These early results suggest that labeled choline PET/CT imaging performed according to current NCCN guidelines may change management and improve care in prostate cancer patients with biochemical failure by identifying patients for referral for salvage radiation therapy, improving radiation planning, and delaying or avoiding use of androgen deprivation therapy.

Lutetium-177-PSMA ([177Lu]-PSMA-617), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA), enabling targeted radiation therapy to metastatic prostate lesions. Our objective was to retrospectively analyze the activity of [177Lu]-PSMA-617 given off-trial to men with metastatic castration resistant prostate cancer (mCRPC) and identify clinical factors associated with PSA response. Electronic medical records of all men treated with [177Lu]-PSMA-617 were reviewed and analyzed. Overall survival was calculated using the Kaplan–Meier method. The association between potential variables and PSA response was analyzed by univariate analysis, using either logistic regression or χ2/Fisher’s exact test. Multivariable analysis was carried out using logistic regression on all categorical variables with a P-value of <0.1 on univariate analysis. Variables found to be statistically significant were then used to define a categorical score. A total of 52 patients received at least one cycle of [177Lu]-PSMA-617. Clinical benefit was observed in 28 patients (52%). PSA decline ≥20% and ≥50% was observed in 26 (50%) and 18 patients (35%), respectively. Achievement of any PSA decline at first measurement was significantly associated with survival. There was a negative association between the number of previous chemotherapy lines and PSA decline above 20%. Univariate analysis followed by multivariable analysis showed that older age and higher hemoglobin were significantly associated with a PSA decline >20%. A score combining these two parameters was significantly associated with PSA response. In summary, [177Lu]-PSMA-617 is active in the ‘real-life’ setting of heavily pretreated men with mCRPC.

Background: Patients with non-small cell lung cancer (NSCLC) presenting with mesenchymal–epithelial transition ( MET) exon 14 skipping mutation have an unfavorable prognosis with standard treatments. Capmatinib is a selective MET inhibitor, which showed promising efficacy in this patient population in early trials. Methods: We performed a retrospective, international, multicenter efficacy and safety analysis in patients with NSCLC treated with capmatinib in an early access program between March 2019 and December 2021. Results: Data from 81 patients with advanced MET exon 14 mutated NSCLC treated with capmatinib in first- or later-line therapy were analyzed. Median age was 77 years (range, 48–91), 56% were women, 86% had stage IV disease, and 27% had brain metastases. For all patients, the objective response rate (ORR) to capmatinib was 58% (95% CI, 47–69), whereas it was 68% (95% CI, 50–82) in treatment-naïve and 50% (95% CI, 35–65) in pretreated patients. The median progression-free survival was 9.5 months (95% CI, 4.7–14.3), whereas it was 10.6 months (95% CI, 5.5–15.7) in first-line and 9.1 months (95% CI, 3.1–15.1) in pretreated patients. After a median follow-up of 11.0 months, the median overall survival was 18.2 months (95% CI, 13.2–23.1). In patients with measurable brain metastases ( n = 11), the intracranial ORR was 46% (95% CI, 17–77). Capmatinib showed a manageable safety profile. Grade ⩾ 3 treatment-related adverse events included peripheral edema (13%), elevated creatinine (4%), and elevated liver enzymes (3%). Conclusion: In patients with MET exon 14 skipping mutation, capmatinib showed durable systemic and intracranial efficacy and a manageable safety profile. This analysis confirms previously reported phase II data in a real-world setting.

