Locally recurrent prostate cancer after previous radiation therapy remains challenging. One of the curative options for these patients is salvage brachytherapy. There are no reports available on the ...use of a biodegradable rectal balloon implantation (RBI) in combination with brachytherapy in patients with recurrent prostate cancer after previous radiotherapy.
Here, we report on a patient with a local recurrence at five years after previous low-dose-rate brachytherapy with a prescribed dose of 145 Gray (Gy) for a low-risk prostate adenocarcinoma. The patient experienced grade 3 rectal toxicity, which was resolved at the time of local recurrence. He was treated with focal high-dose-rate (HDR) brachytherapy of 2 fr. × 13 Gy after RBI implantation. Four years post-salvage treatment, there was no evidence of biochemical recurrence according Phoenix definition, and no gastro-intestinal or genitourinary toxicity.
This case describes the use of RBI implantation in combination with a focal salvage HDR in a patient with recurrent disease, with significant initial grade 3 rectal toxicity after previous irradiation. The use of a biodegradable RBI proved to be a promising solution for such a patient; however, this method needs to be further investigated.
•CXB appears to be an efficacious technique for rectal cancer treatment and may allow rectal preservation in selected patients.•These GEC ESTRO ACROP recommendations recommend dose schemes in for ...rectal CXB.•These recommendations advise reporting of tumour depth to enable future refinement of dose prescription and target definition.•The routine collection and publication of outcome data including patient reported outcomes (PROs) is recommended.
To issue consensus recommendations for contact X-Ray brachytherapy (CXB) for rectal cancer covering pre-treatment evaluation, treatment, dosimetric issues and follow-up. These recommendations cover CXB in the definitive and palliative setting.
Members of GEC ESTRO with expertise in rectal CXB issued consensus-based recommendations for CXB based on literature review and clinical experience. Levels of evidence according to the Oxford Centre for Evidence based medicine guidance are presented where possible.
The GEC ESTRO ACROP consensus recommendations support the use of CXB to increase the chances of clinical complete remission and cure for patients who are elderly with high surgical risk, surgically unfit or refusing surgery. For palliative treatment, the use of CXB is recommended for symptomatic relief and disease control. The use of CXB in an organ-preservation setting in surgically fit patients is recommended within the setting of a clinical trial or registry.
The GEC ESTRO ACROP recommendations for CXB are provided. Recommendations towards standardisation of reporting and prescription are given. Practitioners are encouraged to follow these recommendations and to develop further clinical trials to examine this treatment modality and increase the evidence base for its use. The routine collection of outcomes both clinical and patient-reported is also encouraged.
To develop an approach to the diagnosis and treatment of prostate cancer using one platform for fusion biopsy, followed by focal gland ablation utilizing permanent prostate brachytherapy with and ...without a rectal spacer.
Prostate phantoms containing multiparametric magnetic resonance imaging (mpMRI) regions of interest (ROI) underwent fusion biopsy, followed by image co-registration of positive sites to a treatment planning brachytherapy program. A partial hemi-ablation and both posterior lobes using a Mick applicator and linked stranded seeds were simulated. Dummy sources were modeled as iodine-125 (
I) with a prescribed dose of at least 210 Gy to gross tumor (GTV) and clinical target volume (CTV), as defined by mpMRI visible ROI and surrounding negative biopsy sites. Computer tomograms (CT) were performed post-implant prior to and after rectal spacer insertion. Different prostate and rectal constraints were compared with and without the spacer.
The intra-operative focal volumes of CTV ranged from 6.2 to 14.9 cc (mean, 11.3 cc), and the ratio of focal volume/whole prostate volume ranged between 0.19 and 0.42 (mean, 0.31). The intra- and post-operative mean focal D
of GTV, CTV, and for the entire prostate gland was 265 Gy and 235 Gy, 214 Gy and 213 Gy, and 66.1 Gy and 57 Gy, respectively. On average, 13 mm separation was achieved between the prostate and the rectum (range, 12-14 mm) on post-operative CT. The mean doses in Gy to 2 cc of the rectum (D
) without spacer vs. with spacer were 39.8 Gy vs. 32.6 Gy, respectively.
