Search

Xerostomia is a permanent and devastating sequela of head and neck irradiation, and its consequences are numerous. Pharmaceutical therapy attempts to preserve or salvage salivary gland function through systemic administration of various protective compounds, most commonly amifostine (Ethyol) or pilocarpine. When these agents are ineffective or the side effects too bothersome, patients often resort to palliative care, for example, with tap water, saline, bicarbonate solutions, mouthwashes, or saliva substitutes. A promising surgical option is the Seikaly-Jha procedure, a method of preserving a single submandibular gland by surgically transferring it to the submental space before radiotherapy. Improved radiation techniques, including intensity-modulated radiotherapy and tomotherapy, allow more selective delivery of radiation to defined targets in the head and neck, preserving normal tissue and the salivary glands. Acupuncture may be another option for patients with xerostomia. All of these therapies need to be further studied to establish the most effective protocol to present to patients before radiotherapy has begun. [ABSTRACT FROM AUTHOR]

BACKGROUND: This chapter aims to differentiate between 'alternative' therapies, often promoted falsely as viable options to mainstream lung cancer treatment, and complementary therapies, adjunctive, effective techniques that treat symptoms associated with cancer and its mainstream treatment, and to describe the evidence base for use of complementary therapies.Methods and design: A multidisciplinary panel of experts in oncology and integrative medicine evaluated the evidence for complementary (not alternative) therapies in the care of patients with lung cancer. Because few complementary modalities are geared to patients with only a single cancer diagnosis, symptom-control research conducted with other groups of patients with cancer was also included. Data on complementary therapies such as acupuncture, massage therapy, mind-body therapies, herbs and other botanicals, and exercise were evaluated. Recommendations were based on the strength of evidence and the risk-to-benefit ratio. RESULTS: Patients with lung and other poor-outlook cancers are particularly vulnerable to heavily promoted claims for unproved or disproved 'alternatives.' Inquiring about patients' use of these therapies should be routine because these practices may be harmful and can delay or impair treatment. Mind-body modalities and massage therapy can reduce anxiety, mood disturbance, and chronic pain. Acupuncture assists the control of pain and other side effects and helps reduce levels of pain medication required. Trials of acupuncture for chemotherapy-induced neuropathy and postthoracotomy pain show promising results. Herbal products and other dietary supplements should be evaluated for side effects and potential interactions with chemotherapy and other medications. CONCLUSIONS: Complementary therapies have an increasingly important role in the control of symptoms associated with cancer and cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine carcinoma of the bladder (NEC-bladder) is a rare disease with poor outcomes and variable treatment approaches., Materials and Methods: Patients with localized NEC-bladder treated with surgery or radiation between 2001-2021 were retrospectively identified. Rates of pathologic complete response (pCR) and downstaging were evaluated following NAC in surgically-treated patients. Progression-free survival (PFS) and overall survival (OS) were analyzed with univariable (log-rank) and multivariable (MVA; Cox regression) methods., Results: Sixty-five patients were identified having a median age of 73. The tumor histology distribution was small cell (64.6%) or urothelial with NE differentiation (35.4%). Most patients (69.2%) received NAC. Patients received local therapy by surgery (78.5%) or chemoradiation (21.5%). The majority (62.7%) of surgical patients had ≥ pT2 with 37.3% having nodal involvement (pN+). The pCR and downstaging rates were 21.6% and 35.1%, respectively. At a median follow-up of 60 months (m), the median PFS and OS were 16.4m and 25.9m, respectively. NAC improved PFS (p=0.04) and downstaging improved PFS (p=0.012) and OS (p<0.001). Patients receiving NAC with ypN0 vs. ypN+ had median OS of 69.9m vs 15.3m, respectively (p<0.001). MVA identified receipt of NAC and pN as predictors of PFS; pN was predictive of OS. No differences in PFS or OS were seen between histology of primary tumor. The brain metastasis rate was 10.8% with all patients having small cell histology., Conclusions: Optimized therapy in NEC-bladder includes NAC followed by local consolidation. Ascertainment of ypN0 is associated with long term survival, while pN+ remains associated with poor outcomes., Competing Interests: Disclosure Austin Sim: leadership role (ASTRO non-voting member board of directors). Jingsong Zhang: honoraria (Seagen); participation on Data Safety Monitoring Board (Seagen). Philippe E. Spiess: NCCN panel member for bladder and penile cancer. Roger Li: research support (predicine; veracyte; CG oncology; Valar Labs; Merck); clinical trial protocol committee (CG oncology; Merck; Janssen); Scientific advisor/consultant (Bristol Myers Squibb; Merck, Fergene, Arquer Diagnostics, Urogen Pharma, Lucence, CG Oncology, Janssen, Thericon); Honoraria (SAI MedPartners, Solstice Health Communications, Putnam Associates, UroToday). Javier F. Torres-Roca: intellectual property (RSI) and stock in Cvergenx . G. Daniel Grass: research support (ArteraAI). All other authors state that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Because of improved survival of cancer patients, more patients irradiated for brain metastases develop intracerebral recurrences requiring subsequent courses of radiotherapy. Five studies focused on reirradiation with whole-brain radiation therapy (WBRT) after initial WBRT for brain metastases. Following the second WBRT course, improvement of clinical symptoms was found in 31-68% of patients. Rates of neurotoxicity, such as encephalopathy or cognitive decline, were reported in two studies (1.4% and 32%). In another study, severe or unexpected adverse events were not observed. Survival following the second WBRT course was generally poor, with median survival times of 2.9-4.1 months. The survival prognosis of patients receiving two courses of WBRT can be estimated by a scoring tool considering five prognostic factors. Three studies investigated reirradiation with single-fraction stereotactic radiosurgery (SF-SRS) following primary WBRT. One-year local control rates were 74-91%, and median survival times ranged between 7.8 and 14 months. Rates of radiation necrosis (RN) after reirradiation were 0-6%. Seven studies were considered that investigated re-treatment with SF-SRS or fractionated stereotactic radiation therapy (FSRT) following initial SF-SRS or FSRT. One-year local control rates were 60-88%, and the median survival times ranged between 8.3 and 25 months. During follow-up after reirradiation, rates of overall (asymptomatic or symptomatic) RN ranged between 12.5% and 30.4%. Symptomatic RN occurred in 4.3% to 23.9% of cases (patients or lesions). The risk of RN associated with symptoms and/or requiring surgery or corticosteroids appears lower after reirradiation with FSRT when compared to SF-SRS. Other potential risk factors of RN include the volume of overlap of normal tissue receiving 12 Gy at the first course and 18 Gy at the second course of SF-SRS, maximum doses ≥40 Gy of the first or the second SF-SRS courses, V12 Gy >9 cm3 of the second course, initial treatment with SF-SRS, volume of normal brain receiving 5 Gy during reirradiation with FSRT, and systemic treatment. Cumulative EQD2 ≤100-120 Gy2 to brain, <100 Gy2 to brainstem, and <75 Gy2 to chiasm and optic nerves may be considered safe. Since most studies were retrospective in nature, prospective trials are required to better define safety and efficacy of reirradiation for recurrent or progressive brain metastases.

