Brachytherapy: An overview for clinicians.

Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high-level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high-risk prostate cancer to perform dose escalation and improve progression-free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer.

High-precision tumor resection down to few-cell level guided by NIR-IIb molecular fluorescence imaging.

In vivo fluorescence/luminescence imaging in the near-infrared-IIb (NIR-IIb, 1,500 to 1,700 nm) window under <1,000 nm excitation can afford subcentimeter imaging depth without any tissue autofluorescence, promising high-precision intraoperative navigation in the clinic. Here, we developed a compact imager for concurrent visible photographic and NIR-II (1,000 to 3,000 nm) fluorescence imaging for preclinical image-guided surgery. Biocompatible erbium-based rare-earth nanoparticles (ErNPs) with bright down-conversion luminescence in the NIR-IIb window were conjugated to TRC105 antibody for molecular imaging of CD105 angiogenesis markers in 4T1 murine breast tumors. Under a ∼940 ± 38 nm light-emitting diode (LED) excitation, NIR-IIb imaging of 1,500- to 1,700-nm emission afforded noninvasive tumor­to­normal tissue (T/NT) signal ratios of ∼40 before surgery and an ultrahigh intraoperative tumor-to-muscle (T/M) ratio of ∼300, resolving tumor margin unambiguously without interfering background signal from surrounding healthy tissues. High-resolution imaging resolved small numbers of residual cancer cells during surgery, allowing thorough and nonexcessive tumor removal at the few-cell level. NIR-IIb molecular imaging afforded 10-times-higher and 100-times-higher T/NT and T/M ratios, respectively, than imaging with IRDye800CW-TRC105 in the ∼900- to 1,300-nm range. The vastly improved resolution of tumor margin and diminished background open a paradigm of molecular imaging-guided surgery.

Ultrabright NIR-II Nanoprobe for Image-Guided Accurate Resection of Tiny Metastatic Lesions.

Fluorescence imaging is a vital way to delineate the tumor boundaries. Here, we achieve a NIR-II aggregation-induced emission luminogen (AIEgen) with a fluorescence quantum yield (QY) of 12.6% in water through straightforward alkyl side chain modification. After loading of NIR-II AIEgen into polystyrene (PS) nanospheres, the thermal deactivation pathway is extremely limited, thereby concentrating absorption excitation on fluorescence emission. The fluorescence intensity is further enhanced by 5.4 times, the QY increases to 21.1%, and the NIR-II imaging signal is accordingly enhanced by 8.7 times, surpassing conventional DSPE-PEG carriers. The NIR-II@PS nanoprobe showcases superior resolution and tissue penetration depth compared to indocyanine green (ICG) and short-range near-infrared AIEgens. In vivo investigations underscore its tumor-to-normal tissue ratio (3.9) at 24 h post intravenous injection, enabling complete resection of ≤1 mm metastases under NIR-II bioimaging guidance. Additionally, the PS carrier-nanoparticles exhibit low toxicity in vivo, laying a promising foundation for the future design of medical nanomaterials.

Retrospective analysis of the learning curve in perineal robot-assisted prostate biopsy.

INTRODUCTION: Magnetic resonance imaging-transrectal ultrasound (MRI-TRUS)-fusion biopsy (FBx) of the prostate allows targeted sampling of suspicious lesions within the prostate, identified by multiparametric MRI. Due to its reliable results and feasibility, perineal MRI/TRUS FBx is now the gold standard for prostate cancer (PC) diagnosis. There are various systems for performing FBx on the market, for example, software-based, semirobotic, or robot-assisted platform solutions. Their semiautomated workflow promises high process quality independent of the surgeon's experience. The aim of this study was to analyze how the surgeon's experience influences the cancer detection rate (CDR) via targeted biopsy (TB) and the procedure's duration in robot-assisted FBx. PATIENTS AND METHODS: A total of 1716 men who underwent robot-assisted FBx involving a combination of targeted and systematic sampling between October 2015 and April 2022 were analyzed. We extracted data from the patients' electronic medical records retrospectively. Primary endpoints were the CDR by TB and the procedure's duration. For our analysis, surgeons were divided into three levels of experience: ≤20 procedures (little), 21-100 procedures (intermediate), and >100 procedures (high). Statistical analysis was performed via regression analyses and group comparisons. RESULTS: Median age, prostate-specific antigen level, and prostate volume of the cohort were 67 (±7.7) years, 8.13 (±9.4) ng/mL, and 53 (±34.2) mL, respectively. Median duration of the procedure was 26 (±10.9) min. The duration decreased significantly with the surgeon's increasing experience from 35.1 (little experience) to 28.4 (intermediate experience) to 24.0 min (high experience) (p < 0.001). Using TB only, significant PC (sPC) was diagnosed in 872/1758 (49.6%) of the men. The CDR revealed no significant correlation with the surgeon's experience in either group comparison (p = 0.907) or in regression analysis (p = 0.65). CONCLUSION: While the duration of this procedure decreases with increasing experience, the detection rate of sPC in TB is not significantly associated with the experience of the surgeon performing robot-assisted FBx. This robot-assisted biopsy system's diagnostic accuracy therefore appears to be independent of experience.