Doses above 200 Gy and the implantation of seeds in clinically significant region for focal therapy in phantoms are feasible. All rectal dosimetric parameters improved for the spacer implants, as compared with the non-spacer implants. Further validation of this concept is warranted in clinical trials.
Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) scan is the standard imaging procedure for biochemical recurrent prostate cancer postprostatectomy ...because of its high detection rate at low serum prostate-specific antigen levels. However, existing guidelines for clinical target volume (CTV) in prostate bed salvage external beam radiation therapy (sEBRT) are primarily based on experience-based clinical consensus and have been validated using conventional imaging modalities. Therefore, this study aimed to optimize CTV definition in sEBRT by using PSMA PET/CT-detected local recurrences (LRs).
Patients with suspected LR on PSMA PET/CT postprostatectomy were retrospectively enrolled in 9 Dutch centers. Anonymized scans were centrally reviewed by an expert nuclear medicine physician. Each boundary of the CTV guideline from the Groupe Francophone de Radiothérapie en Urologie (GFRU) was evaluated and adapted to improve the accuracy and coverage of the area at risk of LR (CTV) on PSMA PET/CT. The proposed CTV adaptation was discussed with the radiation oncologists of the participating centers, and final consensus was reached. To assess reproducibility, the participating centers were asked to delineate 3 new cases according to the new PERYTON-CTV, and the submitted contours were evaluated using the Dice similarity coefficient (DSC).
After central review, 93 LRs were identified on 83 PSMA PET/CTs. The proposed CTV definition improved the coverage of PSMA PET/CT-detected LRs from 67% to 96% compared with the GFRU-CTV, while reducing the GFRU-CTV by 25%. The new CTV was highly reproducible, with a mean DSC of 0.82 (range, 0.81-0.83).
This study contributes to the optimization of CTV definition in postprostatectomy sEBRT by using the pattern of LR detected on PSMA PET/CT. The PERYTON-CTV is highly reproducible across the participating centers and ensures coverage of 96% LRs while reducing the GFRU-CTV by 25%.
Oligometastatic cancer is recognized as a separate entity within the spectrum of metastatic disease. It was suggested that patients with oligometastatic disease can obtain long-term survival by ...giving local ablative therapy (LAT) to all visible disease locations. However, the true extent from which metastatic cancer should be called "oligometastatic" is unknown, although a consensus definition for oligometastatic disease is proposed by research organizations, such as the EORTC (maximum of five metastases in three organs). Different states of the oligometastatic disease are defined, such as synchronous vs. metachronous, oligopersistent vs. oligoprogressive disease. All clinical trials including patients with non-small cell lung cancer (NSCLC) are small and most are not randomized. Two small randomized phase II trials on synchronous disease showed an improvement in progression free survival, with the addition of LAT, and one also demonstrated an overall survival benefit. Immune checkpoint inhibitors (ICI) were not part of the treatment in these trials, while ICI significantly improved long-term outcomes of patients with metastatic NSCLC. Radiotherapy might improve the prognosis of patients treated with ICI because of its immunostimulatory effects and the possibility to eradicate metastatic deposits. Here, we summarize the data for adding ablative radiotherapy to the treatment of oligometastatic NSCLC, especially in the ICI era, and discuss the challenges of combined treatment.
•Hyaluronic acid (HA) is an implantable rectum spacer used to decrease rectal radiation dose in prostate cancer radiotherapy.•Hyaluronidase (HAS) is an enzyme that degrades HA, when wrongly ...positioned.•A ratio of HA:HAS of 1:2 has already a decrease of half of volume on the 2nd day.
To determine a dose response relationship of disintegration of a hyaluronic acid (HA) and hyaluronidase (HAS) used in prostate cancer radiotherapy.