An increasing number of patients irradiated for metastatic epidural spinal cord compression (MESCC) experience an in-field recurrence and require a second course of radiotherapy. Reirradiation can be performed with conventional radiotherapy or highly-conformal techniques such as intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiation therapy (SBRT). When using conventional radiotherapy, a cumulative biologically effective dose (BED) ≤120 calculated with an α/β value of 2 Gy (Gy2) was not associated with radiation myelopathy in a retrospective study of 124 patients and is considered safe. In that study, conventional reirradiation led to improvements of motor deficits in 36% of patients and stopped further symptomatic progression in another 50% (overall response 86%). In four other studies, overall response rates were 82-89%. In addition to the cumulative BED or equivalent dose in 2 Gy fractions (EQD2), the interval between both radiotherapy courses <6 months and a BED per course ≥102 Gy2 (corresponding to an EQD2 ≥51 Gy2) were identified as risk factors for radiation myelopathy. Without these risk factors, a BED >120 Gy2 may be possible. Scoring tools have been developed that can assist physicians in estimating the risk of radiation myelopathy and selecting the appropriate dose-fractionation regimen of re-treatment. Reirradiation of MESCC may also be performed with highly-conformal radiotherapy. With IMRT or VMAT, rates of pain relief and improvement of neurologic symptoms of 60-93.5% and 42-73%, respectively, were achieved. One-year local control rates ranged between 55% and 88%. Rates of myelopathy or radiculopathy and vertebral compression fractures were 0% and 0-9.3%, respectively. With SBRT, rates of pain relief were 65-86%. Two studies reported improvements in neurologic symptoms of 0% and 82%, respectively. One-year local control rates were 74-83%. Rates of myelopathy or radiculopathy and vertebral compression fractures were 0-4.5% and 4.5-13.8%, respectively. For SBRT, a cumulative maximum EQD2 to thecal sac ≤70 Gy2, a maximum EQD2 of SBRT ≤25 Gy2, a ratio ≤0.5 of thecal sac maximum EQD2 of SBRT to maximum cumulative EQD2, and an interval between both courses ≥5 months were associated with a lower risk of myelopathy. Additional prospective trials are required to better define the options of reirradiation of MESCC.

