We compared two intensity-modulated radiotherapy techniques for left-sided breast treatment, involving lymph node irradiation including the internal mammary chain. Inverse planned arc-therapy (VMAT) was compared with a forward-planned multi-segment technique with a mono-isocenter (MONOISO). Ten files were planned per technique, delivering a 50-Gy dose to the breast and 46.95 Gy to nodes, within 25 fractions. Comparative endpoints were planning target volume (PTV) coverage, dose to surrounding structures, and treatment delivery time. PTV coverage, homogeneity and conformality were better for two arc VMAT plans; V95%PTV-T was 96% for VMAT vs 89.2% for MONOISO. Homogeneity index (HI)PTV-T was 0.1 and HIPTV-N was 0.1 for VMAT vs 0.6 and 0.5 for MONOISO. Treatment delivery time was reduced by a factor of two using VMAT relative to MONOISO (84 s vs 180 s). High doses to organs at risk were reduced (V30left lung = 14% using VMAT vs 24.4% with MONOISO; dose to 2% of the volume (D2%)heart = 26.1 Gy vs 32 Gy), especially to the left coronary artery (LCA) (D2%LCA = 34.4 Gy vs 40.3 Gy). However, VMAT delivered low doses to a larger volume, including contralateral organs (mean dose [Dmean]right lung = 4 Gy and Dmeanright breast = 3.2 Gy). These were better protected using MONOISO plans (Dmeanright lung = 0.8 Gy and Dmeanright breast = 0.4 Gy). VMAT improved PTV coverage and dose homogeneity, but clinical benefits remain unclear. Decreased dose exposure to the LCA may be clinically relevant. VMAT could be used for complex treatments that are difficult with conventional techniques. Patient age should be considered because of uncertainties concerning secondary malignancies.
PURPOSE: Magnetic resonance–guided radiation therapy (MRgRT) has recently become commercially available, offering the opportunity to accurately image and target moving tumors as compared with computed tomography-guided radiation therapy (CTgRT) systems. However, the costs of delivering care with these 2 modalities remain poorly described. With localized unresectable hepatocellular carcinoma as an example, we were able to use time-driven activity-based costing to determine the cost of treatment on linear accelerators with CTgRT compared with MRgRT. MATERIALS AND METHODS: Process maps, informed via interviews with departmental personnel, were created for each phase of the care cycle. Stereotactic body radiation therapy was delivered at 50 Gy in 5 fractions, either with CTgRT using fiducial placement, deep inspiration breath-hold (DIBH) with real-time position management, and volumetric-modulated arc therapy, or with MRgRT using real-time tumor gating, DIBH, and static-gantry intensity-modulated radiation therapy. RESULTS: Direct clinical costs were $7,306 for CTgRT and $8,622 for MRgRT comprising personnel costs ($3,752 v $3,603), space and equipment costs ($2,912 v $4,769), and materials costs ($642 v $250). Increased MRgRT costs may be mitigated by forgoing CT simulation ($322 saved) or shortening treatment to 3 fractions ($1,815 saved). Conversely, adaptive treatment with MRgRT would result in an increase in cost of $529 per adaptive treatment. CONCLUSION: MRgRT offers real-time image guidance, avoidance of fiducial placement, and ability to use adaptive treatments; however, it is 18% more expensive than CTgRT under baseline assumptions. Future studies that elucidate the magnitude of potential clinical benefits of MRgRT are warranted to clarify the value of using this technology.
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.
Improving the systemic treatment of brain metastases (BM) in primary breast cancer (PBC) is impaired by the lack of genomic characterization of BM. To estimate the concordance of DNA copy-number-alterations (CNAs), mutations, and actionable genetic alterations (AGAs) between paired samples, we performed whole-genome array-comparative-genomic-hybridization, and targeted-next-generation-sequencing on 14 clinical PBC–BM pairs. We found more CNAs, more mutations, and higher tumor mutational burden, and more AGAs in BM than in PBC; 92% of the pairs harbored at least one AGA in the BM not observed in the paired PBC. This concerned various therapeutic classes, including tyrosine-kinase-receptor-inhibitors, phosphatidylinositol 3-kinase/AKT/ mammalian Target of Rapamycin (PI3K/AKT/MTOR)-inhibitors, poly ADP ribose polymerase (PARP)-inhibitors, or cyclin-dependent kinase (CDK)-inhibitors. With regards to the PARP-inhibitors, the homologous recombination defect score was positive in 79% of BM, compared to 43% of PBC, discordant in 7 out of 14 pairs, and positive in the BM in 5 out of 14 cases. CDK-inhibitors were associated with the largest percentage of discordant AGA appearing in the BM. When considering the AGA with the highest clinical-evidence level, for each sample, 50% of the pairs harbored an AGA in the BM not detected or not retained from the analysis of the paired PBC. Thus, the profiling of BM provided a more reliable opportunity, than that of PBC, for diagnostic decision-making based on genomic analysis. Patients with BM deserve an investigation of several targeted therapies.
