scholarly journals Response Assessment and Prediction of Progression-Free Survival by 68Ga-PSMA-11 PET/CT Based on Tumor-to-Liver Ratio (TLR) in Patients with mCRPC Undergoing 177Lu-PSMA-617 Radioligand Therapy

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1099
Author(s):  
Fadi Khreish ◽  
Mona Wiessner ◽  
Florian Rosar ◽  
Zaidoon Ghazal ◽  
Amir Sabet ◽  
...  

At present, little is known about the molecular imaging-based response assessment of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy with 177Lutetium (177Lu-PSMA-617 RLT) in metastatic castration-resistant prostate cancer (mCRPC). Our study evaluated the response to RLT using both molecular imaging and biochemical response assessments, and their potential prediction of progression-free survival (PFS). Fifty-one consecutive patients given two cycles of RLT at 6-week intervals were analyzed retrospectively. 68Ga-PSMA-11 PET/CT was obtained about 2 weeks prior to the first and 4–6 weeks after the second cycle. Molecular imaging-based response using SUVpeak and tumor-to-liver ratio (TLR) was determined by modified PERCIST criteria. ∆TLR and ∆SUV were significantly correlated with ∆PSA (p < 0.001, each). After a median follow-up of 49 months, the median PFS (95% CI) was 8.0 (5.9–10.1) months. In univariate analysis, responders showing partial remission (PRPSA and PRTLR) had significantly (p < 0.001, each) longer PFS (median: 10.5 and 9.3 months) than non-responders showing either stable or progressive disease (median: 4.0 and 3.5 months). Response assessment using SUVpeak failed to predict survival. In multivariable analysis, response assessment using TLR was independently associated with PFS (p < 0.001), as was good performance status (p = 0.002). Molecular imaging-based response assessment with 68Ga-PSMA-11 PET/CT using normalization of the total lesion PSMA over healthy liver tissue uptake (TLR) could be an appropriate biomarker to monitor RLT in mCRPC patients and to predict progression-free survival (PFS) of this treatment modality.

Author(s):  
Florian Rosar ◽  
Felix Wenner ◽  
Fadi Khreish ◽  
Sebastian Dewes ◽  
Gudrun Wagenpfeil ◽  
...  

Abstract Purpose In patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT), the predictive value of PSMA PET/CT-derived response is still under investigation. Early molecular imaging response based on total viable tumor burden and its association with overall survival (OS) was explored in this study. Methods Sixty-six mCRPC patients who received [177Lu]Lu-PSMA-617 RLT within a prospective patient registry (REALITY Study, NCT04833517) were analyzed. Patients received a [68Ga]Ga-PSMA-11 PET/CT scan before the first and after the second cycle of PSMA-RLT. Total lesion PSMA (TLP) was determined by semiautomatic whole-body tumor segmentation. Molecular imaging response was assessed by change in TLP and modified PERCIST criteria. Biochemical response was assessed using standard serum PSA and PCWG3 criteria. Both response assessment methods and additional baseline parameters were analyzed regarding their association with OS by univariate and multivariable analysis. Results By molecular imaging, 40/66 (60.6%) patients showed partial remission (PR), 19/66 (28.7%) stable disease (SD), and 7/66 (10.6%) progressive disease (PD). Biochemical response assessment revealed PR in 34/66 (51.5%) patients, SD in 20/66 (30.3%), and PD in 12/66 (18.2%). Response assessments were concordant in 49/66 (74.3%) cases. On univariate analysis, both molecular and biochemical response (p = 0.001 and 0.008, respectively) as well as two baseline characteristics (ALP and ECOG) were each significantly associated with OS. The median OS of patients showing molecular PR was 24.6 versus 10.7 months in the remaining patients (with SD or PD). On multivariable analysis molecular imaging response remained an independent predictor of OS (p = 0.002), eliminating biochemical response as insignificant (p = 0.515). Conclusion The new whole-body molecular imaging–derived biomarker, early change of total lesion PSMA (TLP), independently predicts overall survival in [177Lu]Lu-PSMA-617 RLT in mCRPC, outperforming conventional PSA-based response assessment. TLP might be considered a more distinguished and advanced biomarker for monitoring PSMA-RLT over commonly used serum PSA.


Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1559 ◽  
Author(s):  
Michele Guida ◽  
Nicola Bartolomeo ◽  
Ivana De Risi ◽  
Livia Fucci ◽  
Andrea Armenio ◽  
...  

Background: A limited degree of progression after a response to treatment is labelled as oligoprogression and is a hot topic of metastatic melanoma (MM) management. Rogue progressive metastases could benefit from local treatment, which could allow the continuation of ongoing systemic therapy, also known as treatment beyond progression (TBP). Methods: We retrospectively reviewed 214 selected MM patients who were treated with v-Raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen-activated-extracellular signal-regulated kinase (MEK) or programmed cell death protein 1 (PD-1) inhibitors and received a local treatment continuing TBP. We performed univariate and multivariable analyses to assess the association between therapy outcomes and a series of clinical and biological features. Results: We identified 27 (10%) oligoprogressed patients treated locally with surgery (14), radiosurgery (11), and electrochemotherapy (2). TBP included PD-1 inhibitors (13) and BRAF/MEK inhibitors (14). The median progression-free survival post oligoprogression (PFSPO) was 14 months (5–19 95% confidence interval (C.I.)). In the univariate analysis, a significantly longer PFSPO was associated with complete response (CR), Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, neutrophils/lymphocytes ratio (N/L) <2, and progression-free survival (PFS) at oligoprogression >11 months. Nevertheless, in the multivariable analysis, only CR and N/L <2 were found to be associated with longer PFSPO. Conclusions: In selected patients, local treatments contribute to controlling oligoprogression for a long time, allowing the continuation of systemic treatment and prolongation of overall survival (OS). Increasing biological and clinical knowledge is improving the accuracy in identifying patients to apply for local ablative therapies.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2489
Author(s):  
Sazan Rasul ◽  
Tim Wollenweber ◽  
Lucia Zisser ◽  
Elisabeth Kretschmer-Chott ◽  
Bernhard Grubmüller ◽  
...  

