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Background Optimal use of bone-modifying agent (BMA) therapy in patients with bone metastases from breast and castrate-resistant prostate cancer (CRPC) is evolving. Methods Patients receiving BMA for bone metastases from breast or CRPC were surveyed. Information was collected on patient and disease characteristics, BMA treatments and perceptions regarding BMA benefits and side effects. Interest in participation in trials of de-escalated BMA therapy was also gauged. Results Of 220 patients contacted, 172 eligible patients responded (response rate 78%). Median age was 67 (range: 21–91); 137 (80%) had breast cancer and 35 (20%) CRPC. Symptomatic skeletal events (SSEs) occurred prior to starting BMAs in 61% (84/137) of breast and 48% (17/35) of CRPC patients. Among breast cancer patients, 47, 33 and 13% received zoledronate, pamidronate and denosumab, respectively. Eighty-five percent (30/35) of CRPC patients received denosumab. De-escalation of therapy was more common among breast cancer patients. Although most patients correctly reported the goals of BMA therapy were to “help stop fractures” (62%) and “[improve] quality of life” (63%), 46.5% felt it prolonged survival and 54% felt it reduced bone progression. Most respondents (102/129, 79%) were comfortable with de-escalating to 6-monthly treatment after 2 years of BMA therapy. Patients considered the most important endpoints of de-escalation studies to be “stability of bone metastases” (45%), “quality of life” (22%) and “SSE rates” (14%). Conclusion Twelve weekly BMA was more common in breast than in prostate cancer. There remain misconceptions about the benefits of BMAs, highlighting potential gaps in patient education. Patients were interested in further BMA de-escalation after 2 years of prior BMA and provided study endpoints that were most important to them. Supplementary Information The online version contains supplementary material available at 10.1007/s00520-021-06238-1.

To assess the effectiveness of docetaxel rechallenge (DR) for metastatic castration-resistant prostate cancer (mCRPC) following chemohormonal therapy for metastatic castrate-sensitive prostate cancer (mCSPC). Additionally, we sought to define clinical factors predicting treatment response.Retrospective analysis of men treated with docetaxel for mCSPC and then rechallenged in the mCRPC setting from four cancer centers in Ontario, Canada. Prostate specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) following DR were evaluated.Fifty five patients were identified between 2015 and 2020. Prior to DR, 94.5% of patients received androgen-receptor axis targeted therapy, 20% received radium-223, and 1.8% received cabazitaxel. Among 54 evaluable patients, 27.8% had a PSA decline ≥50%. Median PFS was 4.1 months (95% CI, 2.1-4.8) and median OS from androgen deprivation therapy initiation was 38.3 months (95% CI, 32.9-41.0). A Gleason Score of ≥8 was an independent predictor of prolonged PFS (HR 0.32, 95% CI, 0.12-0.81; P=0.02).DR following chemohormonal therapy for mCSPC produced a meaningful PSA response in approximately one-quarter of patients, with relatively short PFS. The impact of Gleason Score on docetaxel response warrants further investigation.

Background Smoking is a major risk factor for lung cancer (LC) and transitional cell carcinoma of the bladder (TCC). Current recommendations for LC screening do not include TCC as a risk factor for determining screening eligibility. In this study we aimed to evaluate whether TCC patients constitute a population who might benefit from LC screening. Patients and Methods The Surveillance, Epidemiology, and End Results 18 database was used to determine the incidence, standardized incidence ratio (SIR), and the average time to diagnosis of LC in patients with localized TCC of the bladder (American Joint Committee on Cancer, sixth edition, stages 0-1). Results On the basis of 91,606 patients with localized TCC, The SIR for LC in men was 1.89 (95% confidence interval [CI], 1.8-1.97), significantly different from the risk for all solid tumors. The SIR for LC in women was 2.43 (95% CI, 2.22-2.65), significantly higher than for men. The 5-year incidence of LC was 3.2%, and the 10-year incidence was 5.94%. The average time to diagnosis of LC was 3.4 years, with >80% of LC cases occurring within 5 years of TCC diagnosis. Conclusion Patients with localized TCC have a higher incidence of LC than the general population. The risk is significantly increased among women compared with men. Considering this increased risk, patients with early stage TCC might stand to benefit from LC screening. Additional differences were noted between male and female TCC patients, which bear further study.

