Analysis of MRI radiomic pelvimetry and correlation with margin status after robotic prostatectomy.

INTRODUCTION: To evaluate the use of preoperative magnetic resonance imaging (MRI) as a predictor of positive margins after radical prostatectomy (RP). This is important as such patients may benefit from postoperative radiotherapy. With the advent of preoperative MRI, we posited that pelvimetry could predict positive margins after RP in patients with less-than ideal pelvic dimensions undergoing robotic-assisted laparoscopic surgery. MATERIALS AND METHODS: After IRB approval, data from patients undergoing RP at our center between 1/1/2018 and 12/31/2019 (n = 314) who had undergone prior prostate MRI imaging (n = 102) were analyzed. All RPs were performed using robotic-assisted laparoscopic technique. Data from the cancer center data warehouse were retrieved, to include postoperative T-stage, gland size, responsible surgeon, PSA, patient body mass index, and surgical margin status. These data were analyzed with corresponding pelvimetry data from 91 preoperative scans with complete data and imaging. RESULTS: On multivariable analysis, pathologic T-stage (p = 0.004), anteroposterior pelvic outlet (p = 0.015) and pelvic depth (length of the pubic symphysis; p = 0.019) were all statistically correlated with positive surgical margins. CONCLUSIONS: With the widespread use of MRI in the initial staging of prostate cancer, automated radiomic analysis could augment the critical data already being accumulated in terms of seminal vesical involvement, extracapsular extension, and suspicious lymph nodes as risk factors for postoperative salvage radiation. Such automated data could help screen patients preoperatively for robotic RP.

International case series of metastasis to penis.

Objectives: To evaluate clinical characteristics associated with survival in patients with metastases to the penis. Methods: After approval by the IRB, records of collaborating centres in Leuven, London, Rostock, Amsterdam and Tampa were screened for men presenting with metastatic disease to penis. Multivariate logistic regression analyses were used to identify covariables associated with survival. We analysed clinical data on 34 patients. Results: Primary sites were most frequently prostate (n = 14, 41%) and bladder (n = 9, 26%). Twenty-eight of 34 (82%) presented with metachronous penile metastases, and 11 (32%) patients had penile metastases as the sole metastatic site. Penile metastatic locations were most frequently in the corpora (n = 18; 53%). Seven (21%) patients with penile metastases had priapism on presentation. Systemic therapy was frequent and variable (chemotherapy n = 12; immunotherapy n = 5; hormones n = 3). Local management included either surgery (n = 10) or RT (n = 8). Twelve- and 24-month overall survival rate were 67% and 35%, respectively. No clinical parameter including primary histology, synchronous or metachronous metastases or priapism showed statistical survival benefit or detriment. Conclusion: Metastasis to penis arises most frequently from pelvic primaries. Priapism does not appear to correlate with survival in this large, well-defined series.

An Analysis of Positron Emission Tomography Maximum Standard Uptake Value Among Patients With Head and Neck Cancer Receiving Photon and Proton Radiation.

PURPOSE: One main advantage of proton therapy versus photon therapy is its precise radiation delivery to targets without exit dose, resulting in lower dose to surrounding healthy tissues. This is critical, given the proximity of head and neck tumors to normal structures. However, proton planning requires careful consideration of factors, including air-tissue interface, anatomic uncertainties, surgical artifacts, weight fluctuations, rapid tumor response, and daily variations in setup and anatomy, as these heterogeneities can lead to inaccuracies in targeting and creating unwarranted hotspots to a greater extent than photon radiation. In addition, the elevated relative biological effectiveness at the Bragg peak's distal end can also increase hot spots within and outside the target area. METHODS AND MATERIALS: The purpose of this study was to evaluate for a difference in positron emission tomography (PET) standard uptake value (SUV) after definitive treatment, between intensity modulated proton therapy (IMPT) and intensity modulated photon therapy (IMRT). In addition, we compared the biologic dose between PET areas of high and low uptake within the clinical target volume-primary of patients treated with IMPT. This work is assuming that the greater SUV may potentially result in greater toxicities. For the purposes of this short communication, we are strictly focusing on the SUV and do not have correlation with toxicity outcomes. To accomplish this, we compared the 3- and 6-month posttreatment fluorodeoxyglucose PET scans for 100 matched patients with oropharyngeal cancer treated definitively without surgery using either IMPT (n = 50) or IMRT (n = 50). RESULTS: Our study found a significant difference in biologic dose between the high- and low-uptake regions on 3-month posttreatment scans of IMPT. However, this difference did not translate to a significant difference in PET uptake in the clinical target volume-primary at 3 and 6 months' follow-up between patients who received IMPT versus IMRT. CONCLUSIONS: Studies have proposed that proton's greater relative biological effectiveness at the Bragg peak could lead to tissue inflammation. Our study did not corroborate these findings. This study's conclusion underscores the need for further investigations with ultimate correlation with clinical toxicity outcomes.

