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To determine the incidence and various patterns of radiation-induced liver injury (RILI) and its temporal evolution on fluorodeoxiglucose-positron emission tomography/computed tomography (FDG-PET/CT) after neoadjuvant chemoradiation using precision radiation in patients with esophageal carcinoma.We evaluated 639 patients with locally advanced esophageal carcinoma who had serial FDG-PET/CTs after neoadjuvant chemoradiation. Two readers reviewed the imaging studies in consensus and recorded the cases where new foci of increased FDG uptake were identified within the radiated liver parenchyma. RILI was confirmed by follow-up imaging or percutaneous biopsy.FDG-avid RILI developed in 39/639 (6%) of patients. The caudate and left hepatic lobe were involved in all cases. There were various patterns of increased FDG uptake: 38% of patients had a single focus of increased FDG uptake and 62% had 2 regions of increased FDG uptake, which were focal nodular or diffuse or a combination of focal nodular and diffuse FDG uptake. On CT, 72% of patients had a poorly-marginated region of low attenuation and 28% had a well-defined region of low attenuation with sharp, well-defined linear borders in the location of the radiation, as confirmed by the treatment plan.The caudate and left hepatic lobes were involved in all cases of RILI. The various imaging patterns of RILI on FDG-PET/CT include 1 or 2 regions of increased FDG uptake with a nodular, diffuse, or combined appearance. Awareness of this potential complication of radiation therapy and knowledge of the imaging manifestations of RILI is important to avoid misinterpretation as a metastasis.

Cytotoxic chemotherapies have been a mainstay of cancer treatment but are associated with numerous systemic adverse effects, including impacts on fertility and endocrine health. Irreversible ovarian damage and follicle depletion are the side effects of chemotherapy that can lead to infertility and premature menopause, both being major concerns of young cancer patients. Notably, many women will proceed with fertility preservation, but unfortunately existing strategies do not entirely solve the problem. Most significantly, oocyte and embryo freezing do not prevent cancer treatment-induced ovarian damage from occurring, which may result in the impairment of long-term hormone production. Unfortunately, loss of endogenous endocrine function is not fully restored by hormone replacement therapy. Additionally, while GnRH agonists are standard care for patients receiving alkylating chemotherapy to lessen the risk of premature menopause, their efficacy is incomplete. The lack of more broadly effective options stems, in part, from our poor understanding of how different treatments damage the ovary. Here, we summarise the impacts of two commonly utilised chemotherapies – cyclophosphamide and cis-diamminedichloroplatinum(II) (cisplatin) – on ovarian function and fertility and discuss the mechanisms underpinning this damage. Additionally, we critically analyse current research avenues in the development of novel fertility preservation strategies, with a focus on ferto-protective agents. Lay summary Over the past few decades, advances in the detection and treatment of cancer have dramatically improved survival rates in young women. This means that ensuring patients have a high quality of life after cancer treatment has become a new priority. Therefore, it is important to understand and prevent any long-term negative side effects of cancer treatments, with infertility and early-onset menopause being major concerns for women receiving chemotherapy. The current fertility preservation options available to young women have significant limitations. Therefore, the identification of new approaches to protect fertility has been an intense topic of research in recent years. In this review, we provide information on the negative side effects of two commonly used chemotherapy drugs – cyclophosphamide and cis-diamminedichloroplatinum(II) (cisplatin) – on fertility, and discuss how they cause damage to the ovaries. We also critically analyse recent preclinical studies related to the development of new fertility preservation techniques.

Oncology telemedicine was implemented rapidly after COVID-19. We examined multilevel correlates and outcomes of telemedicine use for patients undergoing radiotherapy (RT) for cancer.Upon implementation of a telemedicine platform at a comprehensive cancer center, we analyzed 468 consecutive patient RT courses from March 16, 2020 to June 1, 2020. Patients were categorized as using telemedicine during ≥1 weekly oncologist visits versus in-person oncologist management only. Temporal trends were evaluated with Cochran-Armitage tests; chi-squared test and multilevel multivariable logistic models identified correlates of use and outcomes.Overall, 33% used telemedicine versus 67% in-person only oncologist management. Temporal trends (pThough toxicities were similar with telemedicine oncology management, there remained lower uptake among non-White patients. Continuing strategies for oncology telemedicine implementation should address multilevel patient, physician, and policy factors to optimize telemedicine's potential to surmount-and not exacerbate-barriers to quality cancer care.

