Alterations of Sexual and Erectile Functions after Brachytherapy for Prostate Cancer Based on Patient-Reported Questionnaires.

The aim of the study was to compare the side effects of high-dose-rate brachytherapy (HDRBT) and low-dose-rate brachytherapy (LDRBT), with a particular focus on the effects on sexual functions and sexual well-being (PROMOBRA study, NCT02258087). Localized low-risk and low-intermediate-risk prostate cancer patients were treated with mono LDR (N = 123, 145 Gy dose) or mono HDR brachytherapy (N = 117, 19/21 Gy). Prior to the treatment and during follow-up (at 3, 6, 9, 12, 18, and 24 months after treatment, and then annually after two years), patients completed patient-reported outcome measurement (PROM) questionnaires EORTC QLQ-PR-25, International Index of Erectile Function (IIEF), and IIEF-5 (SHIM). We compared the patients in different group breakdowns (HDR vs. LDR, hormone naïve and hormone-receiving HDR vs. LDR, hormone naïve and hormone-receiving patients in general, and 19 Gy HDR vs. 21 Gy HDR). In the hormone-naive LDR group, erectile function, orgasm function, sexual desire, satisfaction with intercourse, and overall satisfaction functions significantly decreased compared to baseline throughout the whole follow-up period. However, there were significant decreases in function at a maximum of three time points after HDR therapy without hormone therapy. In hormone-receiving patients, the orgasm function was significantly better in the HDR group at multiple time points compared to the baseline, and sexual desire improved at four time points. According to our results, both LDRBT and HDRBT can be safely administered to patients with localized prostate cancer. In hormone-naive patients, the HDR group showed only recovering decreases in sexual functions, while the LDR group showed a lasting decline in multiple areas. Thus, HDR appears to be more advantageous to hormone-naive patients.

Prostate Cancer Survivors Present Long-Term, Residual Systemic Immune Alterations.

BACKGROUND: The development of cancer and anti-tumor therapies can lead to systemic immune alterations but little is known about how long immune dysfunction persists in cancer survivors. METHODS: We followed changes in the cellular immune parameters of prostate cancer patients with good prognostic criteria treated with low dose rate brachytherapy before and up to 3 years after the initiation of therapy. RESULTS: Patients before therapy had a reduced CD4+ T cell pool and increased regulatory T cell fraction and these alterations persisted or got amplified during the 36-month follow-up. A significant decrease in the total NK cell number and a redistribution of the circulating NK cells in favor of a less functional anergic subpopulation was seen in patients before therapy but tumor regression led to the regeneration of the NK cell pool and functional integrity. The fraction of lymphoid DCs was increased in patients both before therapy and throughout the whole follow-up. Increased PDGF-AA, BB, CCL5 and CXCL5 levels were measured in patients before treatment but protein levels rapidly normalized. CONCLUSIONS: while NK cell dysfunction recovered, long-term, residual alterations persisted in the adaptive and partly in the innate immune system.

Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma.

PURPOSE: Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.1% vs 7.9%, P = .045), and more patients achieved R0 resections (77.0% vs 64.0%, P = .042). These are the toxicity and health-related quality of life (HRQoL) results. METHODS AND MATERIALS: Act.In.Sarc randomized eligible patients 1:1 to either NBTXR3 (single intratumoral injection, volume equivalent to 10% of baseline tumor volume, at 53.3 g/L) activated by external-beam RT (arm A) or external-beam RT alone (arm B) (50 Gy in 25 fractions), followed by surgery in both arms. Here, we report the safety analyses in the all-treated population with a long-term follow-up of at least 2 years, and HRQoL in the intention-to-treat full analysis set. RESULTS: During the on-treatment period, serious adverse events (SAEs) of all grades related to NBTXR3 occurred in 10.1% (9/89) of patients (arm A), and SAEs related to RT occurred in 5.6% (5/89) (arm A) versus 5.6% (5/90) (arm B); postsurgery hospitalization owing to SAEs occurred in 15.7% (14/89) (arm A) versus 24.4% (22/90) (arm B). During the follow-up period, posttreatment SAEs (regardless of relationship) occurred in 13.5% (12/89) (arm A) versus 24.4% (22/90) (arm B). NBTXR3 did not negatively affect HRQoL; during the follow-up period, there was an improvement in most mean Toronto extremity salvage, EuroQoL 5-dimension (EQ-5D), EQ5D02-EQ visual analog scale, reintegration to normal living index, and musculoskeletal tumor rating scale scores. CONCLUSIONS: NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit-risk ratio of NBTXR3 plus RT.

The value of brachytherapy in the age of advanced external beam radiotherapy: a review of the literature in terms of dosimetry.

Brachytherapy (BT) has long been used for successful treatment of various tumour entities, including prostate, breast and gynaecological cancer. However, particularly due to advances in modern external beam techniques such as intensity-modulated radiotherapy (IMRT), volume modulated arc therapy (VMAT) and stereotactic body radiotherapy (SBRT), there are concerns about its future. Based on a comprehensive literature review, this article aims to summarize the role of BT in cancer treatment and highlight its particular dosimetric advantages. The authors conclude that image-guided BT supported by inverse dose planning will successfully compete with high-tech EBRT in the future and continue to serve as a valuable modality for cancer treatment.

