D-CRSE: Diminishing chemotherapy-related side effects through patient education, a mixed-methods pilot study.

OBJECTIVES: Patient education materials regarding self-management of chemotherapy-related side effects are limited, which may result in patients using disreputable sources. We created a brochure that educates patients on common side effects, tools to address problems themselves, and guidance on when to contact their oncologist or seek emergency care. This mixed-methods study conducted at Penn State Cancer Institute evaluates the feasibility of using an educational brochure to improve patient outcomes through education. METHODS: Chemotherapy naïve patients with breast or gastrointestinal (GI) cancer were enrolled in a single-arm clinical trial from December 2021 to 2022. Participants received the educational brochure and were asked to provide their initial impressions. They completed The Emotional Thermometer Scale (ETS) and the Memorial Symptom Assessment Scale (MSAS) to measure changes in patient symptoms and mental health throughout their chemotherapy course at 0, 6, and 12-week intervals. The drop-out rate was recorded as a measure of study feasibility. RESULTS: The study participants were split between the following cancer types: 77.8% breast and 22.2% GI cancer. A significant decrease in overall mean ETS score was observed between baseline and week 6 (p = 0.001) and 12 (p = 0.0004), respectively. Moreover, the mean MSAS psychological symptoms decreased significantly at week 12 compared to baseline (p = 0.005), while no change was observed in physical symptoms (p = 0.101). Of the 40 participants who completed baseline surveys, 37 had at least one additional visit for a drop-out rate of 7.5%. CONCLUSION: This mixed-methods pilot study was successful in demonstrating the feasibility of distributing a standardized educational brochure as an intervention for chemotherapy patients. While participants' emotional scores and psychological symptoms decreased over time, physical symptoms did not, which aligns with side effect progression from cumulative chemotherapy burden.

The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights from 2022.

This special article is the 15th in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief Dr. Kaplan and the editorial board for the opportunity to continue this series, namely the research highlights of the past year in the specialties of cardiothoracic and vascular anesthesiology. The major themes selected for 2022 are outlined in this introduction, and each highlight is reviewed in detail in the main body of the article. The literature highlights, in the specialties for 2022, begin with an update on COVID-19 therapies, with a focus on the temporal updates in a wide range of therapies, progressing from medical to the use of extracorporeal membrane oxygenation and, ultimately, with lung transplantation in this high-risk group. The second major theme is focused on medical cardiology, with the authors discussing new insights into the life cycle of coronary disease, heart failure treatments, and outcomes related to novel statin therapy. The third theme is focused on mechanical circulatory support, with discussions focusing on both right-sided and left-sided temporary support outcomes and the optimal timing of deployment. The fourth and final theme is an update on cardiac surgery, with a discussion of the diverse aspects of concomitant valvular surgery and the optimal approach to procedural treatment for coronary artery disease. The themes selected for this 15th special article are only a few of the diverse advances in the specialties during 2022. These highlights will inform the reader of key updates on a variety of topics, leading to the improvement of perioperative outcomes for patients with cardiothoracic and vascular disease.

Identification and Validation of the Prognostic Impact of Metastatic Prostate Cancer Phenotypes.

INTRODUCTION: Castration-sensitive metastatic prostate cancer is heterogeneous. Our objective is to identify metastatic prostate cancer phenotypes and their prognostic impact on survival. MATERIALS AND METHODS: The National Cancer Database was queried. The Surveillance, Epidemiology, and End Results database was used for validation. Patterns were split into: nonregional lymph node, bone only, and visceral (any brain/liver/lung). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated for the univariate and multivariate Cox proportional hazards regression models, odds ratios were calculated, Kaplan-Meier curves were generated, and a nomogram of the multivariate regression model was created. RESULTS: The training set included 13,818 men; bone only was most common (n = 11,632, 84.2%), then nonregional lymph node (n = 1388, 10.0%), and any visceral (brain/liver/lung; n = 798, 5.8%). Risk of death was increased by metastases to a visceral organ versus nonregional lymph node (HR = 2.26; 95% CI [2.00, 2.56]), bone only metastases versus nonregional lymph node (HR = 1.57; 95% CI [1.43, 1.72]), T-stage 4 versus 1 (HR = 1.27; 95% CI [1.17, 1.36]), Grade Group 5 versus 1 (HR = 1.93; 95% CI [1.61, 2.31]), PSA > 20 ng/mL versus < 10 ng/mL (HR = 1.32; 95% CI [1.23, 1.42]), and age ≥ 80 versus < 50 (HR = 1.96; 95% CI [1.69, 2.29]). On internal validation, the model had C-indices 20.5%, 22.7%, and 14.6% higher than the current staging system for overall survival, 1-year, and 5-year survival, respectively. CONCLUSION: We developed and validated prognostic metastatic prostate cancer phenotypes that can assist risk stratification to potentially personalize therapy. Our nomogram (https://tinyurl.com/prostate-met) may be used to predict survival.