Background: while improvements in immunoradiotherapy have significantly improved outcomes for cancer patients, this treatment approach has nevertheless proven ineffective at controlling the majority of malignancies. One of the mechanisms of resistance to immunoradiotherapy is that immune cells may be suppressed via the myriad of different immune checkpoint receptors. Therefore, simultaneous blockade of multiple immune checkpoint receptors may enhance the treatment efficacy of immunoradiotherapy. Methods: we combined NBTXR3-enhanced localized radiation with the simultaneous blockade of three different checkpoint receptors: PD1, LAG3, and TIGIT, and tested the treatment efficacy in an anti-PD1-resistant lung cancer model in mice. 129 Sv/Ev mice were inoculated with fifty thousand alpha PD1-resistant 344SQR cells in the right leg on day 0 to establish primary tumors and with the same number of cells in the left leg on day 4 to establish the secondary tumors. NBTXR3 was intratumorally injected into the primary tumors on day 7, which were irradiated with 12 Gy on days 8, 9, and 10. Anti-PD1 (200 mu g), alpha LAG3 (200 mu g), and alpha TIGIT (200 mu g) were given to mice by intraperitoneal injections on days 5, 8, 11, 14, 21, 28, 35, and 42. Results: this nanoparticle-mediated combination therapy is effective at controlling the growth of irradiated and distant unirradiated tumors, enhancing animal survival, and is the only one that led to the destruction of both tumors in approximately 30% of the treated mice. Corresponding with this improved response is robust activation of the immune response, as manifested by increased numbers of immune cells along with a transcriptional signature of both innate and adaptive immunity within the tumor. Furthermore, mice treated with this combinatorial therapy display immunological memory response when rechallenged by the same cancer cells, preventing tumor engraftment. Conclusion: our results strongly attest to the efficacy and validity of combining nanoparticle-enhanced radio-therapy and simultaneous blockade of multiple immune checkpoint receptors and provide a pre-clinical rationale for investigating its translation into human patients., This work was supported by Cancer Center Support (Core) Grant CA016672 to The University of Texas MD Anderson Cancer Center; the Goodwin family research fund; the family of M. Adnan Hamed, and the Orr Family Foundation to MD Anderson Cancer Center's Thoracic Radiation Oncology program; an MD Anderson Knowledge Gap award; Nanobiotix.

CD8+ CD103+ TRM cells express high levels of PD1. Flow cytometric analysis for TILs on day 29 from the triple therapy group (RT + α-PD1 + α-MerTK). Cells were gated on CD45 population then on CD4 and CD8, followed by CD8 and CD103 to check for PD1 expression in the final gate.

Purpose:Radiotherapy (RT) traditionally has been used for local tumor control in the treatment of cancer. The recent discovery that radiotherapy can have anticancer effects on the immune system has led to recognition of its ability to sensitize the tumor microenvironment to immunotherapy. However, radiation can also prompt adverse immunosuppressive effects that block aspects of systemic response at other tumor sites. Our hypothesis was that inhibition of the MER proto-oncogene tyrosine kinase (MerTK) in combination with anti-programmed cell death-1 (α-PD1) checkpoint blockade will enhance immune-mediated responses to radiotherapy.Experimental Design:We tested the efficacy of this triple therapy (Radiation + α-PD1 + α-MerTK mAbs) in 129Sv/Ev mice with bilateral lung adenocarcinoma xenografts. Primary tumors were treated with stereotactic radiotherapy (36 Gy in 3 12-Gy fractions), and tumors were monitored for response.Results:The triple therapy significantly delayed abscopal tumor growth, improved survival rates, and reduced numbers of lung metastases. We further found that the triple therapy increased the activated CD8+ and NK cells populations measured by granzyme B expression with upregulation of CD8+CD103+ tissue-resident memory cells (TRM) within the abscopal tumor microenvironment relative to radiation only.Conclusions:The addition of α-PD1 + α-MerTK mAbs to radiotherapy could alter the cell death to be more immunogenic and generate adaptive immune response via increasing the retention of TRM cells in the tumor islets of the abscopal tumors which was proven to play a major role in survival of non-small cell lung cancer patients.

