Evidence for Dirac flat band superconductivity enabled by quantum geometry.

In a flat band superconductor, the charge carriers' group velocity vF is extremely slow. Superconductivity therein is particularly intriguing, being related to the long-standing mysteries of high-temperature superconductors1 and heavy-fermion systems2. Yet the emergence of superconductivity in flat bands would appear paradoxical, as a small vF in the conventional Bardeen-Cooper-Schrieffer theory implies vanishing coherence length, superfluid stiffness and critical current. Here, using twisted bilayer graphene3-7, we explore the profound effect of vanishingly small velocity in a superconducting Dirac flat band system8-13. Using Schwinger-limited non-linear transport studies14,15, we demonstrate an extremely slow normal state drift velocity vn ≈ 1,000 m s-1 for filling fraction ν between -1/2 and -3/4 of the moiré superlattice. In the superconducting state, the same velocity limit constitutes a new limiting mechanism for the critical current, analogous to a relativistic superfluid16. Importantly, our measurement of superfluid stiffness, which controls the superconductor's electrodynamic response, shows that it is not dominated by the kinetic energy but instead by the interaction-driven superconducting gap, consistent with recent theories on a quantum geometric contribution8-12. We find evidence for small Cooper pairs, characteristic of the Bardeen-Cooper-Schrieffer to Bose-Einstein condensation crossover17-19, with an unprecedented ratio of the superconducting transition temperature to the Fermi temperature exceeding unity and discuss how this arises for ultra-strong coupling superconductivity in ultra-flat Dirac bands.

Intelligent infrared sensing enabled by tunable moiré quantum geometry.

Quantum geometric properties of Bloch wave functions in solids, that is, Berry curvature and the quantum metric, are known to significantly influence the ground- and excited-state behaviour of electrons1-5. The bulk photovoltaic effect (BPVE), a nonlinear phenomenon depending on the polarization of excitation light, is largely governed by the quantum geometric properties in optical transitions6-10. Infrared BPVE has yet to be observed in graphene or moiré systems, although exciting strongly correlated phenomena related to quantum geometry have been reported in this emergent platform11-14. Here we report the observation of tunable mid-infrared BPVE at 5 µm and 7.7 µm in twisted double bilayer graphene (TDBG), arising from the moiré-induced strong symmetry breaking and quantum geometric contribution. The photoresponse depends substantially on the polarization state of the excitation light and is highly tunable by external electric fields. This wide tunability in quantum geometric properties enables us to use a convolutional neural network15,16 to achieve full-Stokes polarimetry together with wavelength detection simultaneously, using only one single TDBG device with a subwavelength footprint of merely 3 × 3 µm2. Our work not only reveals the unique role of moiré engineered quantum geometry in tunable nonlinear light-matter interactions but also identifies a pathway for future intelligent sensing technologies in an extremely compact, on-chip manner.

Effects of Radiotherapy for Malignancy in Systemic Sclerosis: A Systematic Review.

OBJECTIVE: Concerns regarding offering radiotherapy to patients with systemic sclerosis (SSc) stem from the potential worsening of SSc manifestations and radiotherapy toxicity. We conducted a systematic review to evaluate the effects of radiotherapy on SSc outcomes and radiotherapy-related toxicity. METHODS: MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were searched for SSc and radiotherapy. Inclusion criteria were SSc diagnosis, subsequent cancer development, and radiotherapy exposure. Outcomes were SSc manifestations (cutaneous thickening, pulmonary fibrosis, and SSc flare) and radiotherapy toxicity (acute and late) using Common Terminology Criteria for Adverse Events for grading. Grade 1 and 2 toxicities were categorized as nonsevere and grade 3 to 5 toxicities as severe. RESULTS: Of 121 patients with SSc undergoing radiotherapy (mean age 56.4 years, 83.3% female, median radiotherapy dose 50 Gy), most did not show worsened SSc skin thickening (74.5%) or pulmonary complications (74%) post radiotherapy. In retrospective studies, the average rates of acute adverse effects were 57.3% for nonsevere and 25.8% for severe, whereas the rates of late adverse effects were 32.4% for nonsevere and 24% for severe. CONCLUSION: Although most patients with SSc do not exhibit significant worsening of SSc manifestations post radiotherapy, there is a variable risk of acute and late toxicity. These findings suggest that although radiotherapy may be a viable option for patients with cancer with SSc, it requires caution.