With improving rates of survival among patients with metastatic malignancies, the request for palliative re-irradiation and re-re-irradiation continues to grow despite an absence of standardized guidelines. With only limited data regarding extra-cranial third-course palliative radiation, many radiation oncologists may feel uncomfortable proceeding with third-course irradiation of the same site. The review explores the available modern data regarding re-re-irradiation. A literature review identified four modern peer-reviewed studies investigating palliative, extra-cranial third-course irradiation with external beam radiation. These studies were retrospective, small, and heterogenous. While they reported comparable rates of pain palliation to first course irradiation and low rates of acute toxicity, interpretation is complicated by heterogeneous treatment parameters and insufficient reporting of cumulative dose equivalents and time intervals. With limited data available, it is critical to prioritize patient safety and quality of life in palliative radiotherapy. Patient selection should be meticulous, considering factors such as initial treatment response and predicted life expectancy. Conformal radiation techniques, strict immobilization, and daily image guidance should be employed to minimize toxicity to organs at risk (OARs). Long-term follow-up is essential for identifying and managing late toxicities effectively. Despite the scarcity of data, retrospective series suggest that extra-cranial third course irradiation can provide effective pain palliation comparable to first-course irradiation with tolerable rates of toxicity. However, careful consideration of patient prognosis and adherence to established principles of palliative radiotherapy are essential in decision-making. Further research and long-term follow-up are needed to refine treatment strategies and ensure safe and efficacious care delivery in this complex clinical scenario.

Purpose of Review: Thirty-day mortality (30DM) is an emerging consideration for determining whether terminally ill adult patients may benefit from palliative radiotherapy (RT). However, the efficacy and ethics of delivering palliative RT at the end of life (EOL) in children are seldom discussed and not well-established., Recent Findings: Palliative RT is perhaps underutilized among patients ≤21 years old with rates as low as 11%. While effective when delivered early, clinical benefit decreases when administered within the last 30 days of life. Pediatric 30DM rates vary widely between institutions (0.7-30%), highlighting the need for standardized practices. Accurate prognosis estimation remains challenging and prognostic models specific to palliative pediatric patients are limited. Discordance between provider and patient/parent perceptions of prognosis further complicates decision-making., Summary: RT offers effective symptom control in pediatric patients when administered early. However, delivering RT within the last 30 days of life may provide limited clinical benefit and hinder optimal EOL planning and care. Early referral for palliative RT, preferably with fewer fractions (five or fewer), along with multidisciplinary supportive care, optimizes the likelihood of maintaining patients' quality of life. Prognosis estimation remains difficult, and improving patient and family understanding is crucial. Further research is needed to refine prognostic models and enhance patient-centered care., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Stereotactic body radiotherapy (SBRT) is widely used for localized prostate cancer and implementation of MR-guided radiotherapy has the advantage of tighter margins and improved sparing of organs at risk. Here we evaluate outcomes and time required to treat using non-adaptive MR-guided SBRT (MRgSBRT) for localized prostate cancer at our institution., Methods: From 9/2019 to 11/2021 we conducted a retrospective review of 80 consecutive patients who were treated with MRgSBRT to the prostate. Patients included low (LR) (5%), favorable intermediate (FIR) (40%), unfavorable intermediate (UIR) (49%), and high risk (HR) (6%). Short-term androgen deprivation therapy was used in 32% of patients. Target volumes included prostate gland and proximal seminal vesicles with an isotropic 3 mm margin. Treatment was prescribed to 36.25 Gy in 5 fractions every other day with urethral sparing. Hydrogel spacer was used in 18% of patients. Time on the linac was recorded as beam on time (BOT) plus total treatment time (TTT) including gating. Analyzed outcomes included PSA response and patient reported outcomes scored by the American Urological Association (AUA) questionnaire and toxicity per CTCAE v5. General linear regression model was used to analyze factors affecting PSA and AUA in longitudinal follow up, and chi-square test was used to assess factors affecting toxicity., Results: Median follow up was 19.3 months (3.8 - 36.6). Median BOT was 4.6 min (2.6 - 7.2) with a median TTT of 11 min (7.6 - 15.8). Pre-treatment vs post-RT median PSA was 6.36 (2.20 - 19.6) vs 0.85 (0.19 - 3.6), respectively ( P < 0.001). PSA decrease differed significantly when patients were stratified by risk category, favoring LR/FIR vs UIF/HR group ( P = 0.019). Four (5%) patients experienced a biochemical failure (BCF), with a median time to BCF of 20.4 months (7.9 - 34.5). Median biochemical failure free survival (BCFFS) was not reached, with 2-yr and 4-yr BCFFS of 97.1% and 72.1%, respectively. Patients with LR/FIR disease had 100% 2-yr and 4-yr BCFFS, whereas patients with UIF/HR had 95% and 41% 2-yr and 4-yr BCFFS ( P = 0.05). Mean pre-treatment AUA was 7.3 (1 - 25) vs 11.3 (1 - 26) at first follow-up; however, AUA normalized to baseline over time. Urethral Dmax ≥35 Gy trended to lower AUA score at all follow-ups ( P = 0.07). Forty-one (51%) patients reported grade 1-2 genitourinary toxicities at the 1 month follow up. Grade 3 toxicity (proctitis) was noted in 1 patient. There was no decrease in any grade rectal toxicity with use of hydrogel spacer (3 vs 6, P = 0.2). No grade ≥4 toxicities was observed., Conclusions: MRgSBRT has the potential for treatment adaptation but this comes at the cost of increased resource utilization. Our experience with non-adaptive MRgSBRT of the prostate highlights its short treatment times as well as efficacy with good PSA control and low toxicity profile., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Yamoah receives grant funding from NCI and American Cancer Society, consulting fees from Janssen R&D. Dr. Latifi receives consulting fees from ViewRay. Dr. Rosenberg receives grant funding and consulting fees from ViewRay. The remaining authors have no disclosures.