Mean arterial pressure to mean pulmonary arterial pressure ratio (mAP/mPAP) has been identified as a strong predictor of perioperative complications in cardiac surgery. We therefore investigated the pharmacokinetic/pharmacodynamic (PK/PD) relationship of inhaled milrinone in these patients using this ratio (R) as a PD marker. Following approval by the ethics and research committee and informed consent, we performed the following experiment. Before initiation of cardiopulmonary bypass in 28 pulmonary hypertensive patients scheduled for cardiac surgery, milrinone (5 mg) was nebulized, plasma concentrations measured (up to 10 h) and compartmental PK analysis carried out. Baseline (R0) and peak (Rmax) ratios as well as magnitude of peak response (∆Rmax-R0) were measured. During inhalation, individual area under effect-time (AUEC) and plasma concentration–time (AUC) curves were correlated. Potential relationships between PD markers and difficult separation from bypass (DSB) were explored. In this study, we observed that milrinone peak concentrations (41–189 ng ml−1) and ΔRmax-R0 (− 0.12–1.5) were obtained at the end of inhalation (10–30 min). Mean PK parameters agreed with intravenous milrinone published data after correction for the estimated inhaled dose. Paired comparisons yielded a statistically significant increase between R0 and Rmax (mean difference, 0.58: 95% CI 0.43–0.73; P 2 = 0.1513; P = 0.045); significance increased after exclusion of non-responders (r = 4787, r2 = 0.2292; P = 0.024). Individual AUEC correlated with ∆Rmax-R0 (r = 5973, r2 = 0.3568; P = 0.001). Both ∆Rmax-R0 (P = 0.009) and CPB duration (P

Summary Background The role of radiotherapy in metastatic renal cell carcinoma is controversial. We prospectively tested the feasibility and efficacy of radiotherapy to defer systemic therapy for patients with oligometastatic renal cell carcinoma. Methods This single-arm, phase 2, feasibility trial was done at one centre in the USA (The MD Anderson Cancer Center, Houston, TX, USA). Patients (aged ≥18 years) with five or fewer metastatic lesions, an Eastern Cooperative Oncology Group status of 0–2, and no more than one previous systemic therapy (if this therapy was stopped at least 1 month before enrolment) without limitations on renal cell carcinoma histology were eligible for inclusion. Patients were treated with stereotactic body radiotherapy (defined as ≤5 fractions with ≥7 Gy per fraction) to all lesions and maintained off systemic therapy. When lesion location precluded safe stereotactic body radiotherapy, patients were treated with hypofractionated intensity-modulated radiotherapy regimes consisting of 60–70 Gy in ten fractions or 52·5–67·5 Gy in 15 fractions. Additional rounds of radiotherapy were allowed to treat subsequent sites of progression. Co-primary endpoints were feasibility (defined as all planned radiotherapy completed with ClinicalTrials.gov , NCT03575611 . Findings 30 patients (six [20%] women) were enrolled from July 13, 2018, to Sept 18, 2020. All patients had clear cell histology and had a nephrectomy before enrolment. All patients completed at least one round of radiotherapy with less than 7 days of unplanned breaks. At a median follow-up of 17·5 months (IQR 13·2–24·6), median progression-free survival was 22·7 months (95% CI 10·4–not reached; 1-year progression-free survival 64% [95% CI 48–85]). Three (10%) patients had severe adverse events: two grade 3 (back pain and muscle weakness) and one grade 4 (hyperglycaemia) adverse events were observed. There were no treatment-related deaths. Interpretation Sequential radiotherapy might facilitate deferral of systemic therapy initiation and could allow sustained systemic therapy breaks for select patients with oligometastatic renal cell carcinoma. Funding Anna Fuller Foundation, the Cancer Prevention and Research Institute of Texas (CPRIT), and the National Cancer Institute.