Uncovering Topological Edge States in Twisted Bilayer Graphene.

Twisted bilayer graphene (t-BLG) has recently been introduced as a rich physical platform displaying flat electronic bands, strongly correlated states, and unconventional superconductivity. Studies have hinted at an unusual Z2 topology of the moiré Dirac bands of t-BLG. However, direct experimental evidence of this moiré band topology and associated edge states is still lacking. Herein, using superconducting quantum interferometry, we reconstructed the spatial supercurrent distribution in t-BLG Josephson junctions and revealed the presence of edge states located in the superlattice band gaps. The absence of edge conduction in high resistance regions just outside the superlattice band gap confirms that the edge transport originates from the filling of electronic states located inside the band gap and further allows us to exclude several other edge conduction mechanisms. These results confirm the unusual moiré band topology of twisted bilayer graphene and will stimulate further research to explore its consequences.

Interventions for the prevention of acute phase chemotherapy-induced nausea and vomiting in adult and pediatric patients: a systematic review and meta-analysis.

PURPOSE: To identify effective and safe interventions to prevent acute phase chemotherapy-induced nausea and vomiting (CINV) in adult and pediatric patients. METHODS: We conducted a systematic review of randomized trials evaluating interventions to prevent acute CINV. Outcomes assessed were complete chemotherapy-induced vomiting (CIV) control, complete chemotherapy-induced nausea (CIN) control, complete CINV control, and discontinuation of antiemetics due to adverse effects. RESULTS: The search identified 65,172 citations; 744 were evaluated at full-text, and 295 (25 pediatric) met eligibility criteria. In patients receiving highly emetogenic chemotherapy (HEC), complete CIV (risk ratio (RR) 1.23, 95% confidence interval (CI) 1.05-1.44) and CIN (RR 1.34, 95% CI 1.10-1.62) control improved when olanzapine was added. The addition of a neurokinin-1 receptor antagonist (NK1RA) to a corticosteroid plus a serotonin-3 receptor antagonist (5HT3RA) also improved complete CIV (RR 1.11, 95% CI 1.08-1.14) and CIN (RR 1.05, 95% CI 1.01-1.08) control. Compared to granisetron/ondansetron, palonosetron provided improved complete CIV control when the 5HT3RA was given alone or when combined with dexamethasone. In patients receiving moderately emetogenic chemotherapy (MEC), dexamethasone plus a 5HT3RA improved complete CIV control compared to a 5HT3RA alone (RR 1.29, 95% CI 1.21-1.39). Only a single meta-analysis evaluating the safety outcome was possible. CONCLUSIONS: For patients receiving HEC, various antiemetic regimens improved CIV and CIN control. For patients receiving MEC, administration of a 5HT3RA plus dexamethasone improved CIV control. Analysis of antiemetic safety was constrained by lack of data.

Biomarker testing and mutation prevalence in metastatic colorectal cancer patients in five European countries using a large oncology database.

Background: The literature on biomarker testing for metastatic colorectal cancer (mCRC) in Europe is scarce. This study aimed to estimate the percentage of mCRC patients from five European countries tested for biomarkers over time. Materials & methods: An oncology database was retrospectively analyzed; evaluated biomarkers were RAS, BRAF and microsatellite instability (MSI). The patients were drug treated during 2018 and tested for relevant biomarkers in 2013-2018. Results: RAS testing was conducted in >90% of mCRC patients from 2014 onwards. BRAF testing increased from 31% of mCRC patients in 2013 to 67% in 2018. MSI testing increased from 10 to 41%. There was no notable trend over time for RAS and BRAF mutation or MSI-high prevalence. Conclusion: Biomarker testing among patients diagnosed with mCRC was increased over time. This study demonstrates the quick uptake of biomarker testing in clinical practice. These findings are significant as biomarker-based drugs are becoming more common.