Context: There are several procedures for surgical nodal staging in clinically node-negative (cN0) penile carcinoma., Objective: To evaluate the diagnostic accuracy, perioperative outcomes, and complications of minimally invasive surgical procedures for nodal staging in penile carcinoma., Evidence Acquisition: A systematic review of the Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov was conducted. Published and ongoing studies reporting on the management of cN0 penile cancer were included without any design restriction. Outcomes included the false negative (FN) rate, the number of nodes removed, surgical time, and postoperative complications., Evidence Synthesis: Forty-one studies were eligible for inclusion. Four studies comparing robot-assisted (RA-VEIL) and video-endoscopic inguinal lymphadenectomy (VEIL) to open inguinal lymph node dissection (ILND) were suitable for meta-analysis. A descriptive synthesis was performed for single-arm studies on modified open ILND, dynamic sentinel node biopsy (DSNB) with and without preoperative inguinal ultrasound (US), and fine-needle aspiration cytology (FNAC). DSNB with US + FNAC had lower FN rates (3.5-22% vs 0-42.9%) and complication rates (Clavien Dindo grade I-II: 1.1-20% vs 2.9-11.9%; grade III-V: 0-6.8% vs 0-9.4%) in comparison to DSNB alone. Favourable results were observed for VEIL/RA-VEIL over open ILND in terms of major complications (2-10.6% vs 6.9-40.6%; odds ratio [OR] 0.18; p < 0.01). Overall, VEIL/RA-VEIL had lower wound-related complication rates (OR 0.14; p < 0.01), including wound infections (OR 0.229; p < 0.01) and skin necrosis (OR 0.16; p < 0.01). The incidence of lymphatic complications varied between 20.6% and 49%., Conclusions: Of all the surgical staging options, DSNB with inguinal US + FNAC had the lowest complication rates and high diagnostic accuracy, especially when performed in high-volume centres. If DSNB is not available, favourable results were also found for VEIL/RA-VEIL over open ILND. Lymphatic-related complications were comparable across open and video-endoscopic ILND., Patient Summary: We reviewed studies on different surgical approaches for assessing lymph node involvement in cases with penile cancer. The results show that a technique called dynamic sentinel node biopsy with ultrasound guidance and fine-needle sampling has high diagnostic accuracy and low complication rates. For lymph node dissection in penile cancer cases, a minimally invasive approach may offer favourable postoperative outcomes., (Copyright © 2023. Published by Elsevier B.V.)

Background: Improvements in radiation delivery and systemic therapies have resulted in few remaining indications for palliative whole brain radiation therapy (WBRT). Most centers preferentially use stereotactic radiotherapy (SRT) and reserve WBRT for those with >15 lesions, leptomeningeal presentation, rapidly progressive disease, or limited estimated survival. Despite regional differences among preferred dose, fractionation, and treatment technique, we predict survival post-WBRT will remain poor-indicating appropriate application of WBRT in this era of SRT and improved systemic therapies., Methods: A multi-center, international retrospective analysis of patients receiving WBRT in 2022 was performed. Primary end point was survival after WBRT. De-identified data were analyzed centrally. Patients receiving WBRT as part of a curative regimen, prophylactically, or as bridging therapy were excluded. The collected data consisted of patient parameters including prescription dose and fractionation, use of neurocognitive sparing techniques and survival after WBRT. Survival was calculated via the Kaplan-Meier method., Results: Of 29,943 international RT prescriptions written at ten participating centers in 2022, 462 (1.5%) were for palliative WBRT. Participating centers were in the United States (n=138), the United Kingdom (n=111), Hong Kong (n=72), Italy (n=49), Belgium (n=45), Germany (n=27), Ghana (n=15), and Cyprus (n=5). Twenty-six different dose regimens were used. The most common prescriptions were for 3,000 cGy over 10 fractions (45.0%) and 2,000 cGy over 5 fractions (43.5%) with significant regional preferences (P<0.001). Prior SRT was delivered in 32 patients (6.7%), hippocampal avoidance (HA) was used in 44 patients (9.5%), and memantine was prescribed in 93 patients (20.1%). Survival ranged from 0 days to still surviving at 402 days post-treatment. The global median overall survival (OS) was 84 days after WBRT [95% confidence interval (CI): 68.0-104.0]. Actuarial survival at 7 days, 1 month, 3 months, and 6 months were 95%, 78%, 48%, and 32%, respectively. Twenty-seven patients (5.8%) were unable to complete their prescribed WBRT., Conclusions: This moment-in-time analysis confirms that patients with poor expected survival are being appropriately selected for WBRT-illustrating the dwindling indications for WBRT-and demonstrates the variance in global practice. Since poor survival precludes patients from deriving benefit, memantine and HA are best suited in carefully selected cases.

