[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. METHODS: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. FINDINGS: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. INTERPRETATION: The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. FUNDING: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company).

Prostate-specific Membrane Antigen Positron Emission Tomography-detected Disease Extent and Overall Survival of Patients with High-risk Nonmetastatic Castration-resistant Prostate Cancer: An International Multicenter Retrospective Study.

Previously, we demonstrated that prostate-specific membrane antigen positron emission tomography (PSMA-PET) revealed distant metastases in 109/200 patients (39% distant nodes, 24% bone, and 6% visceral organ) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features (International Society of Urological Pathology score ≥4 and/or prostate-specific antigen doubling time ≤10 mo) without metastases by conventional imaging. However, the impact of disease extent determined by PSMA-PET on patient outcomes is unknown. We followed these 200 patients for a median of 43 mo after PSMA-PET and retrospectively assessed the association between patient characteristics, PSMA-PET findings, treatment management, and outcomes using a Kaplan-Meier model and Cox multivariable regressions. Among assessed disease characteristics, polymetastatic disease (five or more distant lesions on PET) was independently associated with shorter overall survival (OS; median 61 mo vs not reached; hazard ratio [95% confidence interval], 1.81 [1.00-3.27]; p = 0.050) and time to new metastases (median 38 vs 60 mo; 1.80 [1.10-2.96]; p = 0.019), and initial pN1 status with shorter OS (55 mo vs not reached; 1.94 [1.12-3.37]; p = 0.019). Following PSMA-PET, locoregional salvage therapies were used most commonly in no/local disease (58%), and androgen receptor signaling inhibitors were used in distant metastatic disease (51%). PSMA-PET provides additional risk stratification for patients with nmCRPC. Polymetastatic disease (five or more distant lesions) is associated with worse outcomes. PATIENT SUMMARY: A novel sensitive imaging technology, called prostate-specific membrane antigen positron emission tomography (PSMA-PET), allows doctors to detect the spread of prostate cancer, known as distant metastases, earlier and more accurately than in the past. In our study, PSMA-PET detected none to many metastases in patients who were considered free of distant metastasis by conventional imaging. These findings predicted outcomes and were used to select appropriate treatment.

Impact of Lockdown on Air Quality in the Most Polluted Cities of India.

Background: COVID-19 has become a global pandemic, prompting lockdowns in practically every country. To prevent the spread of the disease, India has enforced a rigorous nationwide lockdown that commenced in March 2020. The lockdown imposed amid the pandemic ensured that most commercial activities and vehicle transportation ceased, resulting in a significant reduction in air pollution levels. Material and Methods: The value of air pollutants PM10, PM2.5, NO2, and SO2 from January to May 2020 was obtained from the Indian Central Pollution Control Board. Before lockdown and during lockdown, relative fluctuations in ambient concentrations of four air contaminants were investigated. The Box-Jenkins approach was used to estimate future air pollution data points using time series data analysis. Results: The PM10 level reduced by 61%, 30%, 68%, 37%, and 43% in the selected cities, respectively. Comparison of other pollutant concentrations before and after the lockdown also found a reduction in ambient pollutant concentrations, resulting in improved air quality. Inference of predicted model values to observed values revealed a significant increase in the concentrations of all pollutants. The percentage increases in AQImean from predicted to observed values were 206% in Ghaziabad, 148% in Delhi, 59% in Hyderabad, and 160% in Cochin. Conclusion: The strict lockdown has resulted in a significant drop in air pollutant levels. Upgrading present technologies could help keep pollution to a minimum of 37% under control. The findings would prompt the government to consider how to strictly reduce vehicle and industrial pollution to improve air quality and maintain improved public health.

Lung Involvement Patterns in COVID-19: CT Scan Insights and Prognostic Implications From a Tertiary Care Center in Southern India.