Summary Background A previous pooled analysis of the STARS and ROSEL trials showed higher survival after stereotactic ablative radiotherapy (SABR) than with surgery for operable early-stage non-small-cell lung cancer (NSCLC), but that analysis had notable limitations. This study reports long-term results of the revised STARS trial, in which the SABR group was re-accrued with a larger sample size, along with a protocol-specified propensity-matched comparison with a prospectively registered, contemporary institutional cohort of patients who underwent video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND). Methods This single-arm prospective trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and enrolled patients aged 18 years or older with a Zubrod performance status of 0–2, newly diagnosed and histologically confirmed NSCLC with N0M0 disease (squamous cell, adenocarcinoma, large cell, or NSCLC not otherwise specified), and a tumour diameter of 3 cm or less. This trial did not include patients from the previous pooled analysis. SABR dosing was 54 Gy in three fractions (for peripheral lesions) or 50 Gy in four fractions (for central tumours; simultaneous integrated boost to gross tumour totalling 60 Gy). The primary endpoint was the 3-year overall survival. For the propensity-matching analysis, we used a surgical cohort from the MD Anderson Department of Thoracic and Cardiovascular Surgery's prospectively registered, institutional review board-approved database of all patients with clinical stage I NSCLC who underwent VATS L-MLND during the period of enrolment in this trial. Non-inferiority could be claimed if the 3-year overall survival rate after SABR was lower than that after VATS L-MLND by 12% or less and the upper bound of the 95% CI of the hazard ratio (HR) was less than 1·965. Propensity matching consisted of determining a propensity score using a multivariable logistic regression model including several covariates (age, tumour size, histology, performance status, and the interaction of age and sex); based on the propensity scores, one patient in the SABR group was randomly matched with one patient in the VATS L-MLND group using a 5:1 digit greedy match algorithm. This study is registered with ClinicalTrials.gov , NCT02357992 . Findings Between Sept 1, 2015, and Jan 31, 2017, 80 patients were enrolled and included in efficacy and safety analyses. Median follow-up time was 5·1 years (IQR 3·9–5·8). Overall survival was 91% (95% CI 85–98) at 3 years and 87% (79–95) at 5 years. SABR was tolerated well, with no grade 4–5 toxicity and one (1%) case each of grade 3 dyspnoea, grade 2 pneumonitis, and grade 2 lung fibrosis. No serious adverse events were recorded. Overall survival in the propensity-matched VATS L-MLND cohort was 91% (95% CI 85–98) at 3 years and 84% (76–93) at 5 years. Non-inferiority was claimed since the 3-year overall survival after SABR was not lower than that observed in the VATS L-MLND group. There was no significant difference in overall survival between the two patient cohorts (hazard ratio 0·86 [95% CI 0·45–1·65], p=0·65) from a multivariable analysis. Interpretation Long-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended. Funding Varian Medical Systems and US National Cancer Institute (National Institutes of Health).

A new α-pyrone analog, arthrifuranone A (1) was isolated from an EtOAc-extract of Arthrinium pseudosinense culture medium. The isolation workflow was guided by a Molecular Networking-based dereplication strategy. The chemical structure of the new compound was elucidated using MS and NMR spectroscopic techniques, and the absolute configuration was established by the Mosher's method and gauge-including atomic orbital NMR chemical shift calculations, followed by DP4 + analysis. The isolated compound was evaluated for its estrogenic activity using the MCF-7 estrogen responsive human breast cancer cells. Compound 1 showed estrogenic activity by increasing the proliferation of MCF-7 cells at the concentration of 3.125 μM via phosphorylation of estrogen receptor-α.

To report early findings from a phase II trial of high-dose radiotherapy (HD-RT) with or without low-dose RT (LD-RT) for metastatic cancer.Eligible patients had metastatic disease that progressed on immunotherapy within 6 months. Patients were given either HD-RT (20-70 Gy total; 3-12.5 Gy/f), or HD-RT + LD-RT (0.5-2 Gy/f up to 1-10 Gy total) to separate lesions, with continued immunotherapy. Radiographic response was assessed per RECIST 1.1 and Immune-Related Response Criteria (irRC). Primary endpoints: (1) 4-month disease control (DCR, complete/partial response [CR/PR] or stable disease [SD]) or an overall response (ORR, CR/PR) at any point in ≥10% of patients, per RECIST 1.1; (2) dose-limiting toxicity within 3 months not exceeding 30%. Secondary endpoint was lesion-specific response.Seventy-four patients (NSCLC, n = 38; melanoma n = 21) were analyzed (39 HD-RT and 35 HD-RT + LD-RT). The median follow-up time was 13.6 months. The primary endpoint was met for 72 evaluable patients, with a 4-month DCR of 42% (47% [16/34] vs. 37% [14/38] in HD-RT + LD-RT vs. HD-RT, P = 0.38), and 19% ORR at any time (26% [9/34] vs. 13% [5/38] in HD-RT + LD-RT vs. HD-RT, P = 0.27). Three patients had toxicity ≥grade 3. LD-RT lesion response (53%) was improved compared to nonirradiated lesions in HD-RT + LD-RT (23%, P = 0.002) and HD-RT (11%, P 0.001). T- and NK cell infiltration was enhanced in lesions treated with LD-RT.HD-RT plus LD-RT safely improved lesion-specific response in patients with immune resistant solid tumors by promoting infiltration of effector immune cells into the tumor microenvironment.

