An expanded safety/feasibility study of the EMulate Therapeutics Voyager™ System in patients with recurrent glioblastoma.

Aim: The EMulate Therapeutics Voyager™ is a simple, wearable, home-use device that uses an alternating electromagnetic field to alter biologic signaling within cells. Objective: To assess the safety/feasibility of the Voyager in the treatment of recurrent glioblastoma (rGBM). Methods: In this study, patients with rGBM were treated with Voyager as monotherapy or in combination with standard chemotherapy at the Investigator's discretion. Safety was assessed by incidence of adverse events associated with the Voyager. Patients were followed until death. Results: A total of 75 patients were enrolled and treated for at least one day with the Voyager (safety population). Device-related adverse events were uncommon and generally did not result in interruption or withdrawal from treatment. There were no serious adverse events associated with Voyager. A total of 60 patients were treated for at least one month (clinical utility population). The median progression-free survival (PFS) was 17 weeks (4.3 months) in the Voyager only group (n = 24) and 21 weeks (5.3 months) in the Voyager + concurrent therapy group (n = 36). The median overall survival (OS) was 7 months in the Voyager only group and 9 months in the Voyager + concurrent therapy group. In patients treated with Voyager + concurrent therapy, the median OS for patients enrolled with their 1st or 2nd recurrence (n = 26) was 10 months, while in patients enrolled with their 3rd or 4th recurrence (n = 10) OS was 7 months. Conclusion: The data support the safety and feasibility of the Voyager for the treatment of rGBM. Further prospective study of the device is warranted. Trial Registration Number: NCT02296580 (ClinicalTrials.gov).

Are high-risk prostate cancer patients being treated equally? The impact of PSA.

BACKGROUND: Patients with high-risk (HR) prostate cancer (PCa) represent a heterogeneous group, however, current treatment guidelines do not consider their specific features. The objective of this study was to evaluate treatment trends and outcomes in HR patients defined by PSA alone and otherwise low-risk features. METHODS: Using the National Cancer Database, we identified patients diagnosed with HR PCa between 2010 and 2016. A study group of patients defined by PSA >20 ng/ml alone and otherwise low-risk features, was compared to a group of HR patients defined by Gleason score or stage. We compared treatment rates over time, the use of concomitant androgen deprivation therapy (ADT), and overall survival (OS). Examination of treatment trends was done using a Z-test analysis. A Kaplan-Meier survival analysis was used to determine 5-year OS with the Log-rank test for comparison. Statistical analyses were completed using R Version 3.5.2. RESULTS: We identified 5,652 patients in the study group and 71,922 in the comparison group. Only 6.8% of the study group had disease ≥cT2, compared to 43.7% in the comparison group. In the study group, 12.5% (709), underwent active surveillance (AS), 36.4% (2,055) radiation therapy (EBRT) and 51.1% (2,888) radical prostatectomy (RP), while the rate of AS, EBRT, and RP in the comparison group were 0.3% (191), 43.0% (30,928), and 56.7% (40,803), respectively. Over the study period, adoption of AS increased from 6.2% in 2010 to 25.0% in 2016 in the study group (P< 0.001), but not in the comparison group. In patients undergoing EBRT, ADT treatment increased from 2010 to 2016 in both groups, though by 2016 only 45.3% of patients in the study group and 86.3% in the comparison group received ADT. The 5-year OS was 93.7% (95% CI 92.8-94.6) in the study group and 89.7% (95% CI 89.2-90.1) in the comparison group (P< 0.001). CONCLUSIONS: Men with HR PCa defined by PSA with otherwise low risk features present at an earlier stage and receive less aggressive therapy than other HR patients. Despite increased rates of AS and decreased use of ADT, these patients appear to have improved survival when compared to other HR patients. These findings suggest that not all HR patients will benefit from aggressive definitive treatment.

Prospective Long-term Health-related Quality of Life Outcomes After Surgery, Radiotherapy, or Active Surveillance for Localized Prostate Cancer.

