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Penile squamous cell carcinoma (PSC) is traditionally treated with surgical resection with significant morbidity. Penile sparing approaches, such as brachytherapy, require expertise, prolonged inpatient stays, poor patient convenience, and heterogenous plans with variable long-term toxicity. In this study, we describe the protocol for novel portable apparatus created for PSC, allowing outpatient hybrid interstitial/surface brachytherapy, improving homogeneity and patient convenience.A portable brachytherapy apparatus was developed utilizing a foley catheter, prostate template, 6F interstitial catheters, 5 mm bolus, and a jock strap. The apparatus allowed for internal and external catheter placement housed in a jock strap to allow mobility and defecation without affecting the implant. High-dose-rate brachytherapy was performed as an outpatient.The apparatus was then used on a 62-year-old male with cT2pN0M0 (stage IIA) PSC with bilateral glans and urethral meatus involvement, who elected for definitive brachytherapy (4000cGy in 10 fractions over 5-days). Given external dwell positions, heterogeneity correction of the template was calculated (AAPM TG186) with2% variation. Patient had minimal impact on his active lifestyle during treatment and had complete clinical response at 3-months. Grade 2 skin desquamation resolved at 2-months, with no necrosis. At 6-months, he was able to resume sexual intercourse, and at 12-months, he remained disease-free with sexual and urinary function intact.Novel portable implant allows for improved patient convenience, reduced inpatient stay, capable of optimizing dosimetry with hybrid brachytherapy. This outpatient treatment allows the opportunity to increase fractionation, offering high local-control and lower toxicity. Future studies utilizing this apparatus for more fractionated regimens with further lower dose-per-fraction (∼3 Gy/fraction) is recommended.

Advances in radiotherapy technology and technique over the last 3 decades have revolutionized radiation treatment options for genitourinary malignancies. The development of more focused and accurate radiation treatment has facilitated safe delivery of dose-escalated treatment that improves disease control and the development of shorter-duration hypofractionated treatment regimens that are more convenient for patients and improve access to treatment. The management of oligometastatic disease is evolving with ablative treatment of oligometastasis and the primary for select patients and shorter-duration palliative treatment regimens. Work is ongoing to personalize radiation treatment regimens for genitourinary malignancies based on molecular biomarkers.

Highlights • Penile cancer impacts numerous quality of life aspects for patients. • Perienal urethrostomy is a reliable mechanism of urinary diversion for many patients with penile cancer. • This study describes that receipt of radiotherapy was not associated with increased risk of stenosis., Objective A lack of demonstrated clinical benefit precludes radiotherapy (RT) from being recommended for pN1/pN2 penile cancer (PeCa) lesions; but it may be recommended in case of extranodal (pN3) disease or for positive resection margins. Perineal urethrostomy (PU) is a technique of urinary diversion in patients with PeCa requiring total or subtotal penectomy as primary therapy. Prior studies suggest PU failure rates of up to 30%, without specific mention of the potential role of RT. When RT is delivered for PeCa it is usually to the pre-pubic fat, groin and lateral pelvis, and not to the region of the PU. Here we describe the role of perioperative RT in a large, multi-institutional registry of PU for PeCa. Methods In our cohort, 299 patients from seven international, high-volume centers in Belgium, Brazil, China, Netherlands, United Kingdom and the United States underwent PU as urinary diversion for PeCa between 2000 and 2020. Demographic and clinicopathologic characteristics were reviewed. Results Median patient age was 67 years and median follow-up was 19 months. Seven patients (2.3%) received pre-operative RT; six of them with chemotherapy. 37 received RT post-operatively, 21 (57%) with chemotherapy. Stenosis of the PU occurred in 35 (12%) of the total population. The majority of these patients (74%) required surgical revision at a median of 6.1 months post-operatively. RT delivery was neither significantly related to PU stenosis (p = 0.16) or to subsequent revision (p = 0.75). Conclusion Receipt of RT was not significantly associated with increased stenosis risk in PeCa patients who underwent PU.

BACKGROUND: The aim of the study was to investigate the safety of combining preoperative stereotactic body radiotherapy (SBRT) with robotic radical prostatectomy (RP) for high risk prostate cancer (HRCaP). Many patients with HRCaP will require adjuvant or salvage radiotherapy after RP. The addition of preoperative SBRT before RP may spare patients from subsequent prolonged courses of RT. MATERIALS AND METHODS: Eligible patients had NCCN HRCaP and received a total of 25 Gy or 30 Gy in five daily fractions of SBRT to the prostate and seminal vesicles followed by robotic RP with pelvic lymphadenectomy 31-45 days later. The primary endpoint was prevalence of acute genitourinary (GU) and gastrointestinal (GI) toxicity. Secondary endpoints were patient-reported quality of life (QOL) and biochemical recurrence (BcR) RESULTS: Three patients received preoperative SBRT to 25 Gy and four received 30 Gy. Median follow-up was 18 months. Highest toxicity was grade 2 and 3 in six (85.7%) and one (14.3%) patients, respectively. All patients developed grade 2 erectile dysfunction and 4 of 7 (57%) developed grade 2 urinary incontinence (UI) within a month after surgery. One patient developed acute grade 3 UI, but there was no grade ≥ 4 toxicity. One patient experienced acute grade 2 hemorrhoidal bleeding. On QOL, acute GU complaints were common and peaked within 3 months. Bowel symptoms were mild. Two patients with pN+ experienced BcR. CONCLUSIONS: Preoperative SBRT before robotic RP in HRCaP is feasible and safe. The severity of acute GU toxicity with preoperative SBRT may be worse than RP alone, while bowel toxicity was mild.