Objective To study whether delivering definitive radiotherapy to sites of oligoprogression in metastatic renal cell carcinoma enabled deferral of systemic therapy changes without compromising disease control or survival. Materials/methods We identified patients with metastatic renal cell carcinoma who received radiotherapy to ≤3 sites of extracranial progressive disease in 2014-2019 at a large tertiary cancer center. Inclusion criteria were (1) controlled disease for ≥3 months before oligoprogression, (2) all oligoprogression sites treated with a biologically effective dose of ≥100 Gy, and (3) availability of follow-up imaging. Time-to-event endpoints were calculated from the start of radiotherapy. Results Seventy-two patients were identified (median follow-up time 22 months, 95% confidence interval [CI] 19-32 months), with oligoprogressive lesions in lung/mediastinum (n=35), spine (n=30), and non-spine bone (n=5). The most common systemic therapies before oligoprogression were none (n=33), tyrosine kinase inhibitor (n=23), and immunotherapy (n=13). At 1 year, the local control rate was 96% (95% CI 87%-99%); progression free survival, 52% (95% CI 40%-63%); and overall survival, 91% (95% CI 82%-96%). At oligoprogression, systemic therapy was escalated (n=16), maintained (n=49), or discontinued (n=7), with corresponding median progression free survival intervals of 19.7 months (95% CI 8.2-27.2 months), 10.1 months (95% CI 6.9-13.2 months), and 9.8 months (95% CI 2.4-28.9 months). Of the 49 patients maintained on the same systemic therapy at oligoprogression, 21 did not subsequently have systemic therapy escalation. Conclusion Patients with oligoprogressive metastatic renal cell carcinoma treated with radiotherapy had comparable progression free survival regardless of systemic therapy strategy, suggesting that radiotherapy may be a viable approach for delaying systemic therapy escalation. Randomized controlled trials comparing treatment of oligoprogression with radiotherapy vs. systemic therapy alone are needed.

PurposeThis study focuses on Vietnamese international students who returned from their overseas doctoral education to home universities in Vietnam (henceforth Vietnamese overseas-trained returnees). The purpose is to explore the experience of these returnees “doing research” (i.e. being research active) when resuming a lecturing role at a Vietnamese regional university. In the context of research now receiving heightened attention in both the wider global higher education (HE) discourse and the Vietnamese HE sector, this study is timely and provides valuable insights.Design/methodology/approachIn total, 76 Vietnamese overseas-trained returnees from varied disciplinary backgrounds completed a questionnaire on their research motivation and their perceived constraints doing research. Eighteen subsequently took part in semi-structured interviews. The study draws on the notion of human agency from the sociocultural perspective to understand the coping strategies of the Vietnamese overseas-educated returnees in response to the challenges they encountered.FindingsThe results show that the returnees' motivations to conduct research varied, fuelled by passion, but constrained by multiple factors. Time constraints, heavy teaching loads, familial roles and lack of specialized equipment are key inhibiting factors in re-engaging in research for these returnees. Addressing them necessitated a great deal of readaptation, renegotiation and agentive resilience on the part of the returnees in employing different coping strategies to pursue research.Practical implicationsThe paper argues for a subtle understanding of the returnees' experience of re-engaging in research that is both complex and contextual. Implications are drawn for research development in the regional Vietnamese HE context and perhaps in other similar settings.Originality/valueThere is little empirical knowledge about how Vietnamese returned graduates – university lecturers – continue doing research after their return. Also underexplored in global discourse is research on foreign-educated returnees doing research, while they are an important source of human resources. The present study, therefore, fills these research gaps.