Two-finger digital rectal examination for the diagnosis of anal fistula: protocol for a randomized controlled trial.

Background: Anal fistula is an anorectal infectious disease caused by a perianal abscess or perianal disease. Accurate anorectal examinations are of great significance. The two-finger digital rectal examination (TF-DRE) has been used in clinical practice, with a lack of comprehensive research on the value of the TF-DRE in the diagnosis of anal fistula. This study will compare the difference in the diagnostic value of the TF-DRE, traditional digital rectal examination (DRE), and anorectal ultrasonography in the diagnosis of anal fistula. Methods: For patients who meet the inclusion criteria, a TF-DRE will be performed to explore the number and location of the external and internal orifices, the number of fistulas, and the relationship between the fistula and the perianal sphincter. A DRE and anorectal ultrasonography will also be performed, and the same data will be recorded. To make a comparison, the final diagnosis results of the clinicians during the operation will be taken as the gold standard, the accuracy of the TF-DRE in diagnosing anal fistula will be calculated, and the significance of the TF-DRE in the preoperative diagnosis of anal fistula will be studied and analyzed. All the statistical results will be analyzed using SPSS22.0 (IBM, USA), and a P value <0.05 will be considered statistically significant. Discussion: The research protocol details the advantages of the TF-DRE compared to the DRE and anorectal ultrasonography in the diagnosis of anal fistula. This study will provide clinical evidence of the diagnostic value of the TF-DRE in the diagnosis of anal fistula. Currently, there is a lack of high-quality research using scientific methods on this innovative anorectal examination method. This study will provide rigorously designed clinical evidence on the TF-DRE. Registration: Chinese Clinical Trials Registry ChiCTR2100045450.

Evaluation of Proton Therapy Reirradiation for Patients With Recurrent Head and Neck Squamous Cell Carcinoma.

Importance: Use of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret. Objective: To evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma. Design, Setting, and Participants: This retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and grade early and late toxic effects. Exposures: Proton therapy reirradiation. Main Outcomes and Measures: Follow-up was defined from the start of PT-ReRT. The Kaplan-Meier method was used for outcomes of interest, including local control (LC), locoregional control, distant metastatic control, progression-free survival, and overall survival (OS). Cox proportional hazards regression modeling was used to assess associations of covariates with OS. Results: A total of 242 patients (median [range] age, 63 [21-96] years; 183 [75.6%] male) were included. Of these patients, 231 (95.9%) had a Karnofsky performance status score of 70 or higher, and 145 (59.9%) had at least a 10-pack-year smoking history. Median (range) follow-up was 12.0 (5.8-26.0) months for all patients and 24.5 (13.8-37.8) months for living patients. A total of 206 patients (85.1%) had recurrent disease vs second primary or residual disease. The median (range) interval between radiation courses was 22 (1-669) months. Median PT-ReRT dose was 70 cobalt gray equivalents (CGE) for the fractionated cohort and 44.4 CGE for the quad shot cohort. For the fractionated cohort, the 1-year LC was 71.8% (95% CI, 62.8%-79.0%) and the 1-year OS was 66.6% (95% CI, 58.1%-73.8%). For the quad shot cohort, the 1-year LC was 61.6% (95% CI, 46.4%-73.6%) and the 1-year OS was 28.5% (95% CI, 19.4%-38.3%). Higher Karnofsky performance status scores (hazard ratio [HR], 0.50; 95% CI, 0.25-0.99; P = .046) and receipt of salvage surgery prior to PT-ReRT (HR, 0.57; 95% CI, 0.39-0.84; P = .005) were associated with improved OS, whereas receipt of quad shot (HR, 1.97; 95% CI, 1.36-2.86; P < .001) was associated with worse OS. There were a total of 73 grade 3 and 6 grade 4 early toxic effects. There were 79 potential grade 3, 4 grade 4, and 5 grade 5 late toxic effects. Conclusions and Relevance: The findings of this cohort study suggest that, compared with previous reports with photon-based reirradiation, patients are living longer with aggressive PT-ReRT; however, surviving patients remain at risk of early and late complications.

Diagnostic and Therapeutic Challenges in a Patient with Synchronous Very High-Risk Prostate Adenocarcinoma and Anal Carcinoma.

A 79-year-old HIV-negative Caucasian man with a medical history of smoking 20 pack-years (quit 40 years prior), early-stage non-small cell lung cancer status post-lobectomy 13 years earlier at an outside hospital without evidence of recurrence, and benign prostatic hypertrophy was diagnosed with synchronous very high-risk prostate adenocarcinoma and early-stage anal basaloid squamous cell carcinoma. He proceeded to undergo concurrent treatment for these tumors, consisting of androgen deprivation therapy, external beam radiation therapy, and a brachytherapy boost for the prostate adenocarcinoma; for the anal carcinoma, he was treated with definitive chemoradiation. Over 3.5 years since the completion of radiotherapy, he remains in clinical and biochemical remission.

