Does hormone therapy modify the position of the gold markers in the prostate during irradiation? A daily evaluation with kV-images

PurposeGold markers are frequently used for a better daily repositioning of the prostate before irradiation. The purpose of this work was to analyze if the combination of an androgen deprivation with the external irradiation could modify the position of the gold markers in the prostate.Patients and methodsTen patients have been treated for a prostate cancer, using three implanted gold markers. The variations of the intermarker distances in the prostate were measured and collected on daily OBI^® kilovoltage images acquired at 0° and 90°. Five patients had a 6-month androgen deprivation started before the external irradiation (H group) and five did not (NH group).ResultsA total number of 1062 distances were calculated. No distance variation greater than 3.7 mm was seen between two markers, in any of the two groups. The median standard deviations of the daily intermarker distance differences were 0.7 mm (range 0.3–1.2 mm) for the H group and 0.6 mm (range 0.2–1.2 mm) for the NH group. The intermarker distances variations were noted as greater than –2 mm, between –2 mm and 2 mm and greater than 2 mm in 16.4, 83.4 and 0.2% for the H group and 1.3, 98.5 and 0.2% for the NH group, respectively.ConclusionThe distance variations remained less than 4 mm in both groups and for all the measurements. In the NH group, the variation of the distance between two markers remained below 2 mm in 98.5%. In the H group, the presence of a reduction of distance above 2 mm in 16.4% of measurements could indicate the shrinkage of the prostate volume.     

(68Ga)-PSMA-PET/CT for the detection of postoperative prostate cancer recurrence: Possible implications on treatment volumes for radiation therapy

PurposeThe aim of this study was to define the pattern of relapse of postoperative prostate cancer in patients by using 68Ga-labeled prostate-specific membrane antigen positron-emission tomography/computed tomography ([⁶⁸Ga]-PSMA PET/CT).Material and methodsForty patients received a (⁶⁸Ga)-PSMA PET/CT for biochemical failure. Following the Radiation Therapy Oncology Group (RTOG) guidelines, the pelvic clinical target volume has been contoured. Bone metastases were considered as outside the clinical target volume. Two subgroups of patients were defined, patients having relapse: (1) inside, or (2) outside the clinical target volume.ResultsGlobally, eight patients out of 32 presented with a positive lymph node failure inside the clinical target volume according to RTOG guidelines (25%), 22 patients had nodal relapses outside this clinical target volume (68.75%) and in two patients nodal relapses occurred both inside and outside of the clinical target volume (6.25%). Overall, 36 positive lymph node lesions were identified: of these, 23 nodal relapses were identified within the clinical target volume contoured according to RTOG and/or at the lomboaortic level (63%). To cover 95% of these 23 relapses, a hypothetical clinical target volume should encompass the nodal regions of the RTOG-defined clinical target volume as well as the paraaortic lymph node level up to T12-L1.ConclusionMost of the patients in the present study, presented with distant lymph node and/or bone metastases. Therefore, larger target volumes should be adopted to treat at least 95% of lymph node regions at risk for an occult relapse.     

Brachytherapy boost (BT-boost) or stereotactic body radiation therapy boost (SBRT-boost) for high-risk prostate cancer (HR-PCa)

Systematic review for the treatment of high-risk prostate cancer (HR-PCa, D’Amico classification risk system) with external body radiation therapy (EBRT) + brachytherapy-boost (BT-boost) or with EBRT + stereotactic body RT-boost (SBRT-boost). In March 2020, 391 English citations on PubMed matched with search terms “high risk prostate cancer boost”. Respectively 9 and 48 prospective and retrospective studies were on BT-boost and 7 retrospective studies were on SBRT-boost. Two SBRT-boost trials were prospective. Only one study (ASCENDE-RT) directly compared the gold standard treatment [dose-escalation (DE)-EBRT + androgen deprivation treatment (ADT)] versus EBRT + ADT + BT-boost. Biochemical control rates at 9 years were 83% in the experimental arm versus 63% in the standard arm. Cumulative incidence of late grade 3 urinary toxicity in the experimental arm and in the standard arm was respectively 18% and 5%. Two recent studies with HR-PCa (National Cancer Database) demonstrated better overall survival with BT-boost (low dose rate LDR or high dose rate HDR) compared with DE–EBRT. These recent findings demonstrate the superiority of EBRT + BT-boost + ADT versus DE–EBRT + ADT for HR-PCa. It seems that EBRT + BT-boost + ADT could now be considered as a gold standard treatment for HR-PCa. HDR or LDR are options. SBRT-boost represents an attractive alternative, but the absence of randomised trials does not allow us to conclude for HR-PCa. Prospective randomised international phase III trials or meta-analyses could improve the level of evidence of SBRT-boost for HR-PCa.     

