Organic Alternatives to Quantum Dots for Intraoperative Near-Infrared Fluorescent Sentinel Lymph Node Mapping:

Intraoperative near-infrared (NIR) fluorescence imaging provides the surgeon with real-time image guidance during cancer and other surgeries. We have previously reported the use of NIR fluorescent quantum dots (QDs) for sentinel lymph node (SLN) mapping. However, because of concerns over potential toxicity, organic alternatives to QDs will be required for initial clinical studies. We describe a family of 800 nm organic heptamethine indocyanine-based contrast agents for SLN mapping spanning a spectrum from 775 Da small molecules to 7 MDa nanocolloids. We provide a detailed characterization of the optical and physical properties of these contrast agents and discuss the advantages and disadvantages of each. We present robust methods for the covalent conjugation, purification, and characterization of proteins with tetra-sulfonated heptamethine indocyanines, including mass spectroscopic site mapping of highly substituted molecules. One contrast agent, NIR fluorescent human serum albumin (HSA800), emerged as the molecule with the best overall performance with respect to entry to lymphatics, flow to the SLN, retention in the SLN, fluorescence yield and reproducibility. This preclinical study, performed on large animals approaching the size of humans, should serve as a foundation for future clinical studies. Mol Imaging (2005) 4, 172 – 181

Survival Outcomes After High-dose Chemotherapy and Stem Cell Transplantation in the Salvage Setting for Relapsed or Refractory Germ Cell Cancers

© 2020 The Author(s). The unrestricted non-commercial use, distribution and reproduction in any medium of CGP articles for academic reasons is allowed, provided that the original work is properly cited.Background/Aim: High-dose chemotherapy (HDCT) and stem cell transplantation (SCT) have been established as the standard of care in patients with relapsed germ cell tumours (GCTs). We evaluated the safety, efficacy and tolerability of HDCT/ SCT in patients with relapsed GCTs. Patients and Methods: Twenty-eight patients with relapsed GCTs, treated with HDCT, were included in this study. The conditioning regime was carboplatin, etoposide, cyclophosphamide and paclitaxel. Clinical, radiological imaging and tumour markers determined treatment outcomes. Results: Median age was 35 years (range=21-57 years) with 26 males and 2 females. Median time to first relapse was 6 months. Median time to progression after 2nd line chemotherapy was 17.3 months. Fourteen patients had peripheral neurotoxicity (≥Grade 2) (50%), 4 patients developed renal failure, 5 had ototoxicity (≥Grade 2) and 1 patient developed acute myeloid leukaemia. Median survival was 62 months and 16 patients (57%) are in clinical follow-up with surveillance. Conclusion: In relapsed GCT patients, median survival may exceed 5 years post-HDCT and SCT.Peer reviewe

A North-West London Experience of the Impact of Treatment Related Toxicity on Clinical Outcomes of Elderly Patients with Germ Cell Tumors

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)Simple Summary: Germ cell testicular cancer is seen in men aged 15–35. Incidence of this cancer in the elderly aged > 45 is less than 10%. The aim of our retrospective study is to understand the treatment-related toxicity in the elderly population, the chemotherapy regimens used, and its tolerability in this age group. Incidence of non-seminomatous germ cell cancer was 42% and incidence of seminoma was 58% in this cohort of patients. We used chemotherapy regimens, similar to those used in the younger population; platinum-based regimens were the backbone of the treatment algorithm. Outcomes were similar to the population group aged 15–35, and around 96% of the population were alive 5 years after and beyond. Toxicity was more common in this age group, and careful consideration should be made for dose modification and appropriate use of supportive therapies. Abstract: Background/Aim: The occurrence of germ cell tumour (GCT) in the elderly is rare, with scarce data available. The aim of this study was to understand the clinical outcomes of patients with GCT in patients aged > 45 years. Materials and Methods: A retrospective study was conducted in a large tertiary cancer centre in north-west London. Between 1 January 2003 and 31 March 2022, 108 cases of GCT in men aged > 45 years were identified and treated at the Mount Vernon Cancer Centre. The median age at diagnosis was 54 years (range = 45–70 years). Results: The 5-year survival rate of all patients was 96%, and the toxicity profile was similar to the younger age group. Conclusion: Older patients with GCT are able to tolerate chemotherapy; however, care must be taken to prevent life-threatening complications using appropriate dose modification.Peer reviewe

Comparison of whole-body MRI, CT, and bone scintigraphy for response evaluation of cancer therapeutics in metastatic breast cancer to bone