Lay abstract Each patient's cancer is unique. To find the best medicine for each patient, doctors perform tests to look at the cancer's genes. It is unknown how often and how well these tests are done. We tried to find this out for patients with cancer of the bowel or rectum that has spread to other organs. We found that an important genetic test called RAS is done in most patients. Other tests, called BRAF and microsatellite instability, are also conducted increasingly frequently. This is important because the results of such tests allow doctors to decide which drug(s) should be the most effective depending on the patient's cancer genes.

Determining Interaction Enhanced Valley Susceptibility in Spin-Valley-Locked MoS2.

Two-dimensional transition metal dichalcogenides (TMDCs) are recently emerged electronic systems with various novel properties, such as spin-valley locking, circular dichroism, valley Hall effect, and superconductivity. The reduced dimensionality and large effective masses further produce unconventional many-body interaction effects. Here we reveal strong interaction effects in the conduction band of MoS2 by transport experiment. We study the massive Dirac electron Landau levels (LL) in high-quality MoS2 samples with field-effect mobilities of 24 000 cm2/(V·s) at 1.2 K. We identify the valley-resolved LLs and low-lying polarized LLs using the Lifshitz-Kosevitch formula. By further tracing the LL crossings in the Landau fan diagram, we unambiguously determine the density-dependent valley susceptibility and the interaction enhanced g-factor from 12.7 to 23.6. Near integer ratios of Zeeman-to-cyclotron energies, we discover LL anticrossings due to the formation of quantum Hall Ising ferromagnets, the valley polarizations of which appear to be reversible by tuning the density or an in-plane magnetic field. Our results provide evidence for many-body interaction effects in the conduction band of MoS2 and establish a fertile ground for exploring strongly correlated phenomena of massive Dirac electrons.

Trends in Management of Oligometastatic Hormone-Sensitive Prostate Cancer.

PURPOSE OF REVIEW: Systemic therapy for patients with hormone-sensitive oligometastatic prostate cancer is non-curative and associated with toxicities. Meanwhile, this population presents unique clinical opportunities to improve outcomes, including the demonstrated benefits of radiotherapy to the primary tumor or oligometastatic sites. RECENT FINDINGS: Recently published randomized studies have demonstrated benefits with the addition of radiotherapy to the primary disease or metastatic lesions in patients with synchronous or metachronous disease. The introduction of novel PET imaging has improved the sensitivity and specificity for detecting metastatic disease and provides an opportunity to better select patients who will benefit from local therapy. The data presented in this review supports revisiting practice guidelines for patients with hormone-sensitive metastatic prostate cancer, particularly in relation to the role of radiotherapy to the primary tumor and sites of oligometastatic disease. Future trials will aim to further establish the role of metastasis-directed therapies in metachronous, synchronous, and castrate-resistant disease.

The development of a 4D treatment planning methodology to simulate the tracking of central lung tumors in an MRI-linac.

PURPOSE: Targeting and tracking of central lung tumors may be feasible on the Elekta MRI-linac (MRL) due to the soft-tissue visualization capabilities of MRI. The purpose of this work is to develop a novel treatment planning methodology to simulate tracking of central lung tumors with the MRL and to quantify the benefits in OAR sparing compared with the ITV approach. METHODS: Full 4D-CT datasets for five central lung cancer patients were selected to simulate the condition of having 4D-pseudo-CTs derived from 4D-MRI data available on the MRL with real-time tracking capabilities. We used the MRL treatment planning system to generate two plans: (a) with a set of MLC-defined apertures around the target at each phase of the breathing ("4D-MRL" method); (b) with a fixed set of fields encompassing the maximum inhale and exhale of the breathing cycle ("ITV" method). For both plans, dose accumulation was performed onto a reference phase. To further study the potential benefits of a 4D-MRL method, the results were stratified by tumor motion amplitude, OAR-to-tumor proximity, and the relative OAR motion (ROM). RESULTS: With the 4D-MRL method, the reduction in mean doses was up to 3.0 Gy and 1.9 Gy for the heart and the lung. Moreover, the lung's V12.5 Gy was spared by a maximum of 300 cc. Maximum doses to serial organs were reduced by up to 6.1 Gy, 1.5 Gy, and 9.0 Gy for the esophagus, spinal cord, and the trachea, respectively. OAR dose reduction with our method depended on the tumor motion amplitude and the ROM. Some OARs with large ROMs and in close proximity to the tumor benefited from tracking despite small tumor amplitudes. CONCLUSIONS: We developed a novel 4D tracking methodology for the MRL for central lung tumors and quantified the potential dosimetric benefits compared with our current ITV approach.