The first experience in Hungary with split-course multimodal treatment in high risk bladder cancer / Az osztott dózisú trimodális kezelés elso hazai alkalmazása nagy kockázatú húgyhólyagdaganat esetében.

Összefoglaló. Az izominvazív vagy nagyon nagy kockázatú, felületes hólyagdaganatok kezelésének arany standardja a radikális húgyhólyag-eltávolítás (cystectomia). Válogatott betegek esetében hasonló hatékonyságú kezelés lehet az osztott dózisú (split-course) trimodális terápia, az endoszkópos tumorreszekció és a kemoirradiáció megszakított ciklusokkal történo alkalmazása. A split-course trimodális terápia a radikális cystectomiához hasonló eredményességu, a késobbi életminoség szempontjából pedig ígéretes kezelési lehetoség lehet megfeleloen kiválasztott betegek esetében. Hazánkban elso alkalommal végzett kezelést ismertetünk a téma szakirodalmi áttekintése mellett. A húgyhólyagtumor transurethralis reszekciója, maximális eradikációja után kemoirradiáció kezdodik, melyet 45 Gy sugárdózis elérésekor ismételt szövettani mintavétel szakít meg. Negatív szövettani eredmény esetén a megkezdett terápia a teljes dózis eléréséig folytatandó. Amennyiben a reszekció során élo tumor észlelheto, a radikális mutét elvégzése javasolt. A korábban transurethralis daganatreszekción négyszer átesett 54 éves beteg lokális immunterápia utáni recidívájának szövettana pT1, 'high grade' urothelialis carcinoma volt. A jól informált, kiváló fizikális statusú beteg kérését figyelembe véve split-course trimodális kezelést végeztünk. Negatív 'staging' vizsgálatok után maximális endoszkópos reszekció, majd kemoirradiáció következett. A 45 Gy besugárzás elérésekor elvégzett ismételt mintavétel azonnal feldolgozott szövettana negatív eredményt mutatott, így késedelem nélkül folytatódott a kemoirradiációs kezelés. Az eddigi kontrollvizsgálatok alapján a beteg komplett remisszióban van. A split-course trimodális terápia a radikális hólyageltávolítás megfelelo alternatívája jól informált, gondosan megválogatott betegek esetében. A szervmegtartó eljárás jobb életminoséget eredményezhet, ugyanakkor a beteget feltétlenül tájékoztatni kell, hogy sikertelenség esetén a radikális mutét is szükségessé válhat. A kezelés sikeres menedzselése csak a társszakmák szoros, jól tervezett együttmuködésével lehetséges. Orv Hetil. 2021; 162(50): 2017-2022. Summary. While radical cystectomy remains the gold standard to treat muscle-invasive or very high risk superficial bladder cancer, well selected patients can be offered split-course multimodal treatment as a similarly effective alternative, combining endoscopic tumor resection and split-course chemoradiotherapy. In highly selected patients, split-course trimodality therapy can lead to survival rates comparable to radical cystectomy with better quality of life outcomes. We present our experience with split-course trimodality treatment used for the very first time in Hungary. Maximal transurethral resection of bladder neoplasm is followed by chemoradiotherapy with repeated bladder biopsy after 45 Gy of irradiation. With negative biopsy results, chemoirradiation should be continued until full dose given. Salvage cystectomy is recommended if viable tumor is detected. Our patient (54), who previously underwent four transurethral bladder tumor resections and local immunotherapy, presented with pT1, high grade urothelial carcinoma recurrence. The well-informed, high performance status patient opted for split-course trimodality treatment. After negative staging scan results, the patient underwent complete endoscopic tumor eradication, followed by chemoradiotherapy. After 45 Gy of irradiation, repeated bladder biopsy was performed. The immediate histopathological examination found no viable tumor, therefore chemoradiotherapy was completed. Follow-up examinations suggest our patient in complete remission. Split-course trimodality treatment can be offered to well-informed and selected patients as a reasonable alternative to radical cystectomy. Though the bladder-sparing approach results in better quality of life, patients must know that in the case of treatment failure, radical cystectomy will likely be offered. Excellent multidisciplinary cooperation is a key to conduct this treatment alternative successfully. Orv Hetil. 2021; 162(50): 2017-2022.

[Trimodal, organ-preserving treatment of organ-confined, muscle-invasive bladder cancer]. / Szervre lokalizált, izominvazív húgyhólyagrák trimodális, szervmegtartó kezelése.

Radical cystectomy is the gold standard treatment in localized muscle-invasive bladder cancer according to today's guidelines. However, in many cases, surgery is not possible due to the patient's general condition, or the patient refuses bladder removal. In such cases, as well as in some selected patients suitable for surgery, trimodal organ preservation therapy is an alternative, which provides the patient with similar survival, local tumor control, so that 80% of patients retain their bladder. In some cases, due to complications or a muscle-invasive local recurrence in the bladder, the bladder may not be retained. At this point, a salvage cystectomy can still save the patient's quality of life and life. Adequate patient selection is a prerequisite for effective trimodal therapy. We summarize the components of organ-preserving treatment, including radiation therapy, its state-of-the-art technology, results and side effects. The results and toxicity of trimodal treatment are compared with those of radical cystectomy.