Impact of percent positive biopsy cores on cancer-specific mortality for patients with high-risk prostate cancer.

OBJECTIVE: A high percent positive biopsy cores (PBC), typically dichotomized at ≥50% is prognostic of worse cancer-specific outcomes for patients with low- and intermediate-risk prostate cancer (CaP). The clinical significance of ≥50% PBC for patients with high-risk disease is poorly understood. We examined the association between ≥50% PBC, compared to <50% PBC, and prostate cancer-specific mortality (PCSM) for patients with high-risk disease. MATERIALS AND METHODS: We identified 7,569 men from the Surveillance, Epidemiology, and End Results program who were diagnosed with high-risk CaP (Gleason score of 8-10, prostate-specific antigen >20 ng/mL, or cT3-T4 stage) in 2010-2011 and had 6 to 24 cores sampled at biopsy. Multivariable Fine and Gray competing risks regression was utilized to examine the association between ≥50% PBC and PCSM. RESULTS: Median follow-up was 3.8 years. 56.2% of patients (4,253) had ≥50% PBC. On competing risks regression, ≥50% PBC was associated with a significantly higher risk of PCSM compared to <50% PBC (adjusted hazard ratio [AHR] 2.00, 95% confidence interval [CI] 1.48-2.70, P < 0.001). On subgroup analyses, ≥50% PBC was associated with a significantly higher risk of PCSM only for cT1-T2 disease (AHR 2.23, 95% CI 1.62-3.07) but not cT3-T4 disease (AHR 0.83, 95% CI 0.39-1.76), with a significant interaction (Pinteraction = 0.016). No significant interactions by Gleason score, prostate-specific antigen level, use of definitive therapy, or number of biopsy cores sampled were observed. CONCLUSION: In this large cohort of patients with high-risk CaP, ≥50% PBC was independently associated with an approximately 2-fold increased risk of PCSM for patients with cT1-T2, but not cT3-T4, tumors. Percent PBC, which is a widely available clinical value, should be routinely used to risk stratify men with high-risk disease and identify patients whom may benefit from treatment intensification.

Risk of Upgrading and Upstaging Among 10 000 Patients with Gleason 3+4 Favorable Intermediate-risk Prostate Cancer.

BACKGROUND: It is unknown whether active surveillance can be safely offered to patients with Gleason 3+4 favorable intermediate-risk (FIR) prostate cancer. OBJECTIVE: To examine the incidence and predictors of upgrading and upstaging among patients with Gleason 3+4 FIR disease. DESIGN, SETTING, AND PARTICIPANTS: The study involved 10 089 patients in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 3+4 disease, prostate-specific antigen (PSA) <10ng/ml, and cT1c-2a prostate cancer with <50% positive biopsy cores (PBCs) who underwent radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression was used to examine predictors of upgrading (pathologic Gleason ≥4+3 or tertiary Gleason 5 in a Gleason 7 tumor) or upstaging (pT3-4/N1). RESULTS AND LIMITATIONS: Some 30.3% of Gleason 3+4 FIR patients were upgraded or upstaged. On multivariable analysis, predictors included higher PSA, percentage PBC, age, and cT2a versus cT1c (all p<0.001), but not black race (p=0.895). When stratified into ordinal variables, PSA 8.1-9.9 versus ≤4.0ng/ml (adjusted odds ratio [AOR] 1.93, 38.3% vs 24.4%), PBC 37.5-49.9% versus <12.5% (AOR 1.79, 37.8% vs 25.1%); highest age quartile (≥67 yr) versus lowest (≤55 yr; AOR 1.46, 35.7% vs 24.7%); and cT2a versus cT1c (AOR 1.33, 34.3% vs 29.8%) were associated with a higher risk of upgrading or upstaging (all p<0.001). Men with PBC <12.5% and PSA ≤4.0ng/ml had a 21.7% risk of more advanced disease. This increased to 44.3% for PBC 37.5-49.9% and PSA 8.1-9.9ng/ml. A limitation of the study is its retrospective nature. CONCLUSIONS: Approximately one in three patients with Gleason 3+4 FIR harbored disease of higher grade or stage. Younger patients with low percentage PBC and PSA and cT1c disease have a lower risk and may be candidates for active surveillance. However, widely available clinical information is insufficient for predicting the risk of more advanced disease, and the development and incorporation of additional tools, including magnetic resonance imaging and genomic tests, are necessary. PATIENT SUMMARY: Nearly one-third of patients with Gleason 3+4 favorable intermediate-risk prostate cancer harbor disease of higher grade or higher stage than their biopsy and clinical examination suggest. These patients would therefore be poor candidates for active surveillance.