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., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Penile squamous cell carcinoma (PSCC) is a rare malignancy in most parts of the world and the underlying mechanisms of this disease have not been fully investigated. About 30-50% of cases are associated with high-risk human papillomavirus (HPV) infection, which may have prognostic value. When PSCC becomes resistant to upfront therapies there are limited options, thus further research is needed in this venue. The extracellular domain-facing protein profile on the cell surface (i.e., the surfaceome) is a key area for biomarker and drug target discovery. This research employs computational methods combined with cell line translatomic (n = 5) and RNA-seq transcriptomic data from patient-derived tumors (n = 18) to characterize the PSCC surfaceome, evaluate the composition dependency on HPV infection, and explore the prognostic impact of identified surfaceome candidates. Immunohistochemistry (IHC) was used to validate the localization of select surfaceome markers. This analysis characterized a diverse surfaceome within patient tumors with 25% and 18% of the surfaceome represented by the functional classes of receptors and transporters, respectively. Significant differences in protein classes were noted by HPV status, with the most change being seen in transporter proteins (25%). IHC confirmed the robust surface expression of select surfaceome targets in the top 85% of expression and a superfamily immunoglobulin protein called BSG /CD147 was prognostic of survival. This study provides the first description of the PSCC surfaceome and its relation to HPV infection and sets a foundation for novel biomarker and drug target discovery in this rare cancer.

Context: Penile cancer is a rare disease but has a significant impact on quality of life. Its incidence is increasing, so it is important to include new and relevant evidence in clinical practice guidelines., Objective: To provide a collaborative guideline that offers worldwide physician and patient guidance for the management of penile cancer., Evidence Acquisition: Comprehensive literature searches were performed for each section topic. In addition, three systematic reviews were conducted. Levels of evidence were assessed, and a strength rating for each recommendation was assigned according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology., Evidence Synthesis: Penile cancer is a rare disease but its global incidence is increasing. Human papillomavirus (HPV) is the main risk factor for penile cancer and pathology should include an assessment of HPV status. The main aim of primary tumour treatment is complete tumour eradication, which has to be balanced against optimal organ preservation without compromising oncological control. Early detection and treatment of lymph node (LN) metastasis is the main determinant of survival. Surgical LN staging with sentinel node biopsy is recommended for patients with a high-risk (≥pT1b) tumour with cN0 status. While (inguinal) LN dissection remains the standard for node-positive disease, multimodal treatment is needed in patients with advanced disease. Owing to a lack of controlled trials and large series, the levels of evidence and grades of recommendation are low in comparison to those for more common diseases., Conclusions: This collaborative penile cancer guideline provides updated information on the diagnosis and treatment of penile cancer for use in clinical practice. Organ-preserving surgery should be offered for treatment of the primary tumour when feasible. Adequate and timely LN management remains a challenge, especially in advanced disease stages. Referral to centres of expertise is recommended., Patient Summary: Penile cancer is a rare disease that significantly impacts quality of life. While the disease can be cured in most cases without lymph node involvement, management of advanced disease remains challenging. Many unmet needs and unanswered questions remain, underlining the importance of research collaborations and centralisation of penile cancer services., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Bladder preservation with trimodal therapy (TMT; maximal tumor resection followed by chemoradiation) is an effective paradigm for select patients with muscle invasive bladder cancer. We report our institutional experience of a TMT protocol using nonadaptive magnetic resonance imaging-guided radiation therapy (MRgRT) for partial bladder boost (PBB)., Methods and Materials: A retrospective analysis was performed on consecutive patients with nonmetastatic muscle invasive bladder cancer who were treated with TMT using MRgRT between 2019 and 2022. Patients underwent intensity modulated RT-based nonadaptive MRgRT PBB contoured on True fast imaging with steady state precession (FISP) images (full bladder) followed sequentially by computed tomography-based RT to the whole empty bladder and pelvic lymph nodes with concurrent chemotherapy. MRgRT treatment time, table shifts, and dosimetric parameters of target coverage and normal tissue exposure were described. Prospectively assessed acute and late genitourinary and gastrointestinal (GI) toxicity were reported. Two-year local control was assessed with Kaplan-Meier methods., Results: Seventeen patients were identified for analysis. PBB planning target volume margins were ≤8 mm in 94% (n = 16) of cases. Dosimetric target coverage parameters were favorable and all normal tissue dose constraints were met. For MRgRT PBB fractions, median table shifts were 0.4 cm (range, 0-3.15), 0.45 cm (0-2.65), and 0.75 cm (0-4.8) in the X, Y, and Z planes, respectively. Median treatment time for MRgRT PBB fractions was 9 minutes (range, 6.9-17.4). We identified 32 out of 100 total MRgRT fractions that may have benefitted from online adaptation based on changes in organ position relative to planning target volume, predominantly because of small bowel (13/32, 41%) or rectum (8/32, 25%). Two patients discontinued RT prematurely. The incidence of highest-grade acute genitourinary toxicity was 1 to 2 (69%) and 3 (6%), whereas the incidence of acute GI toxicity was 1 to 2 (81%) and 3 (6%). There were no late grade 3 events; 17.6% had late grade 2 cystitis and none had late GI toxicity. With median follow-up of 18.2 months (95% CI, 12.4-22.5), the local control rate was 92%, and no patient has required salvage cystectomy., Conclusions: Nonadaptive MRgRT PBB is feasible with favorable dosimetry and low resource utilization. Larger studies are needed to evaluate for potential benefits in toxicity and local control associated with this approach in comparison to standard treatment techniques., Competing Interests: Kujtim Latifi reports consulting fees with ViewRay Inc. Stephen A. Rosenberg reports research funding from ViewRay Inc and serves on the ViewRay Lung Research Consortium. G. Daniel Grass reports consulting fees for MyCareGorithm., (© 2023 The Authors.)