Background: Localized prostate cancer (PCa) treatment is associated with reduced health-related quality of life (HRQoL). Current literature is limited by short-term follow-up. Objective: To prospectively evaluate the 5-yr HRQoL outcomes in men undergoing radical prostatectomy (RP), external beam radiotherapy (EBRT), or active surveillance (AS). Design setting and participants: We prospectively evaluated HRQoL in patients with low-risk/favorable intermediate-risk PCa enrolled in the Center for Prostate Disease Research multicenter database between 2007 and 2017. Intervention: Of 1012 patients included in the study, 252 (24.9%) underwent AS, 557 (55.0%) RP, and 203 (20.0%) EBRT. Patients complete the Expanded Prostate Cancer Index Composite and the 36-item Medical Outcomes Study Short Form at baseline and thereafter each year up to 5 yr after treatment. Outcome measurements and statistical analysis: Temporal changes in HRQoL were compared between treatments and were modeled using linear regression models adjusted for baseline HRQoL, demographic, and clinical characteristics. Results and limitations: RP showed the least irritative symptoms and worse incontinence in comparison with AS (p < 0.001 for both subdomains) or EBRT (p < 0.001 for both subdomains) at all time points. RP sexual domain score was worse than the scores of AS (mean difference 22.3 points, 95% confidence interval [CI] 10.5-27.8, p < 0.001) and EBRT (mean difference 16.9 points, 95% CI 12.5-20.3, p < 0.001) during years 1-3 and not different from that of EBRT (mean difference 2.9 points, 95% CI -4.8 to 8.3, p = 0.3) at years 4 and 5. Bowel function and bother were worse for EBRT than for AS (p < 0.001 for both subdomains) and RP (p < 0.001 for both subdomains) at all time points. During the 3-5-yr period, AS demonstrated the worst decline in all mental health domains (p < 0.001 in comparison with both EBRT and RP). Conclusions: RP results in worse long-term urinary function and incontinence, but in less irritative and obstructive symptoms than EBRT and AS. Sexual domain scores were least affected by AS, while RP shows similar scores to EBRT at long term. Long-term HRQoL changes are critical for advising patients. Patient summary: We evaluated long-term health-related quality of life (HRQoL) in a large US population treated for localized prostate cancer. HRQoL outcomes varied according to treatment modality and time. These changes should inform patients about their expected outcomes following treatment.

The role of multiparametric ultrasound in the detection of clinically significant prostate cancer.

PURPOSE: Transrectal ultrasound (US) imaging is paramount to the successful completion of prostate biopsies. Certain US features have been associated with prostate cancer (PCa), but their utility remains controversial. We explored the role of multiparametric US (mpUS) in the detection of clinically significant PCa. METHODS: We performed a retrospective cohort study to contrast the findings of prostate MRI and mpUS. Patients who underwent MRI, US and biopsy between 2015 and 2021 were included. Biopsies were performed using a systematic approach (12 cores), as well as with MRI (4 cores/lesion) and US (1 core/lesion) targeting. The US features analyzed consisted of: calcifications, hypoechoic lesions and power or color Doppler positivity. Gleason 3 + 4 or higher was used as to define true positives. Measures of diagnostic accuracy were calculated for the different imaging modalities. RESULTS: The final cohort included 74 patients, of which 24 (32.4%) had clinically significant PCa. The concordance between MRI and US was 63.5%. Seven individuals with discordant results had clinically significant PCa. MRI alone was more sensitive (87.5% vs 75%) but less specific (28% vs 32%) than US alone. An all-inclusive approach considering any suspicious US or MRI finding had a sensitivity of 95.8%. A more restrictive approach, targeting lesions noted in both US and MRI, yielded the highest specificity (50.0%) and accuracy (55.4%). CONCLUSION: Biopsy targeting based on US findings can provide additional diagnostic information that may increase sensitivity or specificity. Additional research into this topic could open the door to a more personalized approach to prostate biopsy.

The effect of race on treatment patterns and subsequent health-related quality of life outcomes in men undergoing treatment for localized prostate cancer.