The increasing complexity of healthcare emphasizes the need for continued physician leadership and leadership training. This study aims to determine baseline attitudes toward the perceptions and utility of a leadership development curriculum (LDC) for radiation oncology (RO) residents. A novel longitudinal LDC was implemented for RO residents at our institution from 2018 to 2019. Prior to the curriculum, current and past residents in our institution's RO residency program were surveyed on their attitudes towards leadership in healthcare, emotional intelligence competencies, and leadership training interests. After the completion of the LDC, a post-curriculum survey was forwarded to current residents. The response rate was 84% (21 of 24) for the baseline survey and 90% (9 of 10) for the post-curriculum survey. Having a leadership training curriculum during residency was rated as extremely useful, with top training interests involving leading clinical teams, effective communication strategies, and conflict management. After the LDC, the residents reported high satisfaction with the curriculum and utilization of leadership training into their daily work. Our LDC demonstrates significant potential to engage trainees and improve their leadership skills at the graduate medical education level.

Purpose Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) represents 90% of all chronic prostatitis cases and may occur after radiation therapy (RT) for localized prostate cancer. Medical therapy is effective in approximately 50% of cases, with no therapy demonstrating consistent efficacy in refractory cases. Prostatic artery embolization (PAE) is effective in men with lower urinary tract symptoms and benign prostatic hyperplasia. We report clinical improvement after PAE in a case series of men with CP/CPPS after RT. Methods and Materials Nine men (median age 72 years; range, 61-83 years) with CP/CPPS after RT for prostate cancer underwent PAE. Baseline International Prostate Symptom Score was recorded in 5 patients (median 23; range, 4-26), Chronic Prostatitis Symptom Index score in 6 patients (median 22.5; range, 6-34), and quality of life (QoL) score in 8 patients (median 5; range, 2-6). Median baseline prostate volume was 49 cm3 (range, 22-123 cm3). Patients were followed up at 6 and 12 weeks with QoL, International Prostate Symptom Score, and/or Chronic Prostatitis Symptom Index score and magnetic resonance imaging. Results Technical success (ie, bilateral embolization) was achieved in 78% (n = 7) of patients with the other 2 patients having undergone unilateral embolization with no major complications. Clinical success was seen in 89% (n = 8) of patients and QoL improved in 78% (n = 7) during the follow-up period. Conclusion CP/CPPS after RT for localized prostate cancer is a highly morbid condition, with medical therapy successful in only 50% of cases. PAE may be a successful therapy for medically recalcitrant CP/CPPS, and further studies are necessary to understand the best patient selection and scenario for PAE in the setting of CP/CPPS.

BACKGROUND: To determine whether combining brachytherapy with immunotherapy is safe in prostate cancer (PCa) and provides synergistic effects, we performed a Phase I/II trial on the feasibility, safety, and benefit of concurrent delivery of anti-PD-1 (nivolumab) with high-dose-rate (HDR) brachytherapy and androgen deprivation therapy (ADT) in patients with Grade Group 5 (GG5) PCa. METHODS: Eligible patients were aged 18 years or older with diagnosis of GG5 PCa. Patients received ADT, nivolumab every two weeks for four cycles, with two cycles prior to first HDR, and two more cycles prior to second HDR, followed by external beam radiotherapy. The primary endpoint was to determine safety and feasibility. This Phase I/II trial is registered with ClinicalTrials.gov (NCT03543189). RESULTS: Between September 2018 and June 2019, six patients were enrolled for the Phase I safety lead-in with a minimum observation period of 3 months after nivolumab administration. Overall, nivolumab was well tolerated in combination with ADT and HDR treatment. One patient experienced a grade 3 dose-limiting toxicity (elevated Alanine aminotransferase and Aspartate aminotransferase) after the second cycle of nivolumab. Three patients (50%) demonstrated early response with no residual tumor detected in ≥4 of 6 cores on biopsy post-nivolumab (4 cycles) and 1-month post–HDR. Increase in CD8+ and FOXP3+/CD4+ T cells in tissues, and CD4+ effector T cells in peripheral blood were observed in early responders. CONCLUSION: Combination of nivolumab with ADT and HDR is well tolerated and associated with evidence of increased immune infiltration and antitumor activity.

Patient-generated health data (PGHD), or health-related data gathered from patients to help address a health concern, are used increasingly in oncology to make regulatory decisions and evaluate quality of care. PGHD include self-reported health and treatment histories, patient-reported outcomes (PROs), and biometric sensor data. Advances in wireless technology, smartphones, and the Internet of Things have facilitated new ways to collect PGHD during clinic visits and in daily life. The goal of the current review was to provide an overview of the current clinical, regulatory, technological, and analytic landscape as it relates to PGHD in oncology research and care. The review begins with a rationale for PGHD as described by the US Food and Drug Administration, the Institute of Medicine, and other regulatory and scientific organizations. The evidence base for clinic-based and remote symptom monitoring using PGHD is described, with an emphasis on PROs. An overview is presented of current approaches to digital phenotyping or device-based, real-time assessment of biometric, behavioral, self-report, and performance data. Analytic opportunities regarding PGHD are envisioned in the context of big data and artificial intelligence in medicine. Finally, challenges and solutions for the integration of PGHD into clinical care are presented. The challenges include electronic medical record integration of PROs and biometric data, analysis of large and complex biometric data sets, and potential clinic workflow redesign. In addition, there is currently more limited evidence for the use of biometric data relative to PROs. Despite these challenges, the potential benefits of PGHD make them increasingly likely to be integrated into oncology research and clinical care.