Relationship between biodosimetric parameters and treatment volumes in three types of prostate radiotherapy.

Brachytherapy (BT) and external beam radiotherapy (EBRT) apply different dose rates, overall treatment times, energies and fractionation. However, the overall impact of these variables on the biological dose of blood is neglected. As the size of the irradiated volume influences the biological effect as well, we studied chromosome aberrations (CAs) as biodosimetric parameters, and explored the relationship of isodose surface volumes (ISVs: V1%, V1Gy, V10%, V10Gy, V100%, V150%) and CAs of both irradiation modalities. We performed extended dicentrics assay of lymphocytes from 102 prostate radiotherapy patients three-monthly for a year. Aberration frequency was the highest after EBRT treatment. It increased after the therapy and did not decrease significantly during the first follow-up year. We showed that various types of CAs 9 months after LDR BT, 3 months after HDR BT and in a long time-range (even up to 1 year) after EBRT positively correlated with ISVs. Regression analysis confirmed these relationships in the case of HDR BT and EBRT. The observed differences in the time points and aberration types are discussed. The ISVs irradiated by EBRT showed stronger correlation and regression relationships with CAs than the ISVs of brachytherapy.

Early effects of different irradiation techniques used in the treatment of prostate cancer on urination / A prosztatarák kezelésében alkalmazott besugárzási technikák vizelési képességre gyakorolt korai hatása.

Összefoglaló. Bevezetés: A prosztatarák kezelésében jelentos szerepet kapnak a különbözo sugárterápiás eljárások. Ennek ellenére a vizelési képességre gyakorolt, rövid és hosszú távú mellékhatásaikat objektív vizsgálómódszerrel igen kevés tanulmányban vizsgálták. Célkituzés: Arra a kérdésre kerestük a választ, hogy hogyan változik a korai vizelési képesség a különbözo sugárterápiás eljárások során. Módszerek: A vizsgálatunkban meghatározott protokoll szerint a kezelés elott minden bevont beteggel IPSS-t (nemzetközi prosztatatünet-értékelo lap) töltettünk ki, illetve uroflow (vizeletáramlási) vizsgálatot végeztünk, suprapubicus ultrahanggal meghatározott mictiós residuum méréssel kiegészítve. A sugárkezelés befejezésétol számított 4-6 héten belül ismételten elvégeztük ezeket a vizsgálatokat, melyekbe összesen 26 beteget vontunk be. A kezelési modalitások szerint 6, kis dózisteljesítményu (low-dose rate; LDR) brachytherapiában, 5, nagy dózisteljesítményu (high-dose rate; HDR) brachytherapiában, 12, Cyberknife (CK) készüléken extrém hipofrakcionált sugárkezelésben és 3, lineáris gyorsítón (LINAC) mérsékelten hipofrakcionált sugárkezelésben részesített prosztatarákos beteget választottunk be. A kezelések hasonlósága miatt az LDR- és a HDR-csoportot együttesen brachytherapiás csoportként (BTCS), a CK- és a LINAC-csoportot teleterápiás csoportként (TTCS) vizsgáltuk. Eredmények: A BTCS betegeinél az IPSS- és az uroflow paraméterek korai romlása (IPSS irritatív panaszok: p = 0,003, IPSS obstruktív panaszok: p = 0,011, maximális áramlás: p = 0,003, átlagos áramlás: p = 0,006) szignifikánsnak bizonyult, a TTCS-ban mindösszesen az IPSS irritatív tünetekben volt kimutatható eltérés (p = 0,011). Következtetés: A sugárterápiás modalitás kiválasztása elott javasolható az uroflow és az IPSS-vizsgálat elvégzése. Eredményeink alapján azoknál a betegeknél, akiknél a kezelés elott középsúlyos vagy súlyos dysuriás vizelési panaszok állnak fenn, a brachytherapia helyett teleterápiás módszerek alkalmazását javasoljuk, amelyek kevésbé rontják a betegek korai vizeletürítési képességét. Orv Hetil. 2021; 162(33): 1328-1334. INTRODUCTION: Various radiotherapy procedures are applied in the treatment of prostate cancer. Nevertheless, their early and late side effects measured by uroflow and residual volume measurements have not been studied extensively. OBJECTIVE: We investigated by objective methods the early changes of urination ability after different radiotherapy procedures. METHODS: According to the protocol defined in our study, all patients had their IPSS (international prostate symptom score) determined, as well as their uroflow examinations and measurements of their residual urine via suprapubic ultrasound, carried out before treatment. These tests were then repeated at 4-6 weeks after the end of their radiotherapy. A total of 26 patients were included in the study. 6 patients were treated with low-dose rate (LDR) brachytherapy and 5 patients with high-dose rate (HDR) brachytherapy, 12 patients with Cyberknife (CK) using extreme hypofractionation and 3 patients with moderately hypofractionated radiotherapy with a linear accelerator (LINAC). Due to the similarity of the treatments, the LDR and HDR groups together were also studied as brachytherapy group and the CK and LINAC patients as teletherapy group. RESULTS: We found that the early deterioration of IPSS and uroflow parameters after brachytherapy were significant (IPSS irritative symptoms: p = 0.003, IPSS obstructive symptoms: p = 0.011, maximum flow: p = 0.003, mean flow: p = 0.006), while in teletherapy only the IPSS irritative symptoms worsened significantly (p = 0.011). CONCLUSION: Based on our results, we suggest to perform uroflow examination and IPSS test before selecting therapeutic modality for patients with prostate cancer. In patients with moderate or severe urinary complaints before the treatment, we recommend to use teletherapy rather than brachytherapy. Orv Hetil. 2021; 162(33): 1328-1334.