Background COVID-19, caused by the SARS-CoV-2 virus, has presented an unparalleled challenge and a profound learning curve globally. Among the myriad of investigative tools, CT scans of the chest have become instrumental in assessing the magnitude of lung involvement in the pathogenesis of this disease. Objectives This study aimed to evaluate the distribution and patterns of lung involvement depicted in the CT chest scans of COVID-19 patients admitted to a specialized tertiary care center located in a southern state of India. Methods With clearance secured from the Institutional Ethics Committee, an analytical cross-sectional study was conducted. It encompassed CT chest images from all symptomatic COVID-19 patients within the designated study center during the specified study timeline. Subsequent data analysis ensued. Results Among the 1066 COVID-19 patients evaluated, ground-glass opacities (GGO) were the predominant lung involvement pattern. Distinct patterns, such as GGOs combined with solid consolidation or atelectasis, were noted, with the highest mortality linked to GGOs paired with pneumomediastinum (PM). Data underscored a direct correlation between the extent of lung involvement and patient prognosis, with specific lung regions, namely the right apical, right posterior, right superior basal, left superior lingular, and left inferior lingular segments, showing frequent involvement. Conclusion Amidst the pandemic, our study emphasizes that ground-glass opacities on CT scans are robust indicators of COVID-19 in RT-PCR-positive patients. Early identification can enhance patient management, with findings highlighting a strong link between lung involvement and prognosis. This insight aids in refining patient triage, while further research is warranted to delve deeper into variations in lung involvement and guide treatment advancements.

Adjunctive High-Definition Transcranial Direct Current Stimulation in Brain Glutamate-Glutamine and γ-Aminobutyric Acid, Withdrawal and Craving During Early Abstinence Among Patients With Opioid Use Disorder on Buprenorphine-Naloxone: A Proton Magnetic Resonance Spectroscopy-Based Pilot Study.

OBJECTIVE: Our study aimed to (1) examine the effect of adjunctive high-definition transcranial direct current stimulation (HD-tDCS) in craving and withdrawal among patients with opioid use disorder on buprenorphine-naloxone, and (2) examine effect of HD-tDCS changes in glutamate-glutamine and γ-aminobutyric acid (GABA) at the left dorsolateral prefrontal cortex (DLPFC) among patients with opioid use disorder on buprenorphine-naloxone. METHODS: This was a pilot randomized double-blind, sham-controlled parallel-group study. A total of 28 patients on buprenorphine-naloxone (6/1.5 mg/d) were randomly allocated into 2 groups for active and sham HD-tDCS stimulation. High-definition transcranial direct current stimulation was administered twice daily for consecutive 5 days, from days 2 to 6. The Clinical Opiate Withdrawal Scale (COWS), the Desire for Drug Questionnaire (DDQ), the Obsessive-Compulsive Drug Use Scale (OCDUS), and glutamate-glutamine and GABA at DLPFC via proton magnetic resonance spectroscopy were measured at baseline and on day 7. RESULTS: Both active and sham groups had comparable changes in DDQ, OCDUS (except 2 subcomponents), COWS, and glutamate-glutamine and GABA at DLPFC. In the active HD-tDCS group, statistically significant reductions were observed in DDQ, OCDUS, and COWS but not in glutamate-glutamine and GABA. CONCLUSIONS: The adjunctive active HD-tDCS group showed comparable changes in craving and withdrawal, and glutamate-glutamine and GABA at DLPFC compared with sham HD-tDCS. Craving and withdrawal but not glutamate-glutamine and GABA at DLPFC decreased significantly with adjunctive HD-tDCS. Future studies with larger sample size and online assessment of glutamate-glutamine and GABA would enhance our knowledge.

Radiation Dosimetry in 177Lu-PSMA-617 Therapy.