Penile squamous cell carcinoma (PSCC) remains a worldwide healthcare concern with poor outcomes and inadequate therapeutic options. Molecular characterization continues to describe the intricacies of PSCC biology, which vary by human papillomavirus (HPV) infection. Despite these advancements in our understanding, utilization of targeted therapies remains limited and underexplored. In this study, we evaluated the transcript and protein expression of Nectin-4 (PVRL4) in PSCC tumors and evaluated whether this is related to tumor features or clinical outcomes. Using two separate PSCC cohorts, we demonstrate that the majority of tumors have active transcription of Nectin-4. We then validated our findings using immunohistochemistry in a tissue microarray representing 57 patients with PSCC. We identified that Nectin-4 was expressed at higher levels in patients with high-risk HPV infection. No significant differences were identified in tumor characteristics or various clinical endpoints when comparing tumors with high and low Nectin-4 expression. This study demonstrates that Nectin-4 is expressed in PSCC and may represent a novel therapeutic target., Patient Summary: In this study, we evaluated the expression of Nectin-4, a cell surface protein, in tumors from patients with nonmetastatic penile squamous cell carcinoma (PSCC). To our knowledge, this is the first study to describe elevated expression of Nectin-4 in PSCC, which may suggest its utility as a therapeutic target., (© 2023 The Author(s).)

Introduction: High-dose total body irradiation (TBI) is often part of myeloablative conditioning in acute leukemia. Modern volumetric modulated arc therapy (VMAT)-based plans employ arcs to the inferior-most portion of the body that can be simulated in a head-first position and use 2D planning for the inferior body which can result in heterogeneous doses. Here, we describe our institution's unique protocol for delivering high-dose TBI entirely with VMAT and retrospectively compare dosimetric outcomes with helical tomotherapy (HT) plans. Additionally, we describe our method of oropharyngeal mucosal sparing that was implemented after fatal mucositis occurred in two patients. Methods: Thirty-one patients were simulated and treated in head-first (HFS) and feet-first (FFS) orientations. Patients were treated with VMAT (n = 26) or HT (n = 5). In VMAT plans, to synchronize doses between the orientations, images were deformably registered and the HFS dose was transferred to the FFS plan and used as a background dose when optimizing plans. Six to eight isocenters with two arcs per isocenter were generated. HT was delivered with an established technique. Patients were treated to 13.2 Gy over eight twice daily fractions. Dosimetric outcomes and toxicities were retrospectively compared. Results: Prescription dose and organ at risk (OAR) constraints were met for all patients. Lower lung doses were achieved with VMAT relative to HT plans (7.4 vs 7.7 Gy, P  = .009). Statistically significant improvement in mucositis was not achieved after adopting a mucosal-sparing technique, however lower doses to the oropharyngeal mucosal were achieved (6.9 vs 14.1 Gy, P  = .009), and no further mucositis-related deaths occurred. Conclusions: This full-body VMAT method of TBI achieves dose goals, eliminates risk of heterogenous doses within the femur, and demonstrates that selective OAR sparing with the purpose of reducing TBI-related morbidity and mortality is possible at any institution with a VMAT-capable linear accelerator.

Participation in cancer research trials by minority populations is imperative in reducing disparities in clinical outcomes. Even with increased awareness of the importance of minority patient inclusion in clinical research to improve cancer care and survival, significant barriers persist in accruing and retaining minority patients into clinical trials. This study sought to identify and address barriers to minority accrual to a minimal risk clinical research study in real-time., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting., Methods: This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score., Results: The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes., Conclusions: Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions., (Published by Oxford University Press 2022.)