Five in-vitro models are applicated with 3 ml (ml) HA. For dissolution varying doses of HAS were used: 6 ml, 3 ml, 1.5 ml, and 0 ml. One ml contains 150 International Units (IU). Each HAS was added with saline till the complementary amount of 6 ml. One phantom was solely implanted with a HA 3 ml acting as a control. Length, width and height were measured on different time points: 1st day 4 times, 2nd day 3 times, third day 2 times, and then once daily during one week, with a final measurement 2 weeks after implantation. The experiments were performed in duplicate to exclude variations and confirm the results.
The fastest dissolution was observed with the highest concentration of HAS, already observed at the first time point 2 h after implantation, with volume decrease of 50% on the second day, and less than 1 ml residue (33%) on day 4. The 2 other concentrations of HAS also showed a volume decrease, with less than 2 ml (66%) on day 4. All the applied quantities of HAS are observed with a residue of less than 1 ml after 7 days. After 14 days the control phantom and the saline filled one remains on steady state volume (3 ml).
A dose response was observed by HAS injection: highest volumes of HAS dissolute most swiftly. Using a ratio of HA:HAS of 1:2 results in a decrease to half of initial volume within 24 h. This is of special interest when used in clinical practice following erroneous positioning, and dissolution is urgently needed.
About 50% of non-small cell lung cancer (NSCLC) patients have metastatic disease at initial diagnosis, which limits their treatment options and, consequently, the 5-year survival rate (15%). Immune ...checkpoint inhibitors (ICI), either alone or in combination with chemotherapy, have become standard of care (SOC) for most good performance status patients. However, most patients will not obtain long-term benefit and new treatment strategies are therefore needed. We previously demonstrated clinical safety of the tumour-selective immunocytokine L19-IL2, consisting of the anti-ED-B scFv L19 antibody coupled to IL2, combined with stereotactic ablative radiotherapy (SABR).
This investigator-initiated, multicentric, randomised controlled open-label phase II clinical trial will test the hypothesis that the combination of SABR and L19-IL2 increases progression free survival (PFS) in patients with limited metastatic NSCLC. One hundred twenty-six patients will be stratified according to their metastatic load (oligo-metastatic: ≤5 or poly-metastatic: 6 to 10) and randomised to the experimental-arm (E-arm) or the control-arm (C-arm). The C-arm will receive SOC, according to the local protocol. E-arm oligo-metastatic patients will receive SABR to all lesions followed by L19-IL2 therapy; radiotherapy for poly-metastatic patients consists of irradiation of one (symptomatic) to a maximum of 5 lesions (including ICI in both arms if this is the SOC). The accrual period will be 2.5-years, starting after the first centre is initiated and active. Primary endpoint is PFS at 1.5-years based on blinded radiological review, and secondary endpoints are overall survival, toxicity, quality of life and abscopal response. Associative biomarker studies, immune monitoring, CT-based radiomics, stool collection, iRECIST and tumour growth rate will be performed.
The combination of SABR with or without ICI and the immunocytokine L19-IL2 will be tested as 1st, 2nd or 3rd line treatment in stage IV NSCLC patients in 14 centres located in 6 countries. This bimodal and trimodal treatment approach is based on the direct cytotoxic effect of radiotherapy, the tumour selective immunocytokine L19-IL2, the abscopal effect observed distant from the irradiated metastatic site(s) and the memory effect. The first results are expected end 2023.