Comparative dosimetrical analysis of intensity-modulated arc therapy, CyberKnife therapy and image-guided interstitial HDR and LDR brachytherapy of low risk prostate cancer.

BACKGROUND: The objective of the study was to dosimetrically compare the intensity-modulated-arc-therapy (IMAT), Cyber-Knife therapy (CK), single fraction interstitial high-dose-rate (HDR) and low-dose-rate (LDR) brachytherapy (BT) in low-risk prostate cancer. MATERIALS AND METHODS: Treatment plans of ten patients treated with CK were selected and additional plans using IMAT, HDR and LDR BT were created on the same CT images. The prescribed dose was 2.5/70 Gy in IMAT, 8/40 Gy in CK, 21 Gy in HDR and 145 Gy in LDR BT to the prostate gland. EQD2 dose-volume parameters were calculated for each technique and compared. RESULTS: EQD2 total dose of the prostate was significantly lower with IMAT and CK than with HDR and LDR BT, D90 was 79.5 Gy, 116.4 Gy, 169.2 Gy and 157.9 Gy (p < 0.001). However, teletherapy plans were more conformal than BT, COIN was 0.84, 0.82, 0.76 and 0.76 (p < 0.001), respectively. The D2 to the rectum and bladder were lower with HDR BT than with IMAT, CK and LDR BT, it was 66.7 Gy, 68.1 Gy, 36.0 Gy and 68.0 Gy (p = 0.0427), and 68.4 Gy, 78.9 Gy, 51.4 Gy and 70.3 Gy (p = 0.0091) in IMAT, CK, HDR and LDR BT plans, while D0.1 to the urethra was lower with both IMAT and CK than with BTs: 79.9 Gy, 88.0 Gy, 132.7 Gy and 170.6 Gy (p < 0.001). D2 to the hips was higher with IMAT and CK, than with BTs: 13.4 Gy, 20.7 Gy, 0.4 Gy and 1.5 Gy (p < 0.001), while D2 to the sigmoid, bowel bag, testicles and penile bulb was higher with CK than with the other techniques. CONCLUSIONS: HDR monotherapy yields the most advantageous dosimetrical plans, except for the dose to the urethra, where IMAT seems to be the optimal modality in the radiotherapy of low-risk prostate cancer.

Acute side effects after definitive stereotactic body radiation therapy (SBRT) for patients with clinically localized or locally advanced prostate cancer: a single institution prospective study.

BACKGROUND: The aim of the study was to evaluate acute side effects after extremely hypofractionated intensity-modulated radiotherapy (IMRT) with stereotactic body radiation therapy (SBRT) for definitive treatment of prostate cancer patients. PATIENTS AND METHODS: Between February 2018 and August 2019, 205 low-, intermediate- and high-risk prostate cancer patients were treated with SBRT using "CyberKnife M6" linear accelerator. In low-risk patients 7.5-8 Gy was delivered to the prostate gland by each fraction. For intermediate- and high-risk disease a dose of 7.5-8 Gy was delivered to the prostate and 6-6.5 Gy to the seminal vesicles by each fraction with a simultaneous integrated boost (SIB) technique. A total of 5 fractions (total dose 37.5-40 Gy) were given on every second working day. Acute radiotherapy-related genitourinary (GU) and gastrointestinal (GI) side effects were assessed using Radiation Therapy Oncology Group (RTOG) scoring system. RESULTS: Of the 205 patients (28 low-, 115 intermediate-, 62 high-risk) treated with SBRT, 203 (99%) completed the radiotherapy as planned. The duration of radiation therapy was 1 week and 3 days. The frequencies of acute radiotherapy-related side effects were as follows: GU grade 0 - 17.1%, grade I - 30.7%, grade II - 50.7%, grade III - 1.5%; and GI grade 0 - 62.4%, grade I-31.7%, grade II-5.9%, grade III-0%. None of the patients developed grade ≥ 4 acute toxicity. CONCLUSIONS: SBRT with a total dose of 37.5-40 Gy in 5 fractions appears to be a safe and well tolerated treatment option in patients with prostate cancer, associated with slight or moderate early side effects. Longer follow-up is needed to evaluate long-term toxicity and biochemical control.

Extracorporeal irradiation: biological reconstruction following tumor resection with a large bone defect / Extracorporalis irradiatio: nagy csontdefektussal járó tumorresectiót követo biológiai rekonstrukció.