Photonic control of image-guided ferroptosis cancer nanomedicine.

Photonic nanomaterials, characterized by their remarkable photonic tunability, empower a diverse range of applications, including cutting-edge advances in cancer nanomedicine. Recently, ferroptosis has emerged as a promising alternative strategy for effectively killing cancer cells with minimizing therapeutic resistance. Novel design of photonic nanomaterials that can integrate photoresponsive-ferroptosis inducers, -diagnostic imaging, and -synergistic components provide significant benefits to effectively trigger local ferroptosis. This review provides a comprehensive overview of recent advancements in photonic nanomaterials for image-guided ferroptosis cancer nanomedicine, offering insights into their strengths, constraints, and their potential as a future paradigm in cancer treatment.

Current Application of Navigation Systems in Robotic-Assisted and Laparoscopic Partial Nephrectomy: Focus on the Improvement of Surgical Performance and Outcomes.

Kidney cancer represents the third most prevalent malignancy among all types of genitourinary cancer worldwide. Currently, there is a growing trend of employing partial nephrectomy for the management of large and complex tumors. Surgical outcomes are associated with some amendable surgical factors, including warm ischemic time, pedicle clamping, preserved volume of renal parenchyma, appropriate surgical strategy, and precise resection of the tumor. Improving surgical performance is pivotal for achieving favorable surgical outcomes. Due to advancements in imaging visualization technology and the shift of the medical paradigm toward precision medicine, an increasing number of navigation systems have been implemented in partial nephrectomy procedures. The navigation system can assist surgeons in formulating optimal surgical strategies and enhance the safety, precision, and feasibility of resecting complex renal tumors. In this review, we provide an overview of currently available navigation systems and their feasible applications, with a focus on how they contribute to the improvement of surgical performance and outcomes during robotic-assisted and laparoscopic partial nephrectomy.

Transrectal ultrasound for intraoperative interstitial needle guidance in cervical cancer brachytherapy.

OBJECTIVE: This study aimed to prospectively assess the visibility of interstitial needles on transrectal ultrasound (TRUS) in cervical cancer brachytherapy patients and evaluate its impact on implant and treatment plan quality. MATERIAL AND METHODS: TRUS was utilized during and after applicator insertion, with each needle's visibility documented through axial images at the high-risk clinical target volume's largest diameter. Needle visibility on TRUS was scored from 0 (no visibility) to 3 (excellent discrimination, margins distinct). Quantitative assessment involved measuring the distance between tandem and each needle on TRUS and comparing it to respective magnetic resonance imaging (MRI) measurements. Expected treatment plan quality based on TRUS images was rated from 1 (meeting all planning objectives) to 4 (violation of High-risk clinical target volume (CTVHR) and/or organ at risk (OAR) hard constraints) and compared to the final MRI-based plan. RESULTS: Analysis included 23 patients with local FIGO stage IB2-IVA, comprising 41 applications with a total of 230 needles. A high visibility rate of 99.1% (228/230 needles) was observed, with a mean visibility score of 2.5 ±â€¯0.7 for visible needles. The maximum and mean difference between MRI and TRUS measurements were 8 mm and -0.1 ±â€¯1.6 mm, respectively, with > 3 mm discrepancies in 3.5% of needles. Expected treatment plan quality after TRUS assessment exactly aligned with the final MRI plan in 28 out of 41 applications with only minor deviations in all other cases. CONCLUSION: Real-time TRUS-guided interstitial needle placement yielded high-quality implants, thanks to excellent needle visibility during insertion. This supports the potential of TRUS-guided brachytherapy as a promising modality for gynecological indications.