Developing and Evaluating Multimedia Patient Education Tools to Better Prepare Prostate-Cancer Patients for Radiotherapy Treatment (Randomized Study).

The purpose of this study is to determine the effectiveness of multimedia educational tools to improve CT planning preparation for intensity modulated radiotherapy (IMRT) for prostate cancer. Many patients are not prepared when given verbal preparation instructions to have a full bladder and empty rectum for their IMRT and require being rescanned, which results in additional costs for the patient and the hospital. A pamphlet and video outlining the proper preparation for prostate IMRT was created to decrease additional scans and the associated costs, while increasing patient satisfaction. A controlled, randomized experimental group study was conducted to examine the effectiveness of the multimedia tools (the video and the pamphlet), as compared to the pamphlet only, in preparing patients for their planning CT appointment. We found no statistical difference between the multimedia group and the pamphlet group in patients' preparedness for their appointments and the rescanning rate. However, patients in the multimedia group indicated that they felt more prepared about their treatment after watching the video and stated that they would recommend the video to other patients with prostate cancer. Furthermore, patients who had to wait longer for their planning CT appointment felt less prepared by the materials than those with a shorter wait time. We recommend reducing wait times between appointments as much as possible to increase patients' preparedness for the planning CT. We conclude that providing multimedia treatment information and minimizing wait times increases patients' feelings of preparedness leading to a more positive treatment experience and reducing costly rescans. TRIAL REGISTRATION: ClinicalTrials.gov NCT02410291.

Reirradiation of recurrent node-positive non-small cell lung cancer after previous stereotactic radiotherapy for stage I disease : A multi-institutional treatment recommendation.

BACKGROUND: Practice guidelines have been developed for early-stage and locally advanced non-small cell lung cancer (NSCLC). However, many common clinical scenarios still require individualized decision making. This is true for locoregional relapse after initial stereotactic radiotherapy (stereotactic body radiation therapy or stereotactic ablative radiotherapy; SBRT or SABR), an increasingly utilized curative treatment option for stage I NSCLC. METHODS: A consortium of expert radiation oncologists was established with the aim of providing treatment recommendations. In this scenario, a case was distributed to six radiation oncologists who provided their institutions' treatment recommendations. In this case, a patient developed local and mediastinal relapse after SABR (45 Gy, 3 fractions), comparable to the tumor burden in de novo stage IIIA NSCLC. Treatment recommendations were tabulated and a consensus conclusion was developed. RESULTS: Three institutions recommended evaluation for surgery. If the patient was not a surgical candidate, and/or refused surgery, definitive chemoradiation was recommended, including retreating the primary to full dose. European participants were more in favor of a non-surgical approach. None of the participants were reluctant to prescribe reirradiation, but two institutions prescribed doses lower than 60 Gy. Platinum-based doublets together with intensity-modulated radiotherapy were preferred. CONCLUSION: The institutional recommendations reflect the questions and uncertainties discussed in current stage III guidelines. All institutions agreed that previous SABR is not a contraindication for salvage chemoradiation. In the absence of high-quality prospective trials for recurrent NSCLC, all treatment options recommended in current guidelines for stage III disease can be considered in clinical scenarios such as this.

Evaluation of kidney motion and target localization in abdominal SBRT patients.

