Integrating multi-modal imaging in radiation treatments for glioblastoma.

Advances in diagnostic and treatment technology along with rapid developments in translational research may now allow the realization of precision radiotherapy. Integration of biologically informed multimodality imaging to address the spatial and temporal heterogeneity underlying treatment resistance in glioblastoma is now possible for patient care, with evidence of safety and potential benefit. Beyond their diagnostic utility, several candidate imaging biomarkers have emerged in recent early-phase clinical trials of biologically based radiotherapy, and their definitive assessment in multicenter prospective trials is already in development. In this review, the rationale for clinical implementation of candidate advanced magnetic resonance imaging and positron emission tomography imaging biomarkers to guide personalized radiotherapy, the current landscape, and future directions for integrating imaging biomarkers into radiotherapy for glioblastoma are summarized. Moving forward, response-adaptive radiotherapy using biologically informed imaging biomarkers to address emerging treatment resistance in rational combination with novel systemic therapies may ultimately permit improvements in glioblastoma outcomes and true individualization of patient care.

Clinical significance of prostate cancer identified by transperineal standard template biopsy in men with nonsuspicious multiparametric magnetic resonance imaging.

OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) of the prostate has excellent sensitivity in detecting clinically significant prostate cancer (csCaP). However, whether a negative mpMRI in patients with a clinical suspicion of CaP can omit a confirmatory biopsy remains less understood and without consensus. Transperineal (TP) standard template biopsy (SBx) provides an effective approach to CaP detection. Our aim is to provide a comprehensive understanding of the CaP characteristics detected through TP SBx that are systematically overlooked by mpMRI. METHODS: We conducted a retrospective analysis of all men who underwent prebiopsy mpMRI and subsequent a 20-core TP SBx at our hospital from September 2019 to February 2021. Patients with suspicious mpMRI received a combined TP SBx and targeted biopsy (TBx) (suspicious group), while those without suspicious (negative) mpMRI and who proceeded to biopsy, received TP SBx only (nonsuspicious group). A negative mpMRI was defined as the absence of suspicious findings and/or the presence of low-risk areas with a PI-RADS score of ≤2. Subsequently, we compared and evaluated the clinical and biopsy characteristics between these 2 groups. RESULTS: We identified 301 men in suspicious group and 215 men in nonsuspicious group. The overall CaP detection rate and csCaP detection rate by TP SBx were 74.1%, 38.9% for suspicious group and 43.3%, 14.9% for nonsuspicious group, respectively. csCaP NPV of mpMRI was 85.1% with a csCaP prevalence 28.9%. The greatest percentage of cancer involvement (GPC) in biopsy core from nonsuspicious group was significantly lower than those of suspicious group (40% vs. 50%, p = 0.005), In multivariate logistic analysis, only PSAD > 0.15 ng/ml/cc was identified as an independent and significant predictor of csCaP in nonsuspicious group. CONCLUSION: Within our cohort, false-negative rates of mpMRI for csCaP are substantial, reaching 15%. Nonsuspicious cases may contain a large volume tumor since the high GPC of SBx. For cases with nonsuspicious imaging and higher PSAD, a confirmatory biopsy may be necessary due to the increased risk of missed csCaP by mpMRI.

Concurrent Lapatinib With Brain Radiation Therapy in Patients With HER2+ Breast Cancer With Brain Metastases: NRG Oncology-KROG/RTOG 1119 Phase 2 Randomized Trial.