Radionuclide therapy using the small molecule PSMA bound to the beta-emitting radionuclide, Lutetium-177 (177Lu-PSMA) has demonstrated efficacy and survival benefit castrate resistant metastatic disease and represents a novel new line of therapy. Whilst dosimetry was critical for early development, it was not incorporated into either the TheraP or VISION randomized studies, highlighting the difficulty of adopting dosimetry in routine clinical practice. Accumulated clinical experience has also shown that the common (and generally low grade) toxicities such as nausea, xerostomia, and cytopenias are not readily predicted on the basis of dosimetry estimates. The majority of dosimetry and clinical literature deals with the radiopharmaceutical 177Lu-PSMA-617 which displays relatively consistent patterns of retention among normal tissues and high specificity for metastatic prostate cancer phenotypes. Population dosimetry incorporating estimates to the kidneys, salivary glands, and bone marrow have been widely reported the typical range of doses is becoming well established. There is growing interest on tumor dosimetry in 177Lu-PSMA-617 therapy as an overall modest side-effect profile from primary organ retention has been observed. A focus away from normal organ dosimetry to whole body tumor dosimetry may enable early prediction of treatment failure. Given the safety of 177Lu-PSMA there is also potential to escalate administered radioactivity to further improve outcomes. Importantly, the variability of uptake between individuals, both to tumor and normal organs, has also been highlighted which provides some rationale for the utility of personalized radiation analysis to optimize treatment based on potential toxicity thresholds or tumor control. Methods to perform dosimetry using serial post treatment imaging may incorporate planar, 3D SPECT, or hybrid datasets. Reliable measurements may be obtained through either method, however, continued developments in computational analysis are better suited to fully 3D imaging; particularly in conjunction with volumetric CT to assist with alignment and contouring. Dose analysis over sequential treatment cycles is vital to understand the radiobiology of these treatments which is unique compared to external beam therapy due to dose rate, fractionation scheme, and potential for intratumoral nonuniformity.

Evolution of materials for implants in metastatic spine disease till date - Have we found an ideal material?

"Metastatic Spine Disease" (MSD) often requires surgical intervention and instrumentation with spinal implants. Ti6Al4V is widely used in metastatic spine tumor surgery (MSTS) and is the current implant material of choice due to improved biocompatibility, mechanical properties, and compatibility with imaging modalities compared to stainless steel. However, it is still not the ideal implant material due to the following issues. Ti6Al4V implants cause stress-shielding as their Young's modulus (110 gigapascal [GPa]) is higher than cortical bone (17-21 GPa). Ti6Al4V also generates artifacts on CT and MRI, which interfere with the process of postoperative radiotherapy (RT), including treatment planning and delivery. Similarly, charged particle therapy is hindered in the presence of Ti6Al4V. In addition, artifacts on CT and MRI may result in delayed recognition of tumor recurrence and postoperative complications. In comparison, polyether-ether-ketone (PEEK) is a promising alternative. PEEK has a low Young's modulus (3.6 GPa), which results in optimal load-sharing and produces minimal artifacts on imaging with less hinderance on postoperative RT. However, PEEK is bioinert and unable to provide sufficient stability in the immediate postoperative period. This issue may possibly be mitigated by combining PEEK with other materials to form composites or through surface modification, although further research is required in these areas. With the increasing incidence of MSD, it is an opportune time for the development of spinal implants that possess all the ideal material properties for use in MSTS. Our review will explore whether there is a current ideal implant material, available alternatives and whether these require further investigation.

Assessment of Planting Method and Deficit Irrigation Impacts on Physio-Morphology, Grain Yield and Water Use Efficiency of Maize (Zea mays L.) on Vertisols of Semi-Arid Tropics.