Background: 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., Methods: 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., Results: 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) with <2% 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., Conclusions: 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., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of interest There are no conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cigarette smoking is related to greater cancer incidence, worse cancer-related clinical outcomes, and worse patient quality of life. Few studies have evaluated the role of smoking in patients' experiences of cancer-related symptom burden. This study examined relationships between smoking and total symptom burden as well as the incidence of severe symptoms among adult cancer patients., Patients and Methods: Patients at Moffitt Cancer Center completed self-report surveys as part of routine cancer care. Symptom burden was evaluated as the sum of individual symptom ratings (total symptom burden) and the number of symptoms rated severe (incidence of severe symptoms). Zero-inflated negative binomial modeling was used to evaluate the relationships between smoking status (ever vs never smoker) and symptom burden outcomes controlling for relevant sociodemographic and clinical covariates and accounting for the proportion of participants reporting no symptom burden., Results: This study included 12 571 cancer patients. More than half reported a history of cigarette smoking (n = 6771, 55%). Relative to never smokers, participants with a smoking history had 15% worse expected total symptom burden (ratio = 1.15, 95% confidence interval [CI] 1.11-1.20, P < .001) and 13% more expected severe symptoms (ratio = 1.13, 95% CI 1.05-1.21, P = .001) above and beyond the effects of relevant sociodemographic and clinical characteristics., Conclusion: Results provide support that smoking is associated with worse cancer symptom burden. More research is needed to evaluate how smoking history (ie, current vs former smoker) and smoking cessation influence cancer symptom burden., (© The Author(s) 2022. Published by Oxford University Press.)

Objective: Two benefits of MR-guided radiotherapy (MRgRT) are the ability to track target structures while treatment is being delivered and the ability to adapt plans daily for some lesions based on changing anatomy. These unique capacities come at two costs: increased capital for acquisition and greatly decreased workflow. An adaptive gated stereotactic body radiotherapy (MRgART) treatment routinely takes ~90 min to perform and requires the presence of both a physician and a physicist. This may significantly limit daily capacity. We previously described how "simple cases" were necessary for proton facilities to allow for debt management. In this manuscript, we seek to determine the optimal scheduling of different MRgRT plans to recoup capital costs., Materials/methods: We assumed an MR-linac (MRL) was completely scheduled with patients over workdays of varying duration. Treatment times and reimbursement data from our facility for varying complexities of patients were extrapolated for varying numbers treated daily. We then derived the number of adaptive and non-adaptive patients required daily to optimize the schedules. HOPPS data were used to model reimbursement., Results: A single MRL treating 14 non-gated, non-adaptive IMRT patients over an 8 h workday would take about 4.8 years to cover initial acquisition and installation costs. However, such patients may be more quickly and efficiently treated with a conventional linear accelerator, while MRgART cases may only be treated with an MRL. By treating four of these daily, that same MRL room would cover costs in 2.4 years. Personnel, maintenance costs, and profit further complicate any business case for treating non-adaptive patients or for extending hours., Conclusions: In our previously published paper discussing proton therapy, we noted that debt is not variable with capacity; this remains true with MRgRT. Different from protons, a clinically optimal case load of adaptive patients provides an optimal business case as well. This requires a large patient cadre to ensure continuing throughput. As improvements in MRgRT are brought to the clinic, shorter adaptive and non-adaptive treatment times will help improve the timeframe to recoup costs but will require even more appropriate patients.

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.

Radiation therapy (RT) has not been prominent in the treatment of penile cancer because of poorly reproducible results when used in the adjuvant setting. A genomic signature has recently been described that assays radiosensitivity of tumors and informs radiotherapy doses in these cases. Clinical validation in more than 1600 patients demonstrated associations with both overall survival and time to first recurrence. In addition, the signature predicted and quantified the therapeutic benefit of RT for each individual patient. Since penile cancer patients were not part of this analysis, we applied the model to patients with primary and nodal penile cancer tissue and clinical outcomes. Patient summary : Radiotherapy has not been widely used for treatment of penile cancer. New genetic data suggest that radiation doses commonly used to treat penile cancer are too low. This would explain prior poor results using radiation in this disease., (© 2021 The Author(s).)

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.

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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 NCC N 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., Competing Interests: Conflicts of interest None declared., (© 2021 Greater Poland Cancer Centre.)

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.

Purpose: To monitor intrafraction motion during spine stereotactic body radiotherapy(SBRT) treatment delivery with readily available technology, we implemented triggered kV imaging using the on-board imager(OBI) of a modern medical linear accelerator with an advanced imaging package. Methods: Triggered kV imaging for intrafraction motion management was tested with an anthropomorphic phantom and simulated spine SBRT treatments to the thoracic and lumbar spine. The vertebral bodies and spinous processes were contoured as the image guided radiotherapy(IGRT) structures specific to this technique. Upon each triggered kV image acquisition, 2D projections of the IGRT structures were automatically calculated and updated at arbitrary angles for display on the kV images. Various shifts/rotations were introduced in x, y, z, pitch, and yaw. Gantry-angle-based triggering was set to acquire kV images every 45°. A group of physicists/physicians(n = 10) participated in a survey to evaluate clinical efficiency and accuracy of clinical decisions on images containing various phantom shifts. This method was implemented clinically for treatment of 42 patients(94 fractions) with 15 second time-based triggering. Result: Phantom images revealed that IGRT structure accuracy and therefore utility of projected contours during triggered imaging improved with smaller CT slice thickness. Contouring vertebra superior and inferior to the treatment site was necessary to detect clinically relevant phantom rotation. From the survey, detectability was proportional to the shift size in all shift directions and inversely related to the CT slice thickness. Clinical implementation helped evaluate robustness of patient immobilization. Based on visual inspection of projected IGRT contours on planar kV images, appreciable intrafraction motion was detected in eleven fractions(11.7%). Discussion: Feasibility of triggered imaging for spine SBRT intrafraction motion management has been demonstrated in phantom experiments and implementation for patient treatments. This technique allows efficient, non-invasive monitoring of patient position using the OBI and patient anatomy as a direct visual guide.

