scholarly journals National survey of radiation oncologists’ practice patterns regarding hormone-naïve prostate cancer with bone metastases

2020 ◽  
Vol 50 (10) ◽  
pp. 1188-1194
Author(s):  
Katsumasa Nakamura ◽  
Hitoshi Ishikawa ◽  
Tetsuo Akimoto ◽  
Manabu Aoki ◽  
Shinji Kariya ◽  
...  

Abstract Objective To explore radiation oncologists’ attitudes and practice patterns of radiotherapy for hormone-naïve prostate cancer with bone metastases in Japan. Methods An internet-based survey was distributed to board-certified radiation oncologists of the Japanese Society of Radiation Oncology. Three hypothetical cases were assumed: hormone-naïve prostate cancer with single, three or multiple non-symptomatic bone metastases. The respondents described their attitude regarding such cases, treatment methods and the radiotherapy dose fractionation that they would recommend. Results Among the 1013 board-certified radiation oncologists in Japan, 373 (36.8%) responded to the questionnaire. Most of the respondents (85.0%) believed that radiotherapy may be applicable as a primary treatment for hormone-naïve prostate cancer with bone metastases in some circumstances. For Case 1 (single bone metastasis), 55.0% of the respondents recommended radiotherapy for the prostate and bone metastasis. For Case 2 (three bone metastases), only 24.4% recommended radiotherapy for all lesions, and 31.4% recommended radiotherapy for the prostate only. For Case 3 (multiple bone metastases), 49.1% of the respondents stated that there was no indication for radiotherapy. However, 34% of the respondents still preferred to administer radiotherapy for the prostate. The radiotherapy techniques and dose fractionations varied widely among the respondents. Conclusion Most of the respondent radiation oncologists believed that radiotherapy may be beneficial for hormone-naïve prostate cancer with bone metastases.

2019 ◽  
Vol 20 (16) ◽  
pp. 3899 ◽  
Author(s):  
Mari I. Suominen ◽  
Timothy Wilson ◽  
Sanna-Maria Käkönen ◽  
Arne Scholz

Bone metastasis is a common clinical complication in several cancer types, and it causes a severe reduction in quality of life as well as lowering survival time. Bone metastases proceed through a vicious self-reinforcing cycle that can be osteolytic or osteoblastic in nature. The vicious cycle is characterized by cancer cells residing in bone releasing signal molecules that promote the differentiation of osteoclasts and osteoblasts either directly or indirectly. The increased activity of osteoclasts and osteoblasts then increases bone turnover, which releases growth factors that benefit metastatic cancer cells. In order to improve the prognosis of patients with bone metastases this cycle must be broken. Radium-223 dichloride (radium-223), the first targeted alpha therapy (TAT) approved, is an osteomimetic radionuclide that is incorporated into bone metastases where its high-linear energy transfer alpha radiation disrupts both the activity of bone cells and cancer cells. Therefore, radium-223 treatment has been shown preclinically to directly affect cancer cells in both osteolytic breast cancer and osteoblastic prostate cancer bone metastases as well as to inhibit the differentiation of osteoblasts and osteoclasts. Clinical studies have demonstrated an increase in survival in patients with metastatic castration-resistant prostate cancer. Due to the effectiveness and low toxicity of radium-223, several novel combination treatment strategies are currently eliciting considerable research interest.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e596-e596
Author(s):  
Suguru Kadomoto ◽  
Kouji Izumi ◽  
Takahiro Nohara ◽  
Konaka Hiroyuki ◽  
Yoshifumi Kadono ◽  
...  