Highlights • First study to investigate lymphopenia in NSCLC with postoperative radiotherapy. • Radiation-induced lymphopenia is common is this population. • Lymphopenia is correlated with radiation fraction number and total mean lung dose. • Lymphopenia is an independent risk factor for PFS and OS, particularly in stage III NSCLC., Purpose To investigate the incidence and prognosis of severe radiation-induced lymphopenia (sRIL) after postoperative radiotherapy (PORT) for resected NSCLC. Patients and methods Between 1998 and 2017, 170 patients treated with PORT for NSCLC were retrospectively reviewed. Lymphopenia was divided into tertiles with severe lymphopenia defined as absolute lymphocyte counts (ALC)

The leaf and stem extracts of Boehmeria nivea (BN) collected from three different regions in Korea were screened for their antioxidant, neuroprotective, estrogenic, insulin secretion, and α-glucosidase inhibitory activity. We also examined whether BN extracts regulate cancer cell growth, inflammatory-related gene expression, and lipid accumulation in cellular system. Leaf extracts possessed greater antioxidant, anti-proliferative in cancer cells, neuroprotective, estrogenic activity, and inhibitory effect on pro-inflammatory gene expression than stem extracts. Leaf and stem extracts inhibited lipid accumulation in three T3-L1 adipocytes but did not affect glucose-stimulated insulin secretion in INS-1 cells. We isolated and identified the phytochemical constituents in the n-butanol and ethyl acetate fractions of BN leaves by combining silica gel column chromatography with mass spectrometry and

The efficacy of immunoradiotherapy consisting of radiation therapy and immune checkpoint blockade relies on effectively promoting the systemic antitumor immune response’s activation while simultaneously reducing local factors favoring immune suppression. We previously demonstrated that NBTXR3, a nanoparticle radioenhancer, significantly improved immune responses in a murine anti-PD1-resistant metastatic lung cancer model. We hypothesize that radioactivated-NBTXR3 addition to anti-PD1 and a second-generation anti-CTLA4 could improve treatment effectiveness. To test this hypothesis, we inoculated mice with 344SQR cells in the right and left legs to establish primary and secondary tumors. The primary tumors were intratumorally injected with NBTXR3 nanoparticles on day 7, followed by three fractions of 12 Gy radiation on days 8, 9, and 10. The secondary tumors received two fractions of 1Gy radiation on days 13 and 14. Multiple rounds of anti-PD1, anti-CTLA4 or nonfucosylated anti-CTLA4 were given to the mice. Immune profiling of the tumors revealed that the combination of NBTXR3 with immunoradiotherapy significantly upregulated the activities of a wide range of antitumor immune pathways and reduced the abundance of regulatory suppressor T cells. This combination effectively eradicated the primary and secondary tumors and increased animal survival to 75%. Remarkably, previously treated with NBTXR3-containing treatment, the survivor mice exhibited a long-lasting antitumor memory immune response. This data provides compelling evidence of the efficacy of NBTXR3 to synergize with the immunoradiotherapy approach when combined with an anti-PD1 and multiple checkpoints such as a second generation anti-CTLA4 and show the potential for clinical uses of antitumor immunomodulatory effects of NBTXR3.