We present a case of durable local control achieved in a patient treated with stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) for an abdominal lymph node in the setting of oligometastatic breast cancer. A 50-year-old woman with a history of triple positive metastatic invasive ductal carcinoma of the left breast, stage IV (T3N2M1), underwent neoadjuvant chemotherapy, mastectomy, adjuvant radiotherapy and maintenance hormonal treatment with HER2 targeted therapies. At 20 months after definitive treatment of her primary, imaging showed an isolated progressive enlargement of lymph nodes between hepatic segment V/IVB and the neck of the pancreas. Radiofrequency ablation was considered, however, this approach was decided not to be optimal due to the proximity to stomach, and pancreatic duct. The patient was treated with SMART for 40 Gray in 5 fractions. Two and a half years later, the patient remains without evidence of disease progression. She experienced Grade 2 acute and late toxicity that was successfully managed with medications. This experience shows that SMART is a feasible and effective treatment to control the abdominal oligometastatic disease for breast cancer.
Objective: To evaluate the dosimetric ramifications of simultaneously irradiating the prostate and pelvic lymph nodes (PLNs) with a stereotactic body radiotherapy approach based on rigid registration to intraprostatic markers (IPMs). Methods and materials: Nineteen patients received concurrent SBRT to the prostate and PLNs on a phase II clinical trial. The translational and rotation shifts required for rigid registration to bony anatomy and changes in bladder and rectal anatomy were compared between patients with > 90% and < 90% coverage of the nodal clinical target volume (CTVN ) as drawn on fractional kilovoltage cone-beam CTs. Stepwise multivariable regression models evaluated relationships between these anatomical parameters and the change in V100%CTVN. Results: The average V100%CTVN per patient was 92.4 % (IQR, 90.2 – 96.4 %). For five patients (26.3%), the average was 85.0 % (IQR, 82.4–88.3 %). The left-right and superior-inferior translational shifts, sagittal rotational shift, and change in bladder volume were significantly different ( p < 0.05 for all via Student’s t-test). Changes in bladder height, left/right shift, superior/inferior shift, 3-D shift, and axial rotation as significant predictors of change in dosing of V100%CTVN. Conclusion: While simultaneous SBRT to the prostate and PLNs based on rigid registration to IPMs provides adequate PLN coverage in most instances, overall coverage may be lower than anticipated if anatomy is unstable. Careful evaluation of bladder filling on kV-CBCT before treatment may be the most practical method for estimating accuracy prior to treatment. Advances in knowledge: Simultaneous SBRT to the prostate and PLNs based on rigid registration to IPMs provides adequate PLN coverage in most instances.
Abstract. Up to 40% of patients with renal cell carcinoma (RCC) with initially localized disease eventually develop metastasis following nephrectomy. The current standard of care for metastatic RCC (mRCC) is targeted therapy. However, complete response remains rare. A state of oligometastatic disease may exist, in which metastases are present in a limited number of locations; such cases may benefit from metastasis-directed local therapy, based on the evidence supporting resection of limited-volume metastases, allowing for improved disease control. We retrospectively analyzed 7 cases of response of RCC metastases, in patients treated with targeted therapies followed by radiation therapy (RT) of residual metastatic lesions in Paoli-Calmettes Institute (Marseille, France). We analyzed disease response rates, response to sequential strategy, relapse at the irradiated locations and disease evolution. The median follow-up was 34.1 months (range, 19.2-54.5 months). No progression at the irradiated sites was observed. A total of 5 patients had stable disease at the irradiated locations at the last follow-up; 3 remained in complete remission at the assessment, and 2 were stable. Excellent local response and clinical benefit may be achieved without added toxicity. In conclusion, sequential therapeutic strategies with RT following systemic treatment using sunitinib appear to be highly effective in patients with progressive mRCC and prompt the conduction of further confirmatory trials. IntroductionOne-third of patients diagnosed with renal cell carcinoma (RCC) present with metastasis at initial diagnosis and up to 40% of patients with initially localized RCC eventually develop metastasis following radical or partial nephrectomy (1). The current standard of care for patients with metastatic RCC (mRCC) is targeted therapy, which may reduce tumor burden and improve survival rates compared with historical treatments (2). However, complete response to systemic therapy alone remains extremely rare (3). mRCC has long been a disease for which the resection of metastatic deposits has been considered for patient treatment (4). Patients who undergo metastasectomy tend to exhibit a better outcome, independently of their risk score (5).However, in several cases, patients with metastatic disease are either unfit for surgery or have technically unresectable disease and, therefore, non-invasive metastasis-directed therapy for selected patients may be recommended.For patients with metastatic disease progression and for those who present with distant disease, the median survival is ~20 months, with an expected 5-year survival rate of 30% (6).Among patients with mRCC, certain subgroups have been identified with improved prognosis and a prolonged disease course (7). For these patients, management of limited metastatic disease may be beneficial. A state of oligometastasis may exist, in which metastases are present in a limited number of locations and may benefit from metastasis-directed local therapy, based on the evidence supporting resection ...
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