STAT RT: a prospective pilot clinical trial of Scan-Plan-QA-Treat stereotactic body radiation therapy for painful osseous metastases.

BACKGROUND: Planning and treatment of bone metastases with palliative radiotherapy often requires 1-3 weeks, resulting in patient inconvenience and delayed palliation. We developed an expedited workflow that delivers palliative stereotactic body radiation therapy (SBRT) to painful bone metastases in which CT, planning, quality assurance (QA), and initial treatment are performed one day. This prospective pilot clinical trial evaluates the feasibility, safety, efficacy, and patient satisfaction of this workflow. METHODS: Patients with 1-3 painful bone metastases were prospectively enrolled and treated with 2-5 fractions of 5-10 Gy per fraction. Bone pain, opioid use, patient satisfaction, performance status, and quality of life were evaluated prior to and at 1, 4, 8, 12, 26, and 52 weeks post treatment. Outcomes and treatment-related toxicity were analyzed. RESULTS: Twenty-eight patients were enrolled and 37 metastases treated, receiving an average of 21.6 Gy in 3.1 fractions. Median time from CT simulation to 1st treatment was 6.6 hours. Average worst pain scores were significantly lower at all post-treatment time points with maximal response noted at 3 months. Opioid use was not significantly different from baseline at any follow up. Performance status was significantly increased only at week 12. Bone pain quality of life was significantly increased at all time points except at 52 weeks while general quality of life was significantly increased at only weeks 8 and 26. Ninety-two percent of patients reported being mostly or completely satisfied with the treatment results from week 8 until the end of follow-up. There was no grade 3 or higher toxicities. CONCLUSIONS: Results demonstrate that treating bone metastases with palliative SBRT via a multi-fraction Scan-Plan-QA-Treat patient centric workflow is feasible and safe. Although performance status, general quality of life, and opioid use were not significantly altered, patient satisfaction was high with this same-day treatment workflow.

A Novel Form of Breast Intraoperative Radiation Therapy With CT-Guided High-Dose-Rate Brachytherapy: Results of a Prospective Phase 1 Clinical Trial.

PURPOSE: Existing intraoperative radiation therapy (IORT) techniques are criticized for the lack of image guided treatment planning and energy deposition with, at times, poor resultant dosimetry and low radiation dose. We pioneered a novel method of IORT that incorporates customized, computed tomography (CT)-based treatment planning and high-dose-rate (HDR) brachytherapy to overcome these drawbacks: CT-HDR-IORT. METHODS AND MATERIALS: A phase 1 study was conducted to demonstrate the feasibility and safety of CT-HDR-IORT. Eligibility criteria included age ≥50 years, invasive or in situ breast cancer, tumor size <3 cm, and N0 disease. Patients were eligible before or within 30 days of breast-conserving surgery (BCS). BCS was performed, and a multilumen balloon catheter was placed. CT images were obtained, a customized HDR brachytherapy plan was created, and a dose of 12.5 Gy was delivered to 1-cm depth from the balloon surface. The catheter was removed, and the skin was closed. The primary endpoints were feasibility and acute toxicity. Feasibility was defined as IORT treatment interval (time from CT acquisition until IORT completion) ≤90 minutes. The secondary endpoints included dosimetry, cosmetic outcome, quality of life, and late toxicity. RESULTS: Twenty-eight patients were enrolled. The 6-month follow-up assessments were completed by 93% of enrollees. The median IORT treatment interval was 67.2 minutes (range, 50-108 minutes). The treatment met feasibility criteria in 26 women (93%). The dosimetric goals were met in 22 patients (79%). There were no Radiation Therapy Oncology Group grade 3+ toxicities; 6 patients (21%) experienced grade 2 events. Most patients (93%) had good/excellent cosmetic outcomes at the last follow-up visit. CONCLUSIONS: CT-HDR-IORT is feasible and safe. This promising approach for a conformal, image-based, higher-dose breast IORT is being evaluated in a phase 2 trial.

Intraoperative breast radiation therapy with image guidance: Findings from CT images obtained in a prospective trial of intraoperative high-dose-rate brachytherapy with CT on rails.