PURPOSE: Lapatinib plus whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) was hypothesized to improve the 12-week intracranial complete response (CR) rate compared with either option of radiation therapy (RT) alone for patients with brain metastases (BM) from human epidermal growth factor receptor 2-positive (HER2+) breast cancer. METHODS AND MATERIALS: This study included patients with HER2+ breast cancer with ≥1 measurable, unirradiated BM. Patients were randomized to WBRT (37.5 Gy/3 wk)/SRS (size-based dosing) ± concurrent lapatinib (1000 mg daily for 6 weeks). Secondary endpoints included objective response rate (ORR), lesion-specific response, central nervous system progression-free survival, and overall survival. RESULTS: From July 2012 to September 2019, 143 patients were randomized, with 116 analyzable for the primary endpoint. RT + lapatinib did not improve 12-week CR (0% vs 6% for RT alone, 1-sided P = .97), or ORR at 12 weeks. At 4 weeks, RT + lapatinib showed higher ORR (55% vs 42%). Higher graded prognostic assessment and ≤10 lesions were associated with higher 12-week ORR. Grade 3 and 4 adverse event rates were 8% and 0% for RT and 28% and 6% for RT + lapatinib. CONCLUSIONS: The addition of 6 weeks of concomitant lapatinib to WBRT/SRS did not improve the primary endpoint of 12-week CR rate or 12-week ORR. Adding lapatinib to WBRT/SRS showed improvement of 4-week ORR, suggesting a short-term benefit from concomitant therapy.

Estimated Prostate Volume by Semiautomatic Segmentation of MRI Is More Accurately Correlated with Radical Prostatectomy Specimen Weight than the Volume Calculated by Ellipsoid Formula.

INTRODUCTION: Accurate in vivo prostate volume (PV) estimation is important for obtaining prostate-specific antigen density (PSAD) and further predicting clinically significant prostate cancer (csPCa). We aimed to evaluate the accuracy of multiparametric magnetic resonance imaging (mpMRI)-estimated PV compared to both volume and weight of radical prostatectomy (RP). METHODS: We identified 310 PCa patients who underwent RP following combined targeted and systematic biopsy in our institution from September 2019 to February 2021. The MRI PV was determined using a semiautomated segmentation algorithm. RP PV was calculated using the prolate ellipsoid formula (length × width × height × π/6). Formula (prostate weight = [actual weight-3.8 g]/1.05 g/mL) was applied, and the resulting volume was used in further analysis. RESULTS: The median PV from MRI, RP, and RP weight were 39 mL, 38 mL, and 44 mL, respectively. Spearman's rank correlation coefficients (ρ) were 0.841 (MRI PV vs. RP weight), 0.758 (RP PV vs. RP weight), and 0.707 (MRI PV vs. RP PV) (all p < 0.001). Decreased correlation between the MRI PV and RP PV was observed in the larger (more than 55 mL) prostate. The PSAD derived from MRI PV showed most efficient to detect csPCa in RP specimen (57.9% vs. 57.6% vs. 45.4%). CONCLUSION: MRI PV is correlated better with RP weight than calculated RP PV, especially in larger prostate. The high csPCa detection rate in final pathology suggested that PSAD derived from MRI PV can be confidently used in clinical practice.

A framework for standardised tissue sampling and processing during resection of diffuse intracranial glioma: joint recommendations from four RANO groups.

Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, how to define those regions on the basis of preoperative imaging, and the optimal sample volume. Practical recommendations for tissue sampling are given for people with low-grade and high-grade gliomas, as well as for people with newly diagnosed and recurrent disease. Sampling of liquid biopsies is also addressed. A standardised workflow for subsequent handling of the resected tissue is proposed to avoid information loss due to decreasing tissue quality or insufficient clinical information. The recommendations offer a framework for prospective biobanking studies.

Combined cytotoxic and immune-stimulatory gene therapy for primary adult high-grade glioma: a phase 1, first-in-human trial.