Patient reported outcomes in advanced penile cancer.

OBJECTIVE: Patient reports of their symptom burden (i.e., patient-reported outcomes or PROs) have been shown to direct clinicians' ability to personalize care and improve outcomes. A disciplined assessment of PRO in the population of patients with advanced penile cancer (PeCa) has not previously been undertaken. Our center leveraged a significant cadre of patients with PeCa and a significant experience with a well-established PRO: the Edmonton Symptom Assessment Scale (ESAS). METHODS: After IRB approval, we screened ESAS surveys of 14,781 patients completed between February 2017 and February 2021; these were collected in the Supportive Care and Radiation Oncology clinics. Of these, those with PeCa were divided into 3 cohorts: (A) Those after any partial penectomy procedure without lymph node dissection (LND); (B) Those after partial penectomy procedure with LND; and (C) Those after total penectomy and LND. Patients with recurrent disease were analyzed separately (D). ESAS scores were collated and compared both by individual symptom and cumulatively. RESULTS: Twenty-two PeCa patients completed 122 ESAS surveys in this time and are included in this analysis: a median of 4 ESAS surveys (mean = 5, range = 1-19) were completed by each patient. The symptom with the highest median ESAS score was Tiredness (3.00). Patients with recurrent disease had the highest cumulative symptom score (median score = 30). Patients after total penectomy with LND had a higher cumulative symptom score (14.4) than those with partial penectomy and LND (7.9). Patients with partial penectomy without LND had a cumulative score of 22. CONCLUSIONS: PROs provide an insight into the morbidity of therapies for advanced PeCa, and the most symptoms are reported by patients with recurrent disease.

Outcomes and Toxicities of Nonmedullary Thyroid Tumors Treated with Proton Beam Radiation Therapy.

Purpose: Proton therapy is an emerging therapy for several malignancies owing to its favorable therapeutic ratio. There are very limited data on the use of proton therapy in the management of thyroid carcinoma. Our objective was to review the safety, feasibility, and outcomes of proton therapy for patients with thyroid cancer treated to the head and neck. Methods: From our institution's proton database from 2012 to 2021, we identified 22 patients with thyroid cancer treated with proton beam therapy. We evaluated outcomes and toxicities. Results: Median follow-up was 26 months. Of the 22 patients, 50% were female. The mean age was 65 years. Three patients had anaplastic cancer; 13, papillary carcinoma; 2, follicular carcinoma; and 2, poorly differentiated carcinoma. Forty-six percent had T4 disease. Primary targets were the central neck compartment, level VI, and upper mediastinum. Radiation dose was 60 GyRBE adjuvantly, and 70 GyRBE for gross disease (range, 6000-7600 GyRBE). Eight patients underwent upfront adjuvant radiation, and 3 received definitive radiation for unresectable disease upfront. Eleven patients received either salvage or palliative radiation. Fifty-nine percent of patients had extrathyroidal extension, and 64% of patients had gross disease in the neck before treatment. Fifty percent of patients had metastatic disease before treatment. Sixteen patients received concurrent chemotherapy, 63% of these patients received doxorubicin. For all patients, 1-year local regional recurrence (LRR) was 0%, and overall survival (OS) was 90%. Acute grade 3+ toxicities occurred in 27% of patients, the most frequent being dermatitis (27%). Three patients required a percutaneous endoscopic gastrostomy tube after radiation therapy (RT), 2 owing to progression. There were no grade 4+ toxicities. Conclusions: Proton therapy for thyroid cancer appears feasible and effective with minimal toxicities. Prospective studies comparing proton therapy with intensity-modulated RT, to evaluate the clinical efficacy of using proton therapy to reduce toxicities in patients undergoing radiation for thyroid cancer, are warranted.

Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Oropharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy.