High-dose planned adaptive helical tomotherapy for cutaneous angiosarcoma of the scalp.

PURPOSE: The purpose of this study was to investigate the feasibility and effectiveness of high-dose planned adaptive intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) for cutaneous angiosarcoma (cAS) of the scalp. METHODS: This retrospective cross-sectional included a total of 12 consecutive patients with cAS of the scalp who underwent high-dose planned adaptive IMRT with HT. Prescribed doses were 72.5-74 Gy in 35-37 fractions for the gross tumor volume plus a 1-2 mm margin (PTV1), 58-60 Gy in 29-30 fractions for the clinical target volume plus a 2-3 mm margin (PTV2), and 46 Gy in 23 fractions for the clinical target volume plus a 5-15 mm margin (PTV3) over periods of 7.5, 6 and 4.5 weeks, respectively. RESULTS: The estimated 1­year and 2­year overall survival rate were 65.6% and 27.3%, respectively, and the local progression-free survival at 2 years was 74.1%. All local recurrences were either in or marginal to the PTV2 or PTV3. No local recurrence was observed in the PTV1. All patients tolerated the treatment without grade 3 or higher adverse events during the radiotherapy period. No late adverse events were observed during the follow-up period. CONCLUSION: Planned adaptive high-dose IMRT with HT has the potential to improve local control rate without increasing adverse events.

Stereoscopic X-ray image and thermo-optical surface guidance for breast cancer radiotherapy in deep inspiration breath-hold.

PURPOSE: To investigate the feasibility of a thermo-optical surface imaging (SGRT) system combined with room-based stereoscopic X­ray image guidance (IGRT) in a dedicated breast deep inspiration breath-hold (DIBH) irradiation workflow. In this context, benchmarking of portal imaging (EPID) and cone-beam CT (CBCT) against stereoscopic X­rays was performed. METHODS: SGRT + IGRT data of 30 left-sided DIBH breast patients (1 patient with bilateral cancer) treated in 351 fractions using thermo-optical surface imaging and X-ray IGRT were retrospectively analysed. Patients were prepositioned based on a free-breathing surface reference derived from a CT scan. Once the DIBH was reached using visual feedback, two stereoscopic X­ray images were acquired and registered to the digitally reconstructed radiographs derived from the DIBH CT. Based on this registration, a couch correction was performed. Positioning and monitoring by surface and X-ray imaging were verified by protocol-based EPID or CBCT imaging at selected fractions and the calculation of residual geometric deviations. RESULTS: The median X­ray-derived couch correction vector was 4.9 (interquartile range [IQR] 3.3-7.1) mm long. Verification imaging was performed for 134 fractions (216 RT field verifications) with EPID and for 37 fractions with CBCT, respectively. The median 2D/3D deviation vector length over all verification images was 2.5 (IQR 1.6-3.9) mm/3.4 (IQR 2.2-4.8) mm for EPID/CBCT, both being well within the planning target volume (PTV) margins (7 mm). A moderate correlation (0.49-0.65) was observed between the surface signal and X-ray position in DIBH. CONCLUSION: DIBH treatments using thermo-optical SGRT and X-ray IGRT were feasible for breast cancer patients. Stereoscopic X­ray positioning was successfully verified by standard IGRT techniques.

Protocol-based CT-guided brachytherapy for patients with prostate cancer and previous rectal extirpation-a curative approach.

