapy between 1999 and 2003, and to compare the incidence with the expected rate in a matched general French population. MATERIAL AND METHODS: The cohort included low-risk patients and a selection of "favourable-intermediate" risk patients. All patients were homogeneously treated using an intraoperative dynamic planning prostate brachytherapy technique, with loose 125-iodine seeds and a prescription dose of 145Gy. The mean follow-up was 132 months. RESULTS: The 10-year overall survival for the entire cohort was 92% (95% confidence interval [CI]: 90-94). The 10-year relapse-free survival rate was 82% (95% CI: 79-85). Overall, 61 second cancers were registered. When comparing with a matched general French population, the standard incidence ratio (SIR) for bladder cancer was 1.02 (95% CI: 0.46-1.93). For colorectal cancer, the SIR was 0.45 (95% CI: 0.19-0.89). For lung cancer, the SIR was 0.38 (95% CI: 0.17-0.76). The SIR for all cancers was 0.61 (95% CI: 0.47-0.79). When excluding secondary colorectal and lung cancers (both with low SIRs in this series), the SIR for all cancers was 1.06 (95% CI: 0.77-1.29). CONCLUSION: With a mean follow-up of more than 11 years, this series does not detect any excess risk of second cancers associated with permanent implant prostate brachytherapy. However, due to power limitation, a small increase in the risk of secondary malignancies cannot be totally ruled out.
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Braquiterapia , Segunda Neoplasia Primária/epidemiologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/radioterapia , Idoso , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Radiotherapy is 120 years old. A few months only after the discoveries of Roentgen, Becquerel and Marie and Pierre Curie, a few scientists tried to use the newly discovered rays to treat patients. The question of the name of the first "radiation therapist" remains debated. Although often proposed, Emil Grubbé from Chicago seems to have been disqualified. Leopold Freund from Vienna treated a benign cutaneous lesion. Finally, Victor Despeignes from Lyon appears to be the most serious candidate, having treated in 1896 a gastric cancer, and obtaining a very significant tumour regression. The pioneers of radiotherapy paid a heavy tribute to the development of the specialty; a number of them appears on the - most probably incomplete - list of 352 names engraved on the monument dedicated to the "radiation martyrs" in Hamburg. We must keep in mind that it is only within a few years that a handful of brilliant pioneers built the foundations on which radiotherapy could emerge.
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Radioterapia/história , História do Século XIX , História do Século XX , História do Século XXI , HumanosRESUMO
The article deals with the prevention of cancers only directly related to therapeutic radiation which are distinguished from "secondary cancer". The consideration of the risk of radiation-induced cancers after radiation therapy, although it is fortunately rare events, has become indispensable today. With a review of the literature, are detailed the various involved parameters. The age of the irradiated patient is one of the main parameters. The impact of the dose is also discussed based on the model used, and based on clinical data. Other parameters defining a radiation treatment are discussed one after the other: field with the example of Hodgkin's disease, the type of radiation and the participation of secondary neutrons, spreading and splitting. All these parameters are discussed according to each organ whose sensitivity is different. The article concludes with a list of recommendations to reduce the risk of radio-induced cancers. Even with the advent of conformal radiotherapy, intensity modulation, the modulated volume arctherapy, and the development of specific machinery for the extra-cranial stereotactic, the radiation therapist must consider this risk and use of reasonable and justified control imaging. Although they constitute a small percentage of cancers that occur secondarily after a first malignant tumor, radiation-induced cancers, can not and must not be concealed or ignored and justify regular monitoring over the long term, precisely adapted on the described parameters.
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Neoplasias Induzidas por Radiação/prevenção & controle , Radioterapia/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Doença de Hodgkin/radioterapia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Neoplasias/radioterapia , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/prevenção & controle , Especificidade de Órgãos , Órgãos em Risco , Neoplasias da Próstata/radioterapia , Tolerância a Radiação , Radioterapia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Risco , Adulto JovemRESUMO
PURPOSE: To analyse long-term overall survival, relapse-free survival and late toxicities in a series of 675 patients treated between 1999 and 2003, with a median follow-up of 132 months. PATIENTS AND METHODS: The cohort included low-risk patients and a selection of "favourable-intermediate" risk patients. All patients were homogeneously treated using an intraoperative dynamic planning prostate brachytherapy technique, with loose 125 iodine seeds. Hormone therapy, consisting most often of an anti-androgen alone, was given in 393 patients (58%). RESULTS: The 10-year overall survival was 92% (95% confidence interval [CI]: 90-94) without a significant difference between the low and the select intermediate-risk groups (P=0.17). The 10-year relapse-free survival rate for the entire cohort was 82% (95% CI: 79-85), and was significantly higher in the low-risk group than in the intermediate one (87 vs 71%; P<0.0001). Twenty-six percent of the relapses observed in this series occurred after more than 10 years of follow-up. The 10-year cumulative incidence of grade 3-4 urinary toxicity (whatever the delay and the recovery) was 5.78%. The cumulative incidence of grades 3-4 rectal toxicity in the present series was 1.65% at 10 years. As for sexual toxicity, 61% of our patients retained an erectile capacity at 10 years (with or without oral medication), with age being a major factor. CONCLUSION: With a median follow-up of more than 11 years, this series appears to confirm the excellent long-term results of low-dose rate prostate brachytherapy, both in terms of survival and in terms of toxicity.