INTRODUCTION: Racial differences in Health-Related Quality of Life (HRQoL) after treatment of prostate cancer (PCa) are not well studied. We compared treatment patterns and HRQoL in African American (AA) and non-AA men undergoing active surveillance (AS), radical prostatectomy (RP), or radiation (XRT). METHODS: Men diagnosed with PCa from 2007-2017 in the Center for Prostate Disease Research Database were identified. HRQoL was evaluated using Expanded PCa Index Composite and SF-36 Health Survey. RESULTS: In 1006 men with localized PCa, 223 (22.2%) were AA (mean follow up 5.2 yrs). AA men with low-risk disease were less likely to undergo AS (28.5 vs. 38.8%) and more likely to undergo XRT (22.3 vs. 10.6%) than non-AA men, p < 0.001. In intermediate-risk disease, AA received more XRT (43.0 vs. 26.9%) and less RP (50.5 vs 66.8%), p = 0.016. In all men, RP resulted in worse urinary function and sexual HRQoL compared to AS and XRT. Bowel HRQoL did not vary by treatment in AA men, however, in non-AA men, XRT resulted in worse bowel scores than AS and RP. HRQoL was then compared for each treatment modality. AA men had worse sexual bother (p = 0.024) after RP than non-AA men, No racial differences were found in urinary, bowel, hormonal, or SF-36 scores for men undergoing AS, RP or XRT. CONCLUSION: AA men are less often treated with AS for low-risk disease and are more likely to undergo XRT. AA men experience worse sexual bother after RP, however, the effect of XRT on bowel symptoms is worse in non-AA men.

Impact of COVID-19 on Society of Urologic Oncology fellowship operative volumes.

PURPOSE: The COVID-19 pandemic impacted all aspects of healthcare including surgical training. Our objective was to assess the impact of the pandemic on surgical case volumes of graduating Society of Urologic Oncology (SUO) fellows during the academic years 2019 to 2020 and 2020 to 2021. MATERIALS AND METHODS: Deidentified case logs for graduating SUO fellows from 2017 to 2021 were obtained from the SUO Education Committee. Cases are stratified by category and minimally invasive surgery (MIS) or open approach. Graduates of 2017, 2018, and 2019 were combined into a pre-COVID cohort and compared to COVID-affected 2020 and 2021 cohorts. Total case volumes, case category volumes, and surgical approach type were compared with Kruskal-Wallis test. RESULTS: A total of 173 graduating SUO fellow case logs were analyzed with 100, 38, and 35 in the pre-COVID and COVID-affected 2020 and 2021 cohorts, respectively. All fellow logs were obtained for 2017 to 2020 graduates while 5 of 40 were missing for the 2021 cohort. There was no statistical difference in median total cases across cohorts (P = 0.52). For the first COVID-affected cohort of 2020, they reported significantly fewer total MIS cases in 2020 compared to pre-COVID fellows (median 92.5 vs. 135 pre-COVID, P = 0.002). However, there were no significant differences among the tracked oncologic MIS categories except a statistically significant increase in MIS retroperitoneal lymph node dissection between 2020 and 2021 COVID-affected cohorts (0 vs. 2, P = 0.033) CONCLUSIONS: The oncologic case volumes of the initial SUO fellows graduating during COVID pandemic were minimally affected. This national deidentified data is reassuring that oncologic training has not been impacted by widespread decreases in case volume. However, impacts on individuals, programs or geographic regions may have varied.

Patient reported outcomes and health related quality of life in localized prostate cancer: A review of current evidence.

BACKGROUND: Oncological outcomes after localized prostate cancer (CaP) treatment are excellent and generally considered equivalent across treatment modalities. Thus, short, and long-term patient health related quality of life (HRQoL) is an important factor in treatment discussions. The purpose of this review was to assess the impact of treatment modality for localized CaP on HRQoL as reflected by recent published trials. METHODS: We conducted a literature review using the PubMed database for studies published between January 2010 and January 2021. We included randomized control trials and observational cohort studies examining HRQoL in patients with localized CaP treated with active surveillance, radical prostatectomy, external beam radiotherapy or brachytherapy. RESULTS: Four randomized control trials and 15 prospective cohort studies were reviewed. Current evidence suggests that surgery has the largest short and long-term negative effect on sexual function and incontinence but advantages with regards to bowel function and irritative-obstructive urinary symptoms. Radiation therapy mainly impacts urinary irritative symptoms and bowel bother. Short-term HRQoL outcomes for active surveillance are most favorable, however, during long-term follow up, there is no significant difference in comparison to radiation. Long-term global quality of life impact regarding anxiety, mental, emotional well-being, and fatigue seem to be equivalent between treatment modalities. CONCLUSIONS: The choice of primary treatment modality for localized CaP results in a unique impact profile on cancer specific HRQoL in both the short and long-term periods. Understanding the different adverse events profiles can provide a basis for informing patients and clinicians regarding the impact of disease and treatments on quality of life and allow for a better patient centered discussion.