Összefoglaló. A malignus csonttumorok sebészi ellátása során kialakuló szegmentális csontdefektusok pótlása fontos szempont a végtagmegtartó sebészetben. Felnottkorban a megoldás rendszerint tumorprotézis beültetése, 10 évesnél fiatalabb gyermekeknél azonban ez nehezen alkalmazható módszer a kis csontméret és az igen magas várható szövodményarány miatt. A bemutatott, hazánkban még ritkán alkalmazott beavatkozás, a tumoros csontszegmentum mutét alatti sugárkezelése, visszaültetése megfelelo rekonstrukciós lehetoség a végtag funkciójának megtartása mellett, csökkentve a késobbi reoperációk, protézisrevíziók számát. Célkituzés: A hazánkban eddig az ismertetett módon végzett mutétek bemutatása, az eredmények összevetése nemzetközi irodalmi adatokkal. Módszer: Magyaroszágon eddig 12 alkalommal végeztünk végtagmegtartó mutétet malignus csonttumor miatt 12 évesnél fiatalabb gyermekeknél, és e mutétek során biológiai rekonstrukciós módszerként extracorporalis irradiatiót, autograft-reimplantatiót (ECRT, ECI) végeztünk. A mutétek mindegyike primer malignus csonttumor (Ewing-sarcoma 7 esetben, osteosarcoma 4 esetben, chondrosarcoma 1 esetben) miatt történt. Betegeink átlagéletkora 9 (3-12) év volt, az átlagos utánkövetési ido 32,5 (2-73) hónap. A felmérés során fizikális vizsgálat, valamint minden alkalommal röntgenfelvételek készítése történt, szükség esetén szövettani mintavétellel, vérelemzéssel vagy egyéb képalkotással kiegészítve. Eredményeinket nemzetközi irodalmi adatokkal hasonlítottuk össze. Eredmények: Lokális tumorkiújulást egyetlen esetben sem észleltünk, másik csontot érinto skip ('ugró') metastasis miatt egy alkalommal amputatiót végeztünk. A szövodmények tekintetében eredményeink megfelelnek a nemzetközi irodalomban leírtaknak. Két esetben jelentkezett szeptikus szövodmény (16,7%). A resectiós sík radiológiai átépülése 3-9 hónap alatt történt meg az esetek 60%-ában. Álízület, grafttörés, graft részleges elhalása miatt 3 esetben végeztünk reoperációt, kétszer újabb allograft felhasználásával, egy esetben pedig tumorprotézis beültetésével. Betegeink szubjektív véleménye a módszerrol pozitív, a legtöbb esetben megorizték jó fizikai aktivitásukat, az esetleges reoperációk ellenére végtagjukat terhelik, akár sporttevékenységet is végeznek. Következtetések: Vizsgálatunk alapján az extracorporalis irradiatio hasznos biológiai rekonstrukciós módszer 12 évesnél fiatalabb gyermekek esetében szegmentális csontdefektusok pótlására tumoros indikációval. A felmerülo szövodmények aránya alatta marad a hasonló korban beültetett tumorprotézisek szövodményarányainak, ideális esetben pedig több, további kiterjesztett mutét elkerülheto vele. Szövodmény esetén a késobbiekben tumorprotézis-beültetés mint végtagmegtartó vészmegoldás még mindig elvégezheto. Orv Hetil. 2020; 161(45): 1914-1919. INTRODUCTION: Reconstruction of massive segmental bone defects is a crucial point of limb salvage surgeries after malignant bone tumor resections. Megaendoprostheses implantation is a commonly used method for adult patients, but hardly usable for children below 12 years old, because of the small size of the host bone and multiple mechanic complications. OBJECTIVE: Extracorporeal irradiation and allograft reimplantation (ECRT, ECI) are promising methods for these young children for limb salvage, reducing the number of prostheses revisions, reoperations. METHOD: In Hungary, we performed limb salvage surgery for malignant bone tumor in 12 cases in children under 12 years old, using extracorporeally irradiated autografts as biological reconstruction. All cases were primary bone tumors (Ewing's sarcoma: 7, osteosarcoma: 4, chondrosarcoma: 1). The average age of our patients was 9 (3-12) years, the average follow-up was 32.5 (2-73) months. At follow-up, we performed physical examination, X-ray, and other imaging methods if they were necessary. Our results were compared to international publications. RESULTS: We observed no local recurrence, but in one case we had to perform above-knee amputation, due to a skip metastasis in the proximal tibia. The complication rates were similar to those reported in other papers. Septic complications were treated in two cases (16.7%). Total union of the resection lines was observed at 3-9 months in 60% of all cases. Reoperations were performed due to nonunion, or allograft fracture/partly desorganization in 3 cases, twice with new allograft, and with prostheses in one case. The subjective opinion of our patients is positive, they walk with full weightbearing, some of them do even light sporting activities. CONCLUSIONS: We found extracorporeal irradiation a useful and safe method for children under 12 years old for biological reconstruction after malignant bone tumor resection. Complication rate stays under the rate of growing prostheses complications, in optimal cases further radical, and extensive surgeries may be avoided. In the case of major complications, megaendoprostheses implantation later on is still an option as salvage procedure with limb salvage. Orv Hetil. 2020; 161(45): 1914-1919.

