Introduction
The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving
177
LuLu-PSMA-617 therapy has ...been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the “617 trial”) to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with
177
Lu-PSMA-617.
Materials and methods
The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to
177
LuLu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated.
Results
The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS.
Conclusion
In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving
177
LuLu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0–1 is associated with a longer OS.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Introduction
Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the ...presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement.
Methods
The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with
177
LuLu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6–20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Results
A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6–20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (
p
< 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6–20 lesions (OS: 16 vs. 12 months;
p
= 0.038) as well as diffuse involvement (OS: 11 vs. 7 months;
p
= 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases:
p
< 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia.
Conclusion
The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Our aim was to assess the diagnostic performance of F-18 fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) in detecting hyperfunctioning parathyroid tissue (HPT) in ...patients with elevated parathyroid hormone levels with negative or inconclusive conventional imaging results and to compare the findings with those obtained using technetium-99m sestamibi (MIBI) scintigraphy and neck ultrasonography (US).
Images of 105 patients with hyperparathyroidism who underwent FCH PET/CT, dual-phase MIBI parathyroid scintigraphy (median interval: 42 days), and neck US were retrospectively analyzed. The gold standard was histopathological findings for 81 patients who underwent parathyroidectomy and clinical follow-up findings in the remaining 24 patients. Sensitivities, positive predictive values (PPVs), and accuracies were calculated for all imaging modalities.
Among the 81 patients who underwent parathyroidectomy, either parathyroid adenoma (n = 64), hyperplasia (n = 9), neoplasia (n = 4), or both parathyroid adenoma and hyperplasia (n = 1) were detected, except 3 patients who did not show HPT. Of the 24 (23%) patients who were followed-up without operation, 22 (92%) showed persistent hyperparathyroidism. FCH PET/CT showed significantly higher sensitivity than MIBI scintigraphy and US in detection of HPT (
< 0.01). Sensitivity, PPV, and accuracy of FCH PET/CT were 94.1% (95/101), 97.9% (95/97), and 92.4% (97/105), respectively. The corresponding values for MIBI scintigraphy and US were 45.1% (46/102), 97.9% (46/47), and 45.7% (48/105) and 44.1% (45/102), 93.8% (45/48), and 42.9% (45/105), respectively. Among the 35 patients showing negative MIBI scintigraphy and neck US findings, 30 (86%) showed positive results on FCH PET/CT. FCH PET/CT could demonstrate ectopic locations of HPT in 11 patients whereas MIBI and US showed positive findings in only 6 and 3 patients, respectively.
FCH PET/CT is an effective imaging modality for detection of HPT with the highest sensitivity among the available imaging techniques. Therefore, FCH PET/CT can be recommended especially for patients who show negative or inconclusive results on conventional imaging.
Objective One of the underlying mechanisms of sepsis is thought to be the oxidative damage due to the generation of free radicals. Glutamate, the major excitatory amino acid in the brain, is known to ...play an important role in blood brain barrier (BBB) permeability, brain edema, and oxidative damage in pathological conditions. Riluzole, a glutamate release inhibitor, has been shown to have neuroprotective effects in several animal models. The aim of our study was to investigate the putative protective effect of riluzole against sepsis-induced brain injury. Methods Sepsis was induced by cecal ligation and puncture in Wistar albino rats. Sham operated (control) and sepsis groups received either saline or riluzole (6 mg/kg, s.c.) 30 min after the surgical procedure, and every 12 h as continuing treatment. The effect of riluzole on the survival rate, weight loss, fever, leukocyte count, brain edema, BBB permeability, oxidative damage, and histological observations were evaluated for early (6 h) and late (48 h) phase of sepsis. Results Riluzole, when administered 6 mg/kg s.c., diminishes the sepsis-induced augmentation in weight loss, body temperature, brain edema, increase in BBB permeability, oxidative damage, and brain injury that is observed histologically. Besides increasing the survival rate in sepsis, it has also improved neurological examination scores and the prognosis of the disease. Conclusion According to the results of this study, riluzole appears to have a protective effect for sepsis-induced encephalopathy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim of the study was to estimate the radiation-absorbed doses and to study the in vivo and in vitro stability as well as pharmacokinetic characteristics of lutetium-177 (Lu-177) prostate-specific ...membrane antigen (PSMA)-617.
For this purpose, 7 patients who underwent Lu-177-PSMA therapy were included into the study. The injected Lu-177-PSMA-617 activity ranged from 3.6 to 7.4 GBq with a mean of 5.2±1.8 GBq. The stability of radiotracer in saline was calculated up to 48 h. The stability was also calculated in blood and urine samples. Post-therapeutic dosimetry was performed based on whole body and single photon emission computed tomography/computed tomography (SPECT/CT) scans on dual-headed SPECT/CT system.
The radiochemical yield of Lu-177-PSMA-617 was >99%. It remained stable in saline up to 48 h. Analyses of the blood and urine samples showed a single radioactivity peak even at 24 hours after injection. Half-life of the distribution and elimination phases were calculated to be 0.16±0.09 and 10.8±2.5 hours, respectively. The mean excretion rate was 56.5±8.8% ranging from 41.5% to 65.4% at 24 h. Highest radiation estimated doses were calculated for parotid glands and kidneys (1.90±1.19 and 0.82±0.25 Gy/GBq respectively). Radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p<0.05) (0.030±0.008 Gy/GBq).