BACKGROUND: High-grade gliomas have a poor prognosis and do not respond well to treatment. Effective cancer immune responses depend on functional immune cells, which are typically absent from the brain. This study aimed to evaluate the safety and activity of two adenoviral vectors expressing HSV1-TK (Ad-hCMV-TK) and Flt3L (Ad-hCMV-Flt3L) in patients with high-grade glioma. METHODS: In this dose-finding, first-in-human trial, treatment-naive adults aged 18-75 years with newly identified high-grade glioma that was evaluated per immunotherapy response assessment in neuro-oncology criteria, and a Karnofsky Performance Status score of 70 or more, underwent maximal safe resection followed by injections of adenoviral vectors expressing HSV1-TK and Flt3L into the tumour bed. The study was conducted at the University of Michigan Medical School, Michigan Medicine (Ann Arbor, MI, USA). The study included six escalating doses of viral particles with starting doses of 1×1010 Ad-hCMV-TK viral particles and 1×109 Ad-hCMV-Flt3L viral particles (cohort A), and then 1×1011 Ad-hCMV-TK viral particles and 1×109 Ad-hCMV-Flt3L viral particles (cohort B), 1×1010 Ad-hCMV-TK viral particles and 1×1010 Ad-hCMV-Flt3L viral particles (cohort C), 1×1011 Ad-hCMV-TK viral particles and 1×1010 Ad-hCMV-Flt3L viral particles (cohort D), 1×1010 Ad-hCMV-TK viral particles and 1×1011 Ad-hCMV-Flt3L viral particles (cohort E), and 1×1011 Ad-hCMV-TK viral particles and 1×1011 Ad-hCMV-Flt3L viral particles (cohort F) following a 3+3 design. Two 1 mL tuberculin syringes were used to deliver freehand a mix of Ad-hCMV-TK and Ad-hCMV-Flt3L vectors into the walls of the resection cavity with a total injection of 2 mL distributed as 0·1 mL per site across 20 locations. Subsequently, patients received two 14-day courses of valacyclovir (2 g orally, three times per day) at 1-3 days and 10-12 weeks after vector administration and standad upfront chemoradiotherapy. The primary endpoint was the maximum tolerated dose of Ad-hCMV-Flt3L and Ad-hCMV-TK. Overall survival was a secondary endpoint. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT01811992. FINDINGS: Between April 8, 2014, and March 13, 2019, 21 patients were assessed for eligibility and 18 patients with high-grade glioma were enrolled and included in the analysis (three patients in each of the six dose cohorts); eight patients were female and ten were male. Neuropathological examination identified 14 (78%) patients with glioblastoma, three (17%) with gliosarcoma, and one (6%) with anaplastic ependymoma. The treatment was well-tolerated, and no dose-limiting toxicity was observed. The maximum tolerated dose was not reached. The most common serious grade 3-4 adverse events across all treatment groups were wound infection (four events in two patients) and thromboembolic events (five events in four patients). One death due to an adverse event (respiratory failure) occurred but was not related to study treatment. No treatment-related deaths occurred during the study. Median overall survival was 21·3 months (95% CI 11·1-26·1). INTERPRETATION: The combination of two adenoviral vectors demonstrated safety and feasibility in patients with high-grade glioma and warrants further investigation in a phase 1b/2 clinical trial. FUNDING: Funded in part by Phase One Foundation, Los Angeles, CA, The Board of Governors at Cedars-Sinai Medical Center, Los Angeles, CA, and The Rogel Cancer Center at The University of Michigan.

Detection of extraprostatic extension by transperineal multiparametric magnetic resonance imaging-ultrasound fusion targeted combined with systemic template prostate biopsy.

BACKGROUND: Extraprostatic extension (EPE) of prostate cancer (PCa) on transrectal (TR) needle core biopsy (Bx) is a rare histopathological finding that can help in clinical decision-making. The detection efficiency of the transperineal (TP) approach is yet to be explored. METHODS: We retrospectively reviewed 2848 PCa cases using concomitant systemic template biopsy (SBx) and multiparametric magnetic resonance imaging (MRI)-ultrasound fusion-targeted biopsy (TBx) using the TR (n = 1917) or TP (n = 931) approach at our institution between January 2015 and July 2022. We assessed and compared clinical, MRI, and biopsy characteristics using different approaches (TP and TR) and methods (SBx and TBx). RESULTS: In total, 40 EPE cases were identified (40/2848, 1.4%). TP showed a significantly higher EPE detection rate compared to TR in SBx (TR:0.7% vs. TP:1.6%; p = 0.028) and TBx (TR:0.5% vs. TP:1.2%; p = 0.033), as well as the combined methods (2.1% vs. 1.1%, p = 0.019). A significantly higher incidence of EPEs was found at non-base sites in TP than in TR (76.7% vs. 50%, p = 0.038). SBx showed a higher EPE detection rate than TBx; however, the difference was not statistically significant. TP showed higher prostate-specific antigen density (0.35 vs. 0.17, p = 0.005), higher frequency of GG4-5 in the cores with EPE (65.0% vs. 50.0%, p = 0.020), and more PCa-positive SBx cores (10 vs. 8, p = 0.023) compared to the TR. CONCLUSIONS: TP may improve EPE detection compared with TR and should be applied to patients with adverse pre-biopsy features.

Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways.

Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated in two completed multisite clinical studies. Patients treated with ONC201 following initial radiation but prior to recurrence demonstrated a median overall survival of 21.7 months, whereas those treated after recurrence had a median overall survival of 9.3 months. Radiographic response was associated with increased expression of key tricarboxylic acid cycle-related genes in baseline tumor sequencing. ONC201 treatment increased 2-hydroxyglutarate levels in cultured H3K27M-DMG cells and patient CSF samples. This corresponded with increases in repressive H3K27me3 in vitro and in human tumors accompanied by epigenetic downregulation of cell cycle regulation and neuroglial differentiation genes. Overall, ONC201 demonstrates efficacy in H3K27M-DMG by disrupting integrated metabolic and epigenetic pathways and reversing pathognomonic H3K27me3 reduction. SIGNIFICANCE: The clinical, radiographic, and molecular analyses included in this study demonstrate the efficacy of ONC201 in H3K27M-mutant DMG and support ONC201 as the first monotherapy to improve outcomes in H3K27M-mutant DMG beyond radiation. Mechanistically, ONC201 disrupts integrated metabolic and epigenetic pathways and reverses pathognomonic H3K27me3 reduction. This article is featured in Selected Articles from This Issue, p. 2293.

National Cancer Institute Collaborative Workshop on Shaping the Landscape of Brain Metastases Research: challenges and recommended priorities.

Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and research. At a virtual National Cancer Institute Workshop in September, 2022, key stakeholders convened to define research priorities to address the crucial areas of unmet need for patients with brain metastases to achieve meaningful advances in patient outcomes. This Policy Review outlines existing knowledge gaps, collaborative opportunities, and specific recommendations regarding consensus priorities and future directions in brain metastases research. Achieving major advances in research will require enhanced coordination between the ongoing efforts of individual organisations and consortia. Importantly, the continual and active engagement of patients and patient advocates will be necessary to ensure that the directionality of all efforts reflects what is most meaningful in the context of patient care.

Early vs Delayed Transurethral Surgery in Acute Urinary Retention: Does Timing Make a Difference?

PURPOSE: Our goal was to compare outcomes of early vs delayed transurethral surgery for benign prostatic hyperplasia after an episode of acute urinary retention compared to men without preoperative acute retention. MATERIALS AND METHODS: We conducted a retrospective cohort analysis using data from the New York Statewide Planning and Research Cooperative System from 2002-2016. We identified men ≥40 years old who underwent primary ambulatory transurethral resection or photoselective vaporization of the prostate, assessing surgical failure as time to reoperation or recatheterization. We categorized presurgical acute urinary retention by number of episodes: none (reference), 1, or ≥2 precatheterizations, and time from first retention episode to surgery: none (reference), 0-6 months, and >6 months. We used Fine-Gray competing-risk models to predict surgical failure at 10 years, with presurgical acute retention as the primary predictor, adjusted for age, race, insurance, Charlson Comorbidity Index score, preoperative urinary infection, and procedure type, with death as the competing risk. RESULTS: Among 17,474 patients undergoing transurethral surgery, 10% had preoperative acute retention with a median time to surgery of 2.4 months (IQR: 1-18). Among men with preoperative retention, 37% had ≥6 months of delay to surgery. The 10-year cumulative treatment failure rate was 17.2% among catheter naïve men vs 34.0% with ≥2 precatheterizations and 32.9% with ≥6 months delay to surgery. Delays from catheterization to surgery were associated with higher rates of treatment failure (<6 months SHR 1.49, P < .001; ≥6 months SHR 2.11, P < .001) vs catheter naïve men. CONCLUSIONS: Preoperative acute urinary retention and delay to surgery once catheterized are associated with poorer long-term postoperative outcomes after surgery for benign prostatic hyperplasia.