OBJECTIVES The brain is a rare site for sarcoma metastases. Sarcoma's radioresistance also makes standard whole-brain radiotherapy less appealing. We hypothesize that stereotactic radiation techniques (stereotactic radiosurgery [SRS]/stereotactic fractionated radiotherapy [FSRT]) may provide effective local control. MATERIALS AND METHODS This single-institution retrospective analysis evaluated our experience with linear acceleator-based SRS/FSRT for sarcoma brain metastases. Time to event analysis was estimated via Kaplan-Meier. Univariable/multivariable Cox regression analyses followed to assess the impact of patient and disease characteristics on outcomes. RESULTS Between 2003 and 2018, 24 patients were treated with 34 courses of SRS/FSRT to 58 discrete lesions. The median age at first treatment was 57 years (range: 25 to 87 y). Majority of patients had concurrent lung metastases (n=21; 88%), diagnosed spindle cell sarcoma (n=15; 25%) or leiomyosarcoma (n=12; 21%) histology, and were treated with either SRS (n=43; median dose=19 Gy, range: 15 to 24 Gy) or FSRT (n=17; 3/5 fractions, median dose=25 Gy, range: 25 to 35 Gy). With a median follow-up after brain metastasis of 7.3 months, the 6 month/12 month local control, distant brain control, and overall survival of 89%/89%, 59%/34%, and 50%/38%, respectively. All local failures were of primary spindle cell histology (P

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).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.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.PROs provide an insight into the morbidity of therapies for advanced PeCa, and the most symptoms are reported by patients with recurrent disease.

13 Background: There are limited options for relapsed penile squamous cell carcinoma (PSCC) patients after definitive therapy or chemo-refractory disease. Novel target discovery methods are needed to identify potential treatment options and the cell surface represents an actionable target for molecular and cell-based therapies. We evaluated the cell surface molecular catalogue (e.g., surfaceome) in PSCC to identify underexplored targets. Methods: To evaluate proteins enriched on the surface of PSCC cells, we screened published translatomics data from 5 PSCC cell lines (HPV-negative). Ribosome-bound RNA expression values were then analyzed using a validated surfaceome gene list (n=2,886 proteins) to infer surface presence, which were grouped by consensus protein classes. This was complemented by RNA-Seq (n=37) on resected PSCC tumors (HPV+=16, HPV- = 16, unknown HPV status = 5). We used immunohistochemistry (IHC) to assess protein expression and subcellular localization in PSCC tumors; stain intensity was assessed by a semi-quantitative H-score. Non-parametric statistics compared distributions and Kaplan-Meier analysis estimated overall survival (OS; defined from surgery to death or last follow-up) and groups were compared by log-rank testing. The open-source DRPPM-PATH-SURVEIOR app and R statistical software were used to perform analyses. Results: We identified 604 unique surfaceome proteins which were represented in the top 75% of expression in the PSCC cell line translatome. Half of these proteins have N-glycosylations and 49.5% classified as high-confidence surface targets. The largest proportions of surfaceome proteins included: Receptors (25.6%), Transporters (18.5%), and proteins with unclassified function (32.2%). Of note, 16.2% of this surfaceome linked to at least one compound in the DrugBank database.There was a moderate correlation between cell line and tumor surfaceome RNAs (top 75%; r =0.58, p < 2.2x10-16). We selected targets in the 99% (BSG; CD147; regulates MMPs and lactate transport), 90% (FGFR1; receptor tyrosine kinase) and 75% (SLC16A1; metabolite transporter) of the surfaceome expression. Tumor RNA levels for BSG, FGFR1 and SLC16A1 were elevated, but without differences based on HPV. IHC demonstrated robust expression in tumors with plasma membrane scoring being enriched compared to non-plasma membrane compartments (CD147, p =2.9x10-6; SLC16A1, p = 5.1x10-6; FGFR1, p = 0.007). Of note, patients with elevated BSG RNA (based on median log2 value) had worse OS (p = 0.018), though this lost significance after adjusting for HPV. No differences in OS were seen with FGFR1 or SLC16A1 expression. Conclusions: Our analysis of the surfaceome based on RNA expression was associated with increased protein levels in tumor tissues. Evaluation of the PSCC surfaceome may provide opportunity to investigate novel therapeutic targets, which may be actionable regardless of HPV status.

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 &lt, 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.

Purpose Optimal postoperative radiation therapy (PORT) dose is unclear in penile squamous cell carcinoma (PeSCC). Herein, we characterized the radiosensitivity index (RSI) and genomic-adjusted radiation dose (GARD) profiles in a cohort of patients with PeSCC, and assessed the application of GARD to personalize PORT. Methods A total of 25 PeSCC samples were identified for transcriptomic profiling. The RSI score and GARD were derived for each sample. A cohort of 34 patients was reviewed for clinical correlation. Results The median RSI for PeSCC was 0.482 (range 0.215–0.682). The majority (n = 21; 84%) of cases were classified as radioresistant. PeSCC GARD ranged from 9.56 to 38.39 (median 18.25), suggesting variable therapeutic effects from PORT. We further determined the optimal GARD-based RT doses to improve locoregional control. We found that therapeutic benefit was only achieved in 52% of PeSCC lesions with PORT of 50 Gy, in contrast to 84% benefit from GARD-modeled PORT of 66 Gy. In the clinical cohort, the majority of patients presented with pathological N2 or N3 disease (n = 31; 91%) and was treated with adjuvant concurrent platinum-based chemoradiotherapy (CRT, n = 30; 88%). Fourteen of the 34 patients (41%) had locoregional recurrence (LRR), of which half had LRR within six months of completion of PORT. Conclusions The majority of PeSCC are intrinsically radioresistant with a low GARD-based therapeutic effect from PORT dose of 50 Gy, consistent with the observed high rate of LRR in the clinical cohort. A GARD-based strategy will allow personalizing PORT dose prescription to individual tumor biology and improve outcomes.

