Dexamethasone is a glucocorticoid steroid with anti-inflammatory properties used to treat many diseases, including cancer, in which it helps manage various side effects of chemo-, radio-, and ...immunotherapies. Here, we investigate the tumor microenvironment (TME)-normalizing effects of dexamethasone in metastatic murine breast cancer (BC). Dexamethasone normalizes vessels and the extracellular matrix, thereby reducing interstitial fluid pressure, tissue stiffness, and solid stress. In turn, the penetration of 13 and 32 nm dextrans, which represent nanocarriers (NCs), is increased. A mechanistic model of fluid and macromolecule transport in tumors predicts that dexamethasone increases NC penetration by increasing interstitial hydraulic conductivity without significantly reducing the effective pore diameter of the vessel wall. Also, dexamethasone increases the tumor accumulation and efficacy of ∼30 nm polymeric micelles containing cisplatin (CDDP/m) against murine models of primary BC and spontaneous BC lung metastasis, which also feature a TME with abnormal mechanical properties. These results suggest that pretreatment with dexamethasone before NC administration could increase efficacy against primary tumors and metastases.
Intravital multiphoton microscopy has provided powerful mechanistic insights into health and disease and has become a common instrument in the modern biological laboratory. The requisite high ...numerical aperture and exogenous contrast agents that enable multiphoton microscopy, however, limit the ability to investigate substantial tissue volumes or to probe dynamic changes repeatedly over prolonged periods. Here we introduce optical frequency domain imaging (OFDI) as an intravital microscopy that circumvents the technical limitations of multiphoton microscopy and, as a result, provides unprecedented access to previously unexplored, crucial aspects of tissue biology. Using unique OFDI-based approaches and entirely intrinsic mechanisms of contrast, we present rapid and repeated measurements of tumor angiogenesis, lymphangiogenesis, tissue viability and both vascular and cellular responses to therapy, thereby demonstrating the potential of OFDI to facilitate the exploration of physiological and pathological processes and the evaluation of treatment strategies.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Radiation and Melanoma: Where Are We Now? Bliley, Roy; Avant, Adam; Medina, Theresa M ...
Current oncology reports,
2024-Jun-01, 2024-06-01, 20240601
Journal Article
Recenzirano
This review summarizes the current role of radiotherapy for the treatment of cutaneous melanoma in the definitive, adjuvant, and palliative settings, and combinations with immunotherapy and targeted ...therapies.
Definitive radiotherapy may be considered for lentigo maligna if surgery would be disfiguring. High risk, resected melanoma may be treated with adjuvant radiotherapy, but the role is poorly defined since the advent of effective systemic therapies. For patients with metastatic disease, immunotherapy and targeted therapies can be delivered safely in tandem with radiotherapy to improve outcomes. Radiotherapy and modern systemic therapies act in concert to improve outcomes, especially in the metastatic setting. Further prospective data is needed to guide the use of definitive radiotherapy for lentigo maligna and adjuvant radiotherapy for high-risk melanoma in the immunotherapy era. Current evidence does not support an abscopal response or at least identify the conditions necessary to reliably produce one with combinations of radiation and immunotherapy.
Delivery of blood-borne molecules and nanoparticles from the vasculature to cells in the tissue differs dramatically between tumor and normal tissues due to differences in their vascular ...architectures. Here we show that two simple measures of vascular geometry—δ max and λ—readily obtained from vascular images, capture these differences and link vascular structure to delivery in both tissue types. The longest time needed to bring materials to their destination scales with the square of δ max , the maximum distance in the tissue from the nearest blood vessel, whereas λ, a measure of the shape of the spaces between vessels, determines the rate of delivery for shorter times. Our results are useful for evaluating how new therapeutic agents that inhibit or stimulate vascular growth alter the functional efficiency of the vasculature and more broadly for analysis of diffusion in irregularly shaped domains.
To characterize practice patterns, including temporal trends, in fractionation schedules among patients in the United States undergoing definitive radiation therapy for early-stage glottic cancer and ...to compare overall survival outcomes between fractionation schedules.
We queried the National Cancer Database for patients with TisN0M0, T1N0M0, or T2N0M0 squamous cell carcinoma of the glottic larynx diagnosed between 2004 and 2012 and undergoing definitive radiation therapy. Dose per fraction was calculated to define cohorts undergoing conventional fractionation (CFxn) and hypofractionation (HFxn). Logistic regression was performed to identify predictors of receiving HFxn, and Cox regression was used to determine predictors of death. One-to-one propensity score matching was then used to compare survival between fractionation schedules.
The study included 10,539 patients, with 6576 undergoing CFxn and 3963 undergoing HFxn. Patients with T1 disease comprised a majority of each cohort. Use of HFxn increased significantly over the period studied (P<.001), but even in the final year, nearly one-half of patients continued to receive CFxn. Receipt of HFxn was also independently associated with higher income and facility types other than community cancer programs on logistic regression. On multivariate Cox regression, HFxn was associated with improved survival (hazard ratio HR for death, 0.90; 95% confidence interval CI, 0.83-0.97; P=.008), a finding redemonstrated on univariate Cox regression among a well-matched cohort after propensity score matching (HR, 0.88; 95% CI, 0.80-0.96; P=.003). Subgroup Cox multivariate analysis demonstrated a significant survival advantage with HFxn among patients with T1 disease (HR, 0.90; 95% CI, 0.81-0.99; P=.042) but a nonsignificant benefit among those with Tis (HR, 0.86; 95% CI, 0.57-1.30; P=.472) or T2 (HR, 0.88; 95% CI, 0.76-1.02; P=.099) disease.