PURPOSE: Intraoperative radiation therapy (IORT) is an increasingly popular approach to breast conserving therapy in the treatment of early-stage breast cancer. A drawback to IORT compared with postoperative adjuvant radiation therapy is that it is not performed using image guidance. Our aim was to report on how our institution's unique IORT workflow integrates CT image guidance and how these CT images were used intraoperatively to change applicator positioning. METHODS AND MATERIALS: We retrospectively reviewed the first 29 patients who participated in a prospective clinical trial of breast IORT at our institution. All patients underwent lumpectomy, multicatheter balloon placement, intraoperative CT scan, and high-dose-rate brachytherapy treatment delivery to 12.5 Gy to 1 cm from the balloon surface. This report focuses on the intraoperative CT findings that led to clinical changes, followed by repeat CT for IORT treatment planning. RESULTS: After initial intraoperative CT, 7 patients underwent an additional intraoperative CT scan (24.1%). In 6 patients, the initial intraoperative CT scan identified large air cavities and/or poor tissue conformity. This defect could be improved in all patients with adjustment of the balloon applicator before planning and delivering IORT. Intraoperative CT scan was used in one patient to localize a biopsy clip and aided in excision to negative margin. CONCLUSIONS: In our study, intraoperative CT identifies actionable findings in breast IORT, including residual tumor or errors in applicator positioning, in almost 25% of patients. Clinical results of the described trial will serve to further validate this image-guided approach to IORT.

Accelerated partial breast irradiation with brachytherapy: patient selection and technique considerations.

Accelerated partial breast irradiation (APBI) through breast brachytherapy is a relatively recent development in breast radiotherapy that has gained international favor because of its reduction in treatment duration and normal tissue irradiation while maintaining favorable cancer-specific and cosmetic outcomes. Despite the fact that several large national trials have not reported final results yet, many providers are currently offering APBI to select patients and APBI is listed as a treatment option for selecting patients in the National Comprehensive Cancer Network guidelines. Multiple consensus guidelines exist in selecting patients for APBI, some with conflicting recommendations. In this review, the existing patient selection guidelines are reported, compared, and critiqued, grouping them in helpful subcategories. Unique patient and technical selection factors for APBI with brachytherapy are explored.

Leptomeningeal disease following stereotactic radiosurgery for brain metastases from breast cancer.

Leptomeningeal disease (LMD) is a highly aggressive and usually rapidly fatal condition. The purpose of this study is to identify clinical factors that can serve to predict for LMD at the time of stereotactic radiosurgery (SRS) for brain metastases from breast carcinoma. We conducted a retrospective review of patients with brain metastases from breast cancer treated with SRS from 1995 to 2014 at our institution. Clinical, radiographic, and dosimetric data were collected. LMD was diagnosed by cerebrospinal fluid (CSF) cytology or MRI demonstrating CSF seeding. Comparative statistical analyses were conducted using Cox proportional hazards regression, binary logistic regression, and/or log-rank test. 126 patients met inclusion criteria. Eighteen patients (14 %) developed LMD following SRS. From the time of SRS, the actuarial rate of LMD at 12 months from diagnosis of brain metastasis was 9 % (11 patients). Active disease in the chest at the time of SRS was associated with development of LMD (p = 0.038). Factors including receptor status, tumor size, number of intra-axial tumors, cystic tumor morphology, prior WBRT, active bone metastases, and active liver metastases were not significantly associated with the development of LMD. In patients with brain metastasis from breast cancer that undergo SRS, there is a relatively low rate of LMD. We found that while tumor hormonal status, bone metastases, and hepatic metastases were not associated with the development of LMD, active lung metastases at SRS was associated with LMD. Further research may help to delineate a causative relationship between metastatic lung disease and LMD.

Techniques for intraoperative radiation therapy for early-stage breast carcinoma.

Intraoperative radiation therapy (IORT) is a method of accelerated partial breast irradiation developed to replace other longer courses of radiotherapy with a single radiation session administered at the time of breast-conserving surgery. The purpose of this review is to summarize the advantages and disadvantages of breast IORT techniques that are currently available, as well to consider potential alternative techniques for breast IORT or ultra-short course breast radiotherapy. Furthermore, we highlight the published outcomes for the IORT treatment approaches including: electron therapy, superficial photon therapy and other techniques. Potential future directions of IORT are explored including novel IORT techniques utilizing intraoperative brachytherapy with in-room imaging and rapid treatment planning.

Dosimetric comparison of (192)Ir high-dose-rate brachytherapy vs. 50 kV x-rays as techniques for breast intraoperative radiation therapy: conceptual development of image-guided intraoperative brachytherapy using a multilumen balloon applicator and in-room CT imaging.