e596 Background: It was ambiguous till now to evaluate the change of bone metastasis by various treatments. To quantify the change of bone metastases by enzalutamide, abiraterone, and docetaxel for the castration-resistant prostate cancer (CRPC) with bone metastases (bmCRPC), we employed Bone Scan Index (BSI) on bone scintigraphy. Methods: We retrospectively evaluated the change of PSA and bone metastases of CRPC patients who were treated with enzalutamide (Enz), abiraterone (Abi) and/or docetaxel (DOC) in our hospital. All patients underwent Tc-99m MDP bone scintigraphy. The degree of bone metastases was analyzed using BSI, which was calculated by BONENAVI (FUJIFILM RI Pharma, Japan; EXINIbone, EXINI Diagnostics, Sweden). 19 patients were treated with enzalutamide (8 cases: pre-docetaxel, 11 cases: post-docetaxel). The median PSA of patients treated with Enz was 12.64 ng/ml (1.63-199 ng/ml). And 11 patients were treated with abiraterone (5 cases: pre-docetaxel, 6 cases: post-docetaxel). The median PSA of patients treated with Abi was 26.37 ng/ml (2.29-199 ng/ml). Results: We observed decline of PSA in 18/30 cases (9 cases: pre-DOC, 9 cases: post-DOC). Decline of PSA to 50% or more was observed in 14 cases. In contrast, decline of BSI was observed in 53.3% (16/30) cases and decline of PSA to 25% or more was observed in only 6 cases. BSI decreased in 84.6% (11/13) of pre-DOC setting and in 29.4% (5/17) of post-DOC setting indicating that change of BSI was poor in post-DOC setting. However, DOC had already decreased BSI in 91.7% (11/12) before Abi or Enz treatment. Moreover, the average rate of BSI decline in the patients that BSI decreased by DOC was better than the patients that BSI decreased by Abi/Enz (-48.46% vs -28.56%). Finally, although the rate of BSI change by Enz was weakly correlated with the rate of PSA decline (y = 0.3906x + 25.35, R2 = 0.3423), BSI continued to increase in four cases in spite of PSA decline. Conclusions: BSI using BONENAVI on bone scintigraphy was helpful for evaluating the effectiveness of treatment and following-up of bmCRPC.


2013 ◽  
Vol 23 (7) ◽  
pp. 1311-1317 ◽  
Author(s):  
Aera Yoon ◽  
Chel Hun Choi ◽  
Ha-Jeong Kim ◽  
Jin-Young Park ◽  
Yoo-Young Lee ◽  
...  

ObjectiveThe purpose of this study was to describe the clinical characteristics and to assess the contributing factors in patients developing bone metastasis in uterine cervical cancer.MethodsTwo thousand thirteen patients had a diagnosis of uterine cervical cancer at Samsung Medical Center between June 1994 and December 2011. During the study period, 105 patients with bone metastasis were identified, and their clinicopathologic data were investigated retrospectively.ResultsAmong 105 patients with bone metastasis, 14 patients were excluded and 91 patients were evaluable. The median bone metastasis–free survival was 27 months (range, 0–279 months).The time to bone metastasis was significantly shorter in patients with adenocarcinoma than in patients with squamous cell carcinoma (median duration, 12 vs 29 months;P= 0.016). In addition, it was shorter in patients with stage IIB to stage IV disease than in those with stage I to stage IIA disease (15 vs 22 months;P= 0.02). The median survival after bone metastasis was 10 months, longer in the patients who received radiotherapy (± chemotherapy) than in the patients who received chemotherapy alone as a salvage therapy (12 vs 7 months;P= 0.01). Initial stage, number of bone metastases, location of involved bone, and coexisting metastatic lesion were not associated with the overall survival of the patients.ConclusionsOur study demonstrates that adenocarcinoma, advanced stage (IIB-IV) and initial multiple bone metastases contribute to earlier bone metastasis. Once bone metastasis was recognized, the survival of these patients was poor and no factors were identified to predict survival of those patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Desiree M. Straign ◽  
Claire L. Ihle ◽  
Meredith D. Provera ◽  
Philip Owens