Purpose: To evaluate early-stage prostate cancer (PCa) radiotherapy treatment patterns and outcomes among Ghanaian men (GM) compared with US men (USM). Materials and Methods: This retrospective study consists of 987 National Comprehensive Cancer Network low risk, favorable intermediate risk, and unfavorable intermediate risk PCa patient subgroups; GM (173) and USM (814). Differences in baseline covariates and clinical characteristics between GM and USM were analyzed using χ2 and Mann-Whitney test while Cox Proportional Hazards model was used to assess freedom from biochemical failure differences between the study groups. Results: Median follow-up for this study was 40 months. GM were diagnosed at a younger median age (64 vs. 68 y, P

Aim Describe the Value proposition for radiotherapy (RT) in the United States. Background In the United States since 2005, two forces have worked to decrease RT cost per patient: Federal changes in reimbursement and hypofractionation of treatment courses. We theorize that these have driven stable reimbursement in the context of increasing technology of intensity modulation (IMRT) and image guidance (IGRT). This phenomenon provides increasing Value of the discipline to patients and systems. Materials and methods We searched the Medicare Physician/Supplier data for Program Payments per Person with Utilization for 2000 through 2016. This involves two databases: Enrollment Database (EDB) for 2000–2012 and Common Medicare Enrollment (CME) since 2013. RT payments to individual patients accessing services were retrieved. Results Taking into account the change of calculation algorithm used by CMS in 2013, costs per patient were similar in 2012 and 2003, and 2016 and 2013. Conclusions In the United States, stabilizing costs in the face of increasing work, better outcomes, and decreased toxicity contributes to increasing RT value over the past 10 years.

PI3K-AKT-mTOR signaling pathway dysregulation has been linked to the development of various malignancies, with only limited and conflicting reports in penile squamous-cell carcinoma (PSCC). Tissue microarrays of 57 cases of invasive PSCC were immunohistochemically stained for 3 proteins of the mTOR pathway: PTEN, AKT, and S6. Up-regulation of PI3K-AKT-mTOR and human papillomavirus coinfection in PSCC were associated with favorable disease. PURPOSE: To assess the prognostic value of PI3K-AKT-mTOR signaling pathway up-regulation in a contemporary cohort of penile squamous-cell carcinoma (PSCC) patients. PATIENTS AND METHODS: Tissue microarrays were constructed for 57 patients with invasive PSCC treated at our institution between 2000 and 2013. Immunohistochemical staining was performed for PTEN, AKT, and S6. Human papillomavirus (HPV) in-situ hybridization for high-risk subtypes was also performed. Biomarker expression was evaluated by a semiquantitative H score. Overall survival, disease-specific survival and recurrence-free survival stratified by biomarker expression (low vs. high) were estimated by the Kaplan-Meier method. Multivariable Cox regression models were used to determine predictors of mortality and recurrence. RESULTS: HPV in-situ hybridization was positive in 23 patients (40%). PTEN was down-regulated in 43 patients (75%), while phosphorylated-AKT (p-AKT) and phosphorylated-S6 (p-S6) were up-regulated in 27 (47%) and 12 patients (21%), respectively. In multivariable Cox regression models, patients with low expression of p-AKT had an increased risk of recurrence (hazard ratio [HR] = 3.95; 95% confidence interval [CI], 1.47–10.59; P = .02), while those with low expression of p-S6 had an increased risk of overall mortality (HR = 6.15; 95% CI, 1.55–24.36; P = .01). HPV status was an independent predictor of overall survival (HR = 6.99; 95% CI, 2.42–20.16; P < .001) and disease-specific survival (HR = 6.74; 95% CI, 2.02–22.48; P = .002). CONCLUSION: PI3K-AKTmTOR signaling pathway up-regulation and HPV coinfection in PSCC are associated with favorable disease. mTOR pathway biomarkers along with HPV status may represent novel prognosticators for risk stratification of PSCC patients and may help guide treatment decisions and follow-up strategies. These findings require further investigation.

Background Chordomas and chondrosarcomas are a rare but challenging subset of tumors to treat; however, previous studies have shown benefits from proton therapy, which are thought to be primarily driven by prescription conformality permitting homogeneous tumor dosing and the allowance of higher doses. No retrospective studies to date have directly compared the outcomes of conventional and particle therapy or examined the role of high doses (specifically ≥70 Gy) in definitive radiotherapy (DRT) or perioperative radiotherapy (PRT) for both types of malignancies. Methods A total of 863 patients with chondrosarcoma and 715 patients with chordoma treated with nonpalliative proton or conventional radiation therapy with a dose range of 20 to 80 Gy and at least 15 months of follow-up were identified from the National Cancer Data Base for the years 2003-2014. The primary endpoint of overall survival (OS) was evaluated, and clinical features, including age, sex, grade, clinical stage, and Charlson-Deyo comorbidity index, were compared. Results Patients receiving DRT were older and had more advanced disease. In DRT for chondrosarcoma, a high dose (40.6% vs 16.9%; P = .006) and proton therapy (75.0% vs 19.1%; P = .046) were associated with improved OS at 5 years in a multivariate analysis. In DRT for chordoma, proton therapy was associated with improved OS at 5 years in a multivariate analysis (100% vs 34.1%; P = .031), and a high dose for chordoma was significant for improved OS in a univariate analysis with both DRT (79.0% vs 54.1%; P = .027) and PRT (83.3% vs 77.4%; P = .007). Conclusions In the largest retrospective series to date, dose escalation and proton radiotherapy were associated with improved OS in patients with chondrosarcoma and chordoma despite limited follow-up and access to particle therapy.