NF-κB inhibition by dimethylaminoparthenolide radiosensitizes non-small-cell lung carcinoma by blocking DNA double-strand break repair.

Despite optimal chemotherapy, radiotherapy (RT), and/or surgery, non-small-cell lung carcinoma (NSCLC) remains the leading cause of cancer-related death in the US and worldwide. Thoracic RT, a mainstay in the treatment of locally advanced NSCLC, is often restricted in efficacy by a therapeutic index limited by sensitivity of tissues surrounding the malignancy. Therefore, radiosensitizers that can improve the therapeutic index are a vital unmet need. Inhibition of the NF-κB pathway is a proposed mechanism of radiosensitization. Here we demonstrate that inhibition of the canonical NF-κB pathway by dimethylaminoparthenolide (DMAPT) radiosensitizes NSCLC by blocking DNA double-strand break (DSB) repair. NF-κB inhibition results in significant impairment of both homologous recombination (HR) and non-homologous end joining (NHEJ), as well as reductions in ionizing radiation (IR)-induced DNA repair biomarkers. NF-κB inhibition by DMAPT shows preclinical potential for further investigation as a NSCLC radiosensitizer.

Pathologic Outcomes of Gleason 6 Favorable Intermediate-Risk Prostate Cancer Treated With Radical Prostatectomy: Implications for Active Surveillance.

BACKGROUND: The safety of active surveillance (AS) for Gleason 6 favorable intermediate-risk (FIR) prostate cancer is unknown. To provide guidance, we examined the incidence and predictors of upgrading or upstaging for Gleason 6 FIR patients treated with radical prostatectomy. PATIENTS AND METHODS: We identified 2807 men in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 6 FIR disease (<50% positive biopsy cores [PBC] with either prostate-specific antigen [PSA] of 10-20 ng/mL or cT2b-T2c disease) treated with radical prostatectomy. Logistic regression was used to identify predictors of upgrading (Gleason 3+4 with tertiary Gleason 5 or Gleason ≥4+3) or upstaging (pT3-4/N1). RESULTS: Fifty-seven percent of the cohort had PSA of 10 to 20 ng/mL; 25.5% patients with PSA of 10 to 20 ng/mL and 12.4% with cT2b to T2c disease were upgraded or upstaged. In multivariable analysis, predictors of upgrading or upstaging included increasing age (P = .026), PSA (P = .001), and percent PBC (P < .001), and black race versus white (P = .035) for patients with PSA of 10 to 20 ng/mL and increasing PSA (P = .001) and percent PBC (P < .001) for patients with cT2b to T2c disease. Men with PSA of 15.0 to 20.0 ng/mL or 37.5% to 49.9% PBC with PSA of 10 to 20 ng/mL had >30% risk of upgrading or upstaging, whereas cT2b to T2c patients with <12.5% PBC or PSA <5.0 ng/mL had <10% risk. CONCLUSION: We found that Gleason 6 FIR patients with cT2b to T2c tumors had a low risk of harboring higher grade or stage disease and would be reasonable AS candidates, whereas patients with PSA of 10 to 20 ng/mL had a high risk and might generally be poor AS candidates.

Receipt of definitive therapy in elderly patients with unfavorable-risk prostate cancer.