Agriculture in a water-limited environment is critically important for today and for the future. This research evaluates the impact of deficit irrigation in different planting methods on the physio-morphological traits, grain yield and WUE of maize (Zea mays L.). The experiment was carried out in 2015 and 2016, consisting of three planting methods (i.e., BBF, SNF, and DWF) and four irrigation levels (i.e., I10D: irrigation once in ten days, I40: irrigation at 40% DASM, I50: irrigation at 50% DASM, and I60: irrigation at 60% DASM). The results reveal that varying degrees of water stress due to planting methods and irrigation levels greatly influenced the maize physio-morphological traits and yield attributes. The combined effect of DWF + I50 benefited the maize in terms of higher leaf area, RWC, SPAD values, CGR, and LAD, followed by the SNF method at 60 DAS. As a result, DWF + I50 and SNF + I50 had higher 100 grain weight (30.5 to 31.8 g), cob weight (181.4 to 189.6 g cob-1) and grain yield (35.3% to 36.4%) compared to other treatments. However, the reduction in the number of irrigations (24.0%) under SNF + I50 resulted in a 34% water saving. Thus, under a water-limited situation in semi-arid tropics, the practice of the SNF method + I50 could be an alternative way to explore the physio-morphological benefits in maize.

Actinium-225 Prostate-specific Membrane Antigen Theranostics: Will α Beat ß?

Optimisation of prostate-specific membrane antigen (PSMA) based radioligand therapy (RLT) requires a focus on prospective trials.

The "Spinal Metastasis Invasiveness Index": A Novel Scoring System to Assess Surgical Invasiveness.

STUDY DESIGN: Retrospective review. OBJECTIVE: The aim of this study was to develop a surgical invasiveness index for metastatic spine tumor surgery (MSTS) that can serve as a standardized tool in predicting intraoperative blood loss and surgical duration; for the purpose of ascertaining resource requirements and aiding in patient education. SUMMARY OF BACKGROUND DATA: Magnitude of surgery is important in the metastatic spine disease (MSD) population since these patients have a continuing postoperative oncological process; a consideration that must be taken into account to maintain or improve quality of life. Surgical invasiveness indices have been established for general spine surgery, adult deformity, and cervical deformity, but not yet for spinal metastasis. METHODS: Demographic, oncological, and procedural data were collected from consecutive patients that underwent MSTS. Binary logistic regression, using median values for surgical duration and intraoperative estimated blood loss (EBL), was used to determine statistical significance of variables to be included in the "spinal metastasis invasiveness index" (SMII). The corresponding weightage of each of these variables was agreed upon by experienced spine surgeons. Multivariable regression analysis was used to predict operative time and EBL while controlling for demographical, procedural, and oncological characteristics. RESULTS: Two hundred and sixty-one MSD patients were included with a mean age of 59.7-years and near equal sex distribution. The SMII strongly predicted extended surgical duration (R2 = 0.28, P < 0.001) and high intraoperative blood loss (R2 = 0.18, P < 0.001). When compared to a previously established surgical invasiveness index, the SMII accounted for more variability in the outcomes. For every unit increase in score, there was a 42-mL increase in mean blood loss (P < 0.001) and 5-minute increase in mean operative time (P < 0.001). CONCLUSION: Long surgical duration and high blood loss were strongly predicted by the newly developed SMII. The use of the SMII may aid in preoperative risk assessment with the goal of improving patient outcomes and quality of life.Level of Evidence: 4.

Asymptomatic Construct Failure after Metastatic Spine Tumor Surgery: A New Entity or a Continuum with Symptomatic Failure?

STUDY DESIGN: Retrospective cohort study. PURPOSE: To study the incidence, onset, underlying mechanism, clinical course, and factors leading to asymptomatic construct failure (AsCF) after metastatic spinal tumor surgery (MSTS). OVERVIEW OF LITERATURE: The reported incidence rates for implant and/or construct failure after MSTS are low (1.9%-16%) and based on clinical presentations and revisions required for symptomatic failures (SFs). AsCF after MSTS has not been reported. METHODS: We conducted a retrospective analysis of 288 patients (246 for final analysis) who underwent MSTS between 2005-2015. Data collected were demographics and peri/postoperative clinical and radiological features. Early and late radiological AsCF were defined as presentation before and after 3 months, respectively. We analyzed patients with AsCF for risk factors and survival duration by performing competing risk regression analyses where AsCF was the event of interest, with SF and death as competing events. RESULTS: We observed AsCF in 41/246 patients (16.7%). The mean time to onset of AsCF after MSTS was 2 months (range, 1-9 months). Median survival of patients with AsCF was 20 and 41 months for early and late failures, respectively. Early AsCF accounted for 80.5% of cases, while late AsCF accounted for 19.5%. The commonest radiologically detectable AsCF mechanism was angular deformity (increase in kyphus) in 29 patients. Increasing age (p<0.02) and primary breast (13/41, 31.7%) (p<0.01) tumors were associated with higher AsCF rates. There was a non-significant trend towards AsCF in patients with a spinal instability neoplastic score ≥7, instrumentation across junctional regions, and construct lengths of 6-9 levels. None of the patients with AsCF underwent revision surgery. CONCLUSIONS: AsCF after MSTS is a distinct entity. Most patients with early AsCF did not require intervention. Patients who survived and maintained ambulation for longer periods had late failure. Increasing age and tumors with a better prognosis have a higher likelihood of developing AsCF. AsCF is not necessarily an indication for aggressive/urgent intervention.