Racial and ethnic disparities are well-documented in cancer outcomes such as disease progression and survival, but less is known regarding potential disparities in symptom burden.The goal of this retrospective study was to examine differences in symptom burden by race and ethnicity in a large sample of cancer patients. We hypothesized that racial and ethnic minority patients would report greater symptom burden than non-Hispanic and White patients.A total of 5798 cancer patients completed the Edmonton Symptom Assessment Scale-revised (ESAS-r-CSS) at least once as part of clinical care. Two indicators of symptom burden were evaluated: (1) total ESAS-r-CSS score (i.e., overall symptom burden) and (2) number of severe symptoms (i.e., severe symptomatology). For patients completing the ESAS-r-CSS on multiple occasions, the highest score for each indicator was used. Zero-inflated negative binomial regression analyses were conducted, adjusting for other sociodemographic and clinical characteristics. Symptomology varied across race. Patients who self-identified as Black reported higher symptom burden (p = .016) and were more likely to report severe symptoms (p .001) than self-identified White patients. Patients with "other" race were also more likely to report severe symptoms than White patients (p = .032), but reported similar total symptom burden (p = .315). Asian and Hispanic patients did not differ from White or non-Hispanic patients on symptom burden (ps .05).This study describes racial disparities in patient-reported symptom burden during routine oncology care, primarily observed in Black patients. Clinic-based electronic symptom monitoring may be useful to detect high symptom burden, particularly in patients who self-identify their race as Black or other. Future research is needed to reduce symptom burden in racially diverse cancer populations.

Reduction in setup errors is advocated through daily imaging and adaptive therapy, where the target volume is drawn daily. Previous studies suggest that inter-physician volume variation is significant (1.5 cm standard deviation [SD]); however, there are limited data for intra-physician consistency in daily target volume delineation, which is investigated in this study. Seven patients with lung cancer were chosen based on the perceived difficulty of contouring their disease, varying from simple parenchymal lung nodules to lesions with extensive adjacent atelectasis. Four physicians delineated the gross tumor volume (GTV) for each patient on 10 separate days to see the intra- and inter-physician contouring. Isocenter coordinates (x, y and z), target volume (cm3), and largest dimensions on anterior–posterior (AP) and lateral views were recorded for each GTV. Our results show that the variability among the physicians was reflected by target volumes ranging from +109% to −86% from the mean while isocenter coordinate changes were minimal; 3.8, 1.7 and 1.9 mm for x, y and z coordinates, respectively. The orthogonal image (AP and lateral) change varied 16.3 mm and 15.0 mm respectively among days and physicians. We conclude than when performing daily imaging, random variability in contouring resulted in isocenter changes up to ±3.8 mm in our study. The shape of the target varied within ±16 mm. This study suggests that when using daily imaging to track isocenter, target volume, or treatment parameters, physicians should be aware of personal variability when considering margins added to the target volume in daily decision making especially for difficult cases.

Purpose/Objective(s) To monitor intrafraction motion during spine stereotactic radiosurgery (SRS) treatment delivery with readily available device, we implemented triggered kV imaging using the on-board imager of the medical linear accelerator advanced imaging package. Materials/Methods Triggered kV imaging technique was clinically implemented and applied to 32 spine SBS patients (75 fx, 20 T-spine tumors, 12 L-spine tumors) during VMAT delivery. Currently available trigger options in the medical linear accelerator software package are MU, gantry angle, time, and respiratory gating. Time trigger was selected to acquire kV images every 15 seconds, in an effort to balance temporal resolution with reasonable time for image evaluation. Upon each image acquisition, a 2D projection of the 3D image-guided radiotherapy (IGRT) structures was automatically calculated and updated at arbitrary angles as a qualitative visual guide for patient alignment during treatment delivery. For IGRT structures, patient anatomy (vertebra and spinous process) and orthopedic hardware if present were contoured, with a 1 mm expansion. As the technique depends on visual inspection, decisions could vary depending on interobserver variability. Therefore, a survey of 10 trained physicists (4) and physicians (6) was conducted to evaluate efficiency and accuracy of clinical decision with kV images collected using an anthropomorphic phantom with different CT slice thicknesses and shifts introduced. The survey consisted of 192 sample images. The participants were asked to determine if a shift requiring intervention was observed. Average time per decision was recorded. Results The robustness of our current patient immobilization system was validated in our clinical implementation. Based on visual inspection of projected IGRT contours on planar kV images, appreciable movement was detected in only one fraction (1.3%). However, in this instance, motion was well beyond PTV/PRV margins (2.4 mm) and treatment was stopped to take a CBCT and correct the displacement, which otherwise would have not been detected. From the survey, the average time spent per decision was 7.5 seconds. In all shift directions, detectability was proportional to the shift size and superior detectability was observed with contours drawn using CT images with 1 mm slice thickness. Shifts smaller than 1 mm are less noticeable (12.6%) compared to 2 mm shifts (42.6%). Participant detection capability was dependent on the level of training. Conclusion This approach provides an effective, non-invasive intrafraction motion monitoring solution, using the built in triggered-imaging technique of the medical linear accelerator. One of the benefits this technique offers is that it can serve as a quality assurance approach to verify adequacy of a patient immobilization system. An important limitation is that the monitoring result is qualitative and depends on observer visual detection capability. Enhanced precision and utility could be achieved if an automated quantitative evaluation feature is implemented. Author Disclosure J. Koo: None. L.Nardella: None. M.Degnan: None. J.Andreozzi: None. H.M. Yu: Honoraria; UpToDate. Speaker's Bureau; BrainLab. Advisory Board; Novocure, AbbVie. J.A.Penagaricano: None. P.A. Johnstone: None. D.E. Oliver: None. K.A. Ahmed: Research Grant; Bristol-Myers Squibb, Genentech. S.Rosenburg: Consulting; Novocure. E.J.Wuthrick: Research Grant; BMS. Honoraria; Regeneron/Sanofi, Varian. Consultant; Regeneron/Sanofi, Varian. R. Diaz: Honoraria; Zeiss; Global Health Outreach. V.Feygelman: None. E.G. Moros: Research Grant; Varian Medical Systems. Promote research in the AAPM; American Association of Physicists in Medicine. Promoting research in the AAPM; American Association of Physicists in Medicine. G.Redler: None.