PurposeBoth β1‐ and β2‐adrenoceptor proteins were detected on the cell surface of pancreatic ductal adenocarcinoma. The current study evaluated the association between beta‐blocker use and pancreatic cancer risk.MethodsWe conducted a nested case‐control study in a large population representative database. Each pancreatic cancer case was matched with four controls based on age, sex, practice site, and duration of follow‐up using incidence density sampling. Beta‐blocker use was defined as any prescription prior to index date and was stratified into non‐selective and selective β1‐blockers. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for pancreatic cancer risk associated with beta‐blocker use was estimated using conditional logistic regression.ResultsThe study included 4113 patients with pancreatic cancer and 16 072 matched controls. When compared to never users, there was no association between any beta‐blocker use and pancreatic cancer risk (adjusted OR 1.06, 95% CI 0.97‐1.16, P = .16). Analysis by receptor selectivity showed use of non‐selective beta‐blockers for more than 2 years was associated with a reduced pancreatic cancer risk (OR 0.75, 95% CI 0.57‐1.00, P = .05). When compared to former users both users of selective β1‐blockers and non‐selective beta‐blockers had a reduced pancreatic cancer risk (OR 0.78, 95% CI 0.67‐0.90, P = .001) and (OR 0.67, 95% CI 0.49‐0.92, P = .01), respectively.ConclusionBeta‐blocker use was not associated with increased pancreatic cancer risk. However, long‐term use of beta‐blockers may be associated with decreased pancreatic cancer risk.

IntroductionThe purpose is to describe the method, safety and efficacy of transperineal gold seed placement for image‐guided radiation therapy.MethodsAn ethics committee approved database was used to review records of consecutive patients from October 2008 through December 2013, who underwent transperineal implantation of three gold markers into the prostate using staged local anaesthesia and transrectal ultrasound. Seeds were counted on radiographs from CT simulation, first treatment and last treatment. Retention and use of at least three markers for kV/kV matching was considered a successful implant. A visual analogue scale (VAS) pain assessment was performed. SAS was used for data analysis.ResultsFiducial marker placement was successful for kV/kV matching in 556/581 patients (95.7%). The procedure was aborted due to pain in two patients. Additional sedation during the procedure was required in two patients. Complications include urinary infections (2 patients, <0.5%) and transient haematuria (2 patients, <0.5%). There were no recorded calls requesting additional pain medication or delays in radiation due to complications. The number of seeds identified at simulation: 4 (2 patients), 3 (554 patients), 2 (21 patients), 1 (1 patient), 0 (1 patient). One patient with three seeds and two patients with <2 seeds had cone beam CT instead of kV/kV imaging for image guidance. No seeds were lost after simulation. The mean visual analogue pain score associated with transperineal gold seed insertion met patients' expectations (respectively 4.1 vs. 4.4 P = 0.19).ConclusionOutpatient transperineal insertion of fiducials avoids the rectum, is effective, convenient, well tolerated and has few side effects.

ObjectiveTo evaluate outcomes in prostate cancer patients classified as high-risk (HR) or very high-risk (VHR) who were treated with conformal radiation therapy (CRT) and androgen deprivation therapy (ADT).MethodsBetween 11/2001 and 3/2012, 203 patients with HR disease received CRT to the prostate (78–82 Gy) and pelvic lymph nodes (46–50 Gy) with ADT (6 m-2 years). Median follow-up was 50 months (12 m-142 m). Biochemical failure was defined according to Phoenix definition. Imaging studies were used to identify local, regional or metastatic failure. Four different VHR/HR groupings were formed using the 2014 and revised 2015 NCCN guidelines. Differences were examined using Kaplan Meier (KM) estimates with log rank test and uni- and multivariate Cox regression analysis (MVA).ResultsFailure occurred in 30/203 patients (15%). Median time to failure was 30 m (4 m-76 m). KM estimate of 4 year biochemical disease free survival (b-DFS) for the entire cohort was 87% (95%CI: 82–92%). Four year KM survival estimates for b-DFS, PCSS and OS were comparable for each NCCN subgroup. On univariate analysis, the NCCN subgroups were not predictive of b-DFS at 4 years, however, DMFS was worse for both VHR subgroups (p = .03and .01) respectively. Cox univariate analysis was also significant for: PSA ≥40 ng/ml p = 0.001; clinical stages T2c p = .004, T3b p = .02 and > 4 cores with Gleason score 8–10 p < .03. On MVA, only PSA ≥ 40 ng/ml was predictive for b-DFS or MFS at 4 years (HR: 3.75 and 3.25, p < 0.005).ConclusionPatients with HR and VHR disease treated with CRT and ADT had good outcomes. Stratification into HR and VHR sub-groups provided no predictive value. Only PSA ≥40 ng/ml predicted poor outcomes on MVA. Distant failure was dominant and local recurrence rare, suggesting that improved systemic treatment rather than intensification of local therapy is needed.SummaryPatients with high-risk prostate cancer are most often treated with conformal dose escalated radiation therapy with androgen deprivation. Stratification into high versus very high-risk subgroups using 2014 or revised 2015 National Comprehensive Cancer Network (NCCN) criteria did not impact treatment outcomes. Only Prostate Serum Antigen (PSA) ≥40 ng/ml was predictive of poor prognosis. Distant failure was dominant and local recurrence uncommon which challenges the notion that intensification of local therapy will further improve outcomes in patients with high-risk disease.