From the 33,000 men in the U.S. who die from prostate cancer each year, the majority of these patients exhibit metastatic disease with bone being the most common site of metastasis. Prostate cancer bone metastases are commonly blastic, exhibiting new growth of unhealthy sclerotic bone, which can cause painful skeletal related events. Patient’s current care entails androgen deprivation therapy, anti-resorptive agents, radiation, and chemotherapy to help control the spread of the cancer but little intervention is available to treat blastic bone disease. The transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) pathways are known to regulate bone growth and resorption of destructive lytic bone lesions, yet the role of TGFβ/BMP signaling in prostate cancer blastic vs lytic bone lesions are not fully understood. We hypothesized that to target the BMP/TGFβ pathway, a useful biomarker of bone lytic or blastic pathology would have superior response. We show distinct BMP vs. TGFβ signaling in clinical samples of human prostate cancer bone metastases with either lytic or blastic pathologies. BMPs exhibit distinct effects on bone homeostasis, so to examine the effect of BMP inhibition on healthy bone, we treated mice with the BMP receptor small molecule antagonist DMH1 and saw a modest temporary improvement in bone health, with increased trabecular bone. We next sought to use the BMP inhibitor DMH1 to treat bone metastasis engraftment seeded by a caudal artery injection of the lytic human prostate cell line PC3 in immunodeficient mice. The colonization by PC3 cells to the bone were restricted with DMH1 treatment and bone health was importantly preserved. We next proceeded to test BMP inhibition in an injury model of established bone metastasis via intratibial injection of the MYC-CaP mouse prostate cell line into FVBN syngeneic mice. DMH1 treated mice had a modest decrease in trabecular bone and reduced lymphocytes in circulation without affecting tumor growth. Taken together we show unique responses to BMP inhibition in metastatic prostate cancer in the bone. These studies suggest that profiling bone lesions in metastatic prostate cancer can help identify therapeutic targets that not only treat the metastatic tumor but also address the need to better treat the distinct tumor induced bone disease.


Author(s):  
Shigeaki Higashiyama ◽  
Atsushi Yoshida ◽  
Joji Kawabe

Background: BSI calculated from bone scintigraphy using 99mtechnetium-methylene diphosphonate (99mTc-MDP) is used as a quantitative indicator of metastatic bone involvement in bone metastasis diagnosis, therapeutic effect assessment, and prognosis prediction. However, the BONE NAVI, which calculates BSI, only supports bone scintigraphy using 99mTc-MDP. Aims: We developed a method in collaboration with the Tokyo University of Agriculture and Technology to calculate bone scan index (BSI) employing deep learning algorithms with bone scintigraphy images using 99mtechnetiumhydroxymethylene diphosphonate (99mTc-HMDP). We used a convolutional neural network (CNN) enabling the simultaneous processing of anterior and posterior bone scintigraphy images named CNNapis. Objectives: The purpose of this study is to investigate the usefulness of the BSI calculated by CNNapis as bone imaging and bone metabolic biomarkers in patients with bone metastases from prostate cancer. Methods: At our hospital, 121 bone scintigraphy scans using 99mTc-HMDP were performed and analyzed to examine bone metastases from prostate cancer, revealing the abnormal accumulation of radioisotope (RI) at bone metastasis sites. Blood tests for serum prostate-specific antigen (PSA) and alkaline phosphatase (ALP) were performed concurrently. BSI values calculated by CNNapis were used to quantify the metastatic bone tumor involvement. Correlations between BSI and PSA and between BSI and ALP were calculated. Subjects were divided into four groups by BSI values (Group 1, 0 to <1; Group 2, 1 to <3; Group 3, 3 to <10; Group 4, >10), and the PSA and ALP values in each group were statistically compared. Results: Patients diagnosed with bone metastases after bone scintigraphy were also diagnosed with bone metastases using CNNapis. BSI corresponding to the range of abnormal RI accumulation was calculated. PSA and BSI (r = 0.2791) and ALP and BSI (r = 0.6814) correlated positively. Significant intergroup differences in PSA between Groups 1 and 2, Groups 1 and 4, Groups 2 and 3, and Groups 3 and 4 and in ALP between Groups 1 and 4, Groups 2 and 4, and Groups 3 and 4 were found. Conclusion : BSI calculated using CNNapis correlated with ALP and PSA values and is useful as bone imaging and bone metabolic biomarkers, indicative of the activity and spread of bone metastases from prostate cancer.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9096-9096 ◽  
Author(s):  
W. Wagner ◽  
A. Radmard ◽  
M. Bach ◽  
C. Loitsch ◽  
M. G. Krukemeyer ◽  
...  