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.

Background: Radiation therapy (RT) has been widely used for palliation in multiple myeloma. However, no data exist on symptom assessment and patient-reported outcomes regarding the efficacy of RT in this disease process. This study aims to demonstrate the impact of palliative RT on patient-reported symptoms in patients with multiple myeloma. Materials and Methods: Our Radiation Oncology and Supportive Care Medicine clinics established the use of a modified Edmonton Symptom Assessment Scale (ESAS) in 2015 assessing 12 symptom domains. All had ESAS data available from each encounter. Demographic and clinical data were retrospectively collected from an institutional data warehouse. We examined total and component survey scores for correlated data of patients during radiation treatment and patients not treated with radiation. Results: Clinic records of 30 patients with multiple myeloma seen in the Radiation Oncology and Supportive Care clinics from 2015 to 2018 were retrieved. A total of 91 discrete surveys were collected (1183 data points). Twenty of these were collected from weekly visits from 12 patients receiving RT; the remainder were from new patient or follow up encounters. Odds ratios were lower with radiation therapy for total scores (OR 4.86, p  = .007), as well as several component scores. Conclusions: The use of palliative RT was associated with 5 times lower total symptom scores compared with nonuse. Similar beneficial results were found for several component scores. These patient-reported outcomes strongly suggest that providers should consider palliative radiation for symptomatic multiple myeloma patients. These data should be prospectively validated in a larger cohort of myeloma patients.

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., (© 2020 American Cancer Society.)

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<0.001), which was associated with poorer distant control (hazard ratio=25.8, 95% confidence interval: 3.1-536.4; P=0.003) on univariable analysis, and OS (hazard ratio=7.1, 95% confidence interval: 2.0-26.1; P=0.003) on multivariable analysis., Conclusions: This is the largest patient cohort with sarcoma brain metastases treated with SRS/FSRT, it provides durable local control, despite a reputation for radioresistance. Further prospective evidence is required to determine the impact of primary histology on control and survival following brain metastasis diagnosis.

Background and Purpose: Retroperitoneal sarcoma (RPS) is a rare, complex disease requiring multidisciplinary management. We have previously reported that use of the Revised Edmonton Symptom Assessment Scale (ESAS-r-CSS) allows for proactive symptom management, and we sought to report the results of ESAS-r-CSS screening during pre-operative radiotherapy (RT) for a cadre of patients with RPS., Materials and Methods: We reviewed records of 47 patients with RPS evaluated at our institution between 2015 and 2018. Of this group, 29 non-metastatic patients were treated with definitive intent neoadjuvant RT with at least 2 weekly ESAS-r-CSS reports. A generalized estimating equation model was used to compare 13 symptoms during weekly on-treatment visits compared to baseline scores at week 1 of RT. Additionally, covariate effects of age, gender, dose, tumor size and location were assessed., Results: The population was predominantly male (66%) with median age of 65 years, KPS of 90, and tumor size of 12.8 cm. ESAS scores significantly decreased for anxiety at week 3 ( P  = 0.01), and pain at week 5 ( P  = 0.01). Worse constipation was reported at week 2 ( P  = 0.02). In an exploratory covariate analysis, female gender, age, high dose, and larger tumor size were associated with worse ESAS scores across all time points., Conclusion: Patient reporting of symptoms during radiotherapy through weekly ESAS-r-CSS facilitates timely management in patients with this unique tumor type. Expectant care during RT offers the opportunity to minimize symptom progression or treatment interruptions in a population that generally has worsening side effects., (© 2020 The Authors.)

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.

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.

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., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)

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 χ 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<0.001) with heavier unfavorable intermediate risk disease burden (32.4% vs. 19.2%) compared with USM. Significant differences were identified in median external beam radiotherapy dose (72.4 vs. 78 Gy, P<0.001); brachytherapy utilization (49.7% vs. 80.6%, P<0.001) and androgen deprivation therapy for intermediate risk disease (48.4% vs. 21.0%, P<0.001) between GM and USM, respectively. GM with low risk and favorable intermediate risk PCa were at increased risk of biochemical recurrence compared with USM with adjusted hazard ratio: 5.15 (1.27 to 20.7), P=0.02 and 4.64 (1.20 to 17.92), P=0.02, respectively., Conclusions: Compared with USM, GM with low and favorable intermediate risk PCa may experience less durable disease control following standard treatment recommendations. Results suggest differences in radiation treatment and possible inherent differences between the 2 populations. This data will aid in developing research strategies to improve treatment outcomes in GM.