Importance: Patients with oropharyngeal carcinoma (OPC) treated with radiotherapy often experience substantial toxic effects, even with modern techniques such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) has a potential advantage over IMRT due to reduced dose to the surrounding organs at risk; however, data are scarce given the limited availability and use of IMPT. Objective: To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic OPC treated with IMPT vs IMRT with or without chemotherapy. Design, Setting, and Participants: This retrospective cohort study included patients aged 18 years or older with newly diagnosed nonmetastatic OPC who received curative-intent radiotherapy with IMPT or IMRT at a single-institution tertiary academic cancer center from January 1, 2018, to December 31, 2021, with follow-up through December 31, 2021. Exposures: IMPT or IMRT with or without chemotherapy. Main Outcomes and Measures: The main outcomes were the incidence of acute and chronic (present after ≥6 months) treatment-related adverse events (AEs) and oncologic outcomes, including locoregional recurrence (LRR), progression-free survival (PFS), and overall survival (OS). Fisher exact tests and χ2 tests were used to evaluate associations between toxic effects and treatment modality (IMPT vs IMRT), and the Kaplan-Meier method was used to compare LRR, PFS, and OS between the 2 groups. Results: The study included 292 patients with OPC (272 [93%] with human papillomavirus [HPV]-p16-positive tumors); 254 (87%) were men, 38 (13%) were women, and the median age was 64 years (IQR, 58-71 years). Fifty-eight patients (20%) were treated with IMPT, and 234 (80%) were treated with IMRT. Median follow-up was 26 months (IQR, 17-36 months). Most patients (283 [97%]) received a dose to the primary tumor of 70 Gy. Fifty-seven of the patients treated with IMPT (98%) and 215 of those treated with IMRT (92%) had HPV-p16-positive disease. There were no significant differences in 3-year OS (97% IMPT vs 91% IMRT; P = .18), PFS (82% IMPT vs 85% IMRT; P = .62), or LRR (5% IMPT vs 4% IMRT; P = .59). The incidence of acute toxic effects was significantly higher for IMRT compared with IMPT for oral pain of grade 2 or greater (42 [72%] IMPT vs 217 [93%] IMRT; P < .001), xerostomia of grade 2 or greater (12 [21%] IMPT vs 68 [29%] IMRT; P < .001), dysgeusia of grade 2 or greater (16 [28%] IMPT vs 134 [57%] IMRT; P < .001), grade 3 dysphagia (4 [7%] IMPT vs 29 [12%] IMRT; P < .001), mucositis of grade 3 or greater (10 [53%] IMPT vs 13 [70%] IMRT; P = .003), nausea of grade 2 or greater (0 [0%] IMPT vs 18 [8%] IMRT; P = .04), and weight loss of grade 2 or greater (22 [37%] IMPT vs 138 [59%] IMRT; P < .001). There were no significant differences in chronic toxic effects of grade 3 or greater, although there was a significant difference for chronic xerostomia of grade 2 or greater (6 IMPT [11%] vs 22 IMRT [10%]; P < .001). Four patients receiving IMRT (2%) vs 0 receiving IMPT had a percutaneous endoscopic gastrostomy tube for longer than 6 months. Conclusions and Relevance: In this study, curative-intent radiotherapy with IMPT for nonmetastatic OPC was associated with a significantly reduced acute toxicity burden compared with IMRT, with few chronic toxic effects and favorable oncologic outcomes, including locoregional recurrence of only 5% at 2 years. Prospective randomized clinical trials comparing these 2 technologies and of patient-reported outcomes are warranted.

Non-Adaptive MR-Guided Radiotherapy for Prostate SBRT: Less Time, Equal Results.

BACKGROUND: The use of stereotactic body radiation therapy (SBRT) is widely utilized for treatment of localized prostate cancer. Magnetic-resonance-guided radiotherapy (MRgRT) was introduced in 2014 and has recently been implemented in SBRT for prostate cancer as it provides an opportunity for smaller margins and adaptive daily planning. Currently, the only publications of MRgRT for prostate SBRT describe European clinical experiences which utilized adaptive planning. However, adaptive planning adds significantly to the time required for daily treatment. OBJECTIVES: Since prostate SBRT has demonstrated acceptable toxicity for several years, we did not consider daily adaptation critical to the process of prostate SBRT. After Institutional Review Board approval, we analyzed and now report our experience using MRgRT without adaptation. METHODS: Between 25 September 2019 and 21 December 2020, 35 consecutive patients were treated with MRgRT prostate SBRT at our center. Patients treated with MRgRT included favorable intermediate risk (43%) and unfavorable intermediate risk (54%), and only one patient had low-risk prostate cancer. Nine patients (25%) received adjuvant leuprolide for a median of 4.5 months (range 4-6 m). Our clinical pathway allows for a maximum prostate gland volume of 60 cc; median prostate volume of this cohort was 35.0 cc (range 17-58.4 cc). Median pre-treatment PSA was 6.30 (range 2.55-16.77). Each patient was treated with 36.25 Gy delivered in five fractions over 2 weeks with urethral sparing to a maximal dose of 35 Gy. Target volumes included the prostate gland and proximal seminal vesicles with a 3 mm margin. RESULTS: Median follow-up as of 26 May 2021 was 11.97 months (range 4.37-19.80). First follow-up data are available for all patients, with a median of 1.10 month from completion of treatment (0.63-3.40). The median PSA at first visit was 2.75 (range 0.02-9.00) with a median AUA symptom score of 9 (range 1-24). Second follow-up data are available for 34 patients at a median of 4.45 months (range 2.57-8.90). At second follow-up, the median PSA was 1.60 (range 0.02-5.40) with a median AUA symptom score of 6 (range 1-33). Seventeen patients had third follow-up data with a median of 9.77 months (range 4.70-12.33) after SBRT. The median PSA was 1.13 (range 0.02-4.73) with an AUA score of 9 (2-22) at the third follow-up. We observed a statistically significant decrease in PSA between pre-treatment and at first follow-up (p < 0.005). The most common toxicity was grade 2 urethritis, managed in all cases by tamsulosin. One patient developed grade 2 tenesmus relieved by topical steroids. No cases of grade ≥ 3 toxicity were seen in our patient population. CONCLUSIONS: By avoiding the extra time required for plan adaptation, MRgRT without daily adaptation allows for successful prostate SBRT with manageable toxicity. We continue to reserve our limited adaptive treatment slots for preoperative pancreatic and ultra-central lung SBRT patients, which require time-intensive respiratory gating and adaptive planning.