9096 Background: Multiple painful bone metastases are a common problem in patients suffering from breast and prostate cancer. Side effects of morphines can impair quality of life. Pain reduction can also be achieved by radiotherapy combined with bisphosphonates; however, this treatment is not successful in all patients. Methods: 35 patients with breast and prostate cancer suffering from painful bone metastases (multiple metastases in 29 cases, solitary metastasis in 6 cases: were locally irradiated (30 - 40 Gy over 3 - 4 weeks, conventional dose fractionation). In addition they received a bisphosphonate therapy (zoledronate). Before and after radiotherapy procollagen-I- propeptide and β-crosslaps were measured as parameters for the intensity of bone metabolism. Results: 24 patients experienced complete pain relief, 10 patients partial pain relief and one patient noticed no effect of treatment. The values of procollagen-I-propeptide (normal range 19–102 μg/l) and β-crosslaps (normal range <= 1,0 μg/l) were correlated with treatment success. At pretherapeutical procollagen-I- propeptide levels above 190 μg/l, all patients became entirely free of pain. All patients with β-crosslaps values above 0.5 μg/l became equally free of pain, irrespective of the number of metastases and tumour entity. The mean levels of procollagen-I-propeptide as well as β-crosslaps correlate directly and without exception with analgesia, reduction of pain or persistency of pain as final results. No correlation concerning the values was found before and after therapy. Conclusion: Procollagen-I-propeptide as well as β-crosslaps measurements before the beginning of a radio- and bisphosphonate therapy due to painful bone metastases are an excellent prognostic parameter to predict the success of therapy. Where high initial values (procollagen-I-propeptide > 190 μg/l or β-crosslaps > 0.5 μg/l) were measured, complete analgesia was achieved through therapy. Despite this clinically clear statement, a statistical significance with a t-Test was not evaluable at the current collection of patient data. Therefore, 20 more patients were examined; the results are yet to come. No significant financial relationships to disclose.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16092-e16092
Author(s):  
Masahiro Nozawa ◽  
Isao Hara ◽  
Kazuhiro Nagao ◽  
Hideyasu Matsuyama ◽  
Hirotsugu Uemura

e16092 Background: The potency of zoledronic acid for hormone-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefit of administering zoledronic acid concomitant with androgen-deprivation therapy in treatment-naïve prostate cancer patients with bone metastases, in which the primary endpoint was skeleton-related event (SRE)-free survival at 24 months after treatment. Methods: Treatment-naïve male patients with histologically confirmed adenocarcinoma of the prostate and radiologic evidence of bone metastasis were eligible. Treatment consisted of bicalutamide 80 mg administered orally on Day 1 and every day, goserelin acetate 10.8 mg administered subcutaneously on Day 8 and every 12 weeks, and zoledronic acid 4 mg administered intravenously on Day 8 and every four weeks. Results: Between July 2008 and April 2010, a total of 53 patients were enrolled and 52 evaluable. Median age was 72 years (range, 55 - 86). Median primary PSA was 249.4 ng/ml (range, 2.19 –19201). Median follow-up period was 33.3 months. The SRE-free survival rate at 24 months after treatment was 82.7 %. Median time to PSA progression was 25.9 months (95% confidential interval, 17.97-24.43). The score of the extent of bone diseases was stable or decreased in 73 % of the patients at 24 months after treatment. The grade-3 osteonecrosis of the jaw was reported in three patients (5.8 %). Conclusions: Our results suggest the potency of the early introduction of zoledronic acid for prostate cancer patients with bone metastases. Future studies are certainly required to ascertain the most appropriate timing of the commencement of zoledronic acid for patients with bone-metastatic prostate cancer. Clinical trial information: UMIN000007548.


2012 ◽  
Vol 15 (3) ◽  
pp. 226-232 ◽  
Author(s):  
Almudena Zapatero ◽  
◽  
José López-Torrecilla ◽  
Ismael Herruzo ◽  
Felipe A. Calvo

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