Purpose Perineal urethrostomy (PU) is often the definitive form of urinary diversion in patients with locally-advanced or anatomically unfavorable penile cancer (PC) requiring total penectomy. Here, we report post-operative PU-related complications and PU stenosis rates after total penectomy with PU in a large multicenter cohort of PC patients. Methods We retrospectively reviewed the medical records of 299 patients who underwent PU as a means of urinary diversion for primary PC across seven international centers from 2000 to 2020. The Clavien-Dindo grading system was used to record 30-day post-operative complications. Cumulative incidence of stenosis was evaluated using the Kaplan-Meier method. Results Median patient age was 67 years (interquartile range (IQR) 58–74), and median follow-up was 19 months (IQR 7.2–57). A total of 58 patients (19%) developed a 30-day post-operative complication, of which 45 (79%) were deemed minor (CD Grade I and II). Wound infection (11%; CD grade I–III) and dehiscence (4.0%; CD grade I–III) were the more common complications. The overall incidence of stenosis was 12% (35/299 patients), of which 26 (74%) needed surgical revision (probability of stenosis revision at one year of 9.3%, median time until the revision: 6.1 months (IQR 3.0–13)). Only two stenoses were seen after two years of follow-up. Conclusion We present the most extensive series of PU in the management of PC to date. Wound infections of the primary surgical site were the most common complication. Stenosis occurred mostly within one and a half years after treatment.

Purpose In 2019, the Centers for Medicare and Medicaid Services proposed a new radiation oncology alternative payment model aimed at reducing expenditures. We examined changes in aggregate physician Medicare charges allowed per specialty to provide contemporary context to proposed changes and hypothesize that radiation oncology charges remained stable through 2017. Methods and Materials Medicare physician/supplier utilization, program payments, and balance billing for original Medicare beneficiaries, by physician specialty, were analyzed from 2002 to 2017. Total allowed charges under the physician/supplier fee-for-service program, inflation-adjusted charges, and percent of total charges billed per specialty were examined. We adjusted for inflation using the consumer price index for medical care from the US Bureau of Labor Statistics. Results Total allowed charges increased from $83 billion in 2002 to $138 billion in 2017. The specialties accounting for the most charges billed to Medicare were internal medicine and ophthalmology. Radiation oncology charges accounted for 1.2%, 1.6%, and 1.4% of total charges allowed by Medicare in 2002, 2012, and 2017, respectively. Radiation oncology charges allowed increased 44% from 2002 to 2012 ($987.6 million to $1.42 billion) but decreased by 19% from 2012 to 2017 ($1.15 billion), adjusted for inflation. Total charges allowed by internal medicine decreased 2% from 2002 to 2012 ($8.53 to $8.36 billion), adjusted for inflation, and decreased 16% from 2012 to 2017 ($7.05 billion). When adjusting for inflation, ophthalmology charges increased 18% from 2002 to 2012 ($4.53 to $5.36 billion) and increased 3% from 2012 to 2017 ($5.5 billion). Conclusions Radiation oncology physician charges represent a small fraction of total Medicare expenses and are not a driver for Medicare spending. Aggregate inflation-adjusted charges by radiation oncology have dramatically declined in the past 5 years and represent a stable fraction of total Medicare charges. The need to target radiation oncology with cost-cutting measures may be overstated.

Emergence of the COVID-19 crisis has catalyzed rapid paradigm shifts throughout medicine. Even after the initial wave of the virus subsides, a wholesale return to the prior status quo is not prudent. As a specialty that values the proper application of new technology, radiation oncology should strive to be at the forefront of harnessing telehealth as an important tool to further optimize patient care. We remain cognizant that telehealth cannot and should not be a comprehensive replacement for in-person patient visits because it is not a one for one replacement, dependent on the intention of the visit and patient preference. However, we envision the opportunity for the virtual patient “room” where multidisciplinary care may take place from every specialty. How we adapt is not an inevitability, but instead, an opportunity to shape the ideal image of our new normal through the choices that we make. We have made great strides toward genuine multidisciplinary patient-centered care, but the continued use of telehealth and virtual visits can bring us closer to optimally arranging the spokes of the provider team members around the central hub of the patient as we progress down the road through treatment.

Due to its rarity and lack of prospective studies, clinical evidence for the management of the inguinal lymphatic nodal basin with radiation therapy in penile cancer (PeCa) has been limited. In this report, we review the current literature and further investigated the landscape of radiation sensitivity in nodal metastases of PeCa utilizing our well-established genome-based radiosensitivity index (RSI) platform. We hypothesized that optimal therapeutic gain could be achieved in PeCa stratified by the combination of clinicopathological parameters, genomic heterogeneity, and RSI-based radiation dose prescription (RxRSI). Similar to primary PeCa lesions, we found that the majority of PeCa nodal metastases are genomically radioresistant with significant heterogeneity. RxRSI should be considered to inform and optimize the radiation therapy dose prescription to the individual tumor biology.

Therapy for early stage testicular seminoma has changed radically over the past several decades. Given high cure rates and clinical trials supporting less active therapy in most cases, close observation after radical orchiectomy is now considered standard of care for clinical stage (CS) IA/IB seminoma, with either radiation therapy (RT) or chemotherapy salvage options possible. For CS IIA/IIB seminoma characterized by non-bulky retroperitoneal lymph node involvement (≤5 cm in greatest dimension), RT or combination chemotherapy are the standard of care. Given high comparable survival rates, preventing treatment-related toxicity and second malignancy, and limiting quality of life deficits associated with intense treatment has gained much greater importance. Clinical trials are currently testing the feasibility of retroperitoneal lymph node dissection (RPLND) for low volume CS IIA/IIB metastatic testicular seminoma to this end. Likewise, one cycle of chemotherapy is being evaluated as an adjuvant approach to reduce recurrence rates in CS I disease with unfavorable risk factors. Moreover, recent genomic and molecular studies have recently identified novel signatures and a potential biomarker for testicular seminoma. In this review, we first summarize the evolution of early stage seminoma management and discuss the effectiveness and drawbacks of contemporary treatment strategies. We further outline future perspectives and potential challenges in management of early stage testicular seminoma.