The androgen receptor for the radiation oncologist

Androgen deprivation therapy is widely used in combination with radiotherapy for the treatment of prostate cancer. The knowledge of the biology of the androgen axis could help the radiation oncologist to combine both modalities in an efficient way. Moreover, new drugs have recently been approved and their role in combination with radiation needs pre-clinical and clinical studies. This review summarized the main data on the biology of androgen receptor and the potential implications for the physician. Mechanisms of interactions between androgen deprivation therapy and radiotherapy are also presented and discussed.     

Dose constraints for moderate hypofractionated radiotherapy for prostate cancer: The French genito-urinary group (GETUG) recommendations

Considering recent phase III trials results, moderate hypofractionated radiotherapy can be considered as a standard treatment for low and intermediate risk prostate cancer management. This assessment call for a framework allowing homogeneous and reproducible practices in the different centers using this radiotherapy schedule. The French Genito-Urinary Group (GETUG) provides here recommendations for daily practice of moderate hypofractionated radiotherapy for prostate cancer, with indications, dose, fractionation, pre-treatment planning, volume of interest delineation (target volume and organs at risk) and margins, dose constraints and radiotherapy techniques.     

Medical treatment for biochemical relapse after radiotherapy

This article's purpose was to review the medical data justifying the use of a medical treatment for biochemical relapse after external beam radiotherapy. The MEDLINE database was searched to identify relevant information with the following medical subject headings: “prostate cancer”, “radiotherapy” and “biochemical relapse”. Prognostic factors affecting the overall survival of patients with a biochemical relapse after external beam radiotherapy have been identified: short prostate specific antigen (PSA)-doubling time (< 12 months), high PSA value (> 10 ng/mL) and short interval between treatment and biochemical relapse (< 18 months). If a second local treatment is not feasible, timing to initiate a salvage medical treatment is not defined. Particularly, randomized trials did not demonstrate a significant benefit of an early initiation of androgen deprivation treatment. Some retrospective studies suggest that an early androgen deprivation is justified if poor prognostic factors are found. However, if an androgen deprivation treatment is prescribed, intermittent schedule is non-inferior to a continuous administration and seems to offer a better quality of life. Many non-hormonal treatments have also been evaluated in this setting: only 5-alpha-reductase inhibitors could be proposed in some specific situations. In conclusion, the judicious use of a medical treatment for biochemical relapse is still debated. Given the natural history of this clinical situation, a simple surveillance is justified in many cases.     

Brachytherapy for prostate cancer: Present and future

Based on recent, important publications on the impact of brachytherapy in the management of prostate cancer, we analysed already validated indications and the “under investigations” use of brachytherapy. Published studies (MEDLINE), randomized trials and recommendations were reviewed, as well as Delphi consensus when available. While low-dose rate brachytherapy remains a standard of care for low-risk eligible patients, three randomized trials are now available to consider that combination of external beam radiation therapy with brachytherapy boost (low- or high-dose rate) appears as a recommended treatment for intermediate and high-risk patients. Other indications of prostate brachytherapy (monotherapy and salvage) remain under evaluation. For low-risk patients with good urinary status, low-dose rate brachytherapy alone should be offered. For low-intermediate risk prostate cancer, low-dose rate brachytherapy alone may be offered as monotherapy, while for high-intermediate risk prostate cancer, a combination of external beam radiation therapy (with or without androgen deprivation therapy) plus brachytherapy boost (low- or high-dose rate) should be offered to eligible patients. For patients with high-risk prostate cancer receiving external beam radiation therapy and androgen deprivation therapy, brachytherapy boost (low- or high-dose rate) should be offered to eligible patients. High-dose rate brachytherapy as monotherapy (single dose for low-risk/multifractionated for intermediate and high-risk) must be explored under clinical investigations, as well as salvage brachytherapy for local recurrence.     