The purpose of this study was to evaluate bilateral kidney and target translational/rotational intrafraction motion during stereotactic body radiation therapy treatment delivery of primary renal cell carcinoma and oligometastatic adrenal lesions for patients immobilized in the Elekta BodyFIX system. Bilateral kidney motion was assessed at midplane for 30 patients immobilized in a full-body dual-vacuum-cushion system with two patients immobilized via abdominal compression. Intrafraction motion was assessed for 15 patients using kilovoltage cone-beam computed tomography (kV-CBCT) datasets (n = 151) correlated to the planning CT. Patient positioning was corrected for translational and rotational misalign-ments using a robotic couch in six degrees of freedom if setup errors exceeded 1mm and 1°. Absolute bilateral kidney motion between inhale and exhale 4D CT imaging phases for left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions was 1.51 ± 1.00 mm, 8.10 ± 4.33 mm, and 3.08 ± 2.11 mm, respec-tively. Residual setup error determined across CBCT type (pretreatment, intrafrac-tion, and post-treatment) for x (LR), y (SI), and z (AP) translations was 0.63 ± 0.74 mm, 1.08± 1.38 mm, and 0.70 ± 1.00 mm; while for x (pitch), y (roll), and z (yaw) rotations was 0.24 ± 0.39°, 0.19 ± 0.34°, and 0.26 ± 0.43°, respectively. Targets were localized to within 2.1 mm and 0.8° 95% of the time. The frequency of misalignments in the y direction was significant (p < 0.05) when compared to the x and z directions with no significant difference in translations between IMRT and VMAT. This technique is robust using BodyFIX for patient immobilization and reproducible localization of kidney and adrenal targets and daily CBCT image guidance for correction of positional errors to maintain treatment accuracy.

Incidence of complications other than urinary incontinence or erectile dysfunction after radical prostatectomy or radiotherapy for prostate cancer: a population-based cohort study.

BACKGROUND: Studies of complications resulting from surgery or radiotherapy for prostate cancer have mainly focused on incontinence and erectile dysfunction. We aimed to assess other important complications associated with these treatments for prostate cancer. METHODS: We did a population-based retrospective cohort study, in which we used administrative hospital data, physician billing codes, and cancer registry data for men who underwent either surgery or radiotherapy alone for prostate cancer between 2002 and 2009 in Ontario, Canada. We measured the 5-year cumulative incidence of five treatment-related complication endpoints: hospital admissions; urological, rectal, or anal procedures; open surgical procedures; and secondary malignancies. FINDINGS: In the 32 465 patients included in the study, the 5-year cumulative incidence of admission to hospital for a treatment-related complication was 22·2% (95% CI 21·7-22·7), but was 2·4% (2·2-2·6) for patients whose length of stay was longer than 1 day. The 5-year cumulative incidence of needing a urological procedure was 32·0% (95% CI 31·4-32·5), that of a rectal or anal procedure was 13·7% (13·3-14·1), and that of an open surgical procedure was 0·9% (0·8-1·1). The 5-year cumulative incidence of a second primary malignancy was 3·0% (2·6-3·5). These risks were significantly higher than were those of 32 465 matched controls with no history of prostate cancer. Older age and comorbidity at the time of index treatment were important predictors for a complication in all outcome categories, but the type of treatment received was the strongest predictor for complications. Patients who were given radiotherapy had higher incidence of complications for hospital admissions, rectal or anal procedures, open surgical procedures, and secondary malignancies at 5 years than did those who underwent surgery (adjusted hazard ratios 2·08-10·8, p<0·0001). However, the number of urological procedures was lower in the radiotherapy than in the surgery group (adjusted hazard ratio 0·66, 95% CI 0·63-0·69; p<0·0001) INTERPRETATION: Complications after prostate cancer treatment are frequent and dependent on age, comorbidity, and the type of treatment. Patients and physicians should be aware of these risks when choosing treatment for prostate cancer, and should balance them with the clinical effectiveness of each therapy. FUNDING: Ajmera Family Chair in Urologic Oncology.