OBJECTIVE: There are numerous curative treatment possibilities for prostate cancer. In patients who have undergone rectal extirpation for rectal cancer treatment, curative options are limited due to anatomic changes and previous irradiation of the pelvis. In this analysis, we validate the feasibility of CT-guided transperineal interstitial brachytherapy for this specific scenario. PATIENTS AND METHODS: We analyzed the treatment procedures and outcomes of 5 patients with metachronic nonmetastatic prostate cancer. Ultrasound-guided brachytherapy was not possible in any of the patients. Of these 5 patients, 3 were treated for prostate cancer using temporary brachytherapy with Ir-192 only, and 2 were treated with external-beam radiation therapy and temporary brachytherapy as a boost. CT-guided brachytherapy was performed in all patients. We analyzed the feasibility, efficacy, treatment-related toxicity, and quality of life (EORTC-30, IEFF, IPSS, and ICIQ questionnaires) of the treatments. RESULTS: Median follow-up was 35 months. Two out of five patients received boost irradiation (HDR 2â€¯× 9 Gy, PDR 30 Gy). Three out of five patients were treated with PDR brachytherapy in two sessions up to a total dose of 60 Gy. Dosimetric parameters were documented as median values as follows: V100 94.7% (94.5-98.4%), D2bladder 64.3% (50.9-78.3%), D10urethra 131.05% (123.2%-141.2%), and D30urethra 122.45% (116.2%-129.5%). At the time of analysis, no biochemical recurrence had been documented. Furthermore, neither early nor late side effects exceeding CTCAE grade 2 were documented. CONCLUSION: CT-guided transperineal brachytherapy of the prostate in patients with previous rectal surgery and radiation therapy is safe and represents a possible curative treatment option. Brachytherapy can be considered for patients with metachronic prostate cancer in this specific scenario, albeit preferably in experienced high-volume centers.

Comparison of patient setup accuracy for optical surface-guided and X-ray-guided imaging with respect to the impact on intracranial stereotactic radiotherapy.

PURPOSE: The objective of this work is to estimate the patient positioning accuracy of a surface-guided radiation therapy (SGRT) system using an optical surface scanner compared to an X­ray-based imaging system (IGRT) with respect to their impact on intracranial stereotactic radiotherapy (SRT) and intracranial stereotactic radiosurgery (SRS). METHODS: Patient positioning data, both acquired with SGRT and IGRT systems at the same linacs, serve as a basis for determination of positioning accuracy. A total of 35 patients with two different open face masks (578 datasets) were positioned using X­ray stereoscopic imaging and the patient position inside the open face mask was recorded using SGRT. The measurement accuracy of the SGRT system (in a "standard" and an SRS mode with higher resolution) was evaluated using both IGRT and SGRT patient positioning datasets taking into account the measurement errors of the X­ray system. Based on these clinically measured datasets, the positioning accuracy was estimated using Monte Carlo (MC) simulations. The relevant evaluation criterion, as standard of practice in cranial SRT, was the 95th percentile. RESULTS: The interfractional measurement displacement vector of the SGRT system, σSGRT, in high resolution mode was estimated at 2.5 mm (68th percentile) and 5 mm (95th percentile). If the standard resolution was used, σSGRT increased by about 20%. The standard deviation of the axis-related σSGRT of the SGRT system ranged between 1.5 and 1.8 mm interfractionally and 0.5 and 1.0 mm intrafractionally. The magnitude of σSGRT is mainly due to the principle of patient surface scanning and not due to technical limitations or vendor-specific issues in software or hardware. Based on the resulting σSGRT, MC simulations served as a measure for the positioning accuracy for non-coplanar couch rotations. If an SGRT system is used as the only patient positioning device in non-coplanar fields, interfractional positioning errors of up to 6 mm and intrafractional errors of up to 5 mm cannot be ruled out. In contrast, MC simulations resulted in a positioning error of 1.6 mm (95th percentile) using the IGRT system. The cause of positioning errors in the SGRT system is mainly a change in the facial surface relative to a defined point in the brain. CONCLUSION: In order to achieve the necessary geometric accuracy in cranial stereotactic radiotherapy, use of an X­ray-based IGRT system, especially when treating with non-coplanar couch angles, is highly recommended.

First-in-human validation of a DROP-IN ß-probe for robotic radioguided surgery: defining optimal signal-to-background discrimination algorithm.