Biological dose summation of intensity-modulated arc therapy and image-guided high-dose-rate interstitial brachytherapy in intermediate- and high-risk prostate cancer.

PURPOSE: To present an alternative method for summing biologically effective doses of intensity-modulated arc therapy (IMAT) as teletherapy (TT), with interstitial high-dose-rate (HDR) brachytherapy (BT) boost in prostate cancer. Total doses using IMAT boost was compared with BT boost using our method. MATERIAL AND METHODS: Initially, 25 IMAT TT plus interstitial HDR-BT plans were included, and additional plans using IMAT TT boost were created. The prescribed dose was 2/44 Gy to the whole pelvis, 2/60 Gy to the prostate and seminal vesicles, and 1 × 10 Gy BT or 2/18 Gy IMAT TT to the prostate. Teletherapy computed tomography (CT) was registered with ultrasound (US) of BT, and the most exposed volume of critical organs in BT were identified on these CT images. The minimal dose of these from IMAT TT was summed with their BT dose, and these EQD2 doses were compared using BT vs. IMAT TT boost. This method was compared with uniform dose conception (UDC). RESULTS: D90 of the prostate was significantly higher with BT than with IMAT TT boost: 99.3 Gy vs. 77.9 Gy, p = 0.0034. The D2 to rectum, bladder, and hips were 50.3 Gy vs. 76.8 Gy (p = 0.0117), 64.7 Gy vs. 78.3 Gy (p = 0.0117), and 41.9 Gy vs. 50.6 Gy (p = 0.0044), while D0.1 to urethra was 96.1 Gy vs. 79.3 Gy (p = 0.0180), respectively. UDC overestimated D2 (rectum) by 37% (p = 0.0117), D2 (bladder) by 5% (p = 0.0214), and underestimated D0.1 (urethra) by 1% (p = 0.0277). CONCLUSIONS: Based on our biological dose summation method, the total dose of prostate is higher using BT boost than the IMAT. BT boost yields lower rectum, bladder, and hips doses, but higher dose to urethra. UDC overestimates rectum and bladder dose and underestimates the dose to urethra.

Normal tissue sparing using different techniques for prostate irradiation.

AIM: The aim of this study was to investigate normal tissue sparing through dosimetric parameters of normal tissue volumes using different irradiation techniques for conventional (CFRT) and simultaneously integrated boost (SIB) schedules. BACKGROUND: Several dose-escalation studies for localized prostate cancer (PCa) have shown advanced biochemical relapse-free (bRFS) rates and also better local control for higher total doses using either CFRT or SIB schedules. Besides the most important organs-at-risk, absorbed dose reduction of other surrounding normal tissues are also preferable. In order to analyse the normal tissue sparing, dosimetric parameters of different normal tissue volumes were examined. MATERIALS AND METHODS: Treatment plans for 15 high risk prostate cancer patients were created using RapidArc (RA), Sliding Window (SW) IMRT and 4-field box (3D-CRT) technique. In order to evaluate normal tissue sparing, the volume of pelvic region was divided into six normal tissue cylinders with 1 cm wall thickness, located in each other. RESULTS: All plans met the criteria of target coverage (V95%>95%). All techniques provided the same results for OARs except 3D-CRT for rectum and bilateral femoral heads. The values of V5, V10 and V15 increased in cases which included RapidArc technique and decreased for V20 and V30. CONCLUSIONS: The dosimetric parameters for the cylindrical normal tissue volumes show that using RapidArc technique gives equal or slightly better normal tissue sparing and SIB provided the same normal tissue sparing as CFRT planned with RapidArc.

Acute and Late Toxicity after Moderate Hypofractionation with Simultaneous Integrated Boost (SIB) Radiation Therapy for Prostate Cancer. A Single Institution, Prospective Study.

ASBTRACT: To evaluate the acute and late toxicity using moderately hypofractionated, intensity-modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) to prostate for patients with intermediate and high risk prostate cancer. From 2015 to 2017, 162 patients were treated with IMRT with SIB to the prostate. IMRT plans were designed to deliver 50.4Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes (whole pelvis radiotherapy, WPRT) while simultaneously delivering 57.4 Gy in 28 fractions (2.05 Gy/fraction) to the seminal vesicles and 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate for high risk patients. For intermediate risk patients the same technique was applied, without WPRT. Acute and cumulative late genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Radiation Therapy Oncology Group (RTOG) scoring system. Of the 162 patients enrolled, 156 (96%) completed the treatment as planned. The median follow-up time was 30 months. Seventy-eight patients (48.2%) were treated with WPRT. The rate of acute grade ≥ 2 GI and GU toxicities in all patients were 22% and 58%, respectively. The rate of cumulative late grade ≥ 2 GI and GU toxicities were 11% and 17%, respectively. Acute grade 3 GI and GU toxicities occurred in 1% and 1%. Late grade 3 GI and GU side effects occurred in 5% and 4%, respectively. None of the patients developed grade ≥ 4 toxicity. IMRT with SIB technique using moderate hypofractionation to the prostate is feasible treatment option for intermediate and high risk patients, associated with low rate of severe GU and GI toxicities.