PURPOSE: At our institution, the availability of a shielded procedure room with in-room CT-on-rails imaging allows for the exploration of a high-dose-rate (HDR) brachytherapy approach for breast intraoperative radiation therapy (IORT). We hypothesize that HDR brachytherapy will permit a higher prescription dose without increasing toxicity. In this study, we compare the dosimetry of intraoperative HDR brachytherapy, using multilumen balloon applicator, to IORT with a 50 kV source and then select a prescription dose for a subsequent clinical trial. METHODS AND MATERIALS: The CT scans of 14 patients who had previously received multilumen balloon-based breast brachytherapy were replanned to a standard prescription to the target volume. The same 14 cases were planned to the specifications of a 50 kV x-ray system. Uniform volume optimization and prescription doses were used to permit direct comparisons. All plans were evaluated for the dose homogeneity index, tumor coverage, and dose to normal tissues, including skin, ribs, and heart (for left breast plans). RESULTS: The HDR brachytherapy plans were superior to 50 kV superficial photon plans for IORT in all dosimetric parameters except for the heart and rib dosimetric parameters. Prescription dose of 12.5 Gy to the planning target volume for evaluation yielded a dose to 95 percent of the balloon surface of 19.7 Gy. CONCLUSIONS: Image-guided HDR intraoperative brachytherapy with a multilumen balloon applicator provides superior target volume coverage compared with 50 kV photons, while maintaining doses within tolerance limits for normal tissues. An ongoing prospective clinical trial will evaluate the safety and feasibility of this technique.

A comparative analysis of 3D conformal deep inspiratory-breath hold and free-breathing intensity-modulated radiation therapy for left-sided breast cancer.

Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratory-breath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumes of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p<0.05) in 3D-DIBH for volumes receiving 5% to 80% of the prescription dose for the heart and 5% for the LAD. Mean dose to the LAD and heart were lower in 3D-DIBH (p≤0.01). Mean volumes of the total lung were lower in FB-IMRT for dose levels 20% to 75% (p<0.05), but mean dose was not different. Mean volumes of the right breast were not different for any dose; however, mean dose was lower for 3D-DIBH (p = 0.04). 3D-DIBH is an alternative approach to FB-IMRT that provides a clinically equivalent treatment for patients with left-sided breast cancer while sparing organs at risk with increased ease of implementation.

Primary pericardial malignant mesothelioma and response to radiation therapy.

We report a case of a primary pericardial malignant mesothelioma. A 59-year-old male presented with episodic chest pain and dyspnea on exertion. Cardiac magnetic resonance imaging revealed a large mass in the pericardium attached to the right ventricle. Partial resection of the mass was undertaken revealing malignant mesothelioma, byphasic type. The patient was treated with chemotherapy intermittently over a period of 3 years, but his disease continued to progress. The patient was then treated with definitive radiation therapy to 64 Gy to the primary tumor using a six field 3D conformal technique. The patient remains free of progressive disease 86 months from the time of diagnosis and 50 months from the completion of his radiotherapy.

Treatment of primary liver tumors with Yttrium-90 microspheres (TheraSphere) in high risk patients: analysis of survival and toxicities.

This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3-5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.

Semiconductor nanoparticles as energy mediators for photosensitizer-enhanced radiotherapy.

PURPOSE: It has been proposed that quantum dots (QDs) can be used to excite conjugated photosensitizers and produce cytotoxic singlet oxygen. To study the potential of using such a conjugate synergistically with radiotherapy to enhance cell killing, we investigated the energy transfer from megavoltage (MV) X-rays to a photosensitizer using QDs as the mediator and quantitated the enhancement in cell killing. METHODS AND MATERIALS: The photon emission efficiency of QDs on excitation by 6-MV X-rays was measured using dose rates of 100-600 cGy/min. A QD-Photofrin conjugate was synthesized by formation of an amide bond. The role of Förster resonance energy transfer in the energy transferred to the Photofrin was determined by measuring the degree of quenching at different QD/Photofrin molar ratios. The enhancement of H460 human lung carcinoma cell killing by radiation in the presence of the conjugates was studied using a clonogenic survival assay. RESULTS: The number of visible photons generated from QDs excited by 6-MV X-rays was linearly proportional to the radiation dose rate. The Förster resonance energy transfer efficiency approached 100% as the number of Photofrin molecules conjugated to the QDs increased. The combination of the conjugate with radiation resulted in significantly lower H460 cell survival in clonogenic assays compared with radiation alone. CONCLUSION: The novel QD-Photofrin conjugate shows promise as a mediator for enhanced cell killing through a linear and highly efficient energy transfer from X-rays to Photofrin.