A role of PSMA PET/CT in multimodality imaging approach in adenoid cystic carcinoma.

Adenoid cystic carcinoma is a rare disease and characterised by slow but unrelenting local progression and risk of haematogenous metastases. We present a case of locally unresectable disease where PSMA PET/CT provided complementary staging and early treatment response assessment.

Prostate-specific membrane antigen PET/computed tomography for staging prostate cancer.

PURPOSE OF REVIEW: Molecular imaging with PET/CT targeting the prostate-specific membrane antigen (PSMA) receptor is increasingly utilized in men with prostate cancer (PCa), with clinical indications now expanding beyond biochemical recurrence. PSMA PET/CT often detects sub-centimetre size pathologic nodes and low-volume bone marrow disease that are occult on conventional imaging when the lesion does not cause sclerosis or osteoblastic reaction in surrounding bone. This review focuses on recent evidence for PSMA PET/CT in initial disease staging. RECENT FINDINGS: Several recent studies including a large randomized trial have evaluated the clinical impact of PSMA PET/CT in initial staging of PCa. PSMA PET/CT is more sensitive and accurate than the conventional imaging standard of CT and bone scan. Change in treatment plan or modality of therapy occurs frequently when PSMA PET/CT forms part of the diagnostic algorithm. Hybrid PET/MRI also has potential utility, particularly in evaluating pelvic disease, but evidence base remains very limited. SUMMARY: PSMA PET/CT has emerged as a new standard in primary staging of PCa. Reimbursement by national funding bodies and incorporation into international clinical guidelines is anticipated within the next few years.

The Effect of High Dose Rate Interstitial Implant on Early and Locally Advanced Oral Cavity Cancers: Update and Long-Term Follow-Up Study.

Introduction Brachytherapy, with or without external beam radiation therapy (EBRT), can be an alternative to surgery for organ preservation in early and locally advanced oral cavity cancers. This study aims to evaluate the effect of high dose rate (HDR) interstitial brachytherapy on early and locally advanced squamous cell carcinoma (SCC) of the oral cavity when used alone or as a boost to EBRT. Methods A total of 125 patients with histologically proven stage T1-3/N0-1 SCC of the oral cavity were included in the study. A total of 15 patients with stage I disease received an interstitial implant dose of 3,850 cGy at 350 cGy per fraction, two fractions a day. Another 53 patients had stage II, and 57 patients had stage III disease; these patients received EBRT of 50 Gy in 25 fractions along with an HDR brachytherapy boost of 21 Gy in seven fractions of 3 Gy per fraction twice daily. The stage III patients also received concurrent chemotherapy with injections of cisplatin (70 mg/m2) given every three weeks for three days in divided doses. All node-positive patients received a boost to the node of up to 64 Gy by external beam radiation. Disease response rates, five-year disease-free survival rates, and toxicities were analyzed. Results The median follow-up was 60 months. Among the patients, 103 (82.4%) had a complete response, while 22 (17.6%) had residual disease and were referred for surgical salvage. The five-year disease-free survival was 100% in stage I, 83% in stage II, and 77.2% in stage III; 4% of patients developed grade 3 acute skin toxicity and 23.2% developed acute grade 3 mucositis. Eleven patients died during the follow-up period. Two patients died due to myocardial infarction but had achieved a complete tumor response. One patient had pulmonary tuberculosis and died due to fulminant infection after three years of disease-free survival period. One patient developed a second primary in the brain stem that presented with quadriplegia and expired. Seven patients died due to the progression of the initial disease. Conclusions Proper brachytherapy technique and meticulous planning can minimize the toxicity while providing better tumor control and achieve high local control rates. Brachytherapy, with or without EBRT, can be a surrogate to surgery in early oral cavity cancers as it can achieve organ preservation while providing good functional outcomes.

