Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials

Clarke, Mike; Collins, Rory; Darby, Sarah C.; Davies, Christina; Elphinstone, P; Evans, Vaughan; Godwin, Jon; Gray, Richard; Hicks, Chindo; James, Sam; MacKinnon, Elizabeth; McGale, Paul; McHugh, Theresa; Pető, Richárd; Taylor, Carolyn; Wang, X

doi:10.1016/s0140-6736(05)67887-7

Cited by 4,382 publications

(1,065 citation statements)

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“…These micrometastases can then grow into overt metastatic disease at distant sites, 56 and adjuvant chemotherapy is intended to eliminate microscopically seeded cells. Distant recurrence rates for breast cancer are still between 20–30%, 57 indicating the need for better therapies to kill previously seeded micrometastases. Our previous work revealed that host RON signaling suppressed anti-tumor CD8+ T-cell responses, allowing metastatic outgrowth of seeded tumor cells, but RON inhibitor therapy did not completely prevent outgrowth.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of RON kinase potentiates anti-CTLA-4 immunotherapy to shrink breast tumors and prevent metastatic outgrowth

et al. 2018

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The advent of immune checkpoint blockade as a new strategy for immunotherapy has changed the outlook for many aggressive cancers. Although complete tumor eradication is attainable in some cases, durable clinical responses are observed only in a small fraction of patients, underlining urgent need for improvement. We previously showed that RON, a receptor tyrosine kinase expressed in macrophages, suppresses antitumor immune responses, and facilitates progression and metastasis of breast cancer. Here, we investigated the molecular changes that occur downstream of RON activation in macrophages, and whether inhibition of RON can cooperate with checkpoint immunotherapy to eradicate tumors. Activation of RON by its ligand, MSP, altered the gene expression profile of macrophages drastically and upregulated surface levels of CD80 and PD-L1, ligands for T-cell checkpoint receptors CTLA-4 and PD-1. Genetic deletion or pharmacological inhibition of RON in combination with anti-CTLA-4, but not with anti-PD-1, resulted in improved clinical responses against orthotopically transplanted tumors compared to single-agent treatment groups, resulting in complete tumor eradication in 46% of the animals. Positive responses to therapy were associated with higher levels of T-cell activation markers and tumor-infiltrating lymphocytes. Importantly, co-inhibition of RON and anti-CTLA-4 was also effective in clearing metastatic breast cancer cells in lungs, resulting in clinical responses in nearly 60% of the mice. These findings suggest that RON inhibition can be a novel approach to potentiate responses to checkpoint immunotherapy in breast cancer.

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Section: Resultsmentioning

confidence: 99%

Inhibition of RON kinase potentiates anti-CTLA-4 immunotherapy to shrink breast tumors and prevent metastatic outgrowth

et al. 2018

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“…Adjuvant radiotherapy (RT) for breast cancer is a standard treatment used to improve local tumor control and overall survival 1, 2, 3, 4. Volumetric modulated arc therapy (VMAT) has been evaluated for breast treatment in several publications as attested in a recent review 5.…”

Section: Introductionmentioning

confidence: 99%

Safety and benefit of using a virtual bolus during treatment planning for breast cancer treated with arc therapy