Use of Neoadjuvant Chemotherapy in Elderly Patients With Muscle-Invasive Bladder Cancer: A Population-Based Study, 2006-2017.

Objectives/Introduction Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is associated with survival benefit across patients of all ages, yet it is not offered to many elderly patients. We aimed to evaluate age-based disparity in treatment and outcomes of MIBC. Methods Using the National Cancer Database, we identified patients with MIBC from 2006 to 2017. Use of treatment modalities was compared between age groups. A second analysis compared perioperative outcomes and overall survival (OS) in elderly patients (70 years or older) undergoing RC with NAC vs no NAC. Propensity score weighting (PSW) was used for each analysis. Results In 70,911 patients, use of NAC with RC was lower in patients 70 years or older (7.2% vs 20.9%; P < .001). In patients 70 years or older undergoing RC, NAC was associated with shorter inpatient stay (8.5 vs 9.6 days; P < .001), decreased 30-day readmission (8.6% vs 10.6%; P <.001), and lower 30- and 90-day mortality (1.5% vs 3.1%; P = .01; and 4.9% vs 7.7%; P = .003, respectively). On weighted multivariate regressions, NAC predicted shorter length of stay and lower 30-and 90-day mortality. Elderly patients receiving NAC had improved OS compared with RC alone (P = .0011, 2010-2013; P < .001, 2014-2016). Conclusions Despite increased omission of NAC in patients 70 years or older, elderly patients receiving NAC and RC had improved perioperative outcomes and OS compared with those undergoing RC alone. There may be selection bias unaccounted for with our PSW; however, our results provide compelling evidence that NAC does not compromise surgical outcomes in appropriately selected elderly patients. Patients of advanced age who are candidates for RC should be offered NAC.

Impact of Age and Race on Health-Related Quality of Life Outcomes in Patients Undergoing Radical Prostatectomy for Localized Prostate Cancer.

OBJECTIVES: To investigate impact of age and race on health-related quality of life (HRQoL) in men undergoing radical prostatectomy (RP) using a prospectively maintained, racially diverse cohort. METHODS: The Center for Prostate Disease Research Multicenter National Database was used to identify patients receiving RP from 2007-2017. The Expanded PCa Index Composite and 36 Item Short-Form Health Survey were completed at baseline and regular intervals. Groups were stratified based on age: <60, 60-70, >70. Longitudinal patterns in HRQoL were assessed using linear regression models, adjusting for baseline HRQoL, demographics, and clinical characteristics. RESULTS: In 626 patients undergoing RP, 278 (44.4%) were <60, 291 (46.5%) were 60-70, 57 (9.1%) were >70. Older men had worse baseline urinary bother (P<.01) and sexual HRQoL (P<.01). Baseline urinary function was similar for older and younger men. Post-RP urinary and sexual HRQoL was significantly lower in men >70. However, when adjusting for baseline HRQoL, race, NCCN risk, and comorbidities, no difference was found between age groups in urinary function or bother, or sexual function. Sexual bother was worse in older men until 48 months post-operatively but subsequently improved to levels similar to younger patients. Race independently affected HRQoL outcomes with older African American men reporting worse urinary function and sexual bother. CONCLUSIONS: When accounting for baseline HRQoL, age does not independently predict worse HRQoL outcomes. Older and younger men experience similar declines in urinary and sexual domain scores after RP. Our findings may be used to better inform patients regarding their expected post RP HRQoL and guide treatment decision-making.

Rare Causes of Isolated and Progressive Splenic Lesions: Challenges in Differential Diagnosis, Evaluation, and Treatment of Primary Splenic Lymphomas.