Metabolomic Profiles of Human Glioma Inform Patient Survival.

Aims: Targeting tumor metabolism may improve the outcomes for patients with glioblastoma (GBM). To further preclinical efforts targeting metabolism in GBM, we tested the hypothesis that brain tumors can be stratified into distinct metabolic groups with different patient outcomes. Therefore, to determine if tumor metabolites relate to patient survival, we profiled the metabolomes of human gliomas and correlated metabolic information with clinical data. Results: We found that isocitrate dehydrogenase-wildtype (IDHwt) GBMs are metabolically distinguishable from IDH mutated (IDHmut) astrocytomas and oligodendrogliomas. Survival of patients with IDHmut gliomas was expectedly more favorable than those with IDHwt GBM, and metabolic signatures can stratify IDHwt GBMs subtypes with varying prognoses. Patients whose GBMs were enriched in amino acids had improved survival, while those whose tumors were enriched for nucleotides, redox molecules, and lipid metabolites fared more poorly. These findings were recapitulated in validation cohorts using both metabolomic and transcriptomic data. Innovation: Our results suggest the existence of metabolic subtypes of GBM with differing prognoses, and further support the concept that metabolism may drive the aggressiveness of human gliomas. Conclusions: Our data show that metabolic signatures of human gliomas can inform patient survival. These findings may be used clinically to tailor novel metabolically targeted agents for GBM patients with different metabolic phenotypes. Antioxid. Redox Signal. 39, 942-956.

Gleason Grade Group Concordance between Systematic Template Combining Magnetic Resonance Imaging Fusion Targeted Biopsy and Radical Prostatectomy Specimens: A Comparison of Transperineal and Transrectal Approaches.

OBJECTIVE: To evaluate the Gleason grade (GG) discrepancy between biopsy (Bx) techniques (transperineal [TP] /transrectal [TR] approaches or multiparametric magnetic resonance imaging [mpMRI] targeted biopsy [TBx] / standard template biopsies [SBx]) and radical prostatectomy (RP) specimens. PATIENTS AND METHODS: We identified 310 prostate cancer (PCa) patients who underwent RP following either TP TBx combining SBx (20-core) (n = 105) or TR TBx combining SBx (12-core) (n = 205) from September 2019 to February 2021. The Bx GG was based on the core with the highest GG and clinically significant PCa (csPCa) was defined as grade group 2 or greater prostate adenocarcinoma. RESULTS: TP combined TBx and SBx (CBx) showed a better GG concordance (63.8% vs 57.1%) than the TR approach, but did not reach a statistical significance. TBx demonstrated a significantly higher csPCa detection than SBx in all patients including both approaches (70.2% vs 63.9%, P < .001). TR TBx showed a significantly higher concordance than TR SBx (52.2% vs 41.5%, P = .0.002) while TP TBx did not differ from TP SBx. TP CBx showed the highest Kappa coefficient (κ =0.48) followed by TR CBx (κ = 0.39). Thirty-eight of 69 (55.1%) cases with a GG1 diagnosis in CBx were upgraded to csPCa in RP. TR approach showed a trend of 2.8-fold risk to upgrade to RP csPCa than TP approach (P = .0.065). CONCLUSION: The combination of SBx and TBx led to a better pathological concordance and lower upgrading rate for both TP and TR approaches to RP. With more SBx cores, TP CBx showed a better performance than TR CBx.

NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma.