Associations d’hormonothérapie et de radiothérapie pour le cancer de prostate

Combination of radiotherapy and androgen deprivation is now considered as the standard of care for patients with a localized prostate cancer but poor prognosis factors. Two groups of randomized trials have led to this recommendation: some have compared radiotherapy alone versus hormonal treatment and radiotherapy: these trials demonstrated, now with a long follow-up, an improvement in 10-year survival for the combined treatment. Three recent trials compared androgen deprivation alone or combined with radiotherapy; a benefit in survival was also demonstrated in favour of the combination. Some questions remained concerning the optimal duration of hormonal treatment, in view of its potential side effects. Patients in the intermediate prognostic groups could receive a short-term androgen deprivation, but those with a high Gleason score must be treated with a long-term hormonal treatment. Modalities of radiotherapy, regarding volumes and dose must also be précised in the next years.     

Irradiation hypofractionnée du cancer de prostate : quelles connaissances radiobiologiques en 2017 ?

For prostate cancer, hypofractionation has been based since 1999 on radiobiological data, which calculated a very low alpha/beta ratio (1.2 to 1.5 Gy). 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 4 Gy, and “extreme” hypofractionation, utilizing stereotactic techniques, with fractions of 7 to 10 Gy. 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.     

Migration of intraprostatic fiducial markers and its influence on the matching quality in external beam radiation therapy for prostate cancer

Purpose

To assess the influence of fiducial marker (FM) migration on the matching quality in external beam radiation therapy (EBRT) for prostate cancer.

Materials and methods

The position of FMs were identified using on-board kV imaging (OBI) and their 3-D position established using an in-house reconstruction algorithm for 31 patients with prostate adenocarcinoma. To carry out the match, the positions were overlaid on the digitally reconstructed radiographs (DRR) generated from the planning CT. The distance between each FM was calculated for seven treatments throughout the EBRT course. Four radiotherapy technologists were asked to independently perform and rate the match from OBI to DRR which was then correlated to the extent of FM migration.

Results

All the matches were rated by at least three radiotherapy technologists as “very easy” (“easy” subgroup) for 24 patients (77%), while the other seven patients had their match rated less than “very easy” and considered the “not easy” subgroup. The average daily FM migration was 0.93 ± 0.34 mm for the “easy” subgroup vs. 1.82 ± 0.75 mm for the latter. An average migration >2 mm was seen in five/seven patients in the “not easy” subgroup as compared to none in the “easy” subgroup. There was a trend towards less FM migration and better matching if the planning CT was done later than the day of the FM implant (p = 0.093).

Conclusions

FM migration >2 mm predicts for a more difficult matching process; PTV margins might have to be adjusted or the planning CT repeated.     

Treatment failure prediction for head-and-neck cancer radiation therapy

PurposeTreatment outcome prediction is an important emerging topic in oncologic care. To support radiation oncologists on their decisions, with individualized, tailored treatment regimens increasingly becoming the standard of care, accurate tools to predict tumour response to treatment are needed. The goal of this work is to identify the most determinant factor(s) for treatment response aiming to develop prediction models that robustly estimate tumour response to radiation therapy in patients with head-and-neck cancer.Patients and methodsA population-based cohort study was performed on 92 patients with head-and-neck cancer treated with radiation from 2007 until 2014 at the Portuguese Institute of Oncology of Coimbra (IPOCFG). Correlation analysis and multivariate binary logistic regression analysis were conducted in order to explore the predictive power of the considered predictors. Performance of the models is expressed as the area under the curve (AUC) of the receiver operating characteristics (ROC) curve. A nomogram to predict treatment failure was developed.ResultsSignificant prognostic factors for treatment failure, after multivariate regression, were older age, non-concomitant radiation therapy and larger primary tumour volume. A regression model with these predictors revealed an AUC of .78 for an independent data set.ConclusionFor patients with head-and-neck cancer treated with definitive radiation, we have developed a prediction nomogram based on models that presented good discriminative ability in making predictions of tumour response to treatment. The probability of treatment failure is higher for older patients with larger tumours treated with non-concomitant radiation.     