Background: Limited data about biomarkers are available to predict the outcomes of targeted therapy in metastatic renal cell carcinoma (mRCC). Circulating cell-free DNA (CFD) is elevated in various cancers. Patients and Methods: We performed a prospective study of patients with mRCC who received targeted therapy in the Soroka Medical Center between 2013 and 2015. CFD levels were measured using a simple fluorometric assay. Blood samples for CFD were collected before treatment and at weeks 1, 4, 12, 18, and 24 of treatment. The normal cut-off level of CFD was defined as 800 ng/ml. The association of CFD with objective response, progression-free survival (PFS), and overall survival was tested, with adjustment for known confounding risk factors. Results: A total of 23 patients were included; 18 were treated with first-line therapy and 5 with second- and third-line therapies. Patients with normal pretreatment CFD level had a better PFS versus patients with increased levels (p = 0.023). In multivariate analysis, factors associated with PFS were pretreatment CFD levels (p = 0.020) and Heng risk (p = 0.006). Conclusions: Elevated pretreatment CFD levels measured using a simple fluorometric assay may be associated with a worse PFS in patients with mRCC. A larger prospective study is warranted in order to validate our observation.

117 Background: Since docetaxel has been advanced to the metastatic castrate-sensitive prostate cancer (mCSPC) setting, there is a lack of evidence guiding its re-introduction upon castrate-resistant (CR) progression. We sought to identify clinical characteristics and outcomes of patients subjected to docetaxel rechallenge (DR) following prior docetaxel exposure in the mCSPC realm. Methods: Patients rechallenged with docetaxel following treatment in the mCSPC setting were identified from three academic centres in Ontario, Canada. Retrospective chart reviews were performed to identify clinical, treatment and outcome variables. Results: Of the 45 patients with DR initiated between 06/2015 and 07/2020, the median age was 65, 60% had a Gleason score of ≥8, and 64% had an ECOG of ≤1. 56% had bone only metastasis, 4% lymph node only metastasis, 29% bone and lymph node metastasis, and 11% had visceral metastasis. In the mCSPC setting, 98% of patients received 6 cycles of docetaxel with 13% requiring dose delays. Of 43 informative patients, all had a PSA response to chemohormonal therapy. 91% achieved at least a 50% PSA response (PSA50), of which 40% had a 50-89% PSA reduction and 51% had a ≥90% PSA reduction. 29% of patients obtained a PSA nadir of < 0.2 ng/mL. 16% had CR progression in < 6 months, 56% in 6-12 months, and 28% in > 12 months. DR was initiated after a median of 20.8 months (range 6.0-40.4) following the last dose of docetaxel for mCSPC, and was given as first line treatment for CR disease to 7%, second line to 51%, third line to 40%, and fourth line or beyond to 2% of patients. 69% of patients had received an androgen-receptor axis targeted therapy prior to DR, 18% radium 223, and 7% had received a trial drug. Notably, no patients had received cabazitaxel prior to DR. The median number of cycles of docetaxel received at rechallenge was 5 (range 1-11) with 18% of patients requiring treatment delays. 64% of patients stopped treatment due to progression, 16% due to side effects, 7% at the patient’s request, 7% due to completion of the planned number of cycles, and 6% due to death or other causes. Among 44 informative patients, 23% achieved at least a PSA50, with 18% having a 50-90% PSA reduction, and 5% having a ≥90% PSA reduction. The median time to progression (biochemical, radiographic, or death) was 2.3 months (95%CI 1.7-4.4) and the median overall survival was 11.0 months (95%CI 8.5-14.3). Conclusions: DR following exposure to docetaxel in the mCSPC setting resulted in a PSA50 in only around one quarter of patients. Both the median time to progression and overall survival were found to be short. With future investigations, we hope to identify clinical variables that will help predict which patients might benefit most from DR.

Extragonadal germ cell tumors (GCTs) are relatively uncommon neoplasms, affecting primarily men during the third and fourth decades of life.We describe an unusual case of mediastinal seminoma in a 21-year-old male on chronic peritoneal dialysis for renal failure of uncertain etiology. The patient was treated with chemotherapy consisting of etoposide and cisplatin (EP) combined with hemodialysis. Cisplatin (20 mg/m(2)), and etoposide (50 mg/m(2)) were given on days 1, 3, and 5 for induction. Hemodialysis was started 1 h after completion of etoposide infusion. Following this course of treatment, another 4 cycles of cisplatin (20 mg/m(2)), and etoposide (50 mg/m(2)) were given on successive days from day 1 to 5. Hemodialysis was carried out daily, prior to the start of chemotherapy. Subcutaneous PEG-filgrastim was given on day 6 in all cycles. The patient's status after the first post-induction treatment was complicated by a pseudomonas infection. Tumor response to chemotherapy was prompt with remission lasting to date, 17 months after diagnosis.This case report is the second description of chemotherapy given to a hemodialysis patient with extragonadal GCT. We suggest that treatment with EP combined with hemodialysis according to the presented protocol is feasible, and may result in a favorable outcome.