Covert COVID-19: Cone Beam Computed Tomography Lung Changes in an Asymptomatic Patient Receiving Radiation Therapy.

PURPOSE: COVID-19 profoundly affected the United States, with New York City rapidly becoming the epicenter of the disease. Patients with cancer represent a vulnerable population in this pandemic, with data suggesting a higher risk for severe events and unfavorable outcomes. Timely identification of COVID-19 in patients with cancer has been thwarted by the limited availability of outpatient testing for SARS-CoV-2. Chest computed tomography (CT) plays a major role in the identification of COVID-19 pneumonia, with radiologic hallmarks including bilateral, peripheral ground-glass opacities (GGOs) and consolidation. Patients with cancer undergoing radiation therapy (RT) commonly have daily cone beam computed tomography (CBCT) obtained for image-guided RT, and such imaging frequently includes the chest. METHODS AND MATERIALS: We retrospectively reviewed the CBCT scans of an initially asymptomatic patient undergoing image-guided RT for breast cancer who developed COVID-19 symptoms during the second week of RT. Lung windows of daily CBCT scans were reviewed with diagnostic radiology to survey for changes consistent with COVID-19. Diagnostic CT scans at the time of recovery were obtained and compared with the CBCTs. RESULTS: Five consecutive CBCT scans were retrospectively reviewed. Bilateral, peripheral GGOs were noted on the fourth and fifth CBCT scans in the 2 days before symptom onset. CBCT on the day of RT resumption demonstrated substantial worsening of the GGO compared with scans obtained during the asymptomatic phase. Diagnostic CTs demonstrated bilateral, peripheral GGOs and mediastinal lymphadenopathy, findings suggesting COVID-19 pneumonitis. Repeat diagnostic CT 3 days later showed improved pulmonary findings, and the patient resumed RT without incident. CONCLUSIONS: Familiarity with typical CT changes of COVID-19 pneumonitis may allow for early detection in cancer patients undergoing CBCT for RT treatment. Prompt review of the lung windows is recommended to identify such changes, with the hope that presymptomatic diagnosis leads to expedited patient management, improved outcomes, and a reduction of inadvertent COVID-19 dissemination.

Patterns of Care and Survival of Metastatic Metaplastic Breast Cancer Patients.

BACKGROUND: Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer, usually triple negative disease and chemotherapy refractory. Despite this, the standard of care remains the same as invasive ductal breast cancer. We sought to analyze patterns of care and outcomes among patients with metastatic MBC. METHODS: Patients over 18 years diagnosed with metastatic MBC from 2004-2015 were identified in the National Cancer Database (NCDB). Clinical and demographic details were compared between two groups (chemotherapy vs no chemotherapy). Logistic regression was performed to assess for predictors of receiving chemotherapy. The Kaplan-Meier method was used to assess overall survival (OS) and Cox regression analysis was used to assess the impact of covariates on OS. RESULTS: There were 7,580 patients with MBC of which 417 (5.5%) presented with metastatic disease. Median age was 65 years (interquartile range (IQR) 54-76) and median follow up for living patients was 48 months (IQR 31-77). One hundred and fifty-six (37.4%) patients received chemotherapy. On multivariable logistic regression analyses, treatment at an academic facility was associated with an increased likelihood of receiving chemotherapy (OR 3.14, 95% CI 1.95-5.03, p<0.001) while age ≥65 years (OR 0.54, 95% CI 0.34-0.86, p=0.009) and receipt of hormonal therapy (OR 0.35, 95% CI 0.15-0.85, p=0.021) were associated with a decreased likelihood of receiving chemotherapy. On multivariable Cox regression analysis, higher Charlson-Deyo score (hazard ratio (HR) 1.35-1.78, p<0.05) was associated with worse survival while receipt of chemotherapy (HR 0.76, 95% CI 0.59-0.99, p=0.041) and having insurance (HR 0.34-0.47, p<0.05) were associated with improved survival. Patients who received chemotherapy had improved median (twelve versus eight months), one-year (51% versus 38%), and two-year (35% versus 21%) OS, as compared to those who did not receive chemotherapy (p=0.006).  Conclusions: In this study of MBC patients, there was a survival benefit with palliative chemotherapy in the setting of metastatic disease. As expected, treatment was most often given to younger patients.

Combined rest redistribution thallium-201 SPECT and low-dose dobutamine contractility assessment in a simple and practical new viability protocol.