BACKGROUND: Conservative management of aggressive prostate cancer in the elderly without definitive therapy has been associated with a 10-year prostate cancer-specific mortality of approximately 50%. The authors examined the prevalence of definitive therapy in elderly patients with intermediate-risk or high-risk disease. METHODS: 411,343 patients who were diagnosed from 2004 through 2012 with intermediate-risk or high-risk prostate cancer were identified in the National Cancer Database. Multivariable logistic regression adjusting for sociodemographic characteristics and comorbidity was used to examine the association between age and receipt of definitive therapy, defined as radical prostatectomy or radiotherapy, and of primary androgen deprivation therapy (ADT) among patients who did not receive definitive therapy. RESULTS: In total, 87.1% of high-risk patients and 91.9% of intermediate-risk patients received definitive therapy. When stratified by age, 93.7%, 92.1%, 90.8%, 87.6%, 80.9%, and 55.2% of high-risk patients and 96.1%, 94.7%, 93.4%, 89.7%, 82.7%, and 62.8% of intermediate-risk patients ages <60, 60 to 64, 65 to 69, 70 to 74, 75 to 79, and ≥80 years received definitive therapy, respectively. For both high-risk and intermediate-risk patients, increasing age was significantly associated with a decreased likelihood of receiving definitive therapy overall (both P < .001) and a greater likelihood of receiving primary ADT among those who did not receive definitive therapy (both P < .001). CONCLUSIONS: Older age was significantly associated with a decreased likelihood of receiving definitive therapy and an increased likelihood of receiving primary ADT in this national cohort of patients with intermediate-risk or high-risk prostate cancer. Notably, approximately 40% to 45% of patients aged ≥80 years did not receive definitive therapy. These findings are alarming given the dismal outcomes of conservatively managed unfavorable-risk prostate cancer. Cancer 2017;123:4832-40. © 2017 American Cancer Society.

National Trends and Predictors of Androgen Deprivation Therapy Use in Low-Risk Prostate Cancer.

PURPOSE: Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease. METHODS AND MATERIALS: Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level <10 ng/mL, and cT1-T2a) diagnosed from 2004 to 2012 with complete demographic and treatment information. We used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality. RESULTS: Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; P<.001; incidence, 14.0% vs 6.0% in 2012); treatment in the South (AOR, 1.51), Midwest (AOR, 1.81), or Northeast (AOR, 1.90) versus West (P<.001); and brachytherapy use versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; P<.001). Among 25,196 patients who did not receive local therapy, predictors of primary ADT use included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; P<.001); and treatment in the South (AOR, 1.26), Midwest (AOR, 1.52), or Northeast (AOR, 1.28) versus West (P≤.008). Primary ADT use was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; P<.001) after adjustment for age and comorbidity. CONCLUSIONS: ADT use in low-risk prostate cancer has declined nationally but may remain an issue of concern in certain populations and regions.

Low rates of androgen deprivation therapy use with salvage radiation therapy in patients with prostate cancer after radical prostatectomy.

OBJECTIVE: The RTOG 9601 and GETUG-AFU 16 randomized controlled trials demonstrated that the addition of androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) improves progression-free and, for RTOG 9601, overall survival. We examined national trends in the use of ADT with SRT. MATERIALS AND METHODS: Of the 484,009 patients in the National Cancer Database from 2004 to 2012 with localized or locally advanced prostate cancer treated with radical prostatectomy (RP), 4,200 men received SRT (≥6mo after surgery). We used Pearson's chi-squared test to evaluate changes in ADT use, and multiple logistic regression to examine predictors of ADT use. RESULTS: Overall, 32.1% of SRT patients received ADT, which increased after initial results of RTOG 9601 showed an improvement in metastasis-free survival in 2010 (28.5% in 2008/2009 vs. 34.5% in 2011/2012, P = 0.006). Predictors of ADT use include presurgery prostate-specific antigen>20ng/ml vs.<10ng/ml (adjusted odds ratio [AOR] = 1.34, P = 0.002; 36.7% vs. 29.6%); positive vs. negative margins (AOR = 1.29, P = 0.001; 34.9% vs. 27.8%); Gleason 3+4 (AOR = 1.53; 21.3%), Gleason 4+3 (AOR = 2.40; 32.0%), or Gleason 8 to 10 (AOR = 4.49; 49.2%) vs. Gleason 2 to 6 (P≤0.005 for all; 13.2%); and pathologic T3a (AOR = 1.46; 30.9%), T3b (AOR = 2.50; 47.6%), or T4 (AOR = 4.14; 60.9%) vs. T2 (P<0.001 for all; 19.1%). Starting SRT 12 to 23.9 months (AOR = 0.69; 23.2%) or≥24 months (AOR = 0.25; 8.0%) after RP was associated with decreased odds of ADT use vs. starting SRT 6 to 8.9 months after RP (P≤0.002 for both; 35.0%). CONCLUSION: Although less than one-third of SRT patients from the study era received ADT, there is evidence that physicians and patients have begun slowly adopting this practice with the 2010 reporting of a decrease in the cumulative incidence of metastases with the addition of ADT to SRT. Given the newly reported survival benefit of RTOG 9601, additional work will be necessary to identify which patients benefit the most from the use of ADT with SRT to individualize treatment.