Use of HFxn is increasing and is associated with improved survival over CFxn. Our findings support the broadened use of HFxn for patients with early-stage glottic cancer undergoing definitive radiation therapy.
Abstract Background and purpose Radiotherapy (RT) to the primary nasopharyngeal tumor is frequently offered to patients with metastatic nasopharyngeal carcinoma (mNPC). However, only limited data ...exist to support RT in this setting. We used the National Cancer Database (NCDB) to evaluate outcomes for mNPC patients receiving chemotherapy with and without local RT. Methods The NCDB was queried for patients with mNPC with synchronous metastatic disease at diagnosis who received chemotherapy. Overall survival (OS) was analyzed using the Kaplan–Meier method, Cox proportional hazards models, and propensity score-matched analyses. Results From 2004 to 2013, 718 cases were identified (39% chemotherapy-alone, 61% chemotherapy + RT). At a median follow-up of 4.4 years, RT was associated with improved survival on univariate analysis (median OS 21.4 vs 15.5 months; 5-year OS 28% vs 10%; p < 0.001) and multivariate analyses (HR, 0.61; CI, 0.51–0.74; p < 0.001). Propensity score analysis with matched baseline characteristics demonstrated a similar OS advantage with RT (HR, 0.68; CI, 0.55–0.84; p < 0.001). The benefits of RT remained consistent in models controlling for single vs multi-organ metastases and anatomic sites of metastatic involvement. RT dose was an independent prognostic factor as both a continuous and categorical variable, with OS benefits observed among patients receiving ≥50 Gy. Long-term survival of >10 years was only observed in the RT cohort. Conclusions This analysis supports strategies incorporating local RT with chemotherapy for mNPC. Prospective trials evaluating RT integration for mNPC are warranted.
Abstract
BACKGROUND
Recurrence rates for atypical and anaplastic meningiomas range between 9% and 50% after gross total resection and between 36% and 83% after subtotal resection. Optimal treatment ...of recurrent meningiomas exhibiting atypical/anaplastic histology is complicated because they are often refractory to both surgery and radiation.
OBJECTIVE
To evaluate clinical determinants of recurrence and treatment-specific outcomes in patients with recurrent meningiomas exhibiting atypical/anaplastic histology at our institution.
METHODS
A cohort study was conducted using clinical data of all patients treated for meningiomas with atypical/anaplastic histology at first recurrence between January 1985 and July 2014 at a tertiary cancer center. Predictors of second recurrence were analyzed using competing risks regression models.
RESULTS
Nine hundred eighteen patients with meningioma were screened, of whom 60 (55% female) had recurrent disease with atypical/anaplastic histology at a median age of 58.1 yr at diagnosis. The median follow-up from the time of first recurrence was 36.7 mo, with 32 (53%) patients alive at last follow-up. There was no effect of extent of resection at first recurrence on time to a subsequent recurrence. Inclusion of radiation as primary or adjuvant therapy at first recurrence reduced the risk of progression or subsequent recurrence compared to surgery alone (P = .07).
CONCLUSION
Treatment of recurrent meningiomas with atypical/anaplastic histology remains challenging. Our data, from one of the largest cohorts, suggest better tumor control with the addition of radiation and challenges the importance of extent of resection at first recurrence. A multicenter effort is needed to confirm these findings and propose treatment guidelines.
To report a small substudy of an ongoing large, multi-arm study using functional imaging to assess pre-/intratreatment hypoxia for all head and neck cancer, in which we hypothesized that pre- and ...early-treatment hypoxia assessment using functional positron emission tomography (PET) imaging may help select which human papillomavirus (HPV)-positive (HPV(+)) oropharyngeal cancer (OPC) patients can safely receive radiation de-escalation without jeopardizing treatment outcomes.
Patients with HPV(+) oropharyngeal carcinoma were enrolled on an institutional review board-approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment (18)F-fluorodeoxyglucose and dynamic (18)F-FMISO (fluoromisonidazole) positron emission tomography (PET) scans were performed. For patients with pretreatment hypoxia on(18)F-FMISO PET (defined as a >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done 1 week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis-free, and overall survival rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image guidance.
Thirty-three HPV(+) OPC patients were enrolled in this pilot study. One hundred percent showed pretreatment hypoxia (at primary site and/or nodes), and among these, 48% resolved (at primary site and/or nodes); 30% met criteria and received 10-Gy reduction to the lymph node(s). At the median follow-up of 32 months (range, 21-61 months), the 2-year locoregional control rate was 100%. One patient failed distantly with persistence of hypoxia on (18)F-FMISO PET. The 2-year distant metastasis-free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically.
Hypoxia is present in HPV(+) tumors but resolves within 1 week of treatment in 48% of cases either at the primary site and/or lymph node(s). Our 100% locoregional control rate suggests that intratreatment functional imaging used to selectively de-escalate node(s) to 60 Gy was confirmed safe using our stringent imaging criteria. Intratreatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.
Highlights • We reviewed our experience with the RTOG 8502 regimen for incurable head and neck cancers. • Overall palliative response: 65%. • Grade 3 toxicity in 5% of patients, most commonly ...mucositis. • Greater number of RT cycles correlated with higher palliative response and survival.
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