OBJECTIVE: Rest-redistribution (RR) thallium-201 (Tl-201) imaging is commonly used for myocardial viability evaluation. Contractile reserve (CR) assessment with low-dose dobutamine (LDD) is another method that highly predicts functional recovery following revascularization. In this study, we investigate the feasibility of a new protocol that provides combined Tl-201 uptake, resting and CR functional regional myocardial information in a single examination. METHODS: A total of 41 patients underwent RR-gated-SPECT Tl-201 myocardial perfusion imaging. The LDD infusion was maintained during delayed imaging. Segmental Tl-201 uptake was classified into normal, fixed decrease (mild to absent) and reversible, and sub-classified by wall motion (WM)/thickening (WT) changes between early resting and delayed LDD gated images into normal, fixed or improved dysfunctional (CR present) segments. RESULTS: Out of 820 examined segments, 33 showed no appreciable Tl-201 uptake to evaluate WM/WT. In a dysfunctional myocardium, CR was significantly higher (P < 0.001) in reversible and fixed than in normal Tl-201 segments. The CR in dysfunctional segments with fixed decrease Tl-201 uptake was significantly higher (P < 0.05) in mild and moderate than in severe fixed defects. Both fixed Tl-201 defects and lack of CR were observed more (P < 0.05) in akinetic/dyskinetic than in hypokinetic segments. CONCLUSIONS: Simultaneous assessment of myocardial viability by RR Tl-201 uptake, resting and CR functional regional information is feasible and can be easily attained using this new protocol. Moreover, this protocol requires no additional time or radioactivity when compared with the usual RR Tl-201 protocol. Validation of this protocol with patients' revascularization data is needed.

Survival benefits and predictors of use of chemoradiation compared with radiation alone for early stage (T1-T2N0) anal squamous cell carcinoma.

BACKGROUND: Standard of care treatment for anal squamous cell carcinoma (SCC) is concurrent chemoradiation (CRT). However, the necessity of CRT over radiation alone for T1-2N0 disease is less certain. METHODS: The National Cancer Database (NCDB) was queried to identify patients who received CRT, defined as initiation of chemo and RT within 14 days of each other, or RT alone (without any chemo during initial treatment phase) for cT1-2N0M0 SCC of the anus. The cohort was limited to patients less than 70 years old with Charlson-Deyo Comorbidity Index of 0, receiving a radiation dose range of 4,500-5,940 cGy. Univariable and multivariable logistic regression were performed to assess for predictors of CRT usage. Five-year overall survival (OS) was analyzed using the Kaplan-Meier method with the log rank test both for the full cohort and then on the subsets of T1 and T2 patients. RESULTS: We identified 4,564 patients, of whom 4,371 (95.8%) received CRT and 193 (4.2%) received RT alone. Median follow up was 49.8 months. About 33.5% of patients had cT1N0 disease, while 66.5% of patients had cT2N0 disease. On multivariable logistic regression, patients were more likely to receive CRT if they had T2 disease [OR 2.318 (1.732-3.102), P<0.0001]. Five-year OS was 86.6% for CRT and 79.1% for RT (P=0.001). For T1 patients, 5-year OS was 90.3% with CRT and 84.7% with RT (P=0.114). For T2 patients, 5-year OS was 84.7% with CRT and 72.8% with RT (P<0.0001). Multivariable Cox regression analysis confirmed association between OS and CRT use [HR 0.588 (95% CI: 0.430-0.804), P=0.001]. CONCLUSIONS: The vast majority of patients under age 70 without significant comorbidities are treated with CRT over radiation alone for early stage anal SCC, with better survival associated with CRT.

Association of Nadir Prostate-specific Antigen >0.5 ng/mL after Dose-escalated External Beam Radiation with Prostate Cancer-specific Endpoints.

Objective Prior studies have suggested that prostate-specific antigen (PSA) nadir of 0.5 ng/mL is an important surrogate endpoint for prostate cancer-specific and all-cause mortality. This study analyzed our well-followed patient cohort to assess whether this endpoint was associated with differences in prostate cancer-specific endpoints in patients receiving dose-escalated radiation. Methods Patients with intermediate- or high-risk prostate cancer (≥T2b, or prostate-specific antigen >10 ng/mL, or Gleason score ≥7) who were treated with external beam radiation to a minimum dose of 7560 cGy +/- androgen deprivation between 2003 and 2011 were identified. Biochemical control, distant metastasis-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were compared between those who achieved a nadir PSA ≤0.5 ng/mL with those who did not via Kaplan-Meier analysis. Univariable and multivariable Cox regression was performed on all endpoints to assess their impact on OS. Results There were 367 patients identified with a median follow-up of 99.5 months. Two hundred five patients (55.9%) received androgen deprivation for a median of 24 months (range 1-81 months). Most patients (n = 308, 83.9%) achieved a nadir PSA ≤0.5 ng/mL, which was associated with improvement across all endpoints at 10 years. This included biochemical control (68.0% versus 24.0%, p < 0.001), DMFS (89.6% versus 80.8%, p = 0.019), PCSS (91.1% versus 85.7%, p = 0.01), and OS (55.7% versus 45.8%, p = 0.048). On multivariable analysis, nadir PSA >0.5 ng/mL remained strongly associated with worse outcomes across all endpoints. Conclusions Achievement of nadir PSA ≤0.5 ng/mL after completion of dose-escalated radiation therapy was associated with improvement of all prostate cancer endpoints.