PURPOSE: In radioguided surgery (RGS), radiopharmaceuticals are used to generate preoperative roadmaps (e.g., PET/CT) and to facilitate intraoperative tracing of tracer avid lesions. Within RGS, there is a push toward the use of receptor-targeted radiopharmaceuticals, a trend that also has to align with the surgical move toward minimal invasive robotic surgery. Building on our initial ex vivo evaluation, this study investigates the clinical translation of a DROP-IN ß probe in robotic PSMA-guided prostate cancer surgery. METHODS: A clinical-grade DROP-IN ß probe was developed to support the detection of PET radioisotopes (e.g., 68 Ga). The prototype was evaluated in 7 primary prostate cancer patients, having at least 1 lymph node metastases visible on PSMA-PET. Patients were scheduled for radical prostatectomy combined with extended pelvic lymph node dissection. At the beginning of surgery, patients were injected with 1.1 MBq/kg of [68Ga]Ga-PSMA. The ß probe was used to trace PSMA-expressing lymph nodes in vivo. To support intraoperative decision-making, a statistical software algorithm was defined and optimized on this dataset to help the surgeon discriminate between probe signals coming from tumors and healthy tissue. RESULTS: The DROP-IN ß probe helped provide the surgeon with autonomous and highly maneuverable tracer detection. A total of 66 samples (i.e., lymph node specimens) were analyzed in vivo, of which 31 (47%) were found to be malignant. After optimization of the signal cutoff algorithm, we found a probe detection rate of 78% of the PSMA-PET-positive samples, a sensitivity of 76%, and a specificity of 93%, as compared to pathologic evaluation. CONCLUSION: This study shows the first-in-human use of a DROP-IN ß probe, supporting the integration of ß radio guidance and robotic surgery. The achieved competitive sensitivity and specificity help open the world of robotic RGS to a whole new range of radiopharmaceuticals.

Molecular image-guided surgery in gynaecological cancer: where do we stand?

PURPOSE: The aim of this review is to give an overview of the current status of molecular image-guided surgery in gynaecological malignancies, from both clinical and technological points of view. METHODS: A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image-guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices. RESULTS: The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging. CONCLUSION: After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach.

Lessons learned in application driven imaging agent design for image-guided surgery.

To meet the growing demand for intraoperative molecular imaging, the development of compatible imaging agents plays a crucial role. Given the unique requirements of surgical applications compared to diagnostics and therapy, maximizing translational potential necessitates distinctive imaging agent designs. For effective surgical guidance, exogenous signatures are essential and are achievable through a diverse range of imaging labels such as (radio)isotopes, fluorescent dyes, or combinations thereof. To achieve optimal in vivo utility a balanced molecular design of the tracer as a whole is required, which ensures a harmonious effect of the imaging label with the affinity and specificity (e.g., pharmacokinetics) of a pharmacophore/targeting moiety. This review outlines common design strategies and the effects of refinements in the molecular imaging agent design on the agent's pharmacological profile. This includes the optimization of affinity, pharmacokinetics (including serum binding and target mediated background), biological clearance route, the achievable signal intensity, and the effect of dosing hereon.

Current clinical applications of Cerenkov luminescence for intraoperative molecular imaging.

BACKGROUND: Cerenkov luminescence imaging (CLI) is a new emerging technology that can be used for optical imaging of approved radiotracers, both in a preclinical, and even more recently, in a clinical context with rapid imaging times, low costs, and detection in real-time (Grootendorst et al. Clin Transl Imaging 4(5):353-66, 2016); Wang et al. Photonics 9(6):390, 2022). This brief review provides an overview of clinical applications of CLI with a focus on intraoperative margin assessment (IMA) to address shortcomings and provide insight for future work in this application. METHODS: A literature review was performed using PubMed using the search words Cerenkov luminescence imaging (CLI), intraoperative margin assessment (IMA), and image-guided surgery. Articles were selected based on title, abstract, content, and application. RESULTS: Original research was summarized to examine advantages and limitations of CLI compared to other modalities for IMA. The characteristics of Cerenkov luminescence (CL) are defined, and results from relevant clinical trials are discussed. Prospects of ongoing clinical trials are reviewed, along with technological advancements related to CLI. CONCLUSION: CLI is a proven method for molecular imaging and shows feasibility for determining intraoperative margins if future work involves establishing quantitative approaches for attenuation and scattering, depth analysis, and radiation safety for CLI at a larger scale.