PURPOSE: To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, and secondary objectives included PFS, response rate, and treatment adverse events (AEs) including delayed CNS toxicities. METHODS: NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT and BEV versus BEV alone. Stratification factors included age, resection, and Karnofsky performance status (KPS). Patients with recurrent GBM with imaging evidence of tumor progression ≥ 6 months from completion of prior chemo-RT were eligible. Patients were randomly assigned 1:1 to re-RT, 35 Gy in 10 fractions, with concurrent BEV IV 10 mg/kg once in every 2 weeks or BEV alone until progression. RESULTS: From December 2012 to April 2016, 182 patients were randomly assigned, of whom 170 were eligible. Patient characteristics were well balanced between arms. The median follow-up for censored patients was 12.8 months. There was no improvement in OS for BEV + RT, hazard ratio, 0.98; 80% CI, 0.79 to 1.23; P = .46; the median survival time was 10.1 versus 9.7 months for BEV + RT versus BEV alone. The median PFS for BEV + RT was 7.1 versus 3.8 months for BEV, hazard ratio, 0.73; 95% CI, 0.53 to 1.0; P = .05. The 6-month PFS rate improved from 29.1% (95% CI, 19.1 to 39.1) for BEV to 54.3% (95% CI, 43.5 to 65.1) for BEV + RT, P = .001. Treatment was well tolerated. There were a 5% rate of acute grade 3+ treatment-related AEs and no delayed high-grade AEs. Most patients died of recurrent GBM. CONCLUSION: To our knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to evaluate the safety and efficacy of re-RT in recurrent GBM using modern RT techniques. Overall, re-RT was shown to be safe and well tolerated. BEV + RT demonstrated a clinically meaningful improvement in PFS, specifically the 6-month PFS rate but no difference in OS.

IMPACT the Brain: A Team-Based Approach to Management of Metastatic Breast Cancer With CNS Metastases.

PURPOSE: CNS metastases are associated with decreased survival and quality of life for patients with metastatic breast cancer (MBC). Team-based care can optimize outcomes. IMPACT the Brain is a care coordination program that aims to improve access to team-based care for patients with MBC and CNS metastases. MATERIALS AND METHODS: Patients with MBC and CNS metastases were eligible for enrollment in this care coordination program. A team of specialists supported a dedicated program coordinator who provided navigation, education, specialty referral, and clinical trial screening. A unique intake form developed for the program created personalized, coordinated, and expedited specialty referrals. Patient-reported outcomes and caregiver burden assessments were collected on a voluntary basis throughout enrollment. Data were analyzed using descriptive statistics. RESULTS: Sixty patients were referred, and 53 were enrolled (88%). The median time to program enrollment was 1 day (range, 0-11) and to first visit was 5 days (range, 0-25). On the basis of the program intake form, 47 referrals were made across six specialties, most commonly physical medicine and rehabilitation (n = 10), radiation oncology (n = 10), and neuropsychology (n = 10). Nineteen patients (36%) consented to enroll in clinical trials. CONCLUSION: A tailored team-based care coordination program for patients with MBC and CNS metastases is feasible. Use of a unique intake screening form by a dedicated program coordinator resulted in faster time to first patient visit, enabled access to subspecialist care, and supported enrollment in clinical trials. Future research should focus on intervention development using PRO data collected in this care coordination program.

Efficacy and toxicity with radiation field designs and concurrent temozolomide for CNS lymphoma.

