Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, ...and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454‐489.
Background
The purpose of this study is to evaluate the tolerability of hypofractionated helical tomotherapy (HT) in the treatment of localized prostate cancer.
Materials and methods
We evaluated 48 ...patients with primary adenocarcinoma of the prostate (cT1-T3N0M0) who were treated with hypofractionated HT from August 2008 through July 2011. Hypofractionated regimens included: 68.04 Gy at 2.52 Gy/fraction, 70 Gy at 2.5 Gy/fraction, and 70.2 Gy at 2.6 Gy/fraction. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system.
Results
Thirty-two patients were treated with 68.04 Gy, 5 patients with 70 Gy, and 11 with 70.2 Gy. The median age at diagnosis was 69 years (range 49–87) and the median follow-up 11 months (range 7–40). Grade 2 acute GI toxicity occurred in 9 patients (19 %). No grade 3 or higher acute GI toxicity was observed. Grade 2 and 3 acute GU toxicities occurred in 19 and 6 % of patients, respectively. The incidence of late grade 2 GI and GU toxicity was 4 and 2 %, respectively. No grade 3 or higher late toxicities were observed. Multivariate analysis showed that patients treated at 2.6 Gy/fraction or those who received a total radiation dose ≥70 Gy had higher rates of grade ≥2 acute GU toxicity (
P
= 0.004 and
P
= 0.048, respectively).
Conclusion
Hypofractionated HT in the treatment of localized prostate cancer is well tolerated with no grade 3 or higher early or late GI and GU toxicities. Further research is needed to assess definitive late toxicity and tumor control.
Abstract
This is an interim report on a first in human Phase I dose escalation trial of the combination of two adenoviral vectors expressing HSV1-TK or Flt3L for the treatment of newly diagnosed, ...resectable malignant gliomas. Lack of dendritic cells from the brain precludes anti-glioma immune responses. We combined tumor cytotoxicity (Ad-HSV1TK) with recruitment of dendritic cells to gliomas (Ad-Flt3L) to induce anti-glioma immunity. In experimental models this treatment induces powerful cytotoxic CD8 and CD4 T-dependent anti-glioma immunity, immunological memory, and the capacity to recognize neo-antigens. The trial was approved through a FDA-IND, and all institutional cttees. Treatment was administered intraoperatively following complete glioma resection in newly diagnosed tumors. The trial consisted of vector dose escalation, starting at 1x10^9 v.p., and increasing to 1x10^11 v.p. of each vector, through 6 cohorts of 3 patients each. Two cycles of 14 days of valacyclovir were administered to activate HSV1-TK cytotoxicity. Cycle 1 starts on Day 1–3 post surgery for 14 days, and Cycle 2 on Week 8–12. Standard radiation, i.e., 60 Gy in 2 Gy fractions over 6 weeks, with concurrent temozolomide, was followed by cyclic temozolomide. Examination of tumor samples at primary resection and first recurrence show an increase in the infiltration of inflammatory cells. The experimental treatment was well tolerated. An MTD was not reached. There were approx. 248 AEs, and 26 SAEs; these were not linked to treatment. As secondary outcome, median survival of contemporary controls was 604 days, and median survival of trial patients was 742 days. Our results show for the first time that reprogramming of the host’s brain immune system to recognize gliomas reveals a new approach for the treatment of highly malignant brain tumors. Clinical trial information: NCT01811992.
To provide a scoping review of the economic burden of non-cancerous genitourinary conditions (NCGUC).
A scoping review of the economic costs associated with NCGUC was conducted for literature ...published between 1990-2020. The articles were screened and relevant articles were selected for review. These articles were abstracted with information pertaining to the costs surrounding NCGUC. A descriptive analysis of the data was conducted.
We found 3,298 articles in our scoping review. Of these, we found 39 relevant articles related to pelvic floor dysfunction and pelvic organ prolapse, interstitial cystitis, neurogenic bladder, nocturia, urinary tract infections, urolithiasis, urinary incontinence, benign prostatic hyperplasia, overactive bladder, and erectile dysfunction of which the data was reviewed.
Although the data in estimating the economic burden is limited, existing evidence demonstrates a significant component of health care spending on NCGUC. Much of the spending is out-of-pocket and indirect costs that are difficult to measure which may increase the magnitude of the costs. There is a need for future research that takes a holistic look at the economic impact of NCGUC.
To provide a conceptual framework to guide investigations into burdens of noncancerous genitourinary conditions (NCGUCs), which are extensive and poorly understood.
The National Institute of Diabetes ...and Digestive and Kidney Diseases convened a workshop of diverse, interdisciplinary researchers and health professionals to identify known and hidden burdens of NCGUCs that must be measured to estimate the comprehensive burden. Following the meeting, a subgroup of attendees (authors of this article) continued to meet to conceptualize burden.
The Hidden Burden of Noncancerous Genitourinary Conditions Framework includes impacts across multiple levels of well-being and social ecology, including individual (ie, biologic factors, lived experience, behaviors), interpersonal (eg, romantic partners, family members), organizational/institutional (eg, schools, workplaces), community (eg, public restroom infrastructure), societal (eg, health care and insurance systems, national workforce/economic output), and ecosystem (eg, landfill waste) effects. The framework acknowledges that NCGUCs can be a manifestation of underlying biological dysfunction, while also leading to biological impacts (generation and exacerbation of health conditions, treatment side effects).
NCGUCs confer a large, poorly understood burden to individuals and society. An evidence-base to describe the comprehensive burden is needed. Measurement of NCGUC burdens should incorporate multiple levels of well-being and social ecology, a life course perspective, and potential interactions between NCGUCs and genetics, sex, race, and gender. This approach would elucidate accumulated impacts and potential health inequities in experienced burdens. Uncovering the hidden burden of NCGUCs may draw attention and resources (eg, new research and improved treatments) to this important domain of health.
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