Introduction Sunitinib (sunitinib malate, SU11248, SUTENT; Pfizer, New York, NY) is a novel small molecule receptor tyrosine kinase inhibitor with direct antitumor as well as antiangiogenic activity via targeting the vascular endothelial growth factor, platelet-derived growth factor, KIT, and FLT3 receptor tyrosine kinases. The drug is approved multinationally for the treatment of renal cell carcinoma (RCC), gastrointestinal stromal tumor, and pancreatic neuroendocrine tumor. The safety of sunitinib has been studied in patients with RCC with only a relatively small proportion of patients with grade 2/3 liver toxicity and no grade 4 toxicity. A few case reports described serious liver toxicity, including fatal outcome ascribed to the treatment with sunitinib. Here we report a case of a patient ith RCC and chronic obstructive lung disease accompanied by evere pulmonary arterial hypertension that developed fulminant heatic failure during the first cycle of treatment with sunitinib. A ossible mechanism of toxicity in this case and review of the literature re presented in this report.

Objective The objective of the study was to determine the amniotic fluid soluble intercellular adhesion molecule-1 concentrations in women with preterm labor in relation to intra-amniotic infection. Study design Amniotic fluids from 125 women with preterm labor (78 with preterm delivery and 47 with term deliveries) were examined for both soluble intercellular adhesion molecule-1 concentrations and intra-amniotic infection with Ureaplasma species. A χ 2 test, or Fisher's exact test, when appropriate, was used for statistical analysis. Results In the preterm delivery group, 45% (35 of 78) had intra-amniotic infection with Ureaplasma species, compared with 19% (9 of 47) in the term delivery group ( P = .004). In women with intra-amniotic infection, 26% (9 of 38) had soluble intercellular adhesion molecule-1 levels above 1290 ng/ml. Only 2.3% (1 of 43) in the preterm delivery group without intra-amniotic infection attained this diagnostic level ( P = .004). In contrast, there was no significant difference in soluble intercellular adhesion molecule-1 levels between those with or without intra-amniotic infection in the term delivery group. Conclusion Amniotic fluid soluble intercellular adhesion molecule-1 concentrations exceeding 1290 ng/ml can be used as a marker for intra-amniotic infection with Ureaplasma in patients with preterm labor.

A parturient suffering from preterm premature rupture of membranes at 29-weeks of gestation was hospitalized and staphylococcus was detected in her amniotic fluid. After treatment with antibiotics she delivered a healthy neonate three weeks later. ICAM-1 levels decreased by 20 fold correlating with elimination of the bacteria and prolongation of the pregnancy.

CONCENTRATIONS : A MARKER FOR IMPENDING INTRAAMNIOTIC INFECTION WITH UREAPLASMA AND PRETERM DELIVERY SHULAMITH HOROWITZ, AMNON HADAR, NOA SHANI-SHREM, MOSHE MAZOR, Soroka University Medical Center, Microbiology and Immunology, National Center for Micoplasma, Israel, Beer Sheva, Israel, Soroka University Medical Center, Obstetrics and Gynecology, Beer-Sheva, Israel, Soroka University Medical Center, Obstetrics and Gynecology, Soroka University Medical Center, Beer Sheva, Israel OBJECTIVE: To determine the amniotic fluid ICAM-1 concentrations in women with preterm labor (PTL), according to the presence or absence of intraamniotic (IAI) infection. STUDY DESIGN: Amniotic fluid was obtained by amniocentesis from 132 women with PTL and the samples were examined for ICAM-1 concentrations and for intraamniotic infection with Ureaplasmas and other, less frequent, bacteria. Sixty eight women (51.5%) had preterm delivery (PTD) and 64 women had term deliveries. The statistical significance of the categorical variables was analyzed by c test, or Fisher’s exact test, when appropriate. Odds ratios (95% confidence intervals) were calculated. RESULTS: In the PTD group, 46% (31/68) had IAI with Ureaplasmas, compared to 20% (13/64) in the term delivery group (OR = 3.29, 95% CI 1.47.5; P= .002). The value of ICAM-1 used as the diagnostic cutoff was 1300 ng/ ml [as calculated from a Receiver Operating Characteristic (ROC) curve]. In women with PTD with IAI, 26% (8/31) had ICAM-1 levels above 1300ng/mL whereas none (0/37) in the PTD group without IAI attained this diagnostic level ( P= .001). In parturients with term delivery, there was no significant difference between those with or without IAI, (15% [2/13] had ICAM-1 >1300 ng/mL, compared with 3.9% [2/51], respectively [OR = 4.45, 95% CI 0.4-51.7; P = .13]). CONCLUSION: Amniotic fluid ICAM-1 concentrations exceeding 1300ng/mL might be used as a marker for IAI with Ureaplasma in patients with PTL.