Postoperative radiotherapy in prostate cancer: When and how? – An update review

Radical prostatectomy (RP) has been found to be curative in most cases of prostate cancer (PCa); however, 20–40% of patients have a biochemical recurrence (BCR) of the disease. Prostatic specific antigen prostate–specific antigen (PSA) levels are used to assess patient prognosis after surgery; however, there is no consensus about the optimal PSA level that defines BCR. Detection of very low volume disease and early detection of the disease are very important predictors for clinical outcomes in BCR, as early salvage radiation therapy (SRT) provides a possibility of a cure. The aim of this study is to review briefly about important and controversies in radiotherapy after radical prostatectomy. No guideline exists to select ideal patients for each treatment, but there are tools currently being developed; genetic tests and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) may be able to identify patients with worse outcomes who would benefit from more treatment.     

Irradiation ganglionnaire prophylactique des cancers de prostate

The risk of lymph node invasion, in case of prostate cancer, increases with the clinical stage of the disease, the Gleason score of prostate biopsies and the value of PSA at diagnosis. Historically, beyond 15% risk of lymph node involvement, irradiation of the pelvic areas was performed with prostate radiotherapy (RT) to take into account the risk of occult lymph node metastasis in patients at risk, but the benefit of this therapeutic approach remains to be demonstrated. The data from surgical lymph node dissection seem to question the risk levels, the escalation of the dose on the prostate increases the survival without relapse, the contribution of image-guided radiotherapy, (IGRT) and modulation of intensity (IMRT), decreases the toxicity of pelvic RT. This article reviews the principles of prophylactic ganglion irradiation for prostate cancer and discusses its relevance, current uncertainties, and prospective trials.     

Iris metastasis from prostate carcinoma: A case report and review of the literature

Despite the high incidence of prostate carcinoma, metastases of the uvea are very rare and the iris localization is even more. Only a few cases worldwide have been described so far. We report here the case of a 66-year-old man diagnosed with a metastatic prostate carcinoma. Nine months later, he developed brain and skin metastases. A couple of weeks later, the metastatic lesion appeared on his left iris. He has received whole brain radiation therapy including the iris lesion in the radiation fields. Through this case report and a literature review, we discuss the incidence, the different clinical presentations and the impact on the survival prognosis of this uncommon metastatic site.     

Positron-emission tomography-guided radiation therapy: Ongoing projects and future hopes

Radiation therapy has undergone significant advances these last decades, particularly thanks to technical improvements, computer science and a better ability to define the target volumes via morphological and functional imaging breakthroughs. Imaging contributes to all three stages of patient care in radiation oncology: before, during and after treatment. Before the treatment, the choice of optimal imaging type and, if necessary, the adequate functional tracer will allow a better definition of the volume target. During radiation therapy, image-guidance aims at locating the tumour target and tailoring the volume target to anatomical and tumoral variations. Imaging systems are now integrated with conventional accelerators, and newer accelerators have techniques allowing tumour tracking during the irradiation. More recently, MRI-guided systems have been developed, and are already active in a few French centres. Finally, after radiotherapy, imaging plays a major role in most patients’ monitoring, and must take into account post-radiation tissue modification specificities. In this review, we will focus on the ongoing projects of nuclear imaging in oncology, and how they can help the radiation oncologist to better treat patients. To this end, a literature review including the terms “Radiotherapy”, “Radiation Oncology” and “PET-CT” was performed in August 2019 on Medline and ClinicalTrials.gov. We chose to review successively these novelties organ-by-organ, focusing on the most promising advances. As a conclusion, the help of modern functional imaging thanks to a better definition and new specific radiopharmaceuticals tracers could allow even more precise treatments and enhanced surveillance. Finally, it could provide determinant information to artificial intelligence algorithms in “-omics” models.     