Dermoscopy for common skin problems in Chinese children using a novel Hong Kong-made dermoscope.

OBJECTIVE: To evaluate the dermoscopic features of common skin problems in Chinese children. DESIGN: A case series with retrospective qualitative analysis of dermoscopic features of common skin problems in Chinese children. SETTING: A regional hospital in Hong Kong. PARTICIPANTS: Dermoscopic image database, from 1 May 2013 to 31 October 2013, of 185 Chinese children (aged 0 to 18 years). RESULTS: Dermoscopic features of common paediatric skin problems in Chinese children were identified. These features corresponded with the known dermoscopic features reported in the western medical literature. New dermoscopic features were identified in café-au-lait macules. CONCLUSION: Dermoscopic features of common skin problems in Chinese children were consistent with those reported in western medical literature. Dermoscopy has a role in managing children with skin problems.

A Systematic Review of Phase II/III Trials of Hypofractionated versus Conventionally Fractionated Radiation Therapy in Stage III Non-Small Cell Lung Cancer Patients.

INTRODUCTION: This systematic review evaluated whether curative intent hypofractionated radiation therapy improved survival (primary endpoint) as compared to standard conventionally fractionated radiation therapy for stage III non-small cell lung cancer (NSCLC) patients. Toxicity was also examined as a secondary endpoint. METHODS: Electronic bibliographic databases were searched from 1 January 1990 to 31 March 2024. Phase II and phase III trials were included to assess survival (primary outcome) and toxicity (secondary outcome) for newly diagnosed stage III NSCLC patients. RESULTS: Eight phase II trials (n = 349 participants), 3 randomized phase II trials (n = 382 participants), and 5 randomized phase III trials (n = 811 participants), for a total of 1542 participants, were identified. The published trials were heterogeneous, with a wide variety of dose prescriptions. A wide range of survivals (median survival 13.6 months-42.5 months) and toxicities such as grade 3 or higher esophagitis (0-42%) and grade 3 or higher pneumonitis (0-18%) were reported. CONCLUSIONS: There is no level 1 evidence to date that suggests that any hypofractionated regimen (dose escalated or not) improves survival as compared to conventionally fractionated radiation. The published phase III trials have been powered for superiority (not equivalence) for the hypofractionated arm. Toxicity with hypofractionated regimens may be similar to conventionally fractionated regimens when normal tissue radiotherapy constraints are kept within tolerance limits. It is unclear how the use of systemic therapy may negatively affect radiation toxicity with hypofractionated radiation therapy.

Safety and Efficacy of Stereotactic Body Radiation Therapy for Ultra-central Thoracic Tumors: A Single Center Retrospective Review.

PURPOSE: We sought to evaluate the toxicity and efficacy of stereotactic body radiation therapy (SBRT) for ultracentral thoracic tumors at our institution. METHODS AND MATERIALS: Patients with ultracentral lung tumors or nodes, defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus, treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. All SBRT plans were generated with the goal of creating homogenous dose distributions. The primary endpoint was incidence of SBRT-related grade ≥3 toxicity, defined using the Common Terminology Criteria for Adverse Events (V5.0). Secondary endpoints included local failure (LF), progression-free survival (PFS), and overall survival. Competing risk analysis was used to estimate incidence and identify predictors of severe toxicity and LF, while the Kaplan-Meier method was used to estimate PFS and OS. RESULTS: A total of 154 patients receiving 162 ultracentral courses of SBRT were included. The most common prescription was 50 Gy in 5 fractions (42%), with doses ranging from 30 to 55 Gy in 5 fractions (BED10 range, 48-115 Gy). The incidence of severe toxicity was 9.4% at 3 years. The most common severe toxicity was pneumonitis (n = 4). There was 1 possible treatment-related death from pneumonitis/pneumonia. Predictors of severe toxicity included increased PTV size, decreased PTV V95%, lung V5 Gy, and lung V20 Gy. The incidence of LF was 14% at 3 years. Predictors of LF included younger age and greater volume of overlap between the PTV and esophagus. The median PFS was 8.8 months, while the median overall survival was 44.0 months. CONCLUSIONS: In the largest case series of ultracentral thoracic SBRT to date, homogenously prescribed SBRT was associated with relatively low rates of severe toxicity and LF. Predictors of toxicity should be interpreted in the context of the heterogeneity in toxicities observed.