Postoperative Pain with Hand, Reciprocating, and Rotary Instrumentation Techniques after Root Canal Preparation in Primary Molars: A Randomized Clinical Trial.

AIM: The purpose of this randomized clinical trial was to evaluate the intensity and duration of postoperative pain after pulpectomy of primary teeth using three preparation techniques. MATERIALS AND METHODS: A total of 60 patients were randomly allocated to three groups of 20 patients each, according to the root canal instrumentation techniques used. In group I, the teeth were prepared using manual NiTi K flex files till size 35. In group II, the teeth were prepared using NiTi K flex files till size 35 in reciprocating motion. In group III, the teeth were prepared using Kedo-S pediatric rotary files. After root canal preparation, the canals were obturated with endoflas paste and were restored permanently with composite filling material. The intensity and duration of postoperative pain were evaluated after 6, 12, 24, 48, and 72 hours, using a four-point pain-intensity scale. RESULTS: There was a statistically significant difference among the groups, wherein the postoperative pain was more in NiTi K flex files used in reciprocating motion followed by manual NiTi K flex files and Kedo-S pediatric rotary files. CONCLUSION: Postoperative pain was more with NiTi K flex files in reciprocating motion and was less with Kedo-S rotary files after root canal preparation in primary maxillary molars. HOW TO CITE THIS ARTICLE: Jeevanandan G, Ravindran V, Subramanian EMG, et al. Postoperative Pain with Hand, Reciprocating, and Rotary Instrumentation Techniques after Root Canal Preparation in Primary Molars: A Randomized Clinical Trial. Int J Clin Pediatr Dent 2020;13(1):21-26.

Mechanistic Insights for Optimizing PSMA Radioligand Therapy.

PSMA radioligand therapy is a promising new class of therapy for prostate cancer. Heterogeneity of PSMA expression is an important factor explaining variability in clinical results. The ability to visualize the target with theranostics provides unique mechanistic insights. Potential clinically applicable strategies to improve patient selection and optimize therapeutic efficacy are discussed.See related article by Current et al., p. 2946.

Prognostic biomarkers in men with metastatic castration-resistant prostate cancer receiving [177Lu]-PSMA-617.

PURPOSE: We analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific membrane antigen (LuPSMA) phase 2 trial. METHODS: PET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone. Baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH), prostate specific antigen (PSA) and PSA doubling time were also used in this analysis. We used univariate cox regression analysis and log-rank comparison with optimised cut-offs to find suitable biomarkers prognostic of overall survival from time of enrolment. RESULTS: This analysis identified FDG-positive tumour volume (FDGvol; HR 2.6; 95% CI, 1.4-4.8), mean intensity of PSMA-avid tumour uptake (PSMAmean; HR 0.89; 95% CI, 0.8-0.98), bone scan index (BSI; HR 2.3; 95% CI, 1.2-4.4), ALP (HR 1.1; 95% CI, 1-1.2) and LDH (HR 1.2; 95% CI, 1-1.5) as biomarkers prognostic of overall survival. CONCLUSIONS: In addition to established biomarkers, both FDG and PSMA PET/CT parameters have prognostic significance for survival in men undergoing LuPSMA therapy.