New EAU/ASCO guideline recommendations on sentinel node biopsy for penile cancer and remaining challenges from a nuclear medicine perspective.

INTRODUCTION: The European Association of Urology (EAU) and the American Society of Clinical Oncology (ASCO) recently issued updated guidelines on penile cancer, emphasising dynamic sentinel node biopsy (DSNB) as the preferred method for surgical staging among patients with invasive penile tumours and no palpable inguinal lymphadenopathy. This paper outlines the rationale behind this new recommendation and describes remaining challenges, as well as strategies for promoting DSNB worldwide. MAIN TEXT: DSNB offers high diagnostic accuracy with the lowest postoperative complications compared to open or minimally invasive inguinal lymph node dissection (ILND), prompting its preference in the new guidelines. Nevertheless, despite its advantages, there are challenges hampering the widespread adoption of DSNB. This includes the false-negative rate associated with DSNB and the potential negative impact on patient outcome. To address this issue, improvements should be made in several areas, including refining the timing and interpretation of the lymphoscintigraphy and the single photon emission computed tomography/computed tomography images. In addition, the quantity of tracer employed and choice of the injection site for the radiopharmaceutical should be optimised. Finally, limiting the removal of nodes without tracer activity during surgery may help minimise complication rates. CONCLUSION: Over the years, DSNB has evolved significantly, related to the dedicated efforts and innovations in nuclear medicine and subsequent clinical studies validating its efficacy. It is now strongly recommended for surgical staging among selected penile cancer patients. To optimise DSNB further, multidisciplinary collaborative research is required to improve SN identification for better diagnostic accuracy and fewer complications.

Surgical radioguidance with beta-emitting radionuclides; challenges and possibilities: A position paper by the EANM.

Radioguidance that makes use of ß-emitting radionuclides is gaining in popularity and could have potential to strengthen the range of existing radioguidance techniques. While there is a strong tendency to develop new PET radiotracers, due to favorable imaging characteristics and the success of theranostics research, there are practical challenges that need to be overcome when considering use of ß-emitters for surgical radioguidance. In this position paper, the EANM identifies the possibilities and challenges that relate to the successful implementation of ß-emitters in surgical guidance, covering aspects related to instrumentation, radiation protection, and modes of implementation.

Increasing the Dye Payload of Cetuximab-IRDye800CW Enables Photodynamic Therapy.

Cetuximab (Cet)-IRDye800CW, among other antibody-IRDye800CW conjugates, is a potentially effective tool for delineating tumor margins during fluorescence image-guided surgery (IGS). However, residual disease often leads to recurrence. Photodynamic therapy (PDT) following IGS is proposed as an approach to eliminate residual disease but suffers from a lack of molecular specificity for cancer cells. Antibody-targeted PDT offers a potential solution for this specificity problem. In this study, we show, for the first time, that Cet-IRDye800CW is capable of antibody-targeted PDT in vitro when the payload of dye molecules is increased from 2 (clinical version) to 11 per antibody. Cet-IRDye800CW (1:11) produces singlet oxygen, hydroxyl radicals, and peroxynitrite upon activation with 810 nm light. In vitro assays on FaDu head and neck cancer cells confirm that Cet-IRDye800CW (1:11) maintains cancer cell binding specificity and is capable of inducing up to ∼90% phototoxicity in FaDu cancer cells. The phototoxicity of Cet-IRDye800CW conjugates using 810 nm light follows a dye payload-dependent trend. Cet-IRDye800CW (1:11) is also found to be more phototoxic to FaDu cancer cells and less toxic in the dark than the approved chromophore indocyanine green, which can also act as a PDT agent. We propose that antibody-targeted PDT using high-payload Cet-IRDye800CW (1:11) could hold potential for eliminating residual disease postoperatively when using sustained illumination devices, such as fiber optic patches and implantable surgical bed balloon applicators. This approach could also potentially be applicable to a wide variety of resectable cancers that are amenable to IGS-PDT, using their respective approved full-length antibodies as a template for high-payload IRDye800CW conjugation.

Image-guided high-dose-rate brachytherapy as the method of choice in medically inoperable early-stage endometrial cancer patients.