In participants receiving systemic anticancer therapy for bone-only metastatic breast cancer, whole-body MRI enabled identification of progressive disease earlier than whole-body CT and bone scintigraphy. Background CT and bone scintigraphy have limitations in evaluating systemic anticancer therapy (SACT) response in bone metastases from metastatic breast cancer (MBC). Purpose To evaluate whether whole-body MRI enables identification of progressive disease (PD) earlier than CT and bone scintigraphy in bone-only MBC. Materials and Methods This prospective study evaluated participants with bone-only MBC between May 2016 and January 2019 (ClinicalTrials.gov identifier: NCT03266744). Participants were enrolled at initiation of first or subsequent SACT based on standard CT and bone scintigraphy imaging. Baseline whole-body MRI was performed within 2 weeks of entry; those with extraosseous disease were excluded. CT and whole-body MRI were performed every 12 weeks until definitive PD was evident with one or both modalities. In case of PD, bone scintigraphy was used to assess for bone disease progression. Radiologists independently interpreted images from CT, whole-body MRI, or bone scintigraphy and were blinded to results with the other modalities. Systematic differences in performance between modalities were analyzed by using the McNemar test. Results Forty-five participants (mean age, 60 years ± 13 [standard deviation]; all women) were evaluated. Median time on study was 36 weeks (range, 1–120 weeks). Two participants were excluded because of unequivocal evidence of liver metastases at baseline whole-body MRI, two participants were excluded because they had clinical progression before imaging showed PD, and one participant was lost to follow-up. Of the 33 participants with PD at imaging, 67% (22 participants) had PD evident at whole-body MRI only and 33% (11 participants) had PD at CT and whole-body MRI concurrently; none had PD at CT only (P < .001, McNemar test). There was only slight agreement between whole-body MRI and CT (Cohen κ, 0.15). PD at bone scintigraphy was reported in 50% of participants (13 of 26) with bone progression at CT and/or whole-body MRI (P < .001, McNemar test). Conclusion Whole-body MRI enabled identification of progressive disease before CT in most participants with bone-only metastatic breast cancer. Progressive disease at bone scintigraphy was evident in only half of participants with bone progression at whole-body MRI

Secondary Neoplasms of the Urinary Bladder-Clinical Management and Oncological Outcomes

© Translational Andrology and Urology. All rights reserved.Background: Secondary neoplasms of the bladder account for 4.5% of all bladder neoplasms however there is limited literature reporting management and survival. This is the largest single centre series presented in current literature with long term oncological follow up. Methods: This is a single institutional, retrospective cohort study of patients with a histological diagnosis of a secondary bladder neoplasm from January 2007- December 2017 (n=40). Prognostic variables examined included age at diagnosis, histology, disease free survival and treatment. Kaplan-Meier analysis was used to calculate survival. We used multiple regression analysis to identify the most significant treatments for each population group in terms of their survival. Results: 21 patients were male [53%] with a median age of 68 and 19 were female [47%] with a median age of 64. The most common secondary neoplasms and their median survival were prostate (12 patients [30%], 446 days), colorectal (9 patients [23%], 403 days), ovarian (5 patients [13%], 369 days), cervical (4 patients [10%], 148 days), breast (3 patients [8%], 241 days) lymphoma (3 patients [8%], 145 days), Gastric (2 patients [5%], 66 days), and renal (2 patients [5%], 854 days). Those receiving treatment following a secondary diagnosis demonstrated statistical significance in survival for colorectal (surgery p=0.013), prostate (radiotherapy p=0.0012 and hormonal therapy p=0.004) and ovarian cancer (chemotherapy p=0.00002). Conclusion: Prognosis and treatment depends upon the primary neoplasm. There is some survival benefit in well selected patients receiving treatment following a diagnosis of a bladder secondary.Peer reviewe

Organic Alternatives to Quantum Dots for Intraoperative Near-Infrared Fluorescent Sentinel Lymph Node Mapping

Intraoperative near-infrared (NIR) fluorescence imaging provides the surgeon with real-time image guidance during cancer and other surgeries. We have previously reported the use of NIR fluorescent quantum dots (QDs) for sentinel lymph node (SLN) mapping. However, because of concerns over potential toxicity, organic alternatives to QDs will be required for initial clinical studies. We describe a family of 800 nm organic heptamethine indocyanine-based contrast agents for SLN mapping spanning a spectrum from 775 Da small molecules to 7 MDa nanocolloids. We provide a detailed characterization of the optical and physical properties of these contrast agents and discuss the advantages and disadvantages of each. We present robust methods for the covalent conjugation, purification, and characterization of proteins with tetra-sulfonated heptamethine indocyanines, including mass spectroscopic site mapping of highly substituted molecules. One contrast agent, NIR fluorescent human serum albumin (HSA800), emerged as the molecule with the best overall performance with respect to entry to lymphatics, flow to the SLN, retention in the SLN, fluorescence yield and reproducibility. This preclinical study, performed on large animals approaching the size of humans, should serve as a foundation for future clinical studies