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 722
Author(s):  
Florian Rosar ◽  
Jonas Krause ◽  
Mark Bartholomä ◽  
Stephan Maus ◽  
Tobias Stemler ◽  
...  

The use of 225Ac in prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), either as monotherapy or in combination with 177Lu, is a promising therapy approach in patients with metastatic castration-resistant prostate carcinoma (mCRPC). In this study, we report the efficacy and safety of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in 177Lu-naive mCRPC patients (n = 15) with poor prognosis (presence of visceral metastases, high total tumor burden with diffuse bone metastases or a short PSA doubling time of <2 months). Biochemical (by PSA serum value) and molecular imaging response (by [68Ga]Ga-PSMA-11 PET/CT) was assessed after two cycles of [177Lu]Lu-PSMA-617 RLT, with at least one [225Ac]Ac-PSMA-617 augmentation. In addition, PSA-based progression-free survival (PSA-PFS), overall survival (OS) and toxicity (according to CTCAE) were analyzed. We observed a biochemical- and molecular imaging-based partial remission in 53.3% (8/15) and 66.7% (10/15) of patients, respectively. The median PSA-PFS and OS was 9.1 and 14.8 months, respectively. No serious acute adverse events were recorded. Two out of fifteen patients experienced grade 3 anemia. No other grade 3/4 toxicities were observed. RLT-related xerostomia (grade 1/2) was recorded in 2/15 patients. Our data showed a high clinical efficacy with a favorable side effects profile of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in this highly challenging patient cohort.


2021 ◽  
pp. 78-81
Author(s):  
Devashish Kaushal ◽  
Rajeev Sood

Introduction: Studies on the effects of chemotherapy in Indian Castration-Resistant Prostate Cancer (CRPC) patients are very limited and world data is inconsistent. The purpose of the present study is to assess the effects of Docetaxel therapy in CRPC in Indian patients in terms of survival benet, both progression-free survival, and overall survival. This study also analyzes the effects of various factors on the survival of CRPC patients. Methodology: This is a single institutional prospective observational study. CRPC patients were treated with Docetaxel and followed till death as the primary endpoint or till the end of the study. Survivals were calculated with the Kaplan Meier method. Factors affecting survival were analyzed with univariate and multivariate analysis by log-rank t-test and Cox proportion hazard regression analysis. Result: Out of enrolled 101 patients, 78 were treated with Docetaxel. A decline in PSA (>50% reduction) was observed in 61.54%. Radiological response of regression noted in 40 % Nuclear Bone Scan and 19.23% CT/MRI by RECIST criteria. Progression-free survival and overall survival with Docetaxel (n=78) were 11.8 and 21 months respectively. Hemoglobin less than 11 gm%, Alkaline phosphatase more than 115 IU/dl, PSAmore than 14 ng/ml, Gleason score more than 7 and duration from diagnosis of carcinoma prostate to CRPC less than 24 months, the number of chemotherapy cycles less than 6 were all found to be signicantly associated with poor overall survival in univariate analysis while only Hemoglobin (P=0.0159) showed an independent association with overall survival in multivariate analysis. Conclusion: Overall and progression-free survival of CRPC patients with Docetaxel is 21 & 11.8 months respectively. Hemoglobin, Alkaline phosphatase, PSA, Gleason score, Docetaxel cycle, and duration from diagnosis of carcinoma prostate to CRPC were found to be signicantly associated with poor overall survival.


2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Briones ◽  
Maira Khan ◽  
Amanjot K. Sidhu ◽  
Liying Zhang ◽  
Martin Smoragiewicz ◽  
...  

BackgroundBoth Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT).MethodsWe conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints.ResultsAfter a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively.ConclusionsIn this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). Results The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7–85.2; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2–86.4; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups. Conclusions This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17582-e17582
Author(s):  
Daniel Herrero Rivera ◽  
Ignacio Duran ◽  
Laura Marcos Kovandzic ◽  
Javier Puente ◽  
Begona Mellado ◽  
...  

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.


2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  

Abstract Background: We compared outcomes and toxicity between radiation therapy (RT) with concurrent retrograde super-selective intra-arterial chemotherapy (IACRT) and RT with concurrent systemic chemoradiotherapy (SCRT), for gingival carcinoma (GC). Methods: We included 84 consecutive patients who were treated for GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: Median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT group: 60 Gy; SCRT group:69 Gy). At 3 years, the two groups significantly differed in overall survival (OS; IACRT: 78.75%, 95% confidence interval [CI]: 66.00–87.62; SCRT: 50.37%, 95% CI: 27.58–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.64%, 95% CI: 62.69–85.17; SCRT: 41.96%, 95% CI: 17.65–70.90; P = 0.028) and local control (LC; IACRT: 77.17%, 95% CI: 64.23–86.41; SCRT: 41.96%, 95% CI: 17.65–70.90; P = 0.015). In univariate analysis, age ≥ 65, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with poor OS (P < 0.05). Patients with poorer PS had significantly worse PFS.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. IACRT is an effective and organ-preserving treatment for GC.Trial registration: retrospectively registered


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