Background: There is no consensus on the treatment of central nervous system (CNS) lymphoma refractory to first-line methotrexate-based chemotherapy. Whole brain radiotherapy (WBRT) is sometimes used but may result in unacceptable neurocognitive dysfunction. We examined the efficacy and toxicities of WBRT with or without concurrent temozolomide in CNS lymphoma treatment. Methods: This single-institution IRB-approved retrospective study included adults with CNS lymphoma who received WBRT, either consolidative low-dose WBRT alone or low-dose WBRT with a focal boost to residual disease and were previously treated with high-dose methotrexate. The relationships between the WBRT regimen, concurrent temozolomide, and clinical outcomes and toxicities were assessed using proportional hazards and logistic regression models. Results: A total of 45 patients with a median age of 64 years (range 24-74) treated from 2004 to 2019 were included. In total, 20 patients received concurrent temozolomide. In the WBRT + Boost cohort (n = 32), concurrent temozolomide resulted in better 2-year overall survival (OS) and progression free survival (PFS) (73% OS and 66% PFS) compared to patients treated without concurrent temozolomide (44% OS and 24% PFS). On multivariate analysis, concurrent temozolomide was associated with significantly better PFS (HR 0.28, P = .02). There were no significant differences between the two radiation groups or between those treated with or without concurrent temozolomide, with respect to significant acute hematologic, non-hematologic, and long-term neurocognitive toxicities (P > .05). Conclusions: In this study, concurrent temozolomide with radiotherapy in CNS lymphoma was associated with better PFS and was well tolerated. Low-dose WBRT with a boost is a safe and reasonable treatment approach for focal refractory disease. Prospective research that includes rigorous neurocognitive assessments is now warranted.

Ear-piercing complications in children and adolescents.

QUESTION: Ear piercing is one of the most common forms of body modification seen in children and adolescents presenting to my office. Parents of my younger pediatric patients inquire about potential post-piercing complications and risk factors associated with earlobe infections. What guidance should I give them? Also, are there any specific post-piercing complications to consider for older pediatric patients seeking second piercings in the upper cartilage area? ANSWER: Piercing the earlobe or auricular cartilage continues to be a popular procedure among children and adolescents. Despite its widespread practice, improper aseptic piercing technique, insufficient training, and trauma to the soft tissue during high-pressure piercing (eg, use of spring-loaded ear-piercing instruments) can increase one's susceptibility to infections, bleeding, and microfractures. Other post-piercing complications include embedded earrings, keloids, hypertrophic scarring, and cutaneous hypersensitivity. Early recognition and treatment of infections and perichondritis secondary to transcartilaginous piercings can prevent the progression of severe ear deformities requiring reconstructive surgical interventions.

Detection of clinically significant prostate cancer by transperineal multiparametric magnetic resonance imaging-ultrasound fusion targeted prostate biopsy in smaller prostates.

PURPOSE: Transperineal (TP) multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (TBx) has been shown to detect more clinically significant (cs) prostate cancer (PCa) than standard template biopsies (SBx). Current data supports the inclusion of both TBx and SBx in obtaining an optimal csPCa detection rate. We compared csPCa detection rates in patients with different prostate volumes to examine the benefit of performing TBx in smaller prostates through the TP approach. METHODS: We identified all men who with suspicious lesions on mpMRI and underwent TP TBx (3-core) and concomitant SBx (20-core) in our single hospital from September 2019 to February 2021. Clinical, MRI and biopsy pathological characteristics were evaluated and compared between TBx and SBx. Grade group 2 or greater prostate adenocarcinoma was defined as csPCa. RESULTS: Three hundred and one (n = 301) men were included. The median prostate volume by MRI was 45 ml. The patients were divided by prostate volume into three groups: ≤30ml group (19.9%), >30 to ≤45 ml group (31.3%) and >45ml group (48.8%). Patients in the ≤30ml group showed significantly higher frequency of combined (both TBx and/or SBx) csPCa detection rate (65.0%) than patients in the >45ml group (39.5%) but similar frequency to the >30 to ≤45 ml group (54.2%,). By TBx only (55.0% vs 27.9%) or by SBx only (56.7% vs. 34.0%), patients in the ≤30ml group consistently showed significantly higher rates of csPCa detection than patients in the >45 ml group. In the ≤30ml group, the detection rate of csPCa was comparable by TBx, SBx or when combined. Four of 6 csPCa cases missed by TBx but detected by SBx were present at the base location. CONCLUSION: Our data suggest that performing TBx with limited additional cores may potentially achieve the same csPCa detection rate as the combined SBx and TBx in smaller prostates.