Stereotactic Body Radiation Therapy: A Radiosurgery Society Guide to the Treatment of Localized Prostate Cancer Illustrated by Challenging Cases.

Traditionally, external beam radiotherapy (EBRT) for localized prostate cancer (PCa) involved lengthy courses with low daily doses. However, advancements in radiation delivery and a better understanding of prostate radiobiology have enabled the development of shorter courses of EBRT. Ultrahypofractionated radiotherapy, administering doses greater than 5 Gy per fraction, is now considered a standard of care regimen for localized PCa, particularly for intermediate-risk disease. Stereotactic body radiotherapy (SBRT), a specific type of ultrahypofractionated radiotherapy employing advanced planning, imaging, and treatment technology to deliver in five or fewer fractions, is gaining prominence as a cost-effective, convenient, and safe alternative to longer radiotherapy courses. It is crucial to address practical considerations related to patient selection, fractionation scheme, target delineation, and planning objectives. This is especially important in challenging clinical situations where clear evidence for guidance may be lacking. The Radiosurgery Society endorses this case-based guide with the aim of providing a practical framework for delivering SBRT to the intact prostate, exemplified by two case studies. The article will explore common SBRT dose/fractionation schemes and dose constraints for organs-at-risk. Additionally, it will review existing evidence and expert opinions on topics such as SBRT dose escalation, the use of rectal spacers, the role of androgen deprivation therapy in the context of SBRT, SBRT in special patient populations (e.g., high-risk disease, large prostate, high baseline urinary symptom burdens, and inflammatory bowel disease), as well as new imaging-guidance techniques like Magnetic Resonance Imaging for SBRT delivery.

Randomized Trial of Concomitant Hypofractionated Intensity Modulated Radiation Therapy Boost Versus Conventionally Fractionated Intensity Modulated Radiation Therapy Boost for Localized High-Risk Prostate Cancer (pHART2-RCT).

PURPOSE: The aim of this work is to report on the results of a phase 2 randomized trial of moderately hypofractionated (MH) versus conventionally fractionated (CF) radiation therapy to the prostate with elective nodal irradiation. METHODS AND MATERIALS: This was a single-center, prospective, phase 2 randomized study. Patients with high-risk disease (cT3, prostate-specific antigen level >20 ng/mL, or Gleason score 8-10) were eligible. Patients were randomized to either MH using a simultaneous integrated boost (68 Gy in 25 fractions to prostate; 48 Gy to pelvis) or CF (46 Gy in 23 fractions with a sequential boost to the prostate of 32 Gy in 16 fractions), with long-term androgen deprivation therapy. The primary endpoint was grade ≥2 acute gastrointestinal (GI) and genitourinary (GU) toxicity (Common Terminology Criteria for Adverse Events version 3.0). Secondary endpoints included late GI and GU toxicity, quality of life, and oncologic outcomes. RESULTS: One-hundred eighty patients were enrolled; 90 were randomized to and received MH and 90 to CF. The median follow-up was 67.4 months. Seventy-five patients (41.7%) experienced a grade ≥2 acute GI and/or GU toxicity, including 34 (37.8%) in the MH and 41 (45.6%) in the CF arms, respectively (P = .29). Late grade ≥2 GI (P = .07) and GU (P = .25) toxicity was not significantly different between arms; however, late grade ≥3 GI toxicity was worse in the MH group (P = .01). There were no statistically significant quality-of-life differences between the 2 treatments. There were no statistically significant differences observed in cumulative incidence of biochemical failure (P = .71) or distant metastasis (P = .31) and overall survival (P = .46). CONCLUSIONS: MH to the prostate and pelvis with androgen deprivation therapy for men with high-risk localized prostate cancer was not significantly different than CF with regard to acute toxicity, quality of life, and oncologic efficacy. However, late grade ≥3 GI toxicity was more common in the MH arm.