Dosimetric comparison of inverse optimisation methods versus forward optimisation in HDR brachytherapy of breast, cervical and prostate cancer.

OBJECTIVE: Dosimetric comparison of HIPO (hybrid inverse planning optimisation) and IPSA (inverse planning simulated annealing) inverse and forward optimisation (FO) methods in brachytherapy (BT) of breast, cervical and prostate cancer. METHODS: At our institute 38 breast, 47 cervical and 50 prostate cancer patients treated with image-guided interstitial high-dose-rate BT were selected. Treatment plans were created using HIPO and IPSA inverse optimisation methods as well as FO. The dose-volume parameters of different treatment plans were compared with Friedman ANOVA and the LSD post-hoc test. RESULTS: IPSA creates less dose coverage to the target volume than HIPO or FO: V100 was 91.7%, 91% and 91.9% for HIPO, IPSA and FO plans (p = 0.1784) in breast BT; 90.4%, 89.2% and 91% (p = 0.0045) in cervical BT; and 97.1%, 96.2% and 97.7% (p = 0.0005) in prostate BT, respectively. HIPO results in more conformal plans: COIN was 0.72, 0.71 and 0.69 (p = 0.0306) in breast BT; 0.6, 0.47 and 0.58 (p < 0.001) in cervical BT; and 0.8, 0.7 and 0.7 (p < 0.001) in prostate BT, respectively. In breast BT, dose to the skin and lung was smaller with HIPO and FO than with IPSA. In cervical BT, dose to the rectum, sigmoid and bowel was larger using IPSA than with HIPO or FO. In prostate BT, dose to the urethra was higher and the rectal dose was smaller using FO than with inverse methods. CONCLUSION: In interstitial breast and prostate BT, HIPO results in comparable dose-volume parameters to FO, but HIPO plans are more conformal. In cervical BT, HIPO produces dosimetrically acceptable plans only when more needles are used. The dosimetric quality of IPSA plans is suboptimal and results in unnecessary larger active lengths.

NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial.

BACKGROUND: Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma. METHODS: Act.In.Sarc is a phase 2-3 randomised, multicentre, international trial. Adults (aged ≥18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0-2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53·3 g/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete. FINDINGS: Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group. Two patients in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0·044). In both treatment groups, the most common grade 3-4 treatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3-4 adverse events related to NBTXR3 administration were injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3-4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3-4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred. INTERPRETATION: This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers. FUNDING: Nanobiotix SA.

[Stereotactic body radiation therapy with CyberKnife accelerator for low- and intermediate risk prostate cancer]. / Kis és közepes kockázatú prosztatarákos betegek sztereotaxiás sugárkezelése CyberKnife gyorsítóval: korai radiogén mellékhatások.

We report implementation of stereotactic body radiotherapy (SBRT) for the treatment of early, localized prostate cancer patients, and acute side effects caused by radiation therapy. Between February 2018 and July 2018, 36 prostate cancer patients were treated with SBRT. Treatments were performed with "CyberKnife M6" linear accelerator. In low-risk patients 8 Gy was delivered to the prostate in each fraction. For intermediate risk, 8 Gy to the prostate and 6.5 Gy to the seminal vesicles were delivered by each fraction with a simultaneous integrated boost technique. A total of 5 fractions (total dose 40 Gy) were given every second working days. Acute radiogenic genitourinary (GU) and gastrointestinal (GI) side effects were assessed using the Radiation Therapy Oncology Group (RTOG) score. The duration of radiotherapy was 1 week and 3 days. The frequency of acute radiogenic side effects was as follows: GU grade 0: 13.9%, grade I: 30.6%, grade II: 52.8%, grade III: 2.7%. GI grade 0: 55.5%, grade I: 30.6%, grade II: 13.9%, grade III: 0%. Grade IV-V side effects were not observed. SBRT appears to be a safe and well tolerated treatment in patients with early stage, localized prostate cancer.

[Image-guided radiotherapy for muscle invasive bladder cancer with intravesical lipiodol injection. A new option for bladder sparing treatment]. / Izominvazív hólyagrák képvezérelt sugárkezelése intravesicalisan befecskendezett lipiodolos jelöléssel. A hólyagmegtartó kezelés új lehetosége.