Tyran

Tallet

Resbeut

et al. 2018

J Applied Clin Med Phys

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PurposeThis study evaluates the benefit of a virtual bolus method for volumetric modulated arc therapy (VMAT) plan optimization to compensate breast modifications that may occur during breast treatment.MethodsTen files were replanned with VMAT giving 50 Gy to the breast and 47 Gy to the nodes within 25 fractions. The planning process used a virtual bolus for the first optimization, then the monitors units were reoptimized without bolus, after fixing the segments shapes. Structures and treatment planning were exported on a second scanner (CT) performed during treatment as a consequence to modifications in patient's anatomy. The comparative end‐point was clinical target volume's coverage. The first analysis compared the VMAT plans made using the virtual bolus method (VB‐VMAT) to the plans without using it (NoVB‐VMAT) on the first simulation CT. Then, the same analysis was performed on the second CT. Finally, the level of degradation of target volume coverage between the two CT using VB‐VMAT was compared to results using a standard technique of forward‐planned multisegment technique (Tan‐IMRT).ResultsUsing a virtual bolus for VMAT does not degrade dosimetric results on the first CT. No significant result in favor of the NoVB‐VMAT plans was noted. The VB‐VMAT method led to significant better dose distribution on a second CT with modified anatomies compared to NoVB‐VMAT. The clinical target volume's coverage by 95% (V95%) of the prescribed dose was 98.9% [96.1–99.6] on the second CT for VB‐VMAT compared to 92.6% [85.2–97.7] for NoVB‐VMAT (P = 0.0002). The degradation of the target volume coverage for VB‐VMAT is not worse than for Tan‐IMRT: the median differential of V95% between the two CT was 0.9% for VMAT and 0.7% for Tan‐IMRT (P = 1).ConclusionThis study confirms the safety and benefit of using a virtual bolus during the VMAT planning process to compensate potential breast shape modifications.

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“…Previous studies have shown a strong correlation between the irradiated cardiac volume with cardiac mortality, (1) and the irradiated lung volume associated with functional lung damage (2) . Meta analyses have shown cardiac deaths following breast radiotherapy are associated with the volume of the heart receiving dose in excess of 5 Gy (3) . Cardiac toxicity may be exacerbated during radiation therapy to the left breast or chest wall (4) .…”

Section: Introductionmentioning

confidence: 99%

Translucent poly(vinyl alcohol) cryogel dosimeters for simultaneous dose buildup and monitoring during chest wall radiation therapy

Eyadeh

Weston

Juhász

et al. 2016

J Applied Clin Med Phys

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Chest wall radiation therapy treatment delivery was monitored using a 5 mm thick radiochromic poly(vinyl alcohol) cryogel that also provided buildup material. The cryogels were used to detect positioning errors and measure the impact of shifts for a chest wall treatment that was delivered to a RANDO phantom. The phantom was shifted by ±2,±3, and ±5 mm from the planned position in the anterior/posterior (A/P) direction; these shifts represent setup errors and the uncertainty associated with lung filling during breath‐hold. The two‐dimensional absolute dose distributions measured in the cryogel at the planned position were compared with the distributions at all shifts from this position using gamma analysis (3%/3 mm, 10% threshold). For shifts of ±2,±3, and ±5 mm the passing rates ranged from 94.3% to 95.6%, 74.0% to 78.8%, and 17.5% to 22.5%, respectively. These results are consistent with the same gamma analysis performed on dose planes calculated in the middle of the cryogel and on the phantom surface using our treatment planning system, which ranged from 94.3% to 95.0%, 76.8% to 77.9%, and 23.5% to 24.3%, respectively. The Pinnacle dose planes were then scaled empirically and compared to the cryogel measurements. Using the same gamma metric, the pass rates ranged from 97.0% to 98.4%. The results of this study suggest that cryogels may be used as both a buildup material and to evaluate errors in chest wall treatment positioning during deep‐inspiration breath‐hold delivery. The cryogels are sensitive to A/P chest wall shifts of less than 3 mm, which potentially allows for the detection of clinically relevant errors.PACS number(s): 87.55.km, 87.57.uq

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Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials

Cited by 4,382 publications

References 32 publications

Inhibition of RON kinase potentiates anti-CTLA-4 immunotherapy to shrink breast tumors and prevent metastatic outgrowth

Inhibition of RON kinase potentiates anti-CTLA-4 immunotherapy to shrink breast tumors and prevent metastatic outgrowth

Safety and benefit of using a virtual bolus during treatment planning for breast cancer treated with arc therapy

Translucent poly(vinyl alcohol) cryogel dosimeters for simultaneous dose buildup and monitoring during chest wall radiation therapy

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