The spleen is among the most common extranodal sites for Hodgkin and non-Hodgkin lymphomas (NHLs); however, among lymphomas arising from the spleen, primary splenic lymphomas (PSLs) are rare. The group of PSLs includes primary splenic diffuse large B-cell lymphoma (PS-DLBCL), splenic red pulp small B-cell lymphoma, splenic marginal zone lymphoma (SMZL), and a splenic hairy cell leukemia variant. Delineating between the PSL variants can be challenging, especially as fine-needle aspirate and core needle biopsy of the spleen are not routinely offered at most medical centers. Herein, we describe the clinical course of 2 representative patients who presented with non-specific gastrointestinal symptoms, the first who was diagnosed with PS-DLBCL and the second who was diagnosed with SMZL. We review and contrast the clinical presentations, imaging techniques, and laboratory findings of these discrete lymphoma variants and offer strategies on how to delineate between these varied splenic processes. We also examine the use of splenectomy and splenic needle biopsy as diagnostics and, in the case of splenectomy, a therapeutic tool. Finally, we also briefly review treatment options for these varied lymphoma sub-types while acknowledging that randomized trials to guide best practices for PSLs are lacking.

Combined chemotherapy and radiotherapy improves survival in 1897 testicular Lymphoma patients from a contemporary cohort.

INTRODUCTION: The standard of care (SOC) for primary testicular lymphoma (PTL) is orchiectomy, chemotherapy (CHT), and radiotherapy (RT). We hypothesized that men may not receive SOC and may have worse outcomes. To assess this, we queried the National Cancer Database (NCDB) to analyze treatment patterns and survival in PTL patients. METHODS: The NCDB was queried (2006-2016) for men diagnosed with extranodal lymphoma with primary site testis. Patients were placed in 2 treatment groups (1) orchiectomy with chemotherapy plus radiotherapy (CHT + RT), named the SOC group; and 2) CHT + orchiectomy, or RT + orchiectomy, or orchiectomy alone, grouped as non-SOC. Propensity score matching and Kaplan-Meier analysis were used to investigate 5-year overall survival (OS). RESULTS: Two thousand two hundred thirty-two men with PTL underwent orchiectomy. After exclusions, 891 men were included in the SOC group and 1,006 men were included in the non-SOC group. KM analysis showed 5-year OS was significantly higher in the SOC group vs. non-SOC for all stages (hazard ratio = 0.54, with 95% confidence interval 0.45 to 0.65, P < 0.0001). CONCLUSIONS: This study represents one of the largest PTL cohort reported to date reflecting current treatments and shows men receiving standard of care treatment have significantly improved survival. Additionally, analysis reveals that most men included in the NCDB do not receive the standard of care.

A prospective analysis of health-related quality of life in intermediate and high-risk prostate cancer patients managed with intensity modulated radiation therapy, with vs. without hormonal therapy.

INTRODUCTION: Combined radiotherapy and hormonal treatment are recommended for intermediate- and high-risk prostate cancer (CaP). This study compared the long-term effects on health-related quality of life (HRQoL) of intermediate- and high-risk CaP patients managed with radiation therapy (RT) with vs. without hormone therapy (HT). METHODS: Patients with intermediate- and high-risk CaP enrolled in the Center for Prostate Disease Research diagnosed from 2007 to 2017 were included. EPIC and SF-36 questionnaires were completed and HRQoL scores were compared for patients receiving RT vs. RT + HT at baseline (pretreatment), 6, 12, 24, 36, 48, and 60 months after CaP diagnosis. Longitudinal patterns of change in HRQoL were modeled using linear regression models, adjusting for baseline HRQoL, age at CaP diagnosis, race, comorbidities, National Comprehensive Cancer Network (NCCN) risk stratum, time to treatment, and follow-up time. RESULTS: Of 164 patients, 93 (56.7%) received RT alone and 71 (43.3%) received RT + HT. Both groups reported comparable baseline HRQoL. Patients receiving RT+HT were more likely to be NCCN high risk as compared to those receiving only RT. The RT + HT patients experienced worse sexual function, hormonal function, and hormonal bother than those who only received RT; however, HRQoL recovered over time for the RT + HT group. No significant differences were observed between groups in urinary and bowel domains or SF-36 mental and physical scores. CONCLUSION: Combined RT + HT treatment was associated with temporary lower scores in sexual and hormonal HRQoL compared with RT only. Intermediate- and high-risk CaP patients should be counseled about the possible declines in HRQoL associated with HT.