INTRODUCTION AND AIM: To implement lipiodol as a fiducial marker of the tumor bed for image-guided radiotherapy with simultaneous integrated boost technique as part of radiochemotherapy for muscle invasive bladder tumors. METHOD: Since April 2016, radiochemotherapy was performed in 3 male patients with muscle invasive, transitional cell bladder carcinoma. Prior to radiochemotherapy, tumor bed resection was performed for each patient, at the same time 10 ml of lipiodol solution was injected submucosally into the resection site, thus marking the tumor bed for escalated dose irradiation. During radiochemotherapy 51 Gy (1.7 Gy/die) to the pelvis, 57 Gy (1.9 Gy/die) to the whole bladder, and 63 Gy (2.1 Gy/die) to the lipiodol-labeled tumor bed was delivered with simultaneous integrated boost technique. The accuracy of the irradiation was controlled by daily kilovoltage CT. Early radiogenic urogenital and gastrointestinal side effects were recorded according to Radiation Therapy Oncology Group side-effects grading recommendation. RESULTS: Substantial perioperative side effect or toxicity were not observed during and after the injection of lipiodol. The prescribed dose was successfully delivered in all patients. Radiotherapy duration was 6 weeks. The lipiodol-labeled tumor bed was clearly visible on daily kilovoltage cone beam CT. In one patient grade II cystitis and proctitis was observed, another patient experienced only grade I cystitis. These complaints improved with symptomatic medication. In the third patient no significant side effect occurred. CONCLUSIONS: The injection of lipiodol into the bladder wall is a safe technique, without any perioperative toxicity or complication. The tumor bed demarcated by lipiodol was visible both on treatment planning and kilovoltage CTs. The total treatment time was shortened by 4 days. The treatment was well tolerated, early side effects were moderate, or slight. Orv Hetil. 2017; 158(51): 2041-2047.

Transperineal gold marker implantation for image-guided external beam radiotherapy of prostate cancer : A single institution, prospective study.

PURPOSE: To present the feasibility and complications of transperineal fiducial marker implantation in prostate cancer patients undergoing image-guided radiotherapy (IGRT) METHODS AND MATERIALS: Between November 2011 and April 2016, three radiopaque, gold-plated markers were transperineally implanted into the prostate of 300 patients under transrectal ultrasound guidance and with local anaesthesia. A week after the procedure patients filled in a questionnaire regarding pain, dysuria, urinary frequency, nocturia, rectal bleeding, hematuria, hematospermia or fever symptoms caused by the implantation. Pain was scored on a 1-10 scale, where score 1 meant very weak and score 10 meant unbearable pain. The implanted gold markers were used for daily verification and online correction of patients' setup during IGRT. RESULTS: Based on the questionnaires no patient experienced fever, infection, dysuria or rectal bleeding after implantation. Among the 300 patients, 12 (4%) had hematospermia, 43 (14%) hematuria, which lasted for an average of 3.4 and 1.8 days, respectively. The average pain score was 4.6 (range 0-9). Of 300 patients 87 (29%) felt any pain after the intervention, which took an average of 1.5 days. None of the patients needed analgesics after implantation. Overall, 105 patients (35%) reported less, 80 patients (27%) more, and 94 patients (31%) equal amount of pain during marker implantation compared to biopsy. The 21 patients who had a biopsy performed under general anesthesia did not answer this question. CONCLUSION: Transperineal gold marker implantation under local anesthesia was well tolerated. Complications were limited; rate and frequency of perioperative pain was comparable to the pain caused by biopsy. The method can be performed safely in clinical practice.

[Intraoperative and post-implant dosimetry in patients treated with permanent prostate implant brachytherapy]. / Intraoperatív és posztimplantációs dozimetria összehasonlítása permanens implantációs prosztata-brachyterápiával kezelt betegeknél.

The purpose of our work was to compare intraoperative and four-week post-implant dosimetry for loose and stranded seed implants for permanent prostate implant brachytherapy. In our institute low-dose-rate (LDR) prostate brachytherapy is performed with encapsulated I-125 isotopes (seeds) using transrectal ultrasound guidance and metal needles. The SPOT PRO 3.1 (Elekta, Sweden) system is used for treatment planning. In this study the first 79 patients were treated with loose seed (LS) technique, the consecutive patients were treated with stranded seed (SS) technique. During intraoperative planning the dose constraints were the same for both techniques. All LSs were placed inside the prostate capsule, while with SS a 2 mm margin around the prostate was allowed for seed positioning. The prescribed dose for the prostate was 145 Gy. This study investigated prostate dose coverage in 30-30 randomly selected patients with LS and SS. Four weeks after the implantation native CT and MRI were done and CT/MRI image fusion was performed. The target was contoured on MRI and the plan was prepared on CT data. To assess the treatment plan dose-volume histograms were used. For the target coverage V100, V90, D90, D100, for the dose inhomogeneity V150, V200, and the dose-homogeneity index (DHI), for dose conformality the conformal index (COIN) were calculated. Intraoperative and postimplant plans were compared. The mean V100 values decreased at four-week plan for SS (97% vs. 84%) and for LS (96% vs. 80%) technique, as well. Decrease was observed for all parameters except for the DHI value. The DHI increased for SS (0.38 vs. 0.41) and for LS (0.38 vs. 0.47) technique, as well. The COIN decreased for both techniques at four-week plan (SS: 0.63 vs. 0.57; LS: 0.67 vs. 0.50). All differences were significant except for the DHI value at SS technique. The percentage changes were not significant, except the COIN value. The dose coverage of the target decreased significantly at four-week plans for both techniques. The decrease was larger for LS technique, but the difference between techniques was not significant at this patient number. The dose distribution was more homogenous, but the conformality was worse at four-week plans.