Novel hyaluronan formulation for preventing acute skin reactions in breast during radiotherapy: a randomized clinical trial.

PURPOSE: We conducted a randomized, double-blind, vehicle-controlled clinical trial to investigate the use of a new proprietary hyaluronan (HA) formulation for the prevention of acute skin toxicity in breast cancer patients undergoing radiotherapy (RT). METHODS: Thirty women with breast cancer undergoing whole breast RT were enrolled. Each patient was randomly assigned to HA formulation (study cream, S) on the medial or lateral half of the irradiated breast and the control cream (placebo, P) on the other half. The primary endpoint was physician's evaluation of skin symptoms at week 5 during RT and week 2 post-RT. We also collected patients' independent assessment of skin after RT, patient's product preference, and an independent physician panel assessment of skin reactions based on photographs. RESULTS: Twenty-eight patients were evaluable. On physician's evaluation, there was no significant difference in radiation dermatitis between S and P and no overall preference to either cream at week 5 during or week 2 post-RT. More patients preferred S in evaluating skin appearance and skin reactions, but this did not reach statistical significance. Univariate analysis showed that physicians had an overall preference to the S cream at week 2 post-RT in patients with larger breasts. On the independent panel assessment, 3 reviewers saw no significant difference in radiation toxicity, whereas one reviewer reported better skin outcome with S cream at week 5. CONCLUSIONS: We found a nonstatistically significant patient preference but overall no significant radioprotective effects for this HA formulation compared with placebo except in patients with larger breasts. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov (NCT02165605).

Ultrasound-Guided Placement of Gold Fiducial Markers for Stereotactic Partial-Breast Irradiation.

OBJECTIVE: A novel technique of placing gold fiducial markers in the breast using ultrasound guidance was developed and performed in 51 of 55 consecutive postlumpectomy patients enrolled in a phase I dose escalation trial of accelerated partial-breast irradiation (APBI) using robotic-based stereotactic body radiation therapy (SBRT). CONCLUSION: All 51 postoperative patients underwent successful fiducial placement without complications. Our technique of placing gold fiducial markers in proximity to the seroma cavity is considered safe and effective for breast cancer patients being treated with APBI using robotic-based SBRT.

Cosmetic Outcomes of a Phase 1 Dose Escalation Study of 5-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer.

PURPOSE: Our purpose was to evaluate cosmetic changes after 5-fraction adjuvant stereotactic partial breast irradiation (S-PBI). METHODS AND MATERIALS: Seventy-five women with in situ or invasive breast cancer stage 0, I, or II, with tumor size ≤3 cm, were enrolled after lumpectomy in a phase 1 dose escalation trial of S-PBI into cohorts receiving 30, 32.5, 35, 37.5, or 40 Gy in 5 fractions. Before S-PBI, 3 to 4 gold fiducial markers were placed in the lumpectomy cavity for tracking with the Synchrony respiratory tracking system. S-PBI was delivered with a CyberKnife robotic radiosurgery system. Patients and physicians evaluated global cosmesis using the Harvard Breast Cosmesis Scale. Eight independent panelists evaluated digital photography for global cosmesis and 10 subdomains at baseline and follow-up. McNemar tests were used to evaluate change in cosmesis, graded as excellent/good or fair/poor, from baseline to year 3. Wilcoxon signed rank tests were used to evaluate change in subdomains. Cohen's kappa (κ) statistic was used to estimate interobserver agreement (IOA) between raters, and Fleiss' κ was used to estimate IOA between panelists. RESULTS: Median cosmetic follow-up was 5, 5, 5, 4, and 3 years for the 30, 32.5, 35, 37.5, and 40 Gy cohorts. Most patients reported excellent/good cosmesis at both baseline (86.3%) and year 3 (89.8%). No dose cohort had significantly worsened cosmesis by year 3 on McNemar analysis. No cosmetic subdomain had significant worsening by year 3. IOA was fair for patient-physician (κ = 0.300, P < .001), patient-panel (κ = 0.295, P < .001), physician-panel (κ = 0.256, P < .001), and individual panelists (Fleiss κ = 0.327, P < .001). CONCLUSIONS: Dose escalation of S-PBI from 30 to 40 Gy in 5 fractions for early stage breast cancer was not associated with a detectable change in cosmesis by year 3. S-PBI is a promising modality for treatment of early stage breast cancer.

Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation.

PURPOSE: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. METHODS AND MATERIALS: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohort to 40 Gy. RESULTS: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. CONCLUSION: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for early-stage breast cancer in the adjuvant setting.

Prophylactic cranial irradiation with combined modality therapy for patients with locally advanced non-small cell lung cancer.

Central nervous system (CNS) metastasis is a significant problem for many patients with non-small cell lung cancer (NSCLC). The earlier data reported a high incidence of CNS metastasis in patients with locally advanced NSCLC who were treated with radiotherapy alone. However, poor control of both thoracic and extracranial systemic disease dominated the results of the early trials. The risk for CNS metastasis as the first site of failure remains a significant concern for patients who have completed modern combined modality therapy. With improvements in the treatment of thoracic and systemic disease, there is renewed interest in prophylactic cranial irradiation (PCI). The results from the Radiation Therapy Oncology Group (RTOG) trial of PCI to prevent CNS relapse in patients with locally advanced NSCLC are anticipated.

Radiation practice patterns among United States radiation oncologists for postmastectomy breast reconstruction and oncoplastic breast reduction.

BACKGROUND: For patients requiring radiation therapy following mastectomy or breast reconstruction, there often exist much heterogeneity among practitioners with respect to radiation technique. METHODS AND MATERIALS: A 14-question survey was sent nationwide to 1000 active email addresses from the American Society for Radiation Oncology member directory; 271 radiation oncologists completed the survey. RESULTS: A total of 75.2% of respondents indicate that they do not routinely deflate the ipsilateral tissue expander (TE) prior to radiation, while 11.5% do routinely deflate (P ≤ .01); 52.2% indicate that they typically use bolus when treating their patients with TEs following mastectomy, 36.7% do not, and 11.1% on a case by case basis (P ≤ .01). Of respondents indicating bolus utilization, 32.8% use a bolus of 0.5 cm every other day; 31.4% indicate a bolus of 0.5 cm every day until tolerated; 20.4% use a bolus of 1 cm every other day; 5.8% indicate a bolus of 1 cm every day until tolerated; and 9.5% indicate a customized bolus approach (P ≤ .01). A total of 22.9% of respondents deliver boost to all patients with TE while 42.9% deliver boost only to select patients, and 33.5% indicate no utilization of boost (P ≤ .01). A total of 33.1% indicate that collaborating surgeons routinely place clips at the lumpectomy cavity at the time of breast reduction or complex tissue rearrangement, while 38.3% indicate that clips are occasionally placed, and 28.6% stated clips are not routinely placed (P = .15); 38.7% of respondents routinely deliver a boost for patients undergoing breast reduction only if clips have been placed in the tumor cavity, while 34.6% indicate that a boost is used regardless of clip placement. CONCLUSIONS: Radiation treatments with tissue expanders have become common practice, but details of radiation treatment vary widely. Radiation oncologist and breast surgeons should continue to work to optimize radiation techniques and allow proper localization for radiation boost.