Objective We have previously described the central nature of simple cases for financial feasibility of proton beam therapy centers—especially four- to five-room centers. In the 5 years since that publication, such construction has slowed drastically, and smaller, single-room projects are in vogue. We now seek to show under what circumstances a single-room system is optimally financially viable. Materials and Methods A “standard” construction cost and debt for a single gantry system of $40 million was presumed, with 75% of the construction funded through standard 20-year financing. We then modeled a statistical analysis, deriving the optimal case mix required daily to cover construction and debt service costs. Results We previously published that a single gantry treating only complex patients would need to apply 85% of its treatment slots simply to service debt, though it would cover its debt treating 4 hours of simple patients. As the business model has changed, debt maintenance, profit and operational costs have somewhat reduced the business case for adding a large number of simple patients. Debt maintenance is possible with as little as 13% of daily patients for a 40% Medicare case mix, but these numbers are critically sensitive to continued patient throughput. Conclusions Even in a single-room system, reducing overall debt, using tax-exempt financing, and having a case load emphasizing simple, private payer patients is paramount to fiscal health of the facility. Unused capacity is a huge risk if insufficient patients are available.

Purpose Data on prostate cancer (PCa) treatment in Africa remains under-reported. We present a review of the management of PCa at the cancer center of the largest tertiary referral facility in Ghana, with emphasis on curative treatment. Methods We retrospectively reviewed data on 1,074 patients seen at the National Center for Radiotherapy and Nuclear Medicine from 2003 to 2016. Patient and disease characteristics at presentation are presented using descriptive statistics. The χ2 and Fisher’s exact tests and Mann-Whitney U test were used to analyze differences between categorical and continuous variables, respectively. Methods of survival analysis were used to evaluate the relative risk of biochemical disease-free survival (bDFS). Results Seventy percent of the study population presented with localized disease. High-risk disease presentation accounted for 64.4% of these patients. Only 57.6% of patients with localized disease received curative radiotherapy. The 5-year overall survival for the curative cohort was 96% (interquartile range, 93% to 98%). The 5-year bDFS rates for low-, intermediate-, and high-risk groups were 95%, 70%, and 48%, respectively. Both Gleason score and pretreatment prostate-specific antigen were significant predictors for bDFS in multivariable analysis. Conclusion We show that the majority of patients with PCa have locally advanced disease at the time of presentation for radiotherapy. bDFS was significantly better for low- and intermediate-risk than for high-risk disease. These data emphasize the dire need to re-evaluate screening and patient education of PCa in regions of the world with high incidence and mortality as well as the need for improved access to care and treatment delivery.

Background We analyzed the trends in presentation of squamous cell carcinoma (SCC) of the penis and determined the socioeconomic predictors for locally advanced (cT3-cT4) disease in the United States. Patient and Methods The National Cancer Database was queried for patients with clinically nonmetastatic penile SCC and staging available from 1998 to 2012. Temporal trends per tumor stage were evaluated, and a multivariable logistic regression model was used to identify predictors for advanced presentation during the study period. Results A total of 5767 patients with stage ≤ T1-T2 (n = 5423) and T3-T4 (n = 344) disease were identified. Increasing trends were noted in all stages of penile SCC with a greater proportion of advanced cases over time ( P = .001). Significant predictors of advanced presentation were age > 55 years, the presence of comorbidities, and Medicaid or no insurance ( P Conclusion More penile SCC is being detected in the United States. Our results have demonstrated older age, presence of comorbidities, and Medicaid or no insurance as potential barriers to early access of care in the male population. Understanding the current socioeconomic gaps could help guide targeted interventions in vulnerable populations.

Purpose/objective(s) The management of oligometastatic bladder cancer is unclear. Prior data implies site and burden of metastases vary in prognoses. This study evaluates treatment trends, examines the effect of local therapy on survival, and explores if immunotherapy influences outcomes in patients with de novo oligometastatic bladder urothelial carcinoma. Materials/methods A retrospective analysis of the National Cancer Database (NCDB) was performed by identifying bladder urothelial carcinoma patients with metastases (M1 stage) at diagnosis between 2004 and 2016. Local therapy was classified as high-intensity [HT] (i.e., definitive surgery, radiation [RT] dose > 50 Gy) or low-intensity [LT] (i.e., non-definitive surgery, RT dose Results A total of 11,998 patients were identified with metastases at diagnosis. The median age was 72 years (IQR: 62-80), the majority were Caucasian (87.5%) and male (71.2%). The median follow-up time was 5.5 months (IQR: 2.27-12.62). Patients were treated with definitive surgery (n = 849; 7.1%), perioperative CT (n = 404; 3.4%), CT alone (n = 4,030; 33.6%), RT alone (n = 1,026; 8.6%), CTRT (n = 1,451; 12.1%) or no therapy (n = 3,343; 33.6%). HT and LT were given to 1,083 (9%) and 8,867 (73.9%) patients, respectively. Differences were noted in median OS among treatment groups, such as perioperative CT (OS 16.4 months) or CTRT (> 50 Gy) (12.4 months); P Conclusion This population-based study suggests local aggressive therapy, either surgical or RT (> 50 Gy) is associated with an improved OS benefit in patients with de novo metastatic bladder urothelial carcinoma.