PURPOSE: About 3-9% of patients with endometrial cancer are unable to undergo surgery due to medical comorbidities, including morbid obesity, or age-related frailty syndrome. An alternative curative option is irradiation. The aim of this prospective study was to evaluate clinical outcomes of high-dose-rate intracavitary brachytherapy (HDR-ICBT) treatment in such patients. MATERIALS AND METHODS: Seventy-eight patients with FIGO stage I-II endometrial cancer disqualified from surgery were treated with HDR-ICBT with 45-52,5 Gy prescribed to high-risk clinical target volume (HR-CTV) in 5-9 fractions given once a week. All fractions were planned using computed tomography (CT) scans. RESULTS: The median follow-up time was 67 months. Median age was 79 years (range: 42-93 years). Median body mass index (BMI) was 39,1 kg/m2 (range: 24,2-68 kg/m2). We observed no statistically significant impact of BMI ≥ 40 on overall survival (OS) or prgression free survival (PFS). The 3- and 5-year OS for the whole population were 69% and 55%, respectively. The impact of high risk features (FIGO II, grade 3 or type 2 cancer) on OS was significant (p = 0,049). The 5-year cumulative incidence of local failure, distant metastases and non-cancer death were 12,9% [95% CI: 5,4%-20,5%], 6,4% [95% CI: 0,9%-11,9%], 33,1% [95% CI: 22,3%-43,9%], respectively. The 5-year risk of cancer and non-cancer death were 9% (95% CI: 3%-16%) and 36% (95% CI: 25%-47%), respectively. We observed G1 vaginal apex stenosis only. CONCLUSIONS: CT-guided HDR-ICBT is a feasible and safe management of FIGO stage I endometrial cancer in obese and elderly patients. The survival outcome of the treated group is influenced more by associated comorbidities than by the progression of endometrial cancer.

Focal therapy with high-intensity focused ultrasound for prostate cancer: 3-year outcomes from a prospective trial.

OBJECTIVE: To assess the oncological and functional outcomes of focal high-intensity focused ultrasound (HIFU) in treating localised prostate cancer (PCa), a 3-year prospective study was undertaken using periodic post-ablation saturation biopsies. PATIENTS AND METHODS: Men with two or fewer lesions of grade group (GG) ≤3 PCa were eligible for participation. Additional criteria included a prostate-specific antigen (PSA) level of ≤15 ng/mL, clinical T1c-T2, and a life expectancy of ≥10 years. The primary endpoint was failure-free survival (FFS), defined as absence of clinically significant PCa (csPCa) in- or out-of-field on protocol-mandated saturation biopsy, no whole-gland or systemic salvage treatment, PCa metastasis, or PCa-related death. Results are reported using two distinct definitions of csPCa: (i) the presence of any GG ≥2 and (ii) any GG ≥3 or core involvement of ≥6 mm. Secondary endpoints were functional patient-reported outcome measures addressing urinary, sexual, and bowel function. RESULTS: A total of 91 patients were included: six (7%) with GG1 and 85 (93%) with GG ≥2. In all, 83 (91%) underwent at least one follow-up biopsy. Biopsy attendance at 6, 12, and 36 months was 84%, 67%, and 51%, respectively. The FFS at these time points for any GG ≥2 PCa was 79% (95% confidence interval [CI] 80-88%), 57% (95% CI 48-69%) and 44% (95% CI 34-56%), respectively. Using the second definition, FFS were 88% (95% CI 81-95%), 70% (95% CI 61-81%) and 65% (95% CI 55-77%), respectively. The 3-year cancer-specific survival was 100%, and freedom from metastasis was 99%. Magnetic resonance imaging (MRI) (negative predictive value of up to 89%, 95% CI 84-93%) and relative decrease of PSA values (P = 0.4) performed poorly in detecting residual disease. Urinary and bowel assessment returned to baseline questionnaire scores within 3 months. In all, 17 (21%) patients reported meaningful worsening in erectile function. A significant decrease of PCa related anxiety was observed. CONCLUSIONS: Focal HIFU treatment for localised PCa shows excellent functional outcomes with half of the patients remaining cancer-free after 3 years. Whole-gland treatment was avoided in 81%. Early follow-up biopsies are crucial to change or continue the treatment modality at the right time, while the use of MRI and PSA in detecting PCa recurrence is uncertain.