ImmunoSABR Protocol Code: NL67629.068.18; EudraCT: 2018-002583-11; Clinicaltrials.gov: NCT03705403; ISRCTN ID: ISRCTN49817477; Date of registration: 03-April-2019.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective: The purpose of this review was to summarize the current literature on the assessment and treatment of radiation urethritis and cystitis (RUC) for the development of an evidenced-based ...management algorithm. Material and Methods: The PubMed/MEDLINE database was searched by a multidisciplinary group of experts in January 2021. Results: In total, 48 publications were identified. Three different types of RUC can be observed in clinical practice: inflammation-predominant, bleeding-predominant, and the combination of inflammation- and bleeding-RUC. There is no consensus on the optimal treatment of RUC. Inflammation-predominant RUC should be treated symptomatically based on the existence of bothersome storage or voiding lower urinary tract symptom as well as on pain. When bleeding-predominant RUC has occurred, hydration and hyperbaric oxygen therapy (HOT) should be used first and, if HOT is not available, oral drugs instead (sodium pentosane polysulfate, aminocaproic acid, immunokine WF 10, conjugated estrogene, or pentoxifylline + vitamin E). If local bleeding persists, focal therapy of bleeding vessels with a laser or electrocoagulation is indicated. In case of generalized bleeding, intravesical installation should be initiated (formalin, aluminium salts, and hyaluronic acid/chondroitin). Vessel embolization is a less invasive treatment with potentially less complications and good clinical outcomes. Open- or robot-assisted surgery is indicated in patients with permanent, life-threatening bleeding, or fistulae. Conclusions: Treatment of RUC, if not self-limiting, should be done according to the type of RUC and in a stepwise approach. Conservative/medical treatment (oral and topic agents) should primarily be used before invasive (transurethral) treatments.
•Radiotherapy in patients with inflammatory bowel disease remains controversial.•A biodegradable balloon is inserted between the prostate and the rectal wall.•The balloon pushes the anterior rectal ...wall outside of the high-dose area.•No grade 3 or more rectal toxicities were observed.
Prostate cancer radiotherapy (RT) in patients with (active) inflammatory bowel disease (IBD) remains controversial. We hypothesized that RT in combination with a biodegradable prostate-rectum spacer balloon implantation, might be a safe treatment approach with acceptable toxicities for these high risk for rectal toxicity patients.
We report on a small prospective mono-centric series of 8 patients with all-risk prostate cancer with the comorbidity of an IBD. Four patients had Crohn’s disease and 4 patients had ulcerative colitis. One out of four had an active status of IBD. All patients were intended to be treated with curative high-dose RT: 5 patients were treated with external beam RT (70 Gray (Gy) in 28 fractions), and 3 patients were treated with 125I-implant (145 Gy). Toxicities were scored according to the CTCAE v4.03: acute side effects occur up to 3 months after RT, and late side effects start after 3 months.
Median follow-up was 13 months (range: 3–42 months). Only one acute grade 2 gastro-intestinal (GI) toxicity was observed: an increased diarrhea (4–6 above baseline) during RT, which resolved completely 6 weeks after treatment. No late grade 3 or more GI toxicity was reported, and no acute and late grade ≥2 genitourinary toxicity events were observed.
Prostate cancer patients with IBD are a challenge to treat with RT. Our results suggest that RT in combination with a balloon implant in selective patients with (active) IBD may be promising, however additional validation is needed.
The various rectal endoluminal radiation techniques all have steep, but different, dose gradients. In rectal contact brachytherapy (CXB) doses are typically prescribed and reported to the applicator ...surface and not to the gross tumor volume (GTV), clinical target volume (CTV) or organs at risk (OAR), which is crucial to understand tumor response and toxicity rates. To quantify the above-described problem, we performed a dose modeling study using a fixed prescription dose at the surface of the applicator and varied tumor response scenarios.
Endorectal ultrasound-based 3D-volume-models of rectal tumors and the rectal wall were used to simulate the delivered dose to GTV, CTV and the rectal wall layers, assuming treatment with Maastro HDR contact applicator for rectal cancer with a fixed prescription dose to the applicator surface (equivalent to 3 × 30 Gy CXB) and various response scenarios.
An identical prescribed dose to the surface of the applicator resulted in a broad range of doses delivered to the GTV, CTV and the uninvolved intestinal wall. For example, the equieffective dose in 2 Gy per fraction (EQD2) D90% of the GTV varied between 63 and 231 Gy, whereas the EQD2 D2cc of the rectal wall varied between 97 and 165 Gy.
Doses prescribed at the surface are not representative of the dose received by the tumor and the bowel wall. This stresses the relevance of dose reporting and prescription to GTV and CTV volumes and OAR in order to gain insight between delivered dose, local control and toxicity and to optimize treatment protocols.
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