Background Prostate cancer is a common malignancy of the elderly, and with the aging of the population, the need is growing for therapies suitable for this age group. Lutetium‐177–prostate‐specific membrane antigen (Lu‐PSMA), a radiolabeled small molecule, binds with high affinity to prostate‐specific membrane antigen, enabling beta particle therapy targeted to metastatic castration‐resistant prostate cancer (mCRPC). In a recent single‐arm phase II trial and a subsequent expansion cohort, a prostate‐specific antigen (PSA) decline of ≥50% was observed in approximately 60% of patients receiving Lu‐PSMA. Taking into account the specific challenges and potential toxicities of Lu‐PSMA administration in elderly men, we sought to retrospectively analyze the safety and activity of Lu‐PSMA in men aged older than 75 years with mCRPC. Patients and Methods The electronic medical records of 24 patients aged older than 75 years treated with Lu‐PSMA “off‐trial” were reviewed, and clinical data were extracted. Clinical endpoints were toxicity and activity, defined as a PSA decline ≥50%. Descriptive statistics were performed using Excel. Results The median age at treatment start was 81.7 years (range 75.1–91.9). The median number of previous treatment lines was four. The number of treatment cycles ranged from one to four; the mean administered radioactivity was 6 GBq per cycle. Treatment was generally tolerable; side effects included fatigue (n = 8, 33%), anemia (n = 7, 29%), thrombocytopenia (n = 5, 21%), and anorexia/nausea (n = 3, 13%). Clinical benefit was observed in 12 of 22 patients (54%); PSA decline above 50% was observed in 11 patients (48%) and was associated with significantly longer overall survival. Conclusion Our results indicate that Lu‐PSMA is safe and active in elderly patients with mCRPC. Implications for Practice Lutetium‐177–prostate‐specific membrane antigen (Lu‐PSMA), a radiolabeled small molecule, binds with high affinity to prostate‐specific membrane antigen, enabling beta particle therapy targeted to metastatic castration‐resistant prostate cancer (mCRPC). The recently published single‐arm phase II trial with Lu‐PSMA, describing its safety and activity, did not include patients aged older than 75 years. In this study, Lu‐PSMA activity was retrospectively analyzed in patients aged older than 75 years and results indicate that treatment was tolerable and similarly active in this age group, with no new emerging safety signals. Despite the small cohort size, this analysis suggests that Lu‐PSMA can serve as an advanced palliative treatment line in mCRPC in elderly patients.

This paper investigates the effect of both single-point and diamond-roll dressing techniques on the workpiece surface roughness in grinding. Two empirical surface roughness models are studied – one that incorporates single-point dressing parameters, and another that incorporates diamond-roll dressing parameters. For the experimental conditions used in this research, the corresponding empirical model coefficients are found to have a linear relationship with the inverse of the overlap ratio for single-point dressing and the interference angle for diamond-roll dressing. The resulting workpiece surface roughness models are then experimentally validated for different depths of cut, workpiece speeds and dressing conditions. In addition, the models are used to derive a relationship between overlap ratio for single-point dressing, and interference angle for diamond-roll dressing such that both dressing techniques produce a similar surface finish for a given material removal rate.