Lu-177-PSMA-617 is a highly stable compound both in vitro and in vivo. Lu-177-PSMA-617 therapy seems to be a safe method for the treatment of castration-resistant prostate cancer patients. The fractionation regime that enables the longest duration of tumor control and/or survival will have to be developed in further studies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Three novel series of 2′,4′-difluoro-4-hydroxybiphenyl-3-carboxylic acid derivatives namely 4-substituted-1,2,4-triazoline-3-thiones (
4a–
g); 2-substituted-1,3,4-thiadiazoles (
5a–
g) and ...2-substituted-1,3,4-oxadiazoles (
6a–
g) have been synthesized. Twenty-one of the newly synthesized compounds were tested against various bacteria, fungi, yeast species and virus. In addition, we have replaced the carboxylic acid group of diflunisal with heterocycles and the anti-inflammatory activity of heterocycles reported here. Compound (
5d) showed activity against
Escherichia coli A1 and
Streptococcus pyogenes ATCC-176 at a concentration of 31.25
μg/mL, whereas cefepime, the drug used as standard, has been found less active against the bacteria mentioned above. Compound (
4b) has exhibited activity against
Aspergillus variecolor and
Trichophyton rubrum at a concentration of 31.25 and 15.25
μg/mL, whereas Amphotericin B, the drug used as standard, has been found less active against the yeast and fungi. The highest antiviral activity was found in the 1,3,4-thiadiazole derivative (
5a) having a methyl group at 2nd position against Sindbis virus at 9.6
μg/mL. Compound (
4c) exhibited the highest anti-inflammatory activity (73.03%) whereas diflunisal, the drug used as standard, has been found less active (24.16%). Compound (
5f) presented similar antinociceptive activity with the standard drug (paw withdrawal latency was 19.21
s compared to that of diflunisal which was 19.14
s, in hot plate test).
Display omitted Three novel series of 2′,4′-difluoro-4-hydroxybiphenyl-3-carboxylic acid derivatives namely 4-substituted-1,2,4-triazoline-3-thiones (
4a–
g); 2-substituted-1,3,4-thiadiazoles (
5a–
g) and 2-substituted-1,3,4-oxadiazoles (
6a–
g) have been synthesized.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Nöroendokrin tümörler (NET’ler) nadiren görülen, ancak son
yıllarda artış eğilimi gösteren kanser türlerindendir. NET’lerin
tanı ve klinik yönetiminde Ga-68 DOTA bağlı Somatostatin
Reseptör Hedefli ...Peptitler ile PET/BT görüntülemenin önemi
retrospektif ve prospektif birçok çalışmada bildirilmiştir. Klinik
uygulamalarda Ga-68 işaretli üç farklı somatostatin analoğu
kullanılmaktadır. Rutinde sıklıkla kullanılan Ga-68 işaretli
somatostatin analogları; DOTA-D-Phe-Tyr3-oktreotid (DOTATOC),
DOTA-1-NaI(3)- oktreotid (DOTA-NOC) ve DOTA-DPhe-
Tyr3-oktreotat (DOTA-TATE) bileşikleridir. Çalışmalarda
NET’lerde en sık eksprese olan somatostatin reseptörü 2’ye
(sst-r 2) en yüksek afinite gösteren bileşiğin DOTA-TATE olduğu
gösterilmiştir. Ga-68 DOTA bağlı somatostatin reseptörü
(sst-r) PET/BT, NET’lerin cerrahi öncesi evrelemesinde, tedavi
yanıtının belirlenmesinde, yeniden evrelemede, peptit
reseptör radyonüklit tedavisi öncesi somatostatin reseptör
uptake’inin gösterilmesinde kullanılmaktadır. Bu uygulama
rehberi nükleer tıp uzmanlarına NET’lerde Ga-68 DOTA bağlı
peptit PET/BT’nin standardizasyonunu sağlamak amacı ile
endikasyonları, uygulama tekniği, raporlama ve yorumlama
açısından önerileri kapsamaktadır.
Bu uygulama kılavuzu, temel olarak nükleer tıp hekimleri için,
prostat kanserinde (PK) Galyum-68 prostat spesifik membran
antijeni (Ga-68 PSMA) pozitron emisyon tomografi/bilgisayarlı
tomografi ...(PET/BT) görüntülemesinin standardizasyonunu
sağlamak amacı ile, uygulama tekniği, raporlama ve
yorumlama açısından önerileri içermektedir. Ga-68 PSMA
PET/BT’nin güncel bilimsel yeri ve gelişmekte olan kullanım
endikasyonlarının da tartışıldığı kılavuz önerilerinin, PK’de
Ga-68 PSMA görüntülemenin, doğruluğu ve güvenilirliğini
artırmaya katkı sağlayacağı düşünülmektedir.
Prostat spesifik membran antijeni (PSMA), çoğu prostat
kanserinde (PK) eksprese edilir ve Lutetium-177 (Lu-
177) PSMA radyoligand tedavisi (RLT), tümör dokusunda
β-partikülleri ile hedefe yönelik ...radyasyon tedavisi için ümit
verici, sistemik bir tedavi modalitesidir. Lu-177 PSMA RLT,
kastrasyona dirençli metastatik prostat kanseri (KDMPK)
için yakın zamanda kullanıma sunulmuş olmasına rağmen,
birçok merkezde sürekli artan ilgi ve kullanıma sahiptir.
Tedavi, nispeten az yan etki ile iyi tolere edilir, genel sağkalım
ve yaşam kalitesi üzerinde olumlu bir etkiye sahiptir. Bu
kılavuzun amacı, RLT’nin Lu-177 PSMA’yı “klinik uygulamada
kanıtlanmamış bir müdahale” olarak kullandığı KDMPK’li
hastaları, halihazırda mevcut olan en iyi bilgiye uygun
olarak değerlendirme ve yönetmede nükleer tıp uzmanlarına
yardımcı olmaktır.
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