The implementation of the radiation oncology alternative payment model (RO-APM) has raised concerns regarding the development of MRI-guided adaptive radiotherapy (MRgART). We sought to compare technical fee reimbursement under Fee-For-Service (FFS) to the proposed RO-APM for a typical MRI-Linac (MRL) patient load and distribution of 200 patients. In an exploratory aim, a modifier was added to the RO-APM (mRO-APM) to account for the resources necessary to provide this care. Traditional Medicare FFS reimbursement rates were compared to the diagnosis-based reimbursement in the RO-APM. Reimbursement for all selected diagnoses were lower in the RO-APM compared to FFS, with the largest differences in the adaptive treatments for lung cancer (−89%) and pancreatic cancer (−83%). The total annual reimbursement discrepancy amounted to −78%. Without implementation of adaptive replanning there was no difference in reimbursement in breast, colorectal and prostate cancer between RO-APM and mRO-APM. Accommodating online adaptive treatments in the mRO-APM would result in a reimbursement difference from the FFS model of −47% for lung cancer and −46% for pancreatic cancer, mitigating the overall annual reimbursement difference to −54%. Even with adjustment, the implementation of MRgART as a new treatment strategy is susceptible under the RO-APM.

Patient‐reported outcomes regarding symptom burden may provide valuable information in addition to physician assessment. Systematic collection of patient‐reported outcomes may be an important metric to identify unmet needs and improve quality of patient care. To understand common symptoms of patients seen in radiation oncology clinic, we examined the prospectively collected modified Edmonton Symptom Assessment Scale (ESAS‐r) data to explore symptom clusters. Our clinic established use of a modified Edmonton Symptom Assessment Scale in August 2015. All outpatients presenting for radiation oncology services completed the form at each clinic visit. Symptom clusters are defined by two or more symptoms that are interrelated and occur simultaneously with a high degree of predictability. A sample of 916 de‐identified surveys was assessed statistically using principal component analysis (PCA) with varimax rotation to determine independent clustering between the symptoms queried. We found four major clusters of symptoms: Tiredness (tired, drowsiness; PC1), Loss of Appetite (nausea, lack of appetite; PC2), Low Well‐Being (overall & spiritual well‐being; PC3), and Depression (depression, anxiety; PC4). These accounted for 46%, 9.2%, 7.6%, and 7% of total variance, respectively. Internal consistency using Cronbach's alpha was 0.87, 0.7, 0.82, and 0.87, respectively. The most frequent write‐in item was itchiness, present in 24% of the 148 patients responding. Assessment of patients seen in a large radiation oncology clinic revealed several symptom clusters. {Tiredness and drowsiness} represents a major symptom cluster. Itchiness may be underrecognized.

PURPOSE: Patient perspectives of their symptom burden provide valuable data to clinicians. We have investigated the Edmonton Symptom Assessment Scale (ESAS) extensively in our radiation oncology and supportive care clinics. We were interested in examining whether ESAS data could correlate with anemia. METHODS: Our clinics have used a modified ESAS since 2015; patients now input data directly into the electronic medical record using a tablet interface. Of 9813 patients providing ESAS reports, we retrieved hemoglobin (Hb) data from 8304. Of these, 1351 patients had both performed on the same day. Anemia existed if Hb was < 13.0 g/L (man) or < 12 g/L (woman). RESULTS: When self-reported scores for both tiredness and shortness of breath were 7 and above, the positive predictive value (PPV) for anemia was 80%, and specificity was 97.6%. Corresponding sensitivity was 8.2% and accuracy was 48.9%. This 2-item model could be a valuable screening tool for lack of anemia in cancer patients in the outpatient setting: if patients rate both these ESAS items < 7, there exists < 3% false positive risk. An expanded 5-item model adding lack of appetite, pain, and bone marrow primary site increased sensitivity and accuracy at the expense of specificity and PPV. We consider this less clinically functional than the two-item screen. CONCLUSION: This is one of the first reports of PRO data screening for a clinical sign, in this case, anemia. Predicting freedom from anemia is feasible using 2 ESAS survey questions: tiredness and shortness of breath.

Objectives The role of local disease control in the oligometastatic setting is evolving. Stereotactic body radiation therapy (SBRT) is a noninvasive treatment option for oligometastases; however, using ablative radiation doses for adrenal metastases raises concern given the proximity to radiosensitive organs. Novel treatment techniques may allow for selective dose escalation to improve local control (LC) while minimizing dose to nearby critical structures. Materials and methods We retrospectively reviewed patients with adrenal oligometastases treated with SBRT from 2013 to 2018. LC, disease-free survival, and overall survival were estimated using Kaplan-Meier methods. Predictors of outcomes were evaluated by log-rank and Cox proportional hazard analyses. Results We identified 45 adrenal oligometastases in 41 patients treated with SBRT. The median age at treatment was 67 years (range, 40 to 80). The most common primary histologies were non-small cell lung cancer (51%), renal cell carcinoma (24%), and small cell lung cancer (10%). The median prescription dose was 50 Gy (range, 25 to 60 Gy), with 30 (67%) lesions receiving ≥50 Gy and 14 (31%) receiving 60 Gy. In total, 26 (58%) lesions received a simultaneous-integrated boost. Of the 42 treatment simulations, 26 (62%) were supine, 5 (12%) prone, and 11 (26%) in the left lateral decubitus position. At a median follow-up of 10.5 months, there were 3 local failures with a 12-month LC rate of 96%. Conclusions Adrenal SBRT for oligometastatic disease is a feasible, noninvasive option with excellent LC and minimal toxicity. Lesions in close proximity to radiosensitive organs may benefit from dynamic patient positioning and selective simultaneous-integrated boost techniques to allow for dose escalation, while also limiting toxicity risks.