Toxicité et qualité de vie comparées après curiethérapie par iode 125 et radiothérapie stéréotaxique des cancers prostatiques

Quality of life is a major issue for good prognostic prostate cancer, for which brachytherapy is one of the reference treatments. Stereotactic Body Radiotherapy (SBRT) is a recent alternative however not yet validated as a standard treatment. This review of the literature reports and compares the toxicities and the quality of life, either after exclusive brachytherapy with iodine 125 or after SBRT. The comparison is made with the limitations of the absence of randomized trial comparing the two treatment techniques. Acute toxicity appears to be lower after SBRT compared to brachytherapy (from 10 to 40 % versus 30 to 40 %, respectively). Conversely, acute and late gastrointestinal toxicity (from 0 to 21 % and from 0 to 10 % of grade 2, respectively) appears more frequent with SBRT. Late urinary toxicity seems identical between both techniques (from 20 to 30 % of grade 2), with a possible urinary flare syndrome. Both treatments have an impact on erectile dysfunction, although it is not possible to conclude that a technique is superior because of the limited data on SBRT. SBRT has better bowel and urinary (irritation or obstruction) quality of life scores than brachytherapy; while sexual and urinary incontinence remain the same. The absence of randomized trial comparing SBRT with brachytherapy for prostate cancers does not allow to conclude on the superiority of one technique over another, thus justifying a phase III medicoeconomic evaluation.     

Radiation therapy for malignant pleural mesothelioma

The treatment of malignant pleural mesothelioma with radiation has always been a technical challenge. For many years, conventional radiation therapy was delivered after extrapleural pneumonectomy with acceptable results. Novel radiation treatment techniques, such as intensity modulated radiation therapy (IMRT) were introduced, but the early experience with IMRT demonstrated troubling toxicity. Recent reports from institutions have demonstrated that with greater experience, IMRT, both in the setting of extrapleural pneumonectomy or pleurectomy, can be delivered safely. A recent study, SAKK 17/04, questions the role of using radiation after extrapleural pneumonectomy.     

La radiothérapie externe guidée par l’imagerie dans le cancer de la prostate ; comment,quand et pourquoi ?

Novel techniques of prostate cancer radiotherapy require increased precision, which is allowed by Image Guided Radiation Therapy (IGRT), using fiducial markers and orthogonal radiographs, cone beam computed tomography, magnetic resonance imaging, ultrasound, and/or transponders. IGRT may reduce the toxicity of radiation therapy, but there is no clear recommendation on the best IGRT technique and how often it should be applied.     

Ultrasound-guided transrectal implantation of gold markers for prostate localization during external beam radiotherapy: complication rate and risk factors

PURPOSE: To report the complication rate and risk factors of transrectally implanted gold markers, used for prostate position verification and correction procedures. METHODS AND MATERIALS: In 209 consecutive men with localized prostate cancer, four gold markers (1 x 7 mm) were inserted under ultrasound guidance in an outpatient setting, and the toxicity was analyzed. All patients received a questionnaire regarding complications after marker implantation. The complications and risk factors were further evaluated by reviewing the medical charts. RESULTS: Of the 209 men, 13 (6.2%) had a moderate complication, consisting of pain and fever that resolved after treatment with oral medication. In 1.9% of the men, minor voiding complaints were observed. Other minor transient complications, defined as hematuria lasting >3 days, hematospermia, and rectal bleeding, occurred in 3.8%, 18.5%, and 9.1% of the patients, respectively. These complications were seen more often in patients with advanced tumor stage, younger age, and shorter duration of hormonal therapy. CONCLUSION: Transrectal gold marker implantation for high-precision prostate radiotherapy is a safe and well-tolerated procedure.