Background High-risk (HR) prostate cancer (PCa) is a heterogeneous disease leading to difficulties in designing appropriate inclusion criteria for clinical trials. Objective To describe clinical predictors of organ-confined disease in HR or very-high-risk (VHR) PCa patients staged with multiparametric magnetic resonance imaging with endorectal coil (mp-MRI-ER). Design, setting, and participants We reviewed 366 HR/VHR PCa patients who had preoperative mp-MRI-ER, and underwent radical prostatectomy and extended pelvic lymph node dissection between 2006 and 2015. Intervention Radical prostatectomy with preoperative mp-MRI-ER. Outcome measurements and statistical analysis We used multivariable logistic regression modeling to assess for associations with ≤ pT2N0 stage and multivariable cox modeling to assess for associations with biochemical failure. Results and limitations Of 366 patients, 132 had ≤ pT2N0 disease. For the entire cohort, negative staging mp-MRI-ER (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.06–2.83, p = 0.03), lower prostate-specific antigen (PSA; OR 0.98, 95% CI 0.97–1.00, p = 0.02), and fewer cores of Gleason ≥8 cancer (OR 0.86, 95% CI 0.79–0.93, p = 0.0002) were associated with ≤pT2N0 disease. In HR patients only, negative mp-MRI-ER (OR 3.41, 95% CI 1.73–6.72, p = 0.0004) and fewer than four cores of Gleason ≥8 disease (OR 3.38, 95% CI 1.20–9.56, p = 0.02) were still associated with ≤pT2N0 disease. Lack of non–organ-confined disease on MRI was associated with superior biochemical recurrence-free survival (p = 0.02). Limitations of this study include lack of a central review or quality control of the MRI reporting. Conclusions In HR PCa, negative staging mp-MRI-ER, fewer positive cores of Gleason >8, and lower PSA were significant predictors of pathologic organ-confined disease. Improved prediction of organ-confined disease in HR patients may allow for their inclusion into studies evaluating treatments from which they would otherwise be excluded based solely on their HR status. Patient summary In patients with high-risk prostate cancer, prostate magnetic resonance imaging along with other clinical parameters may help determine which patients are likely to have disease confined to the prostate and thus be eligible for clinical trials that they otherwise might be excluded from based on their high-risk status alone.

Purpose MRI-assisted radiosurgery (MARS) is a modern technique for prostate brachytherapy that provides superior soft tissue contrast. The purpose of this analysis was to evaluate treatment planning factors associated with urinary toxicity, particularly damage to the membranous urethra (MUL) and external urethral sphincter (EUS), after MARS. Material and Methods We retrospectively reviewed 227 patients treated with MARS. Comparisons were made between several factors including preimplantation length of the MUL and EUS dosimetric characteristics after implantation with longitudinal changes in American Urological Association (AUA) urinary symptom score. Results Rates of grade 3 urinary incontinence and obstructive urinary symptoms were 4% and 2%. A piecewise mixed univariate model revealed that MUL and V200, V150, V125, and D5 to the EUS were all associated with increased rates of urinary toxicity over time. On univariate logistic regression, MUL >14.2 mm (odds ratio [OR] 2.03 per cm3, 95% confidence interval [CI] 1.10–3.77, p = 0.025), V125 to the EUS (OR 3.21 cm3, 95% CI 1.18–8.71, p = 0.022), and use of the I-125 isotope (OR 3.45, 95% CI 1.55–7.70, p = 0.001) were associated with subacute urinary toxicity (i.e., that occurring at 4–8 months). Optimal dose-constraint limits to the EUS were determined to be V200 Conclusions MARS brachytherapy provides detailed anatomic information for treatment planning, implantation, and quality assurance. Overall rates of urinary toxicity are low; however, several dosimetric variables associated with the EUS were found to correlate with urinary toxicity.

Purpose Clinical trials are considered the gold standard in evidence-based medicine, yet few patients with cancer ultimately enroll. Here we examine patients screened for thoracic radiation oncology clinical trials to better understand enrollment trends. Methods and Materials A prospective database tracking screening and enrollment for patients referred for thoracic radiation oncology consultation at our institution from 2016 to 2019 was evaluated. Proportional enrollment rates, patient and disease characteristics, self-reported socioeconomic factors, and reasons for ineligibility or nonenrollment across 17 radiation therapy trials were compared. Results Enrollment data on 2372 patients were available for analysis. Of these patients, 40.0% (949) were deemed “not eligible” (NE) for any trial or were unwilling to be further screened. Reasons for ineligibility included stage (44%), histology (13%), radiation therapy not indicated (12%), patient decision (7%), and enrollment in a competing medical or surgical oncology trial (5%). The remaining 60.0% (1423) were “potentially eligible” (PE) for one or more trials. Most had non-small cell lung cancer (71%) or esophageal cancer (16%), and there were significantly fewer stage IV PE (29%) versus NE (49%) patients (P Conclusions Only 12% of patients screened for radiation therapy trials ultimately enrolled, and more than two-thirds had no trial available or were found ineligible. In addition, 19% of potential eligible patients did not enroll because the patient or physician declined. Future trials may benefit from pragmatic designs with more inclusive enrollment criteria and multidisciplinary engagement of referring providers.