Patterns of care and outcomes of postoperative radiation for low-grade gliomas in United States hospitals.

It is unclear whether there is a survival benefit with postoperative radiation for low-grade gliomas deemed to be high-risk. We sought to analyze patterns of care and outcomes of radiation use. We accessed the National Cancer Database to identify patients with WHO grade II oligodendroglioma or astrocytoma between 2010 and 2012. Multivariable logistic regression was used to identify predictors of radiation use and multivariable Cox regression was used to identify covariables associated with differences in survival. There were 1952 patients included in this study, of which 518 (26.5%) received postoperative radiation. The majority had oligodendroglioma histology (n = 1121, 57.4%) compared to astrocytoma (n = 831, 42.6%). There were 1626 patients who were either ≥40 years old or underwent a subtotal resection ("high-risk"), and from these 495 (30.4%) received postoperative radiation. On multivariable logistic regression treatment at an academic facility (OR 0.72) was associated with a lower likelihood of receiving postoperative radiation. Astrocytoma histology (OR 2.08), age ≥40 years (OR 2.23), tumor size ≥6 cm (OR 1.64), subtotal resection (OR 1.55), and chemotherapy use (OR 3.93) were associated with an increased likelihood of postoperative radiation. On multivariable analysis, astrocytoma histology (HR 3.49, p < 0.001) and receipt of radiation (HR 2.06, p < 0.001) were associated with worse overall survival. GTR (HR 0.51, p = 0.001) was associated with improved overall survival. Patients treated in United States hospitals are not routinely referred for postoperative radiation for high-risk, low-grade gliomas. Patients who received radiation did not do better than those who did not receive radiation.

Cost reduction associated with heparin-induced thrombocytopenia panel ordering for enoxaparin versus heparin for prophylactic and therapeutic use: A retrospective analysis in a community hospital setting.

BACKGROUND: Most hospitals still use unfractionated heparin (UFH) as the primary agent for venous thromboembolism (VTE) prophylaxis in the hospital setting due to ease of use and insignificant cost. However, the risk of heparin-induced thrombocytopenia (HIT) has led some groups to favor other options for therapeutic and prophylactic anticoagulation. This is particularly relevant in light of recent data demonstrating a lower rate of HIT in patients receiving enoxaparin compared with UFH. This study examines the cost-effectiveness of enoxaparin, compared to UFH for prophylactic and therapeutic usage in hospitals. METHODS: We conducted a retrospective chart review of patients who underwent HIT panel testing at the Inspira Health Network, Vineland campus (an approximately 262-bedded community hospital located in southern New Jersey that services a population of approximately 61,050) from the period of April 1, 2015 through December 31, 2016. The starting date represents the time from which enoxaparin became the primary alternative anticoagulant available at this hospital. Records of the total usage and cost of UFH and enoxaparin for the specified time period were collected from the hospital pharmacy database for evaluation, as were records of HIT panels. The information was analyzed to determine the frequency of HIT panel testing orders for patients receiving UFH versus those receiving enoxaparin. Annual cost-savings for the hospital were extrapolated using the comparative incidence of HIT panels and associated costs, including increased length of stay, hematology/oncology consultation, use of an alternative anticoagulant, critical bleeding requiring transfusion, and complications of HIT-associated thrombosis. These variables were multiplied by the incidence rate for each specified drug and usage to determine the daily cost for each drug. RESULTS: The use of enoxaparin did not result in a significant decrease in the ordering of HIT panels in the hospital, with a relative rate ratio of 0.948 (95% confidence interval: 0.336, 2.21). When the data were stratified to examine prophylactic and therapeutic anticoagulation, there was a marked difference in the frequency of HIT testing. The rate ratio of HIT panel orders for patients receiving therapeutic enoxaparin rather than intravenous (IV) UFH was 0.118 (0.006, 0.625). These numbers were used to extrapolate the total daily cost of enoxaparin compared with IV UFH; therapeutic enoxaparin cost $30.66, while IV UFH cost $162.30. IV UFH use was associated with a higher incidence rate of HIT panel orders, and consequently a higher daily cost due to the likelihood of increased length of stay, use of alternative anticoagulation, bleeding requiring transfusion, and request for expert consultation. CONCLUSION: In this study, the use of enoxaparin was associated with a significant cost-saving over IV UFH when used for therapeutic anticoagulation, but this cost saving was not observed for prophylactic anticoagulation.