Incidence of Skin and Respiratory Immune-Related Adverse Events Correlates With Specific Tumor Types in Patients Treated With Checkpoint Inhibitors.

Checkpoint inhibitors (CPIs) increase antitumor activity by unblocking regulators of the immune response. This action can provoke a wide range of immunologic and inflammatory side effects, some of which can be fatal. Recent studies suggest that CPI-induced immune-related adverse events (irAEs) may predict survival and response. However, little is known about the mechanisms of this association. This study was undertaken to evaluate the influence of tumor diagnosis and preexisting clinical factors on the types of irAEs experienced by cancer patients treated with CPIs. The correlation between irAEs and overall survival (OS) was also assessed. All cancer patients treated with atezolizumab (ATEZO), ipilimumab (IPI), nivolumab (NIVO), or pembrolizumab (PEMBRO) at Virginia Mason Medical Center between 2011 and 2019 were evaluated. irAEs were graded according to the Common Terminology Criteria for Adverse Events (Version 5) and verified independently. Statistical analyses were performed to assess associations between irAEs, pre-treatment factors, and OS. Of the 288 patients evaluated, 59% developed irAEs of any grade, and 19% developed irAEs of grade 3 or 4. A time-dependent survival analysis demonstrated a clear association between the occurrence of irAEs and OS (P < 0.001). A 6-week landmark analysis adjusted for body mass index confirmed an association between irAEs and OS in non-Small Cell Lung Cancer (NSCLC) (P < 0.03). An association between melanoma and skin irAEs (P < 0.01) and between NSCLC and respiratory irAEs (P = 0.03) was observed, independent of CPI administered. Patients with preexisting autoimmune disease experienced a higher incidence of severe irAEs (P = 0.01), but not a higher overall incidence of irAEs (P = 0.6). A significant association between irAEs and OS was observed in this diverse patient population. No correlation was observed between preexisting comorbid conditions and the type of irAE observed. However, a correlation between skin-related irAEs and melanoma and between respiratory irAEs and NSCLC was observed, suggesting that many irAEs are driven by a specific response to the primary tumor. In patients with NSCLC, the respiratory irAEs were associated with a survival benefit.

Intraperitoneal Rupture of a Synovial Sarcoma of the Kidney.

Primary renal synovial sarcoma is an aggressive, extremely rare disease. Nearly all reported cases are characterized by SYT-SSX gene translocation (X;18)(p11;q11). We describe the case of a 43-year-old woman who presented with an intraperitoneal rupture of this rare sarcoma followed by a right radical nephrectomy. Follow-up imaging 1 month after surgery revealed peritoneal carcinomatosis. She began systemic chemotherapy with doxorubicin and dacarbazine, progressed after 3 months, and is currently receiving single-agent ifosfamide. Only one instance of intraperitoneal rupture has been reported previously. This case report contributes to the characterization of this rare disease.

Palliative TACE for hepatic metastases of chromophobe renal cell carcinoma.

We describe the case of a man with chromophobe renal cell carcinoma (chRCC) and numerous metastatic lesions restricted to the liver. Despite extensive courses of various systemic targeted chemotherapies, progressive disease was noted on CT and MRI and the patient suffered from persistent abdominal pain associated with his metastatic lesions. The liver lesions and associated symptoms were effectively palliated with serial transarterial chemoembolisation (TACE). While it is unclear if TACE has impacted his overall survival, this case encourages the use of TACE for palliative intent for patients with metastatic chRCC.

Drug metabolism and pancreatic cancer.

Pancreatic cancer remains a fatal disease in the majority of patients. The era of personalized medicine is upon us: customizing therapy according to each patient's individual cancer. Potentially, therapy can be targeted at individuals who would most likely have a favorable response, making it more efficacious and cost effective. This is particularly relevant for pancreatic cancer, which currently portends a very poor prognosis. However, there is much to be done in this field, and more studies are needed to bring this concept to reality.

Novel oral taxane therapies: recent Phase I results.

The oral taxanes are analogues of existing taxanes with a possible broad range of antitumor activity. They also have the potential advantages of ease of administration, better efficacy and lesser toxicity than currently available taxanes. These drugs have been used in several Phase I clinical trials, the methodology and results of which will be reviewed here.