Elective pelvic nodal irradiation in the setting of ultrahypofractionated versus moderately hypofractionated and conventionally fractionated radiotherapy for prostate cancer: Outcomes from 3 prospective clinical trials.

Background and purpose: Data is needed regarding the use of ultrahypofractionated radiotherapy (UHRT) in the context of prostate cancer elective nodal irradiation (ENI), and how this compares to conventionally fractionated radiotherapy (CFRT) ENI with CFRT or moderately hypofractionated radiotherapy (MHRT) to the prostate. Materials and methods: Between 2011-2019, 3 prospective clinical trials of unfavourable intermediate or high-risk prostate cancer receiving CFRT (78 Gy in 39 fractions to prostate; 46 Gy in 23 fractions to pelvis), MHRT (68 Gy in 25 fractions to prostate; 48 Gy to pelvis), or UHRT (35-40 Gy in 5 fractions to prostate +/- boost to 50 Gy to intraprostatic lesion; 25 Gy to pelvis) were conducted. Primary endpoints included biochemical failure (Phoenix definition), and acute and late toxicities (CTCAE v3.0/4.0). Results: Two-hundred-forty patients were enrolled: 90 (37.5 %) had CFRT, 90 (37.5 %) MHRT, and 60 (25 %) UHRT. Median follow-up time was 71.6 months (IQR 53.6-94.8). Cumulative incidence of biochemical failure (95 % CI) at 5-years was 11.7 % (3.5-19.8 %) for CFRT, 6.5 % (0.8-12.2 %) MHRT, and 1.8 % (0-5.2 %) UHRT, which was not significantly different between treatments (p = 0.38). Acute grade ≥ 2 genitourinary toxicity was significantly worse for UHRT versus CFRT and MHRT, but not for acute grade ≥ 3 genitourinary, or acute gastrointestinal toxicities. UHRT was not associated with worse late toxicities. Conclusion: ENI with UHRT resulted in similar oncologic outcomes to CFRT ENI with prostate CFRT/MHRT, with worse acute grade ≥ 2 GU toxicity but no differences in late toxicity. Randomized phase 3 trials of ENI using UHRT techniques are much anticipated.

Prostate high dose-rate brachytherapy as monotherapy for low and intermediate-risk prostate cancer: Efficacy results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy: A 9-year update.

BACKGROUND AND PURPOSE: High dose-rate (HDR) brachytherapy as a monotherapy is an accepted treatment for localized prostate cancer, but the optimal dose and fractionation schedule remain unknown. We report on the efficacy of a randomized Phase II trial comparing HDR monotherapy delivered as 27 Gy in 2 fractions vs. 19 Gy in 1 fraction with a median follow-up of 9 years. MATERIALS AND METHODS: Enrolled patients had low or intermediate-risk disease, <60 cc prostate volume and no androgen deprivation use. Patients were randomized to 27 Gy in 2 fractions delivered one week apart vs a single fraction of 19 Gy. RESULTS: 170 patients were randomized: median age 65 years, median follow-up 107 months and median baseline PSA 6.35 ng/ml. NCCN risk categories comprised low (19 %), favourable (51 %), and unfavourable intermediate risk (30 %). The median PSA at 8 years was 0.08 ng/ml in the 2-fraction arm vs. 0.89 ng/ml in the single-fraction arm. The cumulative incidence of local failure at 8 years was 11.2 % in the 2-fraction arm vs. 35.9 % in the single-fraction arm (p < 0.001). The incidence of distant failure at 8 years was 3.8 % in the 2-fraction arm and 2.5 % in the single-fraction arm (p = 0.6). CONCLUSIONS: HDR monotherapy delivered in two fractions of 13.5 Gy demonstrated a persistent cancer control rate at 8 years and was well-tolerated. Single-fraction monotherapy yielded poor oncologic control and is not recommended. These findings contribute to the ongoing discourse on optimal HDR monotherapy strategies for low and intermediate-risk prostate cancer.