The utilization of MGMT promoter methylation testing in United States hospitals for glioblastoma and its impact on prognosis.

Multiple studies have identified O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status to be an important prognostic factor in glioblastoma (GBM). We used the National Cancer Data Base (NCDB) to analyze completeness of coding for MGMT as well as to compare outcomes of GBM patients treated with adjuvant chemoradiation based on MGMT promoter methylation status (positive, negative, unknown). Patients diagnosed with GBM from 2010 to 2012 who received adjuvant chemoradiation were identified. MGMT promoter methylation status was obtained. The Kaplan-Meier method was used to assess overall survival (OS) by coding status of MGMT promoter methylation (positive, negative, unknown) and Cox regression analysis was used to assess impact of covariables on OS. There were 12,725 patients who met the study criteria, of which 626 (4.9%) were MGMT+, 1,037 (8.1%) were MGMT- and 11.062 (86.9%) were coded as unknown/not coded. Treatment at academic centers was strongly associated with MGMT promoter status testing (OR 2.23, p < 0.001), as well as hospital facility within the Northeast (OR 1.55, p < 0.001). The median and 2-year OS was 20 months and 40.2% for MGMT+ compared to 15 months and 24.1% for MGMT-, respectively (p < 0.001). For those coded as MGMT unknown, median and 2-year OS was 14.6 months and 27.5%, which was significantly worse compared to MGMT+ (p < 0.001) but not compared to MGMT- (p = 0.78). On multivariable analysis, MGMT+ was strongly associated with improved OS (HR 0.74, p < 0.001). Despite convincing evidence that MGMT promoter methylation status has a strong influence on prognosis; it appears to be a highly underutilized test in United States hospitals.

Moderating effects of sleep duration on diabetes risk among cancer survivors: analysis of the National Health Interview Survey in the USA.

BACKGROUND: Growing evidence suggests that cancer and diabetes may share common risk factors such as age, race/ethnicity, obesity, insulin resistance, sedentary lifestyle, smoking, and alcohol consumption. However, little is known about how habitual sleep duration (a known cardiometabolic risk factor) may affect the relationship between cancer and diabetes. The aim of this study was to investigate whether sleep duration moderated the relationship between history of cancer and diabetes. METHODS: Data were extracted from the National Health Interview Survey dataset from 2004 to 2013 containing demographics, chronic diseases, and sleep duration (N=236,406). Data were analyzed to assess the moderating effect of short and long sleep durations on cancer and diabetes mellitus. RESULTS: Our findings indicate that short sleep (odds ratio [OR] =1.07, 95% CI =1.03-1.11, P<0.001) and long sleep (OR =1.32, 95% CI =1.26-1.39, P<0.001) were associated with diabetes mellitus in fully adjusted models. However, only long sleep duration significantly moderated the relationship between cancer and diabetes (OR =0.88, 95% CI =0.78-0.98, P<0.05). CONCLUSION: Our findings indicate that for cancer survivors, short sleep was associated with higher self-reported diabetes and long sleep duration may act as a buffer against diabetes mellitus, as the likelihood of self-reported diabetes was lower among cancer survivors who reported long sleep duration. IMPACT: Findings from the current study have clinical and public health implications. Clinically, comprehensive sleep assessments and sleep interventions to improve sleep are needed for cancer survivors who have comorbid diabetes. Our findings can also spur public health reform to make sleep an important component of standard cancer survivorship care, as it reduces other chronic disease like diabetes.

Statins and New-Onset Diabetes in Cardiovascular and Kidney Disease Cohorts: A Meta-Analysis.

BACKGROUND: Statins have long been prescribed for the primary and secondary prevention of cardiovascular disease (CVD) and kidney disease. Their benefits and efficacy are widely accepted in current clinical practice, but like any other therapeutic agents, they have adverse effects. One of the emerging concerns with statin therapy is the development of new-onset diabetes mellitus (NODM), a dreaded risk factor for CVD and kidney disease and widely viewed as CVD equivalent. Accumulating evidence indicates that NODM is a consequence of statin use. METHODS: We conducted a meta-analysis of studies reporting on associations between NODM and statin use. Based on strict exclusion criteria, a total of 11 studies were selected. Their data were analyzed using Comprehensive Meta-Analysis® statistical software and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: The cumulative fixed effect for use of statin therapy and incident NODM was an OR of 1.61 (95% CI 1.55-1.68, p < 0.001). Our results suggest that statin therapy is associated with NODM, such that there is a small but significant risk of NODM among patients receiving statin for CVD prevention therapy. However, this high-risk population also has other diabetes risk factors (such as obesity and hypertension) contributing to the development of NODM. CONCLUSIONS: It is imperative that patients on statin therapy be monitored carefully for NODM. However, it can be argued that the risk of statin therapy is offset by the multitude of cardiovascular and kidney-